EMJ Urology 12.1 2024

Urology

Review of

Congress 2024

Courtney Rowe and Jas Singh discuss robotic surgery and reconstructive urology Interviews

Advancements in Prostate Cancer Management Feature

28 Results of Buccal Mucosa Graft Urethroplasty With or Without Reconstruction of the Meatus

Borisenkov and Pandey

41 Contemporary Views on Performance Indicators with Audit-Feedback for Bladder Cancer Treatment

Paramananthan Mariappan

Artificial Intelligence in Robotic Urologic Surgery

Defining Urethral Complications of Intermittent Catheterisation Using Hydrophilic Catheters: A Scoping Review

Linsenmeyer et al. 68 Ureterocutaneous Fistula in the Setting of Recurrent Gluteal Abscesses: A Case Report

Alapatt et al. 74 Incidental Zinner Syndrome in Nigeria: A Case Report

Takure et al.

Editorial Board

Editor-in-Chief

Dr Abdullah Erdem Canda Koç University, Türkiye

Editorial Board

Prof Riccardo Autorino Rush University, Chicago, Illinois, USA

Prof Dr Jean de la Rosette Academic Medical Center, the Netherlands

Dr Selçuk Güven Necmettin Erbakan University, Türkiye

Prof Jørgen Bjerggaard Jensen Aarhus University Hospital, Denmark

Mr Marius Rebek The Princess Alexandra Hospital NHS Trust, Harlow, UK

Dr Roberto Sanseverino Azienda Sanitaria Locale Salerno, Italy

Dr Alan J Wein University of Pennsylvania, Philadelphia, USA

Prof Henry Woo University of Sydney, Australia

Aims and Scope

EMJ is an online only, peer-reviewed, open access general journal, targeted towards readers in the medical sciences. We aim to make all our articles accessible to readers from any medical discipline.

EMJ allows healthcare professionals to stay abreast of key advances and opinions across Europe.

EMJ aims to support healthcare professionals in continuously developing their knowledge, effectiveness, and productivity. The editorial policy is designed to encourage discussion among this peer group.

EMJ is published quarterly and comprises review articles, case reports, practice guides, theoretical discussions, and original research.

EMJ also publishes 18 therapeutic area journals, which provide concise coverage of salient developments at the leading European congresses. These are published annually, approximately 6 weeks after the relevant congress. Further details can be found on our website: www.emjreviews.com

Editorial Expertise

EMJ is supported by various levels of expertise:

• Guidance from an Editorial Board consisting of leading authorities from a wide variety of disciplines.

• Invited contributors are recognised authorities from their respective fields.

• Peer review, which is conducted by EMJ’s Peer Review Panel as well as other experts appointed due to their knowledge of a specific topic.

• An experienced team of editors and technical editors.

Peer Review

On submission, all articles are assessed by the editorial team to determine their suitability for the journal and appropriateness for peer review.

Editorial staff, following consultation with either a member of the Editorial Board or the author(s) if necessary, identify three appropriate reviewers, who are selected based on their specialist knowledge in the relevant area.

All peer review is double blind. Following review, papers are either accepted without modification, returned to the author(s) to incorporate required changes, or rejected.

Editorial staff have final discretion over any proposed amendments.

Submissions

We welcome contributions from professionals, consultants, academics, and industry leaders on relevant and topical subjects.

We seek papers with the most current, interesting, and relevant information in each therapeutic area and accept original research, review articles, case reports, and features.

We are always keen to hear from healthcare professionals wishing to discuss potential submissions, please email: editorial.assistant@emjreviews.com

To submit a paper, use our online submission site: www.editorialmanager.com/e-m-j

Submission details can be found through our website: www.emjreviews.com/contributors/authors

Reprints

All articles included in EMJ are available as reprints (minimum order 1,000). Please contact hello@emjreviews.com if you would like to order reprints.

Distribution and Readership

EMJ is distributed through controlled circulation to healthcare professionals in the relevant fields across Europe.

Indexing and Availability

EMJ is indexed on DOAJ, the Royal Society of Medicine, and Google Scholar®; selected articles are indexed in PubMed Central®.

EMJ is available through the websites of our leading partners and collaborating societies.

EMJ journals are all available via our website: www.emjreviews.com

Open Access

This is an open-access journal in accordance with the Creative Commons Attribution-Non Commercial 4.0 (CC BY-NC 4.0) license.

Congress Notice

Staff members attend medical congresses as reporters when required.

This Publication

ISSN 2053-4213

EMJ Urology is published once a year. For subscription details please visit: www.emjreviews.com

All information obtained by EMJ and each of the contributions from various sources is as current and accurate as possible. However, due to human or mechanical errors, EMJ and the contributors cannot guarantee the accuracy, adequacy, or completeness of any information, and cannot be held responsible for any errors or omissions. EMJ is completely independent of the review event (EAU 2024) and the use of the organisations does not constitute endorsement or media partnership in any form whatsoever.

Front cover and contents photograph: Paris, France home of the EAU 2024 © Givaga / stock.adobe.com

EMJ Podcasts

The EMJ Podcast aims to provoke conversations around the latest trends and innovations in healthcare, provide engaging and educational content for healthcare professionals, and hosts conversations with physician entrepreneur, Jonathan Sackier.

Listen today

www.emjreviews.com

Editor

Evgenia Koutsouki

Editorial Managers

Anaya Malik, Darcy Richards

Copy Editors

Noémie Fouarge, Katheeja Imani, Jenna Lorge

Editorial Co-ordinators

Abigail Craig

Editorial Assistants

Victoria Antoniou, Ada Enesco, Helena Bradbury, Ellen Charge, Laith Gergi, Aleksandra Zurowska

Creative Director

Tim Uden

Design Manager

Stacey Rivers

Senior Designer

Roy Ikoroha, Steven Paul

Designers

Owen Silcox

Junior Designers

Dillon Benn Grove, Shanjok Gurung

Head of Sales

Robert Hancox

Senior Project Manager

Michael Stevenson

Marketing Director

Kristina Mestsaninova

Chief Content Officer

Justin Levett

Chief Commercial Officer

Dan Healy

Founder and Chief

Executive Officer

Spencer Gore

Welcome letter

Dear Readers,

Evgenia Koutsouki Editor

It is with great pleasure that I welcome you to the 2024 issue of EMJ Urology, featuring content from the 39th European Association of Urology (EAU) Annual Congress. Among key themes discussed in this year’s congress were the emerging role of artificial intelligence in urology, advances in kidney stone management, improvement of prostate cancer diagnosis and staging, and novel treatments for urologic cancer.

Our review of EAU24 contains an in-depth report of a joint session on prostate cancer management, and a selection of abstracts on topics ranging from a bladder cancer scoring system to urethroplasty and other surgical procedures.

We are also proud to feature interviews with experts who discuss advances in reconstructive urology, robotic surgery, and patient care.

Make sure not to miss our infographic, which explores how artificial intelligence can help overcome challenges in robotic surgery, and what the future holds.

Finally, you will find two interesting case reports discussing incidental Zinner syndrome in Nigeria, and a ureterocutaneous fistula in the setting of recurrent gluteal abscesses.

I would like to close by thanking our amazing contributors, reviewers, and Editorial Board for ensuring the high quality of content in this issue. Until our next issue in 2025, I hope you enjoy reading through the journal!

Contact us

Editorial enquiries: editor@emjreviews.com

Sales opportunities: salesadmin@emjreviews.com

Permissions and copyright: accountsreceivable@emjreviews.com

Reprints: info@emjreviews.com

Media enquiries: marketing@emjreviews.com

Foreword

Dear Colleagues,

It is a great pleasure for me to welcome you to the latest edition of EMJ Urology.

From reconstructive urology to robotic surgery, this new issue covers innovative topics in the field, exploring the evolving landscape of urology practice. You can find a selection of peer-reviewed articles, abstracts, interviews with specialty leaders, and a review of the 39th European Association of Urology (EAU) Congress, Europe’s biggest urological event. Every year, EAU attracts great attention worldwide, and the 2024 meeting was no different. Held in the vibrant French capital, EAU24 offered a range of cutting-edge lectures, video surgery sessions, and hands-on training courses, shaping the next generation of urologists.

Our peer-reviewed articles present crucial insights into rare urologic anomalies, including Zinner syndrome and ureterocutaneous fistula, guiding clinicians in the diagnosis and management of complex, and often underdiagnosed, conditions. In this issue, you will also find an infographic on the emerging role of artificial intelligence in robotic surgery, a fascinating topic for clinicians in the field, as well as interviews with experts in paediatric urology, reconstructive urology, and robotics.

I would like to take this opportunity to thank all of the contributors for this issue, and invite you all to submit your work to EMJ Urology

I hope you enjoy reading the new issue!

A. Erdem Canda Professor of Urology, Koç University School of Medicine, Department of Urology, Istanbul, Türkiye

EAU 2024

Review of the European Association of Urology (EAU) Congress 2024

Location: Paris, France

Date: 5th–8th April 2024

Citation: EMJ Urol. 2024;12[1]:10-16. https://doi.org/10.33590/emjurol/GQMH4154.

THIS YEAR, the vibrant French capital provided the backdrop for Europe’s biggest urological event, with over 10,000 attendees travelling to Paris for the 39th European Association of Urology (EAU) Congress. Featuring talks by nearly 1,000 speakers from 124 countries, EAU24 offered a packed 4-day programme, with live surgeries, state-of-the-art lectures, and insightful case discussions and debates on cutting-edge science.

The EAU Secretary General, Arnulf Stenzl, extended a warm welcome to all congress attendees in the opening ceremony, which featured a dazzling performance by the Parisian cabaret dance show. He began by highlighting the importance of collaboration in urology, acknowledging that the success of EAU would not be possible without teamwork. Stenzl also noted that the time and effort of devoted individuals is equally valuable to the field of urology, and every year, EAU recognises these exceptional personalities with the prestigious EAU Annual Awards.

The award presentations kicked off with the introduction of two new EAU honorary members, Hassan Aboul-Enein, from Mansoura University Urology and Nephrology Center, Egypt; and Jens Rassweiler, from Heidelberg University, Germany. Nicolas Mottet, Centre Hospitalier Universitaire de Saint-Étienne, Saint-Priest-enJarez, France, was presented with the EAU Willy Gregoir Medal, for his significant contributions to the development of urology in Europe, and

his service to the EAU guidelines. Christopher Chapple, Sheffield Teaching Hospitals, UK, was honoured with the EAU Frans Debruyne Lifetime Achievement Award, for his enduring contributions to the activities and growth of the EAU.

"The success of EAU would not be possible without teamwork."

A key focus of the EAU is to acknowledge young urological academic talent, offering the opportunity for young urologists to be seen by the urology community, and rewarded for their work in the field. Giorgio Gandaglia, San Raffaele Hospital, Milan, Italy, received the EAU Crystal Matula Award, a prestigious prize given to a promising urologist aged 40 years or under, who has the potential to become a future leader in European urology. This year, innovation in urology was also celebrated in the opening ceremony, with the EAU Innovators in Urology Award presented to Prokar Dasgupta, King’s College London, UK, a pioneer in robotic surgery, who recently completed his 10,000th robotic procedure.

Further awards were granted to David D’Andrea, Medical University of Vienna, Austria, for the best European paper published on minimally invasive surgery in urology; and Ivo de Vos, Erasmus Medical Center, Rotterdam, the Netherlands, for the best paper published on clinical or

experimental studies in prostate cancer. For his outstanding contributions to patient advocacy, Erik Briers, Europa Uomo, Antwerp, Belgium, was awarded the EAU Patient Advocacy Medal of Excellence.

The comprehensive programme of EAU24 reached far beyond Europe, with speakers from Asia, Africa, North and South America, and Australia joining the European experts in 14 ‘Urology Beyond Europe’ sessions, to discuss current challenges, and look ahead into the next decade of urology. Key themes from these joint sessions included the emerging role of artificial intelligence in robotics, advances in kidney stone management, improvement of prostate cancer diagnosis and staging, and novel treatments for urologic cancers. These innovative topics

were also reflected in EAU24’s award-winning abstracts. Oliver Wiseman, Addenbrookes Hospital, Cambridge, UK, was awarded first prize in a non-oncology speciality for his abstract on flexible ureterorenoscopy and extracorporeal shockwave lithotripsy for lower pole stones. Colin Belliveau, Centre Hospitalier de l'Université de Montréal, Canada, was given the first prize in oncology abstracts, for his work on PSMA-PETguided intensification of salvage radiotherapy after radical prostatectomy in a Phase II randomised controlled trial.

Read on for more highlights from EAU24, and come back next year for our coverage of EAU25, which will be held in Madrid, Spain, from the 21st–24th March. ●

A Targeted Approach to Bladder Cancer Treatment

RECENT findings presented at the 39th EAU Congress in Paris, France, could shift the treatment landscape for bladder cancer towards more effective, targeted therapies.

Results from IMvigor011, a global, double-blind, randomised Phase III trial, revealed that >90% of patients with muscle-invasive bladder cancer (MIBC) who had a negative circulating DNA test following surgery, and remained negative on follow-up for up to 2 years (N=171), did not relapse. These outcomes were irrespective of the stage the tumour was at, or whether it showed elevated levels of PD-L1. “Focusing treatment on those at risk and sparing the very low-risk group potentially life-altering treatment-related side effects is attractive,” stated lead author Thomas Powles, Barts Cancer Institute, Queen Mary University of London, UK.

CheckMate 274, another global, randomised Phase III trial, evaluated the efficacy of nivolumab in high-risk MIBC after surgery. Over 700 patients were included in the study, with half given nivolumab, and half given placebo, every 2 weeks for the 12 months following radical cystectomy. Levels of PD-L1, which is specifically targeted by nivolumab, were also tested for each patient.

Results showed that patients with MIBC on nivolumab had an average of 22 months before recurrence, compared to 10 months for those on placebo. Furthermore, in the PD-L1 group, patients on nivolumab had an average of over 4 years without recurrence, compared to just over 8 months for those on placebo.

Although still at an early stage, the latest findings reveal that patients on nivolumab survive on average for nearly 6 years (69.5 months), compared to just over 4 years (50.1 months) for those on placebo. “Although we already knew that nivolumab improved disease-free survival in muscle-invasive urothelial carcinoma patients who received radical surgery, overall survival is what really matters following local treatment, such as radical surgery. These interim findings, which show that overall survival also improves, are very encouraging, particularly as this hasn’t been the case in other recent immunotherapy trials," explained Joost Boorman, Erasmus University Medical Centre, Rotterdam, the Netherlands, who chaired the session where both trials were presented. While the team currently does not have enough follow-up data to separate the PD-L1 group, analyses show that overall survival is likely to be even higher for this group. ●

"Patients on nivolumab survive on average for nearly 6 years compared to just over 4 years for those on placebo."

Prostate Cancer Screening: Longer Intervals Explored

LOW-RISK males can undergo prostate cancer screening every 5 years through a simple blood test, according to a recent study presented at the EAU 2024 Congress in Paris, France. The prostate-specific antigen (PSA) blood test checks the level of PSA, a marker for prostate cancer. The study, conducted in Germany, focused on over 12,500 male participants aged 45–50 enrolled in the ongoing PROBASE trial. This trial aimed to determine effective screening protocols for prostate cancer.

Participants were divided into three groups based on their initial PSA levels. Those with PSA levels under 1.5 ng/mL were considered low-risk and underwent a follow-up test after 5 years. Those with PSA levels between 1.5–3 ng/mL were deemed intermediate risk, and had a follow-up in 2 years, while those with PSA levels over 3 ng/ mL were considered high-risk and received an MRI and biopsy.

Over 20,000 male participants were recruited and identified as low-risk; among these, 12,517 retested at age 50, only 1.2% had elevated PSA levels, leading to further MRI and biopsies. Ultimately, only 0.13% of the total cohort were diagnosed with prostate cancer.

Lead researcher Peter Albers, Heinrich Heine University Düsseldorf, Germany, suggests raising the threshold for low-risk from 1 ng/mL to 1.5 ng/ mL could allow for longer screening intervals, potentially up to 7, 8, or 10 years, with minimal

additional risk. This could have significant implications, given the large number aged between 45–50 in Europe.

Prostate cancer screening has always been a concern because of false positives and false negatives. However, advancements such as MRI scans and active surveillance are changing the landscape, enabling more precise diagnosis and management.

Prostate cancer screening guidelines in Europe are inconsistent and unclear, leading to varied levels of testing, and unequal access to early detection. Katharina Beyer, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands, said: “Some countries' guidelines are actively against screening; others are non-committal; and a few, such as Lithuania, have some form of screening.” This makes access to tests depend on individual requests, disadvantaging the less informed, and highlighting disparities in early diagnosis. Philip Cornford, Liverpool University Hospitals National Health Service (NHS) Trust, UK, and Chair, European Association of Urology (EAU) Prostate Cancer Guidelines Committee, noted similar issues in the UK.

There is a need for more organised prostate cancer screening, and each country must design a screening programme that suits them the best. ●

"Prostate cancer screening has always been a concern because of false positives and false negatives."

Oral Vaccine for Urinary Tract Infection: Potential Alternative

To Antibiotics?

FINDINGS from a study conducted at the Royal Berkshire Hospital, Reading, UK, were recently presented at the 39th EAU Congress in Paris, France. Summarising their latest abstract, titled ‘Assessing the long-term efficacy and safety of Uromune® bacterial vaccine in the initial cohort: a 9-year study in the UK for treating recurrent urinary tract infections in men and women', the team detailed the promising potential of new vaccine, MV140, for recurrent urinary tract infections (UTI).

UTIs are a prevalent bacterial infection affecting both males and females, characterised by abdominal pain, fever, frequent urination, and in some cases, haematuria. The MV140 vaccine was trialled as a treatment option for those suffering with recurrent UTIs. Bob Yang, Royal Berkshire National Health Services (NHS) Foundation Trust, UK, who co-led the research, stated: “Before having the vaccine, all our participants suffered from recurrent UTIs, and for many women, these can be difficult to treat." Developed by ImmunoTek (Southlake, Texas, USA), MV140 contains four bacterial species in a suspension of water, and is available off-license in 26 countries. The study itself was comprised of 72 females and 17 males, all aged over 18

years, and UTI-free when initially offered the vaccine. It was administered with two sprays of a pineapple-flavoured suspension under the tongue every day for 3 months.

"This follow-up data suggests it could be a game changer for UTI prevention if it’s offered widely."

Remarkably, 48% of all participants reported being infection-free during the 9-year followup. The average infection-free time across the cohort was 54.7 months (56.7 months for females; 44.3 months for males). Expressing optimism, Yang commented: “This is a very easy vaccine to administer, and could be given by general practitioners as a 3-month course. Many of our participants told us that having the vaccine restored their quality of life. While we’re yet to look at the effect of this vaccine in different patient groups, this follow-up data suggests it could be a game changer for UTI prevention if it’s offered widely, reducing the need for antibiotic treatments.” ●

Urine Test Proves A Valid Alternative to Painful Cystoscopies

A SIMPLE urine test can reduce the number of cystoscopies necessary in follow-up of patients at high risk of bladder cancer by over half, according to new research presented at the EAU Annual Congress 2024. Cystoscopies are generally safe procedures; however, they cause pain and discomfort, and can lead to urinary infections and bleeding. A study conducted by Thomas Dreyer, Aarhus University Hospital, Denmark, has shown that these procedures could be avoided in a large number of patients.

"It reduces demand on our resources and helps to make healthcare more accessible."

Dreyer and colleagues recruited 313 patients, half of whom received the standard three cystoscopies per year. The other half were randomised to receive just one cystoscopy per year, with their remaining two follow-up cystoscopies replaced with the Xpert® Bladder Cancer Monitor (Cepheid, Sunnyvale, California, USA) urine biomarker test. This test monitors patients for recurrence of bladder cancer by measuring levels of five target mRNAs, or genetic markers. The researchers chose to trial this particular biomarker test as it had previously shown promising results in patients at high-risk of bladder cancer. Any patients who received a positive result on their urine test were called

into the hospital for a cystoscopy to check for evidence of the cancer returning.

After 2 years, only 44% of follow-up appointments involved a cystoscopy amongst the patients primarily receiving the urine test, compared to nearly 100% in those receiving the standard treatment. The team additionally found that the urine test had the potential to pick up cancer recurrence before any disease was visible through the cystoscopy. Many patients had a ‘false positive’ test, in which the urine test was positive but the cystoscopy was clear, of whom more than 50% showed evidence of recurrence at a later visit.

The research team concluded that a urine test can provide an painless alternative to a cystoscopy in many cases, which is preferable for many patients, who dread their follow-up appointments. Other experts in the field are hopeful that this research may change clinical practice going forward, commenting: “This trial shows us a possible means of reducing cystoscopies. If the final results later this year do confirm that the urine test can pick up cancer recurrence as effectively as cystoscopies, then this is something we need to look at introducing into clinical practice as soon as possible, because it reduces demand on our resources and helps to make healthcare more accessible.” ●

App-Based Therapy Revamps Bladder Emptying Disorders Treatment

COMBINING pelvic floor exercises and behavioural therapy could be more effective than current medical treatments at helping males with frequent urges to urinate, according to initial findings presented at the EAU 2024 Annual Congress. Bladder emptying disorders affect a large proportion of males aged over 50, creating an estimated annual cost of 7 billion EUR across Europe.

"Making this form of therapy available digitally could be a game changer."

Clinical guidelines currently recommend physiotherapy, behavioural therapy, and lifestyle changes; however, due to a lack of evidence, these are often overlooked by clinicians. The bladder emptying disorder therapy trial is the world’s first randomised controlled trial to look at the combination of pelvic floor training, behavioural therapy, and bladder control techniques for mild, moderate, and severe bladder emptying disorders in males; all delivered as a convenient app-based therapeutic.

The 12-week study looked at 237 males aged over 18 years from across Germany. Patients

were separated into two randomised groups, with one receiving standard medical care, and the other given access to the Kranus Lutera (Kranus Health, Munich, Germany) app-based therapy alongside standard care. Throughout the study, participants were requested to keep a urination diary, and to complete questionnaires that looked both into the severity of their symptoms and their overall quality of life.

Initial results have revealed that the app-based therapy led to significant improvements in urinary tract symptoms, including hesitancy, straining, frequent urges to urinate, and emptying the bladder effectively. However, the study only compared data of patients experiencing symptoms due to an overactive bladder or an enlarged prostate; other forms of bladder emptying disorder were not compared.

Christian Gratzke, University Hospital Freiburg, Freiburg im Breisgau, Germany, who co-led the trial, said: “Up until now, there has been little data available to back physiotherapy. We’re confident that we now have that data, and making this form of therapy available digitally could be a game changer for the millions of males who struggle day-to-day with issues emptying their bladder.” ●

Advancements in Prostate Cancer Management

Authors: Helena Bradbury, EMJ, London, UK

Citation: EMJ Urol. 2024;12[1]:17-20. https://doi.org/10.33590/emjurol/YYYW6494.

The 39ᵗʰ Annual Congress for the European Association of Urology (EAU) was held in the vibrant city of Paris, France, between 5ᵗʰ–8ᵗʰ April 2024. A joint session co-organised by the EAU and the American Confederation of Urology (CAU) featured outstanding talks relating to the management of malignant and benign genito-urinary diseases. Experts from around the world gathered to delve into the latest innovations, research findings, and clinical practices shaping the field of urology.

IS PROSTATE MRI THE NEW GOLD STANDARD?

Marcelo Langer Wroclawski, Centro Universitário Faculdade de Medicina do ABC, Santo André, Brazil, opened his talk with an alarming statistic: over 50,000 new cases of prostate cancer are diagnosed every year. Whilst conventional screening reduces the relative risk of death from prostate cancer by approximately 20%, this carries a risk of overdiagnosis. This leads to overtreatment, with over 40% of patients treated with radiotherapy or chemotherapy, even if diagnosed with low-risk prostate cancer. In an effort to combat overdiagnosis and overtreatment, Wroclawski stressed the need for a diagnostic tool, with a high negative predictive value, so that biopsies are only performed for those who really need it.

According to Wroclawski, the solution is MRI. The Prostate Imaging-Reporting and Data System (PI-RADS) is a scoring tool used by radiologists to determine the likelihood of prostate cancer; a score of 1 means a low probability of prostate cancer, and a score of 5 means a high probability that you have prostate cancer that needs to be treated. The incidence of clinically significant prostate cancer for PIRADS 1, 2, 3, 4 (positive), and 5 (positive), was 2%, 4%, 20%, 52%, and 89%, respectively. As highlighted by Wroclawski, the integration of a pre-biopsy MRI stage allows us to move to a more tailored approach

in identifying patients that should proceed with biopsies. This approach was shown to increase the detection of clinically significant prostate cancer cases by 18%, as well as decreasing the detection of clinically insignificant cases by 40%, and avoiding unnecessary biopsies, which carry their own set of complications, in 49% of cases.

UPDATE ON PROSTATE-SPECIFIC ANTIGEN PET/CT

Wolfgang Fendler, Department of Nuclear Medicine, University of Duisburg-Essen, and German Cancer Consortium-University Hospital Essen, Germany, subsequently provided an update on the use of prostate-specific membrane antigen (PSMA)-PET/CT imaging for prostate cancer detection. PSMA is a glutamate carboxypeptidase II that is highly expressed in primary and metastatic prostate cancer, and is thus targeted by radioligands for both diagnostic PET imaging and radiotherapy. Fendler referenced several studies assessing the detection capabilities of PSMA-PET in all stages of prostate cancer, from initial to advanced, with promising results in sensitivity, specificity, positive predictive value, and management impact, amongst others.

Despite encouraging evidence on PSMA-PET prostate cancer detection, more randomised clinical trials are needed to validate PSMA-

PET, and establish its place in the clinical management of prostate cancer. Fendler touched on PRIMORDIUM, a randomised, international trial-in-progress that is utilising PSMA-PET to identify those at high-risk for prostate cancer recurrence following radical prostatectomy. This treatment cohort will then receive apalutamide, a next-generation nonsteroidal androgen receptor antagonist, in combination with radiotherapy and luteinizing hormone-relating agonist.

Looking to the future, Fendler identified four fields that he believes to be important in providing evidence on PSMA-PET and survival. These included PSMA-direct radioligand therapy, metastasis-directed treatment, salvage radiation therapy, and curative-intent radiation therapy.

TRANSPERINEAL PROSTATE BIOPSY: THE PROS AND CONS

The landscape of prostate biopsy methods was a subsequent subject of debate, spearheaded by Christian Gratzke, Department of Urology, Albert-Ludwigs-University, Freiburg, Germany; and R.R Tourinho-Barbosa, Department of Urology, Institut Mutualiste Montsouris, Université Paris-Descartes, France. Transperineal

and transrectal biopsies are two techniques used to collect sample tissue from the prostate to diagnose cancer. In the former, the biopsy needle is inserted through the wall of the rectum to reach the prostate gland, whilst in the latter, the needle enters through the skin between the scrotum and anus.

Opening his defence of transperineal biopsy, Gratzke quoted a common argument: “Transrectal biopsies are so easy to perform. I hardly ever see any severe infections as a complication. So why is there a need for transperineal biopsies?” He discussed a study that compared the rate of infections between two patient groups: those receiving transperineal biopsy without antibiotic prophylaxis, and those receiving transrectal biopsy with targeted prophylaxis. Of the total 658 participants, zero transperineal infections were reported, compared to four (1.4%) transrectal biopsy infections (p=0.059). Importantly, the detection of clinically significant cancer, that requires immediate treatment, was similar (53% transperineal versus 50% transrectal).1

These discoveries not only affirm the effectiveness of transperineal biopsy, but also alleviate the demand for healthcare resources, as emphasised by Gratzke. For instance, providing

targeted prophylaxis with biopsy requires a rectal culture from the patient; a nurse practitioner and/ or physician to select and prescribe antibiotics based on the antibiogram results and patient allergies; and finally, the patient must adhere to the planned antibiotic regime, and the physician must verify treatment compliance. These demands deplete resources and time, and even with the use of prophylaxis there is still an albeit small risk of infection following transrectal biopsy.

Presenting the counterargument, TourinhoBarbosa stressed the negative associations of transperineal biopsy, namely the increased risk of acute urinary retention, higher cost, and lower tolerability. Furthermore, he referred to several recent studies illustrating lower infection rates for transrectal biopsies, contrasting with earlier literature. Additionally, findings from studies such as the Prostate Biopsy Effects on Prostate Cancer Detection (ProBE-PC) study indicate comparable detection rates between both biopsy techniques.

Tourinho-Barbosa concluded his argument with an insightful question: “Should we focus solely on the route, or instead on improving the detection rate of clinically significant disease?” In answer to this, he drew on new technologies, such as Micro-US, which is capable of revealing lesions not seen on MRI, and suitable for both biopsy approaches.

INDICATIONS, ADVANTAGES, AND DISADVANTAGES OF FOCAL TREATMENT MODALITIES

Focal therapy refers to the removal of the cancer, whilst leaving the rest of the organ intact, with the aim to retain as much function as possible, and minimise any adverse effects. Rafael Sanchez-Salas, Department of Surgery, Division of Urology, McGill University, Montréal, Québec, Canada, drew on the benefits and current challenges facing focal therapies.

The Focal Lesion Ablative Microboost in Prostate Cancer (FLAME) trial investigated whether focal boosting of the macroscopic visible tumour with external beam radiotherapy increases biochemical disease-free survival in patients with localised prostate cancer. This Phase III, multicentre, randomised controlled trial comprised 571 patients with intermediate- and high-risk prostate cancer, enrolled between 2009‒2015. Patients received either the standard treatment of 77 Gy to the entire prostate, or a focal boost up to 95 Gy to the intraprostatic lesions. Findings demonstrated that at the 5-year follow-up, the biochemical disease-free survival was significantly higher in the focal boost compared to standard radiotherapy: 92% to 85%, respectively. These findings suggest promising prospects for the future of prostate cancer treatment, indicating that implementing the focal boost technique could potentially enhance longterm outcomes for patients undergoing radiotherapy.

In his concluding remarks, Sanchez-Salas emphasised that focal therapy remains a dedicated risk assessment process, and that definitive data about long-term cancer control are still lacking.

RELIABILITY OF IMAGING MODALITIES FOR FOCAL TREATMENT

Jochen Walz, Institut Paoli-Calmettes Cancer Center, Marseille, France, discussed the reliability of imaging modalities for focal treatment of prostate cancer. Drawing on two separate studies, Walz emphasised how two factors, the reader’s expertise and biopsy operator, can significantly impact the detection rate of clinically significant prostate cancer. For instance, the percentage of missed T3 prostate cancers dropped from 22% to 3% when read by experts compared to general multiparametric MRI, whilst detection rate fluctuated from 27‒53% solely based on the operator’s skill in targeted biopsy.

Systematic biopsy is where samples of tissue are removed from different areas of the prostate to examine under a microscope, whereas targeted biopsy uses advanced imaging techniques to identify areas of the prostate suspicious for cancer, and then directly biopsies them. Generally, the detection and classification of prostate cancer, based on the Gleason score, is

References

1. Hu JC et al. Transperineal versus transrectal magnetic

superior in targeted biopsies. Yet, as highlighted by Walz, even with targeted biopsy, there remains a potential 30% chance of classification change for radical prostatectomy specimens, casting doubt on the reliability of grading from targeted biopsies.

Further explaining his argument, Walz referenced a 2017 study, which demonstrated that MRI underestimates cancer volume, especially for lesions with a high imaging suspicion score and high Gleason score. In his closing remarks, he stressed the importance of patient selection for focal therapy. Template-guided biopsy provides the best evaluation; however, it is not yet applicable in routine. MRI is the best alternative but, as emphasised by Walz, the “quality chain” of the MRI-based pathway is very important. This includes MRI acquisition, MRI reporting, lesion targeting, and pathology reporting.

CONCLUSION

The joint EAU and CAU session brought to light key advancements and debates in urological care. From the adoption of MRI as the primary diagnostic tool for prostate cancer to discussions on the efficacy of transperineal biopsies, and the potential of focal therapies, the congress highlighted a shift towards personalised, targeted approaches. ●

resonance imaging–targeted and systematic prostate biopsy to prevent infectious complications:

the PREVENT randomized trial. Eur Urol. 2024:S03022838(23)03342-0.

Abstract Reviews

Sharing insights presented at the European Association of Urology (EAU) 2024 Annual Meeting, the following abstract reviews spotlight exciting new developments in the field.

8. Department of Urology, IRCCS Regina Elena National Cancer Institute, Rome, Italy

9. Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

10. Division of Urology, European Institute of Oncology (IEO)-IRCCS, Milan, Italy

11. Division of Urology, University of Turin, Italy

12. San Luigi Gonzaga Hospital, Turin, Italy

13. Istituto Nazionale Tumori di Napoli, IRCCS Fondazione G. Pascale, Naples, Italy

14. Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA

Carcinoma: A Multiinstitutional Analysis (ROBUUST 2.0 Collaborative Group)

Authors: Francesco Ditonno,1,2 Antonio Franco,1,3

Alessandro Veccia,2 Eugenio Bologna,1,4,5 Zhenjie Wu,6 Linhui Wang,6 Firas Abdollah,7 Marco Finati,7 Giuseppe Simone,8 Gabriele Tuderti,8 Emma Helstrom,9 Andres Correa,9 Ottavio De Cobelli,10 Matteo Ferro,10 Francesco Porpiglia,11,12 Daniele Amparore,11,12 Antonio Tufano,13 Sisto Perdonà,13 Raj Bhanvadia,14 Vitaly Margulis,14 Stephan Broenimann,15 Nirmish Singla,15 Dhruv Puri,16 Ithaar H. Derweesh,16 Dinno F. Mendiola,17 Mark L. Gonzalgo,17 Reuben Ben-David,18 Reza Mehrazin,18 Sol C. Moon,19 Soroush Rais-Bahrami,19 Courtney Yong,20 Farshad S. Moghaddam,21 Alireza Ghoreifi,21 Chandru P. Sundaram,20 Hooman Djaladat,21 Alessandro Antonelli,2 *Riccardo Autorino1

1. Department of Urology, Rush University, Chicago, Illinois, USA

2. Department of Urology, University of Verona, Italy

3. Department of Urology, Sant'Andrea Hospital, La Sapienza University of Rome, Italy

4. Department of Maternal-Child and Urological Sciences, Sapienza University of Rome, Italy

5. Policlinico Umberto I Hospital, Rome, Italy

6. Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China

7. Vattikuti Urology Institute, Henry Ford Hospital, Detroit, Michigan, USA

15. Brady Urological Institute, School of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, USA

16. Department of Urology, University of California San Diego School of Medicine, La Jolla, USA

17. Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Florida, USA

18. Department of Urology, Icahn School of Medicine at Mount Sinai, New York, USA

19. Department of Urology, Heersink School of Medicine, University of Alabama at Birmingham, Alabama, USA

20. Department of Urology, Indiana University, Indianapolis, USA

21. Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, USA

*Correspondence to ricautor@gmail.com

Disclosure: The authors declare no conflicts of interest and no additional funding.

Keywords: Nephroureterectomy, robotic surgical procedures, transitional cell carcinoma, ureter.

Citation: EMJ Urol. 2024;12[1]:21-23. https://doi.org/10.33590/emjurol/WWIK9228.

BACKGROUND AND AIMS

Patients with high-risk upper tract urothelial carcinoma (UTUC) typically undergo radical nephroureterectomy (RNU), while kidney-sparing surgery (KSS) is most commonly reserved for those in the low-risk category.1 However,

comparability in terms of oncological outcomes between KSS and RNU in high-risk patients has been suggested.2,3 In this context, the specific role of a robot-assisted approach in high-risk patients has not been thoroughly investigated.

This multi-institutional retrospective cohort study aims to directly compare the oncological and functional outcomes of high-risk patients with distal ureteral tumours undergoing either robotassisted distal ureterectomy (RADU) or robotassisted RNU (RANU).

MATERIALS AND METHODS

Robotic Surgery for Upper Tract Urothelial Cancer Study (ROBUUST) is an international, multicentre, ongoing registry of patients who underwent RNU or KSS (segmental ureterectomy or endoscopic ablation) for UTUC at participating centres from 2015–2022. The ROBUUST database was queried to retrieve high-risk patients, according to European Association of Urology (EAU) risk stratification criteria,1 by distal ureteral tumours, who underwent RADU or RANU.

Local recurrence-free survival (RFS), distant metastasis-free survival (MFS), and overall survival (OS) were estimated using the Kaplan–Meier method with a 3-year cut-off, and log-rank test was used to assess the statistical difference between cohorts. After adjusting for potential confounders, a multivariable Cox proportional hazard model was plotted to evaluate significant predictors of each oncological outcome. Functional outcomes included serum creatinine and estimated glomerular filtration rate (eGFR) at post-operative Day 1, discharge, post-operative 3 and 12 months, and last follow-up; and eGFR variation between baseline and time of last follow-up.

RESULTS

A 3-year RFS of 8.7 months (95% confidence interval [CI]: 5–12) was observed in the RANU group, compared to 6 months for the RADU

group (95% CI: 6–10), with no significant differences between the two treatment groups (p=0.5; Figure 1A). RANU patients had a 3-year MFS of 7 months (95% CI: 4–12), compared to RADU patients who achieved a 3-year MFS of 12 months (95% CI: 3–18), with no differences between the two groups (p=0.5; Figure 1B). A 3-year OS of 17 months (95% CI: 4–24) for the RADU group, and 18 months (95% CI: 9–21) for the RANU group was observed, with no difference between the two (p=0.8; Figure 1C). In the multivariate Cox proportional hazard model, surgical treatment did not emerge as a significant predictor for either RFS (hazard ratio [HR]: 0.64; 95% CI: 0.53–1.22), MFS (HR: 0.86; 95% CI: 0.66–2.60), or OS (HR: 0.86; 95% CI: 0.77–1.30). At last follow-up, patients undergoing RADU had significantly better post-operative renal function, with a significantly higher mean (±standard deviation) eGFR variation in the RANU group compared to the RADU group (p=0.01).

CONCLUSION

The authors’ findings suggest comparable outcomes in terms of RFS, MFS, and OS between RADU and RANU patients, and an advantage in terms of postoperative renal function preservation. Moreover, a significantly better preservation of postoperative renal function was observed among RADU patients. Given its advantages, KSS should be considered as a potential suitable option for selected patients with high-risk distal ureteral UTUC. ●

References

1. Rouprêt M et al. European Association of Urology Guidelines on upper urinary tract urothelial carcinoma: 2023 update. Eur Urol. 2023;84(1):49-64.

2. Hendriks N et al. Survival and long-term effects of kidney-sparing surgery versus radical nephroureterectomy on kidney function in patients with upper urinary tract urothelial carcinoma. Eur Urol Open Sci. 2022;40:104-11.

3. Veccia A et al. Segmental ureterectomy for upper tract urothelial carcinoma: a systematic review and metaanalysis of comparative studies. Clin Genitourin Cancer. 2020;18(1):e10-20.

Figure 1: Kaplan–Meier analysis comparing robot-assisted distal ureterectomy and robot-assisted nephroureterectomy patients for time-to-event outcomes.

RADU: robot-assisted distal ureterectomy; RANU: robot-assisted radical nephroureterectomy.

The International Bladder Cancer Group IntermediateRisk Non-muscle Invasive Bladder Cancer Scoring System Predicts the Need for Intervention for Patients on Active

Surveillance

Authors: Roberto Contieri,1,2,3 Wei Shen Tan,2 Nicolò Maria Buffi,1,2 Giovanni Lughezzani,1,2 Valentina Grajales,2 Mark Soloway,4 Paolo Casale,3 Rodolfo Hurle,3 *Ashish M. Kamat2

1. Department of Biomedical Sciences, Humanitas University, Milan, Italy

2. Department of Urology, University of Texas MD Anderson Cancer Center, Houston, USA

3. Department of Urology, IRCCS Humanitas Research Hospital, Milan, Italy

4. Division of Urology, Memorial Hospital, Hollywood, California, USA

*Correspondence to akamat@mdanderson.org

Disclosure: Kamat is a consultant or advisory board member for Abbott Molecular, Arquer Diagnostics, ArTara Therapeutics, Asieris Pharmaceuticals, AstraZeneca, BioClin Therapeutics, Bristol Myers Squibb, Cepheid, Cold Genesys, Eisai, Engene, Ferring Pharmaceuticals, FerGene, Imagine Pharma, Janssen, MDxHealth, Medac, Merck, Pfizer, Photocure, ProTara Therapeutics, Roviant Sciences, Seattle Genetics, Sessen Bio, Theralase Technologies, TMC Innovation, and US Biotest; has received grants and/or research support from Adolor Corporation, Bristol Myers Squibb, FKD Industries, Heat Biologics, Merck, Photocure, SWOG/NIH, Specialized Programs of Research Excellence (SPORE), and AIBCCR; and holds the patent for Cytokine Predictors of Response to Intravesical Therapy (CyPRIT) jointly with UT MD Anderson Cancer Center. Tan was a consultant to Combat Medical. The other authors have no conflicts of interest to disclose.

Keywords: Active surveillance, bladder cancer, intermediate risk.

Citation: EMJ Urol. 2024;12[1]:24-25. https://doi.org/10.33590/emjurol/WLRT8648.

BACKGROUND AND AIMS

Patients with low-grade (LG) Ta non-muscle invasive bladder cancer (NMIBC) exhibit a high recurrence rate, while cancer-specific mortality remains notably low.1 Consequently, preserving patient quality of life through treatment deintensification emerges as a critical objective, simultaneously ensuring a minimal risk of progression to muscle-invasive bladder cancer.

In this context, active surveillance (AS) is increasingly recognised as a feasible management strategy for patients with small, presumably LG, recurrences of NMIBC.2,3 The International Bladder Cancer Group (IBCG) recently introduced a novel scoring system for intermediate-risk NMIBC.4 This study aims to assess the efficacy of the IBCG intermediaterisk (IR) scoring system in predicting the need for delayed transurethral resection of the bladder tumour among patients with LG NMIBC under active surveillance.

MATERIALS AND METHODS

The Bladder Italian Active Surveillance (BIAS) registry was utilised. The BIAS project is a prospectively maintained AS database of patients with a history of pathologically confirmed LG Ta/T1a NMIBC. The inclusion criteria for BIAS patient cohort include: LG papillary NMIBC, ≤5 apparent LG NMIBC at recurrence, tumour ≤1 cm in diameter, absence of gross haematuria, and no high-grade cancer cells on urine cytology. Subsequent transurethral resection of bladder tumour (TURBT) was offered to patients who no longer met the inclusion criteria or patient choice. The primary endpoint was the rate of delayed TURBT for AS events. Multivariable Cox proportional hazards analysis was used to determine factors associated with delayed TURBT following AS.

RESULTS

A total of 163 patients with LG Ta/T1 (208 AS events) were included for analysis. Delayed TURBT was performed in 109 patients (131 events), with a median follow-up of 24 months

Figure 1: Kaplan–Meier analysis for freedom from delayed transurethral resection stratified by risk-factor groups according to active surveillance events (n=208).

(interquartile range: 8–60 months). The median age was 71.6 years (interquartile range: 66.0–79.0), and 80.4% of the patients were male. Patients with no risk factors, one risk factor, and two or more risk factors accounted for 41 (20%), 120 (58%), and 47 (22%) AS events, respectively. Patients with no risk factors were three times more likely to continue AS compared to those with three or more risk factors at 24-month follow-up (61% versus 19%; Figure 1). A multivariable Cox regression model reported that the IBCG scoring system was associated with delayed TURBT (1–2 risk factors [hazard ratio: 1.8; 95% confidence interval: 1.06–3.06; p=0.030], three or more risk factors [hazard ratio: 3.76; 95% confidence interval: 2.07–6.81, p<0.001]), after adjusting for age and T stage. Grade progression occurred in 6% (n=10) of events, and stage progression developed in 3% (n=4) of events, in the cohort. Importantly, no patient developed NMIBC. The IBCG-IR scoring system was not associated with a higher risk of grade (p=0.9) or stage progression (p=0.2).

CONCLUSION

This collaborative research demonstrates that the IBCG IR-NMIBC scoring system effectively predicts the probability of sustained AS in patients from the BIAS study. Consequently, this scoring system facilitates enhanced patient counselling, and supports more informed collaborative decision-making between patients and physicians before initiating an AS regimen. ●

References

1. Simon M et al. Multiple recurrences and risk of disease progression in patients with primary low-grade (TaG1) non-muscle-invasive bladder cancer and with low and intermediate EORTC-risk score. PLoS One. 2019;14(2):e0211721.

2. Soloway MS et al. Expectant management of small, recurrent, noninvasive papillary bladder tumors. J Urol. 2003;170(2 Pt 1):438-41.

3. Contieri R et al. When and how to perform active surveillance for low-risk non-muscle-invasive bladder cancer. Eur Urol Focus. 2023;9(4):564-6.

4. Tan WS et al. Intermediate-risk non-muscle-invasive bladder cancer: updated consensus definition and management recommendations from the international bladder cancer group. Eur Urol Oncol. 2022;5(5):505-16.

Twenty-Year FollowUp of Large-Volume Low-Grade Urothelial Carcinoma: LongTerm Outcomes in Patients Undergoing

Ureteroscopic Versus Nephroureterectomy Therapy

Authors: *Guy Verhovsky,1 Andrew Fishman,1 Wayne DeBeatham,1 Michael Grasso2

1. Department of Urology, Phelps Memorial, Northwell Health, Sleepy Hollow, New York, USA

2. Department of Urology, New York Medical College, Sleepy Hollow, New York, USA

*Correspondence to guy.verchovsky@gmail.com

Disclosure: The authors have declared no conflicts of interest.

Keywords: Follow-up, low grade, kidney, upper tract, urothelial cancer.

Citation: EMJ Urol. 2024;12[1]:26-27. https://doi.org/10.33590/emjurol/GYNV1898.

BACKGROUND AND AIMS

According to the European Association of Urology (EAU) Guidelines, tumour size exceeding 2 cm serves as a crucial factor in stratifying high-risk upper urinary tract urothelial carcinoma (UTUC) cases, prompting the recommendation of nephroureterectomy.1 However, in scenarios involving a solitary kidney, bilateral disease, or significant comorbidities, a conservative (kidneysparing) surgical approach is considered.1 Notably, ureteroscopic treatment has demonstrated promising short-term oncologic outcomes in managing large, multifocal, lowgrade UTUC.2 Yet, to effectively stratify risk for this subset of patients, there remains a critical need for long-term data on progression and survival rates.

MATERIALS AND METHODS

A previously published cohort analysis2 was analysed on a selective population of patients diagnosed with high-volume, low-grade urothelial carcinoma (upper tract tumour burden >3 cm) between 2002–2011. This database was updated through 2023 to include long-term outcomes.

Patients were stratified into two groups. Group 1 (ureteroscopic treatment), comprised those with a solitary kidney, bilateral disease, and patients who chose endoscopic therapy because of major comorbidities. Fifty-three percent (9/17) of the patients in Group 1 had a solitary kidney at the time of presentation. Group 2 (nephroureterectomy) included those treated according to established guidelines.

Demographic, clinical, and pathological data were collected, and a thorough longitudinal follow-up extending up to 20 years was conducted, including assessments of recurrence rates, disease progression, and overall survival.

RESULTS

Among the 160 patients diagnosed with UTUC during this period, 45 (28.12%) were identified as high-volume, low-Grade urothelial carcinoma; 17 (37.5%) of these patients were in Group 1, with nine (53%) having a solitary kidney (Table 1). The median follow-up period was 16.8 (range: 14.8–20.0) years, and 11.2 (8.0–15.4) years (p<0.01). Group 1 underwent significantly more ureteroscopy procedures, with 10.2 (6.0–12.0) compared to 6.1 (4.0–10.0) in Group 2 (p=0.03). Estimated overall survival rates (years) in Groups 1 and 2 were not statistically significantly different between the two groups (Table 1). Group 1 patients progressed to high-grade disease in 50% of patients over 15 years (Table 2).

CONCLUSION

The authors’ study presents the longest followup of patients with high-volume, low-grade UTUC, who have been treated with endoscopic management. This elderly population has no statistically significant difference in overall

URS: ureteroscopy.

survival at 10-, 15-, and 20-years of follow-up. Ureteroscopic treatment with surveillance is not only technically feasible, but is a reasonable alternative to nephroureterectomy in the elderly, high-risk patient population over long-term follow-up. Patients should be counselled that there is around a 50% chance of progression in Grade during 15-year surveillance, underscoring the need for continued ureteroscopic surveillance in this cohort. Patients must also be aware that progression in Grade commonly reflects progression in Stage and metastatic disease, but may not impact the overall survival in this subset of older patients. ●

References

1. European Association of Urology (EAU). EAU Guidelines: Upper Urinary Tract Urothelial Cell Carcinoma. Available at: https://uroweb.org/guidelines/upper-urinary-tracturothelial-cell-carcinoma. Last accessed: 11 April 2024.

2. Grasso et al. Ureteroscopic and extirpative treatment of upper urinary tract urothelial carcinoma: a 15-year comprehensive review of 160 consecutive patients. BJUI. 2012;110(11):1618-26.

Table 1: Survival analysis.

Table 2: Ureteroscopy progression and metastasis.

Results of Buccal Mucosa Graft Urethroplasty With or Without Reconstruction of the Meatus

Authors: *Mikhail Borisenkov,1 Abhishek Pandey1

1. Department of Urology, Sana Klinikum Hof, Germany *Correspondence to borisenkovmb@gmail.com

Disclosure: The authors have declared no conflicts of interest.

Keywords: Buccal mucosa graft, urethral stricture, urethroplasty.

Citation: EMJ Urol. 2024;12[1]:28-29. https://doi.org/10.33590/emjurol/ADUS5939.

BACKGROUND AND AIMS

Approximately 15–20% of patients who undergo urethroplasty (UP) with buccal mucosa graft (BMG) will suffer urethral stricture recurrence.1

The authors’ aim was to examine whether the stricture recurrence rate was influenced by reconstruction of the meatus (MR) during UP.

Table 1: Patient characteristics.

Group 1 (MR)

MATERIALS AND METHODS

The authors enrolled 1,954 patients with urethral strictures who underwent a UP using BMG from April 1994–April 2023 at their institution. Of these patients, 1,658 underwent a single-stage procedure (always ventral onlay). In cases of MR, a glans tunnelling was performed. Inclusion criteria were as follows: single-stage UP of the penile urethra (≤10 cm long; minimum distance to the sphincter: 5 cm), and no history of hypospadias. Advised follow-up was as follows: uroflow and residual urine (standing 3 months in the first 2 years, and then 6 months), and patient self-reported questionnaires on quality of life, morbidity, and satisfaction. In cases of maximum flow <20 mL/sec, residual urine >50 mL, or urinary tract infection, a urethroscopy and/or a urethrography were recommended. A stricture recurrence was defined as any instrumentation to the urethra during follow-up.

RESULTS

In 7.4% of patients (123/1,658), penile strictures were defined. The MR was performed in 46.3% of patients (57/123; Group 1). Group 2 (without MR) consisted of 44.7% of patients (55/123). The meatal involvement was unknown in 8.9% of patients (11/123). For patient characteristics see the table below (Table 1).

Group 2 (No MR) P value

Stricture Length (cm) 5.0 (IQR: 4.0; 7) 5.0 (IQR: 4.0; 7) P=0.520

Patient Age (years) 50 (IQR: 42; 65) 66 (IQR: 56; 74) P<0.001*

Median Number of Pre-operations 4 (IQR: 2; 5) 4 (IQR: 2; 5.5) P=0.440

Median Follow-Up (months) 34 (IQR: 7.5; 59) 22 (IQR: 7.5; 46) P=0.530

Stricture Recurrence 4/35 (11.4%) 5/39 (12.8%) P=0.990

*Denotes statistical significance. IQR: interquartile range; MR: meatus reconstruction.

From a total of 123 patients, data regarding stricture recurrence were available in 66.7% (87/123). Stricture recurrence occurred in 12.2% of these patients (10/82). There was no statistical difference between the two groups of patients.

Complications were observed in a total of 14.6% of patients (18/123), of whom 2.4% (3/123) were above Grade 3(*), according to Clavien-Dindo. In Group 1, three fistulas (one surgically treated*), three wound healing disorders, two cases of deep vein thrombosis, and one case of delirium, were observed across eight patients. In Group 2, one fistula, two wound healing disorders, three BMG-rejections on first miction voiding cystourethrogram, one penile deviation*, and one pulmonary embolism* were observed across eight patients. Two additional complications (one wound healing disorder and one BMG-rejection

on first voiding cystourethrogram) occurred in patients in whom meatal involvement was unknown.

CONCLUSION

The reconstruction of meatus during urethroplasty with buccal mucosa graft does not influence the stricture recurrence rate. The patient undergoing this type of surgery should be informed that the most important complications are fistula formation, impaired wound healing, and deep vein thrombosis. ●

References

1. Mangera A et al. A systematic review of graft augmentation urethroplasty techniques for the treatment of anterior urethral strictures. Eur Urol. 2011;59(5): 797-814.

Abstract Highlights

The following highlights spotlight abstracts presented at the 39th Annual European Association of Urology (EAU) Congress. Selected abstracts reflect the evolving landscape of clinical and surgical practice in urology, including timely topics such as advances in prostate cancer detection, robotic surgery for management of urinary tract complications, and analysis of oncological outcomes in kidney transplant recipients.

Citation: EMJ Urol. 2024;12[1]:30-40. https://doi.org/10.33590/emjurol/ATMF3542.

Award-Winning Abstract: PSMA-PET-Guided Intensification of Salvage Radiotherapy After Radical Prostatectomy

PROSTATE-specific membrane antigen (PSMA)PET imaging can influence decision-making in prostate cancer, improving survival outcomes. The research, presented by Colin Belliveau, Centre Hospitalier de l'Université de Montréal, Québec, Canada, was awarded best abstract in oncology at the 39th EAU Annual Congress.

The team conducted a Phase II, multicentre randomised controlled trial to determine if PSMAPET-guided intensification of salvage radiotherapy (PSMAiSRT) after radical prostatectomy (RP) improves failure-free survival (FFS). A total of 128 patients with biochemical failure (prostate specific antigen >0.1 ng/mL) following RP, and planned for salvage radiotherapy (SRT), were enrolled between May 2018–February 2021.

Patients were randomised 1:1 to standard-ofcare SRT or 18F-DCFPγL PSMA-PET/CT prior to treatment, and SRT was subsequently intensified targeting newly identified disease sites detected on PSMA-PET/CT. Analysis of the primary FFS endpoint was based on the number of failure events reported. FFS was measured from the last day of RT to the date of biochemical recurrence (nadir+0.2 ng/mL), locoregional failure, distant metastasis, initiation of the next line of therapy, or death from any cause, whichever occurred first.

Intensified SRT was delivered in 33/64 patients who underwent PSMA-PET/CT (28% addition of pelvic SRT, 3% addition of metastases-directed RT, 30% lymph node boost, and 23% prostate bed boost). The use of adjuvant hormonal therapy (6–24 months) was equally high in both arms (86% control; 84% PSMAiSRT). The authors found that, at median follow-up of 37 months, PSMAiSRT significantly improved FFS outcomes (control: 20 failure events; PSMAiSRT: 10 failure events; P=0.04; hazard ratio: 0.46; 95% confidence interval: 0.21–0.98). To date, the study reports no differences in metastasis-free survival based on conventional imaging (control: 4 events; PSMAiSRT: 5 events), and in overall survival (one death in each arm).

"At median follow-up of 37 months, PSMAiSRT significantly improved FFS outcomes."

This study demonstrates improved prostate cancer control outcomes with PSMAiSRT after RP. The authors emphasised that, considering a variable worldwide access to PSMA-PET imaging, patients planned for SRT after RP should be prioritised access, given its positive impact on outcomes. A Phase III randomised controlled trial is currently completing accrual, and will shed further light on those patients who benefit most from PSMAiSRT. ●

Award-Winning Abstract: Optimal Clinical and Cost-Effective Ways to Manage Kidney Stones

RENAL tract stones are prevalent, and the European Association of Urology (EAU) usually recommends extracorporeal shock wave lithotripsy (ESWL) and flexible ureteroscopic stone treatment (FURS) as first-line treatment. PUrE, a randomised controlled trial, investigated the best clinical and costeffective approach for lower pole kidney stones, and was awarded best abstract in a non-oncology specialty at the 39th EAU Annual Congress.

Oliver Wiseman, Department of Urology, Cambridge University Hospitals National Health Service (NHS) Trust, UK, and colleagues, conducted a pragmatic multicentre, open-label, superiority randomised controlled trial to determine whether ESWL or FURS offers the best outcomes. They assessed which treatment option provided a better quality of life, clinical effectiveness, and cost-effectiveness for individuals with lower pole kidney stones ≤10 mm.

The trial received ethics approval from the North of Scotland NHS Research Ethics Committee, and randomised 461 patients (230 to ESWL and 231 to FURS) across participating NHS urology departments. The health status area under the curve was measured weekly with the EuroQol 5-Dimension 5-level questionnaire until 12 weeks post-intervention, to determine the primary outcome.

During the 12-week period, the average health status for the FURS group (n=164) was 0.807 (standard deviation: 0.205), and for the ESWL group (n=188) was 0.826 (standard deviation: 0.207); with a slight difference of 0.024 (95% confidence interval: -0.004, 0.053) favouring FURS after accounting for an initial baseline imbalance. FURS achieved a higher rate of complete stone clearance (72%) compared to ESWL (36%). The incremental cost-effectiveness ratio for FURS was 65,163 GBP per quality-adjusted life year gained. At a threshold of 20,000 GBP per quality-adjusted life year gained, there was a 99.9% probability that ESWL was cost-effective. The study's limitations include the inability to conceal the identity of the participants and healthcare providers. Additionally, there were variations in waiting times between interventions, although adjusting for this yielded similar treatment effect estimates.

The PUrE investigation revealed that for lower pole stones measuring ≤10 mm, ESWL proved to be a more economical option compared to FURS. Although FURS had higher rates of complete stone clearance, there was no significant discrepancy in patient health status between the two methods. ●

"The trial received ethics approval from the North of Scotland NHS Research Ethics Committee, and randomised 461 patients."

Impact of Systematic Sampling on Prostate Biopsy Results

THE BENEFIT of adding systematic sampling to a targeted MRI/transrectal ultrasound (TRUS) fusion biopsy for prostate cancer (PCa) is unclear. New research presented at the 39th EAU Congress, held from 5th–8th of April 2024, aimed to identify patients who could benefit from systematic sampling in terms of newly diagnosed PCa, and clinically significant prostate cancer (csPCa). It did this by comparing the observed cancer detection rate.

The team recruited patients submitted to both systematic sampling and MRI/TRUS fusion biopsy at Araba University Hospital, Vitoria-Gasteiz, Spain, from 2018–2021 (n=188). For each patient, the McNemar test was used to compare the global result of the biopsy considering only the targeted sampling, with the combination of the targeted and the systematic ones. Subgroup analyses were performed according to the Prostate Imaging-Reporting and Data System (PIRADS) score of the index lesion on MRI, prostate-specific antigen (PSA) density, and

the personal history of previous systematic biopsies. The team defined csPCa as International Society of Urological Pathology (ISUP) Grade ≥2.

Overall, addition of systematic sampling to targeted sampling led to an increased cancer detection rate of PCa and csPCa. Results from the subgroup analyses further showed that biopsy-naïve patients, and those with a PIRADS score ≤3, did not show any benefit from the addition of the systematic sampling. Patients with a PSA density ≤0.15 only benefitted in terms of PCa detection.

The study concluded that patients might benefit from the addition of systematic sampling while being submitted to an MRI/TRUS fusion biopsy for newly diagnosed PCa and csPCa. Patients with lesions scored as PIRADS 4–5, a PSA density ≥0.15, and a history of previous biopsies, seemed to benefit the most from the addition of systematic sampling to targeted sampling. ●

"Addition of systematic sampling to targeted sampling led to an increased cancer detection rate of PCa and csPCa."

Liquid Biomarkers for Clinically Significant Prostate Cancer Detection

LIQUID biomarkers may enhance detection of clinically significant prostate cancer (csPCa), helping to avoid unnecessary prostate biopsies. A recent study presented at the 39th EAU Congress, held in Paris, France, from 5th–8th April 2024, aimed to assess the diagnostic accuracy of multi-analyte biomarkers for csPCa detection.

In March 2023, the researchers conducted a comprehensive literature search through PubMed, Web of Science, and Scopus for prospective and retrospective studies that reported the diagnostic performance of liquid biomarkers for csPCa detection. They included all studies that explored patients with suspected PCa, and those that compared patients positive for liquid biomarker to those with negative liquid biomarker. Outcomes of interest were the diagnostic performance of liquid biomarkers for csPCa detection, and identification of optimal thresholds for each biomarker. A total of 49 studies were eligible for this meta-analysis.

"Outcomes of interest were the diagnostic performance of liquid biomarkers for csPCa detection."

Using each representative threshold based on the Youden index, the team found that the pooled sensitivity and specificity for detecting csPCa were 0.85 and 0.37 for prostate cancer antigen 3 (PCA3), 0.85 and 0.52 for prostate health index (PHI), 0.87 and 0.58 for 4K, 0.82 and 0.56 for SelectMDx, 0.85 and 0.54 for ExoDx, and 0.82 and 0.59 for MyProstateScore, respectively. Diagnostic odds ratio was highest for 4K (8.84), followed by MyProstateScore (7.00), and PHI (6.28). According to the metaanalysis incorporating multiple thresholds, the corresponding sensitivity was 0.77 for 4K, 0.69 for PHI, and 0.63 for PCA3; and specificity was 0.72 for PHI, 0.70 for 4K, and 0.69 for PCA3.

To conclude, the study found that 4K had the highest diagnostic performance for detecting csPCa among all commercial liquid biomarkers. Based on calculations of optimal thresholds in the meta-analysis, 4K was also found to have the highest sensitivity for csPCa detection, and PHI the highest specificity. Nevertheless, the team emphasised the importance of combination strategies between liquid and imaging biomarkers during clinical decision-making. ●

Insights Into Non-muscle Invasive Bladder Cancer Outcomes

RECIPIENTS of kidney transplants are at greater risk of bladder cancer compared to the general population. With limited existing research on the outcomes and characteristics of de novo bladder cancer in kidney transplant recipients, Simone Livoti, University of Turin School of Medicine, Italy, and colleagues, conducted a large international cohort study. Results of this study were presented at the 39th Congress of the EAU, held in Paris, France from the 5th–8th April 2024.

Subjects included in the study were kidney transplant recipients who had received a de novo bladder cancer diagnosis between 2000–2022. It was a multicentre retrospective collaboration across eight international referral centres, with 89 patients in total (mean age: 64 years; interquartile range: 56–68). The measured outcomes were recurrence-free survival, progression-free survival, cystectomy-free survival, and overall survival.

Results revealed that the median time from kidney transplantation to bladder cancer diagnosis was 98 months. The clinical stage of the tumour at diagnosis was cTa, cT1, cT2, cT3, and cT4 in 25 (29%), nine (10%), 27 (31%), 25 (29%), and one (1%) patient, respectively. Regarding the primary outcomes, 37% underwent a radical cystectomy, 38% had experienced disease recurrence, and 9% progression. Furthermore, the overall survival rate at 1, 3, and 5 years was 78%, 53%, and 47%, respectively.

Overall, this study has made important steps in identifying the oncological outcomes in kidney transplant recipients with de novo bladder cancer. It is the largest series reporting oncological outcomes in this patient population type, and highlights the tailored management they specifically require. ●

"Results revealed that the median time from kidney transplantation to bladder cancer diagnosis was 98 months."

Robotic Surgery in Managing Urinary Complications Post-kidney

Transplant

URINARY tract (UT) complications following kidney transplantation occur in approximately 5–10% of cases and can lead to significant morbidity. Surgical repair is often the treatment of choice, with a high success rate. Robotic surgery offers the advantages of minimally invasive procedures, especially in complex cases. Presented at the EAU 2024 congress, held from 5th–8th April 2024, this study aims to evaluate the efficacy and safety of robotic surgery in the management of UT complications in kidney transplant recipients.

The protocol for robotic surgery is as follows: prior to surgery, a nephrostomy (NP) tube is placed, and a pyelography and CT scan are performed. A modified robotic pelvic surgery protocol is employed for the surgical technique, with robotic ultrasound (US) being a crucial tool, and a double J stent is always placed. Postoperatively, all tubes remain open for 24 hours, after which the NP tube is closed and removed between Days 5–7 if no complications arise. In cases of reimplantation, a bladder catheter remains in place for between 5–7 days. The double J stent is removed at Week 4. Follow-up includes US after double J stent removal, control at 3, 6, and 12 months, and subsequently annually.

This cohort study included kidney transplant recipients who underwent robotic surgery for UT complications between January 2018–September 2023. A total of 28 patients were included in the study, the largest series reported.

Among the 28 patients, there were 26 cases of stenosis, and two ureteral fistulas. For distal stenosis, a robotic uretero-vesical reimplantation was performed in 12 cases, while upper and long UT stenosis cases underwent robotic anastomosis to the native ureter (16 cases). One case required conversion to open surgery due to adhesions. The median surgical time was 150 minutes (interquartile range [IQR]: 113–170), and the median hospital stay was 3 days (IQR: 2–6). In 26 out of 28 patients, all urinary drainage was successfully removed, representing a 93% success rate, with a median follow-up of 13 months (IQR: 6–20). As for complications, there were eight cases of graft pyelonephritis, and two cases of haematuria. There were two stricture recurrences, considered a failure of the surgical technique.

"Robotic uretero-vesical reimplantation was performed in 12 cases."

Robotic surgery for managing UT complications following kidney transplantation is effective and safe in both the short and long term. It offers the advantages of minimally invasive surgery with enhanced surgical precision, particularly in complex cases. Notably, this study represents the largest reported series of such cases, adding knowledge in the field of kidney transplantation and robotic surgery. ●

Robot-Assisted Radical Cystectomy and Peritoneal Metastasis

CONCERNS about robot-assisted radical cystectomy (RARC) leading to a higher incidence of peritoneal metastasis than open radical cystectomy (RC) are frequent among urologists. Despite RARC being the standard of care for patients with muscle-invasive bladder cancer, the procedure needs to be validated in real-world clinical practice, as the frequency of peritoneal metastasis has only been analysed in clinical trials.

"Frequency of peritoneal metastasis has only been analysed in clinical trials."

In order to analyse the results of RARC, a research team from the Hirosaki University Graduate School of Medicine, Japan, retrospectively looked at 415 cases of radical cystectomy (open RC versus RARC), taking place from 2011–2023. The frequency of peritoneal metastasis was examined, risk factors identified, and oncological outcomes assessed. In total, the open RC group was made up of 271 patients

(median age: 71 years), and the RARC group consisted of 144 individuals (median age: 69 years).

The team found that incidence of peritoneal metastasis was similar between the open RC (n=13; 4.8%) and RARC (n=6; 4.2%). Multivariate logistic regression analysis showed that the robotic approach was not significantly associated with peritoneal metastasis (odds ratio: 0.99; P=0.98). Pre-operative high risk factor (cT34 or N+) was significantly associated with peritoneal metastasis. Additionally, they found that neoadjuvant chemotherapy was significantly associated with reduction of peritoneal metastasis (odds ratio: 0.25; P=0.01).

This analysis, presented at the 2024 EAU Congress, held in Paris on 5th–8th April, demonstrated that RARC is not a significant factor for recurrence-free survival and overall survival, but post-operative pathological high risk was identified as a significant factor for recurrence-free survival and overall survival. ●

Empower Pathway for Testicular Cancer Follow-Up

A NEW pathway for encouraging patients with testicular cancer to self-manage has proven to be promising, according to research presented at the EAU Congress 2024, held in Paris, France from 5th–8th April. The so-called Empower Pathway aims to combat the inconsistent management of treatment and encouragement of self-management often found in consultantled clinics, by holistically managing patients in follow-up, and, at the same time, educating them on long-term physical, psychological, and social sequelae of treatment.

The Empower Pathway was trialled in a 15-month long pilot study of 120 patients, with the aim of providing a personalised stratified follow-up. Post-treatment patients who had completed 6 months of consultant-led surveillance were invited to participate in the programme, and no patients in clinical trials, who have cancer, or with treatment complexity in follow-up care, were included. An advanced nurse practitioner model was used to facilitate holistic care. Finally, patients were only re-referred to a consultant-led clinic when disease recurrence was confirmed.

An integrated pathway was created, focusing on physical, mental, and social health. Each consultation included a shared care plan, and induction included a video seminar pack, a patient leaflet, and information on the scope of

practice. Initially, 100 patients (mean age: 39.6 years) were surveyed in October 2022, and again in October 2023. Of this initial group, 1% of consultations requested onward GP referral, and 12% required internal referral. The majority (87.5%) of patients felt that lifestyle and exercise were adequately addressed by the Empower Pathway, and all patients felt that mental health was addressed, as well as efforts made to understand and listen to health concerns. Every patient also reported feeling that effort was made to involve them in what mattered to them as individuals in their care.

"An integrated pathway was created, focusing on physical, mental, and social health."

The researchers concluded that the Empower Pathway follow-up model resulted in improved patient outcomes when run alongside traditional, consultant-led clinics. Patients generally responded well to the more personalised approach, and, as a result, this pathway may have the potential to change the approach to follow-up not only in patients with testicular cancer, but in other tumour groups. ●

Study Identifies Optimal Treatment Regimens for Metastatic Prostate Cancer

TRIPLET therapy regimens have shown promising results for patients with metastatic hormonesensitive prostate cancer (mHSPC). Presented at the EAU 2024 congress, held from the 5th–8th of April, this research focuses on the novel guideline-recommended treatment combination of androgen receptor signalling inhibitors (ARSI) plus docetaxel plus androgen-deprivation therapy (ADT). Which patients stand to benefit the most from this innovative approach remains unclear.

To address this gap, researchers conducted a systematic review, meta-analysis, and network meta-analysis to evaluate the efficacy of triplet therapy compared to doublet treatment regimens in patients with mHSPC, stratified by disease volume. The study analysed data from eight randomised controlled trials, that were retrieved from three databases and meeting abstracts. The primary measure of interest was overall survival (OS), following the guidelines outlined by the PRISMA guideline and AMSTAR2 checklist.

The findings revealed that triplet therapy, consisting of ARSIs plus docetaxel plus ADT, significantly improved OS compared to docetaxel plus ADT, in patients with both high- and lowvolume mHSPC. Specifically, the pooled hazard ratios for OS were 0.73 (95% confidence interval [CI]: 0.64–0.84) for high-volume

disease, and 0.71 (95% CI: 0.52–0.97) for low-volume disease.

When comparing ARSI with docetaxel added to ADT, no statistically significant difference in OS was observed across disease volumes. However, through analysis of treatment rankings, darolutamide plus docetaxel plus ADT emerged as the preferred regimen for patients with highvolume disease, with an improved OS of 90%. Enzalutamide plus ADT showed the highest likelihood of improved OS in those with lowvolume disease, with an improvement of 84%.

Triplet therapy demonstrates an improvement in OS for patients with mHSPC compared to docetaxel-based doublet therapy, regardless of disease volume. However, the study suggests that the optimal treatment approach may vary depending on disease volume, with triplet therapy being more favourable for high-volume cases, and ARSI plus ADT potentially sufficient for low-volume disease management. These findings provide crucial insights for clinicians in tailoring treatment strategies for patients with mHSPC, ultimately leading to improved outcomes, and better patient care. ●

"Triplet therapy demonstrates an improvement in OS for patients with mHSPC compared to docetaxel-based doublet therapy."

Bladder Cancer: Challenging the Treatment Paradigm

BACILLUS Calmette–Guérin (BCG) is the gold standard treatment in intermediate and high-risk non-muscle invasive bladder cancer (NMIBC). However, a substantial proportion of patients are unresponsive to BCG therapy, posing a significant clinical challenge. Although current treatment paradigms recommend against administration of additional BCG in BCG-unresponsive patients, a recent study presented at the 39th Annual EAU Congress, held from 5th–8th of April 2024, reports that additional rescue BCG demonstrates efficacy in this patient population.

The team performed a review of consecutive patients diagnosed with NMIBC between January 2000–September 2021, approved by the Institutional Review Board (IRB), to identify those who met BCG-unresponsive criteria. They analysed the outcomes of patients who received rescue BCG as primary therapy; the primary outcome was event-free survival (EFS), defined as any high-grade recurrence, progression, or death. The Kaplan–Meier method was used to estimate EFS, cystectomy-free survival, progression to muscle-invasive or metastatic-free survival, and overall survival.

The study identified 163 patients with BCGunresponsive disease, of whom 35 received rescue BCG as primary treatment.

Twenty-six (74%) patients showed no disease after rescue BCG; of these, 25 (96%) received maintenance. Median follow-up was 5.9 years. Kaplan–Meier estimates of EFS after rescue BCG were 68% at 12 months, 62% at 24 months, and 48% at 36 months. In the 2 years following rescue BCG, 21 patients still had no evidence of disease, four progressed to muscle-invasive bladder cancer, and nine recurred without progression. Of these, two had cystectomy, and seven had further bladder-sparing therapies. This resulted in cystectomy-free survival at 12, 24, and 36 months of 88% (95% confidence interval [CI]: 72–95), 79% (95% CI: 61–90), and 79% (95% CI: 61–90), respectively. Progressionfree survival at 12, 24, and 36 months was 91% (95% CI: 82–100), 88% (95% CI: 77–100), and 76% (95% CI: 61–94), respectively. Overall survival at 12, 24, and 36 months was 94% (95% CI: 86–100), 91% (95% CI: 82–100), and 85% (95% CI: 73–98), respectively.

Results from this study challenge the current treatment paradigms for patients with BCGrefractory NMIBC. The authors emphasise the need for further randomised clinical trials to evaluate the potential of rescue BCG as a suitable therapy for BCG-unresponsive NMIBC. ●

"The study identified 163 patients with BCG-unresponsive disease, of whom 35 received rescue BCG as primary treatment."

Contemporary Views on Performance Indicators with Audit-Feedback

for Bladder Cancer Treatment

Interviewees: Paramananthan Mariappan1,2

1. Edinburgh Bladder Cancer Surgery, Department of Urology, Western General Hospital, National Health Service (NHS) Lothian, UK

2. Edinburgh Medical School, College of Medicine and Veterinary Medicine, University of Edinburgh, UK

Disclosure:

Mariappan has received honoraria, has been on the advisory panel, and/or received sponsorship from Baxter Pharmaceuticals, Bristol Myers Squibb, Coloplast, Ethicon (Johnson & Johnson), Janssen Pharmaceuticals, medac, Photocure, and Storz Medical.

Acknowledgements: Medical writing assistance was provided by Hannah Moir, EMJ, London, UK. The interviewee was given the opportunity to review the article.

Disclaimer: The views and opinions expressed are those of the speaker and not necessarily those of medac or EMJ.

Support: The publication of this article was funded by medac.

Keywords: Benchmarks, bladder cancer, cancer surgery, detrusor muscle sampling, non-muscle-invasive bladder cancer (NMIBC), progression, quality performance indicators (QPI), recurrence, single instillation, transurethral resection of bladder tumour (TURBT).

Citation: EMJ Urol. 2024;12[1]:41-47. https://doi.org/10.33590/emjurol/IQWK4133.

Interview Summary

EMJ conducted an interview with Param Mariappan, who is a Consultant Urological Surgeon, Director of Edinburgh Bladder Cancer Surgery, at Western General Hospital Edinburgh, and an Honorary Professor at the University of Edinburgh, UK. Mariappan is a renowned clinician-researcher in the field of urological cancer, with a keen interest in improving the treatment experience and outcomes in patients receiving bladder cancer surgery. Mariappan sits on the European Association of Urology (EAU) Bladder Cancer Guideline panels, and the Core Committee of the International Bladder Cancer Group (IBCG), and is a medical advisor to the Fight Bladder Cancer charity.

In this interview, Mariappan discusses the importance of achieving appropriate benchmarks for the treatment of non-muscle-invasive bladder cancer (NMIBC), and evaluates the impact of transurethral resection of bladder tumour (TURBT) on recurrence and progression. He talks about his extensive research and recent publication findings, which aim to establish national quality performance indicator (QPI) programmes that include quality of detrusor muscle sampling and use of single instillation of chemotherapy (mitomycin C; SI-MMC) after TURBT for the improvement of outcomes in patients with bladder cancer.

INTRODUCTION

Bladder cancers are classified into muscleinvasive and non-muscle-invasive, the latter accounting for 75% of cases.1 Accurate and timely diagnosis and treatment are crucial, as bladder cancer can become life-threatening.1 However, there has been no significant improvement in survival rates in the last 30 years.2 The initial TURBT is vital for both diagnostic and therapeutic purposes, and facilitates the determination of prognosis. Mariappan, the lead author of a recent publication that assessed benchmarks on time to recurrence and progression in NMIBC, was interviewed.3

Could You Discuss the Current Guidelines for Non-muscle-Invasive Bladder Cancer Diagnosis and Treatment?

Around half of patients with NMIBC have lowgrade non-invasive cancers (Stage Ta LG/ G1).1 The other half have high-grade disease, which can either be non-invasive, or invasive (Stage T1 HG/G3).1 When you delve deeper into it, the distinction between the proportions of these types is largely based on historical data.1,4 The issue is that a proportion of what are deemed to be high-grade NMIBC are actually muscle-invasive, and these are potentially lifethreatening. An element of my work aims to improve diagnostic accuracy through the initial TURBT so that these aggressive cancers are effectively and efficiently identified from the outset, and correct risk grouping can be ascribed.

Apart from the safety element, the initial TURBT is very important for two purposes. The first is to obtain information, identifying tumour characteristics: size, number, location, and presence of carcinoma in situ (CIS). The second is to clear the visible cancer and identify the disease extent, including CIS when possible. This can be augmented by optical enhancements; for example, photodynamic diagnosis or narrowband imaging.5,6 So, when the case is presented to the multidisciplinary team (MDT), we have information for risk-adapted treatment selection.

How Important Is It to Stratify Patients Into Risk Groups?

The risk group determines what adjuvant treatment and surveillance regime they receive, including frequency of surveillance and upper tract imaging, which is recommended for highrisk and very high-risk groups.1

Patients are divided into low-, intermediate-, high-, and very high-risk (Table 1). The IBCG and EAU have different categorisation criteria (Table 1).1,7,8 Low-risk are solitary small tumours, pathologically low-grade and non-invasive, and require complete TURBT, followed by a single instillation of intravesical chemotherapy (SI-MMC in the UK).4 On the other hand, patients with high-risk, high-grade (Ta or T1) undergo TURBT; although guidelines may not recommend single instillation of chemotherapy, this may still be used because the grade or stage of the cancer would not be known at the time of the initial TURBT.1,7,8 Intermediate-risk are those who fall between these two groups. In the UK, patients get TURBT, single instillation, followed by a course of intravesical instillation, usually over 6 weeks, and are kept on close surveillance.4

Are There Any Concerns with Current Practices, and What is the Adherence to Perioperative Care After Resection?

Prior to 2002, NMIBC management focused on single intravesical instillation, or adjuvant installation of chemotherapy to augment TURBT (Figure 1). A study published in 2002 demonstrated, for the first time, variance across centres of excellence, indicating that the quality of the initial resection played a significant role in recurrence rates.9 It became apparent that the surgeon had something to do with these outcomes being variable from centre to centre.9 As a result, I brought quality control and continuous quality improvement into the equation, with a search for surrogates and benchmarking.10 This research demonstrated that detrusor muscle sampling and surgeon experience were associated with lower recurrence rates;10 and we validated this work within two other cohorts, recommending a benchmark for good quality TURBT.11

Guidelines now highlight the importance of the quality of TURBT.12 The EAU emphasises the importance of detrusor muscle sampling in the appropriate patient, single instillation, and

Table 1: Risk groups determined by classification approach and recommended primary treatment per guidelines.1,7

Risk group

Low risk

Classification approach

EAU • A primary, single, TaT1 LG/G1 tumour <3 cm in diameter without CIS in a patient ≤70 years

• A primary Ta LG/G1 tumour without CIS with at most ONE of the additional clinical risk factors*

IBCG Solitary primary low-grade Ta

Intermediate risk EAU Patients without CIS who are not included in either the low-, high-, or very high-risk groups

IBCG Multiple or recurrent low-grade tumours

Primary treatment

One immediate single instillation of intravesical chemotherapy after TURBT

High risk

EAU All T1 HG/G3 without CIS, EXCEPT those included in the very high-risk group. All patients with CIS, EXCEPT those included in the very high-risk group. Stage, grade with additional clinical risk factors:

• Ta LG/G2 or T1G1, no CIS, with all three risk factors*

• Ta HG/G3 or T1 LG, no CIS, with at least two risk factors*

• T1G2, no CIS, with at least one risk factor*

IBCG

Very high risk EAU

• Ta HG/G3 and CIS with all three risk factors*

• T1G2 and CIS with at least two risk factors*

• T1 HG/G3 and CIS with at least one risk factor*

• T1 HG/G3 no CIS with all three risk factors*

A single, immediate chemotherapeutic instillation after TURBT

With or without immediate instillation, offer 1-year full-dose BCG treatment (induction plus 3 weekly instillations at 3, 6, and 12 months), or instillations of chemotherapy (the optimal schedule is not known) for a maximum of 1 year

Chemotherapy and BCG and maintenance, OR intravesical BCG with maintenance or intravesical chemotherapy

Full-dose intravesical BCG for 1–3 years (induction plus 3 weekly instillations at 3, 6, 12, 18, 24, 30, and 36 months), is indicated

• In patients with very high-risk tumours, offer immediate radical cystectomy. Discuss intravesical fulldose BCG instillations for 1–3 years, and immediate radical cystectomy should be discussed with these patients.

• In case radical cystectomy is not feasible or refused by the patient, full-dose intravesical BCG for 1–3 years should be offered.

*Additional clinical risk factors are: age >70; multiple papillary tumours; tumour diameter ≥3 cm. Carcinoma in situ cannot be managed by an endoscopic procedure alone, and should be offered either intravesical BCG instillations or radical cystectomy.

BCG: Bacillus Calmette-Guérin; CIS: carcinoma in situ; EAU: European Association of Urology; IBCG: International Bladder Cancer Group; N/A: not applicable; TURBT: transurethral resection of bladder tumour.

Figure 1: Timeline for evolution of the management of non-muscle invasive bladder cancer in Edinburgh, UK.

Detrusor muscle resection in the first complete TURBT is a surrogate marker of resection quality. It is dependent on a surgeon’s experience and is independently associated with an increased risk of early reccurence.10

Quality of surgeons’ resection may be responsible for recurrence.9

1980s 2000s

Use of single installation or adjuvant installation of chemotherapy to augment TURBT.

Real-world experience from Scotland QPI Programme facilitated highquality TURBT.3,14

Real-world experience from Scotland’s QPI Programme facilitated high-quality TURBT.13

2010s 2020s 2024

EAU Guidelines Update.12 Importance of transurethral resection.

Validation study confirms detrusor muscle status at first complete TURBT and surgeon’s experience independently predicts quality of TURBT.11

EAU Guidelines Update.1 Use of a bladder diagram to record operations. Sampling the detrusor muscle as an important surrogate.

EAU Guidelines Update April 2024 (includes Quality Indicators)

EAU: European Association of Urology; TURBT: transurethral resection of bladder tumour; QPI: Quality Performance Indicators.

the use of the bladder diagram to document tumour characteristics (size, number, location, and appearance) and completeness of resection (including a TURBT checklist), which will be expanded in the 2024 Guideline Update.1

There are barriers to the instillation of chemotherapy following TURBT. These challenges range from surgeons’ prejudices or lack of belief in the evidence, to lack of drug access or obtaining it from the pharmacy, delays in prescribing, fear of bladder perforation, and a lack of standard pro forma that describes the need for instillation.15

RECENTLY

YOU PUBLISHED AN ARTICLE ON ACHIEVING BENCHMARKS FOR NATIONAL QUALITY INDICATORS

What Was Your Primary Motivation Behind This Research?

When I began as a consultant, I noticed that patients with bladder cancer were not

necessarily managed in a way that provided comprehensive information for their diagnosis. The information available to the MDT tended to be patchy, and it was observed that higher recurrence rates and progression were not only associated with muscle-invasive cancer.

In 2005, I conducted a prospective performance audit based on a simple, reproducible, objective surrogate measure: the sampling of the detrusor muscle. This was done to evaluate the surgeon’s performance, and determine if there was any association between detrusor muscle sampling, experience, and recurrence rate.10 This work led us to consider introducing benchmarks to assess the quality of TURBT.11

Performing the initial operation properly and thoroughly; documenting everything, including a standard description of the tumour; use of a standardised pathology checklist, describing grade, stage, depth of invasion, variant histology, and the presence or absence of CIS, among others;16 and an MDT overview, are quality elements that improve standards of care. Additionally, administering a single instillation of chemotherapy afterwards,

and selectively performing re-resection, are very important factors.

We introduced these standards into Scotland’s Quality Performance Indicators (QPI) programme in 2014; and in 2020, we published evidence behind the recurrence rate at first check cystoscopy, consequent to the QPI programme.13 In 2024, we described 5-year recurrence and progression outcomes from this cohort.3

How Were Targets (Benchmarks)

Derived or Defined for the Quality Performance Indicators for Nonmuscle-Invasive Bladder Cancer?

To improve treatment outcomes, a benchmark was established using our five-factor quality measure,11 the ‘pentafecta’ (Table 2).11,14,17

I planned to introduce these benchmarks as standards to the regional South East Scotland Cancer Network (SCAN);10 however, this fortuitously coincided with the Scottish Government’s Better Cancer Care policy,18 through which we had the QPI programme. I was fortunate to lead the QPI programme development,14 to improve cancer outcomes,10,17 unify standards, and reduce variability across the country.3,14,18

What Key Outcomes Were Identified, and What Significance Do These Have to Clinical Practice?

These benchmarks were developed to improve outcomes, and to allow more precise risk stratification by the MDT, which enables us to offer adjuvant treatment accordingly.10,11

Two key quality indicators emerged that could influence recurrence and progression: meeting the hospital target for sampling detrusor muscle, and performing a single instillation of chemotherapy.14

We also found, for the first time to my knowledge, a significant reduction in cancer progression associated with the SI-MMC, based on the newest classification of progression (from Ta to T1, G1 to G2, low-grade to high-grade, or G2 to G3).3

We introduced ‘tolerance’ into our targets for situations where certain procedures may not be appropriate. Centres meeting the 80% target of detrusor muscle sampling showed significantly better recurrence and progression risk.3 Also, SIMMC was associated with a 20.4% reduction in recurrence rate and progression.3 The audit and feedback mechanism within the QPI programme improved performance over time.3,10,11

Can You Elaborate on the Approaches Adopted During Your Research, and How They Have Evolved?

Data collection, ensuring safety, dedicated clinicians, and experience are as important as

1. Experienced surgeons carrying out the operation or supervising the TURBT.

2. Ensuring the use of a bladder diagram to document the tumour features.

3. Documenting the completion of resection.

4. Sampling the detrusor muscle.

5. Using a single instillation of chemotherapy (e.g., single instillation of mitomycin C after TURBT).

transurethral resection of bladder tumour.

TURBT:

Table 2: In-house ‘pentafecta’ quality performance indicator benchmarking.11,14,17

meeting benchmarks. We review and modify the QPIs every 3 years based on performance data, and emerging evidence.14 In patients with low-grade, small, non-invasive tumours; thin-looking bladders; or small tumours in the elderly, detrusor muscle sampling is not always necessary, and could be dangerous. The denominator for measuring the target for detrusor muscle sampling has shifted from ‘all NMIBC’ to only patients with high-grade NMIBC.19 Similarly, SI-MMC after initial resection is not recommended for patients with a thinned-out or perforated bladder, or if the patient has had bleeding or muscle-invasive cancer. Our new target is 80% use of a SI-MMC following initial TURBT for low-grade non-invasive cancer, up from 60%.19

How Do Quality Indicators Impact Tumour Progression and Recurrence?

The European Organisation for Research and Treatment of Cancer (EORTC) risk calculators20 have shown that if someone has prior recurrence, their prognostic risk of progression is higher.1 I think that, by reducing recurrence with SIMMC and identifying risk groups, we implement measures to reduce progression. Currently, we have a large database of patient information, which allows for detailed analysis of factors contributing to the reduction in progression.

Secondly, the definition of cancer progression in previous studies was limited to muscle-invasive cancer. We have expanded to include lesser levels of cancer progression (low-grade to highgrade, Ta to T1, or G1 to G2 or G3) proposed by the IBCG.7

WHAT ARE THE IMPLICATIONS FOR ACHIEVING BENCHMARKS IN FUTURE PRACTICE?

From a Scottish context, centres that do not adhere to the evidence-based recommendations will hopefully take note of our audit from Scotland, and strive not to be the outlier.3 This approach also empowers patients and the public by providing them with information.

Future clinical trials should utilise centres of excellence that meet specific benchmarks based on their performance in NMIBC. We are introducing a new dimension: considering the audit process, and examining our own practice.10,11 We hope this will reduce the variability between centres that was previously described.9 These are simple interventions that can influence outcomes.

By using a QPI programme, we are constantly assessing performance and providing feedback. This encourages continuous improvement. It’s about constantly trying to improve, and using surrogates as our benchmarks.11,13 Only then will we continue to improve patient outcomes. We are providing the evidence to support the use of these benchmarks. We have now shown that these benchmarks translate to real-world clinical outcomes.

WHAT ARE YOUR NEXT STEPS AND FUTURE VISION FOR BLADDER CANCER CARE?

Implementing QPI programmes can aid treatment outcomes, peer comparisons, and, potentially, clinical trials involved in future drug development. Future steps include using benchmarks in NMIBC within a novel risk calculator.3 In addition, we are evaluating the necessity of a re-resection, in whom to use SI-MMC, and exploring biomarkers for the management and surveillance of bladder cancer.

The use of benchmarks, quality control, and continuous quality improvement are crucial for improving patient outcomes. Everyone in the bladder cancer care community has a part to play, making it a way of life. The initial TURBT is the most important part of the patient’s journey for bladder cancer. When done properly, it can avoid unnecessary repeat surgery, save time, and improve survival. A risk stratification system can help determine the most appropriate treatment pathway. In my opinion, one of the best ways to benchmark a urology service is by how well they manage patients with NMIBC. The quality of a urology centre could be judged by the quality of its TURBT, such as lower (<10%) early recurrence rate at the first follow-up cystoscopy at 3 months.13

References

1. Gontero P et al. EAU Guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). 2024. Available at: https://uroweb.org/ guidelines/non-muscle-invasivebladder-cancer. Last accessed: 20 March 2024.

2. Cancer Research UK (CRUK). Bladder cancer survival statistics. 2014. Available at: https://www. cancerresearchuk.org/healthprofessional/cancer-statistics/ statistics-by-cancer-type/bladdercancer/survival#heading-Zero. Last accessed: 20 March 2024.

3. Mariappan P et al. Achieving benchmarks for national quality indicators reduces recurrence and progression in non–muscleinvasive bladder cancer. Eur Urol Oncol. 2024;DOI:10.1016/j. euo.2024.01.012.

4. National Institute for Health and Care Excellence (NICE). Bladder cancer: diagnosis and management. 2015. Available at: https://www.nice.org.uk/guidance/ ng2/ifp/chapter/treating-nonmuscle-invasive-bladder-cancer. Last accessed: 20 March 2024.

5. Mariappan P et al. Real-life experience: early recurrence with hexvix photodynamic diagnosisassisted transurethral resection of bladder tumour vs good-quality white light TURBT in new nonmuscle-invasive bladder cancer. Urology. 2015;86(2):327-31.

6. Mariappan P et al. Predicting grade and stage at cystoscopy in newly presenting bladder cancers-a prospective double-blind clinical study. Urology. 2017;109:134-9.

7. Kamat AM et al. Definitions, end points, and clinical trial designs for non-muscle-invasive bladder cancer: recommendations from the International Bladder Cancer Group. J Clin Oncol. 2016;34(16):1935-44.

8. Tan WS et al. Intermediate-risk non-muscle-invasive bladder

cancer: updated consensus definition and management recommendations from the International Bladder Cancer Group. Eur Urol Oncol. 2022;5(5):505-16.

9. Brausi M et al. Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: a combined analysis of seven EORTC studies. Eur Urol. 2002;41(5):523-31.

10. Mariappan P et al. Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience. Eur Urol. 2010;57(5):843-9.

11. Mariappan P et al. Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: validation across time and place and recommendation for benchmarking. BJU Int. 2012;109(11):1666-73.

12. van der Meijden APM et al. EAU guidelines on the diagnosis and treatment of urothelial carcinoma in situ. Eur Urol. 2005;48(3):36371.

13. Mariappan P et al. Enhanced quality and effectiveness of transurethral resection of bladder tumour in non-muscle-invasive bladder cancer: a multicentre real-world experience from Scotland's quality performance indicators programme. Eur Urol. 2020;78(4):520-30.

14. Mariappan P, Project Collaborators. The Scottish bladder cancer quality performance indicators influencing outcomes, prognosis, and surveillance (Scot BC Quality OPS) clinical project. Eur Urol

Focus. 2021;7(5):905-8.

15. Dunsmore J et al. What influences adherence to guidance for postoperative instillation of intravesical chemotherapy to patients with bladder cancer? BJU Int. 2021;128(2):225-35.

16. Varma M et al. Dataset for histopathological reporting of tumours of the urinary collecting system (renal pelvis, ureter, urinary bladder and urethra). Available at: https://www.rcpath. org/static/e2c11ff6-780a-471ea21a4dc48788d35b/Dataset-fortumours-of-the-urinary-collectingsystem.pdf. Last accessed: 20 March 2024.

17. Mariappan P. Propensity for quality: no longer a tenuous proposition in bladder cancer. Eur Urol. 2020;78(1):60-2.

18. National Health Service (NHS) Scotland. Better cancer care, an action plan. NHS, Edinburgh, Scotland. 2008. Available at: https://www.gov.scot/ binaries/content/documents/ govscot/publications/strategyplan/2008/10/better-cancer-careaction-plan/documents/0067458pdf/0067458-pdf/ govscot%3Adocument/0067458. pdf. Last accessed: 20 March 2024.

19. National Health Service (NHS) Scotland et al. Bladder cancer clinical quality performance indicators engagement document. 2021. Available at: https://consult. gov.scot/nhs/bladder-cancerquality-performance-indicators/ user_uploads/bladder-cancerqpis-v4-0---engagementdocument.pdf. Last accessed: 11 April 2024.

20. Sylvester RJ et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466-77.

Q1

Interviews

Two experts discuss their impressive careers with EMJ, and shed light on their proudest achievements and biggest challenges to date. Conversations are centred around current topics: advances in reconstructive urology, robotic surgery, and a focus on patient care.

Courtney Rowe

Connecticut Children's Medical Center, Hartford, Connecticut, USA; UConn Health, Farmington, Connecticut, USA.

Citation: EMJ Urol. 2024;12[1]:48-50. https://doi.org/10.33590/emjurol/10309007.

What inspired you to pursue a career as a paediatric urologist? How has your pre-medical background influenced you?

Medicine is a second career for me. I was in graduate school at New York University (NYU), USA, doing interactive computer sculpture, but I found the long hours alone in the laboratory too lonely for a career. I had to completely reinvent myself to go to medical school with pre-med classes, the Medical College Admissions Tests, everything! But my interest in technology and tinkering never left me. With the scopes and robotics, urology was a perfect fit. I love the paediatric side, because reconstructive surgery lets me be creative. Plus, as a mother of three, it is easy to work closely with kids and families. I am not fazed by crying, and I am an expert in one-handed diaper changes.

"I know that every person my patients meet is focused on caring for them as children."

Q2

As the Director of the Reconstructive Urology Program at Connecticut Children’s Medical Center, Hartford, USA, what are the main focuses and goals you are working to achieve?

In some areas of urology, patients have chronic conditions that will require a lifetime of management. Reconstructive paediatric urology is a little different. Our goal is to rebuild the anatomy so that, ultimately, the paediatric urologist is no longer needed, and the child can have a great quality of life without us. Getting there often requires balance and a light touch, making sure children have good urinary and sexual function without over-medicalising or traumatising them. There is no point getting a child dry if you do it in a way that makes them so terrified of doctors that they avoid them for the rest of their lives. That’s part of why I like working at a standalone children’s hospital. I know that every person my patients meet is focused on caring for them as children, not just on their medical needs. Ultimately, if all of us have done

our job well, children’s lives might look a little different because of their urologic differences, but they won’t ever be held back.

Q3

Reconstructive urology is an area of your expertise. What are some of the unique challenges synonymous with this area of surgical practice?

Reconstructive urology is the oppositive of ‘cookbook medicine’. Every child and every condition is unique, and so every surgical approach is unique. I use a lot of skills from my art days: the ability to think in three dimensions, to be creative, and to adapt my materials to the surroundings. These complex reconstructions are often team affairs; I routinely work with paediatric surgery, orthopaedic surgery, and other urologists. Co-ordinating those teams and gathering different perspectives, while not losing sight of the main goals of surgery, can be challenging. We all have big egos and strong opinions as surgeons! But ultimately, I’m glad for the extra heads focused on the best care for these complex patients.

Q4

In addition to your clinical role, you also work as a translational researcher, focusing on improved healing after urologic reconstructive surgery. Can you tell us a bit more about how you use regenerative medicine to enhance post-operative outcomes?

In my mind, research is an important adjunct to clinical care. We can provide the best possible clinical care based on today’s knowledge, but if we don’t also contribute to tomorrow’s knowledge, we will stop advancing. Now, as a researcher, I’m a little selfish in that I also want to see my work impact patients in my own lifetime. Others out there are doing cool things to grow new organs. Someday they may revolutionise the surgical field, but we all know getting there will take time. So, instead of focusing on the replacement side of regenerative medicine, I decided to focusing on healing. What can I use to get tissues to heal better? How do I deliver interventions to the tricky parts of the body urologists work on, like the urethra, the bladder, and the ureters? One of my main projects is a collaboration with a biomaterial scientist to develop a new material for a stent that can

deliver drugs to the urethra or ureter. I plan to use it to help the urethra heal from trauma or surgery, but the technology could be used to deliver any drug to any urologic lumen.

Q5You recently co-authored the study ‘Development of a Wound-Healing Protocol for In Vitro Evaluation of Urothelial Cell Growth’. What were the key learning points from this article, and how do these findings contribute to the existing literature on urethral healing?

When I started my research into urethral healing, I expected to be able to jump right into product development and translation. Instead, what I found was a real dearth of basic science foundation in terms of our understanding of urothelial healing; just a scattering of papers here and there. It’s a difficult area of the body to study. Plus, because of the stigma against urologic body parts, there is not a lot of public attention or money in this space. I have had to go back to the drawing board and really start from scratch, developing approaches and protocols to study the urethra in vitro. I did this work to further my own research and product development, but I also hope that by taking the time to publish on basics, like protocols, I will set other researchers up for continued success in this space.

Q6

How have you seen technology impact the field of urology over the years that you have been practicing? Are there any innovations on the horizon that you are particularly excited to see translated into practice?

The past decades of urology have seen a boom of mechanical technological advancement: robotic surgery, better and better ureteroscope technology, lasers, and improved techniques to use them. My hope for the future is biological advancement. We’ve seen immunotherapy and gene therapy begin to take off for medical illnesses. I’m excited to see innovations, like my urethral stent, that will bring the opportunity for biologic modifications into the surgical space as well.

Q7

What do you see as your proudest achievement to date since joining Connecticut Children’s Medical Center?

Early in my career, I had a patient with the rare condition of cloacal exstrophy, whose family had moved to Connecticut to get better care, after a failed surgery in another state had left her with her bladder still outside her body. At first, I referred the case to an out-of-state institution. But her revision surgery kept getting delayed, and travelling many hours for care was a huge burden for this family who had literally given up everything to get better medical care for their child. Watching their experience, I asked myself: Is this the kind of care I would want for my own children? This pushed me to develop a statewide collaborative, with out-of-state mentorship for bladder exstrophy care. With the support of this collaborative, I performed a revision surgery, which has been an amazing success. That patient is now thriving, as is her family now that they are not spending so much time on her medical needs. Her mother even went back to school, and now works at our hospital! The path this patient led me down was ultimately a lot more work than just referring these complex cases elsewhere, but it launched my career in reconstructive urology, as well as my research focus on healing after surgery. I’m proud that I took the harder road, and proud of what it has allowed me to accomplish.

"Ultimately, we do not move the needle on improving patient care if our innovations are never able to get out of the lab."

Q8Where can we expect to see your research and clinical focus lie in the next 5 years?

Ultimately, we do not move the needle on improving patient care if our innovations are never able to get out of the lab. When I started with translational research, I naïvely thought that once I had developed a technology that was successful at improving outcomes, I could just pass it off, and it would successfully transition into clinical use. Everyone wants something that makes outcomes better, right? I have since learnt that most products fail not because they do not work, but because they could not transition into the marketplace. To me, there is no point in innovating if I cannot also, someday, impact patients. That means setting my inventions up for success from the beginning by developing new technologies, with a plan for their future commercialisation built in from early on. I am branching out into learning about entrepreneurship and commercialisation. It is an entirely new set of skills, but I am excited to see where it brings me in the future! ●

Q1

Citation:

Jas Singh

Assistant Professor of Surgery (Urology), McGill University, Montréal, Quebec, Canada.

Citation: EMJ Urol. 2024;12[1]:51-53. https://doi.org/10.33590/emjurol/10305519.

Specialising in functional and reconstructive urology, was there a particular person or event that encouraged you down this path as a urologist?

My interest in functional and reconstructive urology first developed early, during my residency training at the University of Manitoba, Winnipeg, Canada, where I worked closely with two of my mentors, Eric Saltel and Robert Bard. Seeing the work that they did daily, and the rapid difference they made in the lives of patients, gained my interest, and encouraged me to delve further into the subspeciality and the role it plays in the lives of patients. This early interest was solidified during a case I will never forget, in which a 26-year-old female patient had suffered for many years with persistent intractable urinary incontinence. It wasn’t until one of my mentors, Eric Saltel, became involved, and led to the diagnosis of an ectopic ureteral insertion of the urethra, that a plan was finally established. The patient underwent a successful reconstructive procedure, and I remember seeing the patient in the recovery area where she was crying inconsolably, as she told me: “My suffering is finally over, and now I can get on with my life.”

That was the moment for me that I will never forget.

Q2 Could you update us on your current research concerning hyperbaric oxygen therapy (HBOT), and its applications in urology?

HBOT has been investigated for clinical application in several disease states, both urological and non-urological. In urology

specifically, some of the applications include management in intractable interstitial cystitis, radiation-induced haemorrhagic cystitis, erectile dysfunction, and to accelerate healing of urological wounds. HBOT works by increasing O2 delivery to inflamed and damaged tissue by restoring the cellular function of fibroblasts, macrophages, and granulocytes during the process of wound healing, and to accelerate neovascularisation in ischaemic tissue injured by the effects of radiation-induced endarteritis obliterans.

My current research efforts are aimed at understanding and evaluating the application of HBOT as a regenerative and restorative therapy for patients with urinary tract fibrosis, and as a perioperative supplement in the reconstructive urological patient, to improve surgical and clinical outcomes. Much work continues to be required in understanding how HBOT can be optimally applied as a regenerative therapy in the urological patient.

Q3 Where can we expect to see your research focus lie in the near future, and which areas within your specialty do you think warrant the most urgent attention?

The subspeciality of functional and reconstructive urology is currently seeing a surge in new technologies and improved techniques. With the regulatory approval of new technologies, and the increasing widespread adoption of these techniques, clinical studies will be required to best understand the impact of these therapies, and the conditions required for optimal outcomes. This is where I see a

large portion of my future research endeavours will lie. Specifically, we desperately need more randomised controlled trials in functional and reconstructive urology, and widespread multiinstitutional and multi-investigator collaboration, to provide the best quality evidence to inform clinical decision-making, and optimise patient care.

"The subspeciality of functional and reconstructive urology is currently seeing a surge in new technologies and improved techniques."

Q4 What was your most recent publication in the area of reconstructive urology, and what were the key points for clinicians to take away from this paper?

We recently published a study assessing outcomes in patients who have undergone ureteral reconstruction with ileal bowel interposition following treatment for abdominal and pelvic malignancy. This series is unique, in that it comprises a relatively large but specific patient population of survivors of cancer who have undergone ileal interposition with or without concomitant ileal cystoplasty, at

the time of either resection of their primary cancer (urological and non-urological), or in a delayed manner as the result of treatment for complications (ureteral stricture) resulting from surgical devascularisation, or radiationinduced injury. Despite being a heterogenous patient group, the results confirm the safety and versality of this technique, and continued surgical success with ileal interposition for ureteral reconstruction for long-segment ureteral defects, while preserving renal function.

Q5

Your career to date has involved attendance and presentations at several international congresses, such as podium and poster sessions at American Urological Association (AUA) Annual Meetings. How important are these large conferences for both clinicians and their patients?

Scientific meetings are the best opportunity to connect with old colleagues and develop new ones, while both sharing new scientific advancements, and learning from those achieved by others. These meetings are great opportunities for individuals from all backgrounds to come together, with the aim of sharing new knowledge, and gaining inspiration for new avenues of research and collaboration. Conferences are also a great opportunity

to learn about the latest technologies and products showcased by our industry partners. It is important to mention that these meetings are not just for physicians, but also for nurses, allied health professionals, trainees, and, very importantly, patients. It gives an opportunity for all parties to share their experiences and knowledge to improve everyone’s understanding of diseases and the effects of treatment. The COVID-19 pandemic showed the world that while we can still meet virtually to share knowledge and ideas, the value of in-person interaction should never be underestimated.

Q6

What do you see as your proudest achievement to date, considering the multiple articles you have published, and presentations you have delivered within the field of urology?

It may sound a bit cliché, but my proudest achievement has been, and continues to be, the care I offer to my patients. While research represents the cornerstone of innovation and advancement, and teaching trainees represents ‘giving back’ to future urologists and surgeons, the ability to understand a patient’s problem, provide a solution, and see it work, continues to be the biggest achievement I seek to achieve every time I set foot inside the hospital and operating room.

"My proudest achievement has been, and continues to be, the care I offer to my patients."

Q7 Are there any particular innovations in the specialty of robotics and reconstructive urology that you predict will be incorporated into practice soon?

The application of established robotic surgical platforms, along with newly emerging systems, has received considerable attention and exploration in reconstructive urology. The advantages of robotic surgery, including reduced blood loss, reduced post-operative pain, improved cosmesis, and reduced length of hospitalisation, are making it a possibility for reconstructive urological patients with complex surgical histories and anatomy. Furthermore, the enhanced optic capabilities to visualise structures deep in the pelvis and retroperitoneum have enhanced access for the surgeon. Despite this, the widespread adoption of robotics for functional and reconstructive urological procedures continues to be hampered by steep learning curves, the lack of widespread standardised training, and considerably increased operative times for surgeons early in the learning curve.

I think that recent advancements in surgical simulation models and artificial intelligence approaches will prove to be valuable additions to surgical training, helping to bring more surgeons up to speed, and improving the application of robotics to reconstructive urological procedures, allowing for accurate pre-operative planning in complex situations. ●

Artificial Intelligence in Robotic Urologic

Citation: EMJ Urol. 2024;12[1]:54-55. https://doi.org/10.33590/emjurol/GNRC8769.

1. Artificial Intelligence1

Artificial intelligence

Machine learning

Any technique that enables machines to mimic human intelligence.

2. Robotic Urologic Surgery

2-4

The da Vinci systemTM remains the main robotic surgical system used since its first approval in 2000 by the US Food and Drug Administration (FDA).

ADVANTAGE

Reduced surgeon fatigue

A subset of AI that uses statistical methods to enable machines to ‘learn’ tasks without explicit programming.

Deep learning

ADVANTAGE

Smaller incisions: less blood loss, less pain, less risk of infection

ADVANTAGE

Easier access to area being operated on

ADVANTAGE

Enhanced visualisation: highly magnified, 3D high resolution image

ADVANTAGE

Greater range of motion, dexterity, and precision

References

1. MathWorks. What is Artificial Intelligence? Available at https://in.mathworks.com/ discovery/artificial-intelligence.html. Last accessed: 15 March 2024.

2. Mehta A et al. Embracing robotic surgery in low- and middle-income countries: potential benefits, challenges, and scope in the future. Ann Med Surg (Lond). 2022;84:104803.

3. Koukourikis P, Rha KH. Robotic surgical systems in urology: what is currently available? Investig Clin Urol. 2021;62(1):14-22.

4. Mayor N et al. Past, present and future of surgical robotics. Trends Urol. 2022;13(1):7-10.

5. Zuluaga L et al. AI-powered real-time annotations during urologic surgery: the future of training and quality metrics. Urol Oncol. 2024;42(3):57-66.

A subset of machine learning that uses artificial neural networks to mimic the learning process of the human brain.

ADVANTAGE

Faster recovery, shorter hospital stay, faster return to daily life

DISADVANTAGE

Lack of experienced robotic surgeons and appropriate training programmes can lead to adverse events during robotic procedures

DISADVANTAGE

High cost of robotic systems is a barrier in lowto middle-income countries

6. American College of Surgeons (ACS); McCartney J. AI is poised to “revolutionize” surgery. Available at: https://www.facs.org/for-medical-professionals/news-publications/ news-and-articles/bulletin/2023/june-2023-volume-108-issue-6/ai-is-poised-torevolutionize-surgery/. Last accessed: 15 March 2024.

7. Imperial College London; Erh-Ya (Asa) Tsui. Application of artificial intelligence (AI) in surgery. Available at: https://www.imperial.ac.uk/news/200673/application-artificialintelligence-ai-surgery/. Last accessed: 10 March 2024.

8. Vanderbilt School of Engineering. The future of robotic surgery: 3 trends to look for. Available at: https://blog.engineering.vanderbilt.edu/the-future-of-robotic-surgery-3trends-to-look-for#:~:text=Experts%20anticipate%20that%20the%20integration,the%20 precision%20of%20robotic%20procedures. Last accessed: 15 March 2024.

3. AI can overcome challenges in robotic surgery5-7

AI can be used as a learning tool for robotic surgeons at different stages of their careers (recording surgeries, stocking datasets, etc.).

AI can be used to predict adverse events during surgery, such as intra-operative bleeding, to improve patient safety, and evaluate risk of post-operative complications.

Integration of AI with augmented reality can boost the ability of surgical robotic systems to perceive complex in vivo environments, and perform tasks with higher precision, safety, and efficiency.

Intra-operative assistance by AI can tailor a personalised approach for each patient, by analysing surgeries as they are performed, and providing decision support to surgeons in real-time. AI can anticipate the next 15-30 seconds of an operation, and suggest safe or less safe locations for incision.

4. What’s Next for Robotic Surgery8

AI can also provide algorithms to identify patients in need of organ transplants, evaluate potential donors, and match donors and recipients, to improve transplant decisions, and optimally allocate donor organs.

Minimally invasive procedures:

• Micro-robotics, for drug delivery, tissue repair, or exploratory surgery

• Single port robotic surgery

Ethical and legal frameworks for robotic automation, AI-driven decision-making, and safeguarding patient privacy.

Telesurgery to expand access to healthcare in remote, underserved, or disadvantaged regions.

Defining Urethral Complications of Intermittent Catheterisation Using Hydrophilic Catheters: A Scoping Review

Authors:

Disclosure:

*Todd Linsenmeyer,1-3

Chris Harding,4,5 Angie Rantell,6,7

Stefania Musco,8 Emmanuel Chartier-Kastler,9,10 Andrei Krassioukov,11 Piet Eelen,12 Diana Durieux,13 Ased Ali,14,15 Diane Newman16

1. Department of Urology, Kessler Institute for Rehabilitation, West Orange, New Jersey, USA

2. Department of Physical Medicine and Rehabilitation, Rutgers New Jersey Medical School, Newark, USA

3. Department of Surgery (Urology), Rutgers New Jersey Medical School, Newark, USA

4. Department of Urology, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK

5. Translational and Clinical Research Institute, Newcastle University, UK

6. Department of Urogynaecology, King’s College Hospital NHS Foundation Trust, London, UK

7. Brunel University, London, UK

8. Department of Neuro-Urology, Careggi University Hospital, Florence, Italy

9. Department of Urology, Sorbonne University, Paris, France

10. Urology Department, University Hospitals Pitié-Salpêtrière, Paris, France

11. International Collaboration on Repair Discoveries (ICORD), Division of Physical Medicine and Rehabilitation, University of British Columbia, Vancouver, Canada

12. National Multiple Sclerosis Center, Melsbroek, Belgium

13. Medical Affairs, Continence Care, Convatec, Søborg, Denmark

14. Medical Affairs, Continence Care, Convatec, London, UK

15. Yorkshire Regional Spinal Injuries Centre, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK.

16. Division of Urology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA

*Correspondence to talinsenmeyer@gmail.com

Linsenmeyer has been a consultant and served on the advisory board for Convatec. Harding has been a consultant for Mylan Pharmaceuticals and Teleflex Medical; has received speaker honoraria from Allergan, Astellas Pharma, Convatec, and Medtronic; has received fellowship and travel grants from Medtronic; has received research funding from the National Institute for Health Research and The Urological Foundation; and is chair of the European Association of Urology (EAU) Guidelines Panel for Female Lower Urinary Tract Symptoms. Rantell has been a consultant and/or speaker for AbbVie, B. Braun, Convatec, Coloplast, Hollister, Consilient Health, and Laborie. Musco has received funding, been a consultant and/or speaker for Convatec, Hollister, Coloplast, and Medice (Arzneimittel Pütter). ChartierKastler has received funding, been a consultant and/or invited speaker for AbbVie, B. Braun, Boston Scientific, Coloplast, Convatec, Medtronic, TBF Lab, and UroMems. Krassioukov has received research funding from the Canadian Institute for Health Research, Canadian Foundation for Innovation and BC Knowledge Development Fund, International Spinal Research Trust, PRAXIS Spinal Cord Institute, Wings for Life Research Foundation, and U.S. Department of Defense; has been a speaker/consultant for

Coloplast; and has served on the advisory board for Coloplast, Convatec, and ONWARD. Eelen has been a consultant and received presenting fees from Biogen Idec, Convatec, Merck, and Novartis Pharmaceuticals. Durieux and Ali are employees of Convatec. Newman has received research funding from Convatec, Hollister and National Institutes of Health; has been a consultant for Cosm and Urovant; and is Editor for Digital Science Press.

Acknowledgements: Medical writing assistance was provided by Harsimran Bajwa, T-minus, London, UK, and Hannah Moir, EMJ, London, UK. The authors would like to acknowledge the invaluable contributions of the late Linda Cardozo, OBE, a renowned Professor and Consultant Urogynaecologist, whose initial involvement and discussions were instrumental in shaping this manuscript. Her enduring legacy continues to inspire their work.

Disclaimer: This article is intended for healthcare professionals.

Support: The publication of this peer reviewed article was supported by Convatec.

Keywords: Catheter, catheter-associated complications (CAC), catheter technology, haematuria, hydrophilic catheters, intermittent catheter-associated complications (ICACS), intermittent catheterisation (IC), urethral complications, urethral trauma.

Citation: EMJ Urol. 2024;12[1]:56-67. https://doi.org/10.33590/emjurol/VZIG5312.

Abstract

This scoping review emphasises the significance of various complications such as urinary tract infections (UTI), urethral pain, urethral trauma, damage, and haematuria, when understanding and reporting complications experienced during intermittent catheterisation using hydrophilic-coated and newer catheters with integrated hydrophilic properties.

Currently, there is a lack of consistency and interchangeability in the definitions of bladder and urethral complications in published literature, particularly in the case of urethral trauma and damage.

A search of the literature was conducted in accordance with established Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA) guidelines. By mapping the terminology used in articles, and providing insight into the current gap in the definition of complications related to catheter use, the authors highlight the urgent need for standardisation in the definitions of complications associated with catheter use. This will enhance research and education, and better manage and address intermittent catheter-associated complications (ICAC), promoting best practices in catheter education, use, and selection.

INTRODUCTION

Catheters have been utilised since ancient times to assist individuals incapable of voluntarily

emptying their bladder. Clean intermittent selfcatheterisation became prominent in the 1970’s giving individuals more autonomy to manage this procedure themselves.1,2 Presently, intermittent

catheterisation (IC) is considered the goldstandard for neurogenic lower urinary tract dysfunction in those with good hand function, or a willing caregiver. 3-5

In a roundtable discussion in April 2023,6 the authors focused on ICACs, and identified several complications linked to intermittent catheter use.1-5 The discussion also highlighted limitations in previous studies, including the lack of detailed baseline information about the study populations, and that the outcomes related to intermittent catheterisation use were not sufficiently aligned with urethral complications.7 This therefore underscores the challenge of establishing true incidence and prevalence data for each complication.

More well-structured clinical trials are needed to provide a detailed analysis of adverse events related to intermittent catheterisation.

This scoping review aims to systematically map the terminology used in articles that evaluate ‘hydrophilic’ intermittent catheters, including catheters with a hydrophilic coating, or newer devices with hydrophilic properties incorporated into the catheter material, such as the integrated amphiphilic surfactant, with a particular focus on terms related to ICACs.

It should be noted that the focus of this scoping paper is on hydrophilic intermittent catheter complications, and it is not an in-depth review on the many aspects of catheter-associated urinary tract infections. A recommendation for a comprehensive definition of the symptoms of catheter-associated urinary tract infection (CAUTI) is outside the scope of this review.

METHODS

This review adheres to PRISMA.8 The literature search strategy was focused on PubMed, Cochrane Library, Embase, and Google Scholar, containing the following combination of terms: “urethral AND (hydrophilic OR coated OR integrated amphiphilic surfactant) AND (intermittent AND [catheterisation OR catheterization OR catheter OR dilatation]) AND (pain OR discomfort OR sticking OR stickiness OR haematuria OR hematuria OR bleeding OR urethral trauma OR trauma OR obstruction

OR neurological urinary tract dysfunction OR retention OR bladder outlet obstruction OR false passage OR stricture OR stenosis OR scarring).”

Literature was limited to human studies published from 1990–October 2022, and written in English. Two reviewers screened all identified literature, and evaluated the titles, abstract, and full text. In instances of disagreements, resolution was sought through consultation with a third reviewer.

RESULTS

Selection of Data

The systematic search identified a total of 400 articles, of which 41 were evaluated: 17 original articles16-32 and 24 review/meta-analysis articles (Figure 1).11,13-15,33-52 Additionally, a hand search identified seven more original articles.53-59 A total of 48 articles were analysed. This illustrates the search strategy, and reflects the quality of the literature base.

GENERAL DEFINITIONS OF URETHRAL COMPLICATIONS/TRAUMA

This scoping review identified three main categories when reviewing the literature for ICACs: definitions of urethral complications; complications in association with defining urethral trauma; and definition of intermittent catheterisation complications.

Not only were there different categories discussing intermittent catheterisation complications, but there was a wide variety of descriptions of these complications within each of these categories. This highlights the challenges and needs for this scoping review to unpack the significant overlap between these categories.

Definitions of Urethral Complications

In the existing literature, the term ‘urethral complications’ is frequently used to describe the side effects associated with IC, as evidenced by numerous studies.17,18,23,27,28,32-35,37,40,43-45,47-50,55,56,59 However, this term often lacks a precise

Figure 1: Schematic of the systematic search across PubMed, Embase, Cochrane Library, and Google Scholar to select articles for analysis.

Identification

Identified 400 articles from PubMed, Embase, Cochrane, and Google Scholar

Screening

321 articles after duplicates (79) removed

Eligibility

179 articles full text screened for eligibility

Inclusion

41 articles included for evaluation

CAUTI: catheter-associated urinary tract infection.

definition, and is typically represented with considerable variability (Supplementary Table 1). The complications range from paired complications, e.g., ‘UTIs and haematuria’,32 and ‘strictures and false passages’,18 to extended lists of multiple complications, such as ‘urethral false passage, urethral strictures, gross haematuria, and recurrent UTIs’27 among others. This lack of specificity in definition across various articles underscores the need for a more standardised description of these complications.

The range of complications associated with IC mentioned in the literature varies widely, from one to as many as 20 different types, with UTIs often identified as the most common complication.35,58 In terms of multiple

Excluded:

- Not written in English (9)

- Retracted (2)

- No full text available (78)

- Not related to the subject (14)

- Related only to indwelling (15)

- Not peer-reviewed (24)

Excluded:

- Includes only CAUTIs (47)

- No mention of trauma (27)

- No clear definition of urethral trauma and/or complication (19)

- No measurement of urethral trauma-related outcomes (45)

Included:

- Seven additional articles following hand search

complications, four articles specifically discuss dual issues: for instance, UTIs coupled with urethral trauma,31 or UTIs coupled with haematuria,32 each pair representing a separate outcome. Notably, Hakansson et al.30 report a high incidence of UTIs in 77% of IC users,59 and urethral trauma in 30%.61

In contrast, some sources focus their definitions of complications specifically on outcomes induced by trauma, excluding UTIs. For example, one study40 highlights complications such as bleeding, urethral stricture, and false passage. Similarly, another source50 details complications like strictures, false passages, urethritis, and other conditions stemming from urethral trauma.

More comprehensive definitions of complications associated with IC are found in other publications,45,47 specifically eight distinct complications, including ‘UTI, urethral stricture, haematuria, bladder stones, false passage, pain or discomfort, and upper tract complication of renal scarring’ (Supplementary Table 1). Others, such as Prieto,47 categorise complications into two distinct groups: one that considers UTIs, and another that does not.

At the other end of the spectrum, definitions of IC-related urethral complications vary widely. For instance, Kanti et al.48 documents as many as 14 different complications, while another36 lists up to 20. The approach taken in Kanti et al.48 presents a comprehensive range of catheterisation complications, which are not categorised by catheter type, suggesting an extensive coverage of complications induced by IC.

The most elaborate description of urethral complications is found in Li et al.,38 which identifies 20 complications associated with catheterisation. These are further categorised into various groups, including hypersensitivityrelated issues, catheter blockage, and malignancy, among others. While this source examines outcomes from all types of catheterisations, not exclusively IC, their comprehensive definitions, along with those from other sources, are systematically compiled in Supplementary Table 1

Additionally, in one instance,33 the phrase ‘urethral problems’ is used, encompassing a range of issues such as discomfort, blockage, infection, haematuria, trauma to the urethra, prostate, or bladder, and expulsion. This description summarises the variety of complications mentioned in

Supplementary Table 1

Key Points on the Definitions of Urethral Complications

• Broad versus specific: some studies provide broad definitions that include a wide range of complications; others offer more specific lists, focusing on complications like strictures, false passages, and haematuria.

• Inconsistency in classification: the definitions vary significantly from one study to another,

with some categorising complications as acute or long-term, and others not making such distinctions.

• Frequency and severity: some definitions highlight the frequency of certain complications, such as urethral bleeding, while others mention the severity of the challenges these complications pose.

• Differing emphasis: studies also differ in their emphasis on complications. While UTIs are commonly mentioned, some definitions emphasise the mechanical trauma induced by catheterisation, and others highlight less common complications, such as catheter blockage and urinary tract malignancy.

Complications in Association with Defining Urethral Trauma

In numerous instances, the side effects of IC have been commonly characterised as ‘urethral complications’. Among the 48 articles that provided a definition or explanation regarding urethral trauma or urethral complications, 20 mentioned UTIs.

UTIs were frequently segregated into a distinct category from other urethral complications, notably urethral trauma.

Subsequently, a count of articles incorporating various specific complication outcomes was undertaken, with a particular emphasis on those independent of UTIs. Urethral bleeding, which encompasses both gross and microscopic haematuria, was cited in 16 articles,13,23,27,28,32,35,37,40,43,45,47,49,53,55,57,59 and stricture was noted in 14 articles13,18,27,37,39,40,43,45,47,49,50,53,55,59 as a definition of urethral complications. Inflammation of the urethra, alternately referred to as urethritis, emerged as the third most frequently mentioned urethral complication, cited on 11 occasions. Additionally, false passage and epididymitis were included in the definitions provided in eight18,27,40,45,47,50,55,57 and four37,43,47 articles, respectively. Other outcomes forming part of the urethral complication definition reported less frequently were related to patient experience (e.g., sticking, pain), UTI-related outcomes (e.g., bladder stones, encrustation, urosepsis), and allergic reactions.

Key Points on the Definitions of Urethral Trauma

• Severity: definitions of urethral trauma (Supplementary Table 2) range from irritation to severe conditions.

• Assessment methods: there is a lack of a standardised indirect and direct method for assessing urethral trauma. Previously suggested techniques include measurement of withdrawal friction-force of catheters, urethral cell counts, urethral cytology, and the presence of haematuria as possibilities,30 but to date none have been universally accepted.

• Associated risks: the sequelae of urethral trauma are frequently mentioned, with a particular emphasis on the increased risk of UTIs, and the potential for long-term complications like strictures.

• Symptoms and indicators: symptoms like pain and bleeding are commonly used to describe urethral trauma, while the presence of haematuria is often used as an indicator of trauma severity.

• Long-term impact: the long-term impacts of urethral trauma, such as stricture formation, and its effect on the quality of life and bladder management, are acknowledged as significant concerns in the definitions provided.

Definition and Description of the Frequency of Intermittent Catheterisation Complications

A total of 48 articles in those who used intermittent catheterisation for their bladder management were scrutinised for their description of complications. The review revealed eight types of complications affiliated with intermittent catheterisation and urethral trauma. The complications considered in these articles were independent of CAUTIs. The complications identified were haematuria, microhaematuria, stricture, false passage, epididymal-orchitis, urethritis, and urethral irritation.

Liao et al.52 defined haematuria, noted for its various terminology including ‘urethral bleeding’ and ‘gross haematuria’, as visible blood presence in the urine. Out of the articles analysed, 13 omitted this complication, 31 cited or measured

haematuria with no additional explication, and seven offered a definition or a broad explanation of the term.13,24,37,38,41,51,52 Two among them noted the utilisation of dipstick analysis for haematuria measurement.24,38 Various causes of haematuria

were speculated, ranging from urethral trauma50 to a result of CAUTI36 (Table 1).

Conversely, microhaematuria is associated with haematuria, but is only observable microscopically.51,52 Of the 48 articles, 35 did not mention this complication, nine mentioned it without elaboration, and six gave measurement methods or provided an explanation.22,25,30,41,51,52 Detection methodologies, according to the literature, incorporate dipstick usage,22,25,30 or microscopic observation of urine for red blood cells.51,52 Occasionally, both methods are employed41 (Table 1).

Urethral strictures emerged as the second most reported traumatic side effect of IC. From the selected 48 articles, 17 omitted this complication, 22 mentioned it, and 11 gave an explanation/definition.16,17,28,35,36,39,40,43,45,51,52 Some definitions were brief,36,51 and others detailed, e.g., ‘The method for stricture evaluation is a maximum flow rate <14 mL/s or endoscopic or radiographic examination’.52 Repeated catheterisation causing urethral damage is cited as a typical cause for stricture formation, leading to inflammation,16,17,35,40,43 with one article38 noting sex-specific causative variations (Table 1).

In relation to intermittent catheterisation urethral trauma-related complications, false passage, or ‘via falsa’, was the third most common. Of the articles, 19 mentioned it without additional explanation, five provided explanations/ definitions,35,36,40,45,51 and the rest did not measure or analyse this complication. Engberg et al.45 articulated a clear definition: ‘A false passage in the urethra is the formation of an epithelialised tract created when the catheter is inserted against the urethral wall rather than guided through the urethral lumen and into the bladder vesicle’.45 Two articles considered the outcome a consequence of urethral stricture35,40 or forceful catheter insertion36 (Table 1).

Epididymitis and epididymo-orchitis are wellcharacterised in the medical realm, and were mentioned in 18 articles, with three providing descriptions.40,48,51 A precise definition was

Table 1: Detailed definitions of complications associated with intermittent catheterisation as identified in the analysed articles.

Outcome Description of Complication

Haematuria

Microhaematuria

‘Hematuria was measured after each catheterization using an automatically analyzed urine multi-dipstick’24

‘Studies have used different terms such as urethral bleeding, haematuria and gross hematuria to describe the same condition’52

‘Haematuria the presence of red blood cells in the urine, urethral bleeding, or gross and microscopic haematuria’13

‘(macroscopic) hematuria or visible bleeding to represent urethral trauma’51

‘Bleeding episodes as a primary indicator to assess urethral trauma’41

‘Hematuria was identified by erythrocyte dipstick or a history of gross blood in the urine’38

‘Blood in the urine, derivative complication to CAUTI’37

‘Microhaematuria was measured daily by erythrocyte dipstick test, during weeks 3 and 4 in the institutional period. The average number of measurements per participant was 10.0’25

‘Dipstick analysis of blood content in urine from first normal micturition after two catheterisations performed, the results were as erythrocytes/ µL’30

‘Had some degree of haematuria on dipstick analysis’22

‘The presence of red blood cells (RBC) in high power field under the microscope’52

‘The presence of blood cells in urine samples observed by microscope’51

‘Microhaematuria using dipsticks and microscopic analysis of red blood cells’41

Stricture

‘Urethral stricture is the direct consequence of a urethral inflammatory response to repeated urethral catheterisation’17

‘Urethritis and urethral stricture formation represent severe degrees of urethral trauma and their sequelae’16

‘Cystoscopic and radiological evidence of urethral stricture disease during their follow-up’28

‘Women can develop urethral strictures as a result of such trauma. In males, the effects of traction are more apparent’39

‘Although strictures can result from repeated tissue damage, those catheterising regularly become more skilful, thus reducing trauma’43

‘The relationship of IC and urethral stricture is complex. Repeated in-and-out (1time) catheterization may be used to maintain urethral patency in patients with a urethral stricture’45

‘Bladder outlet obstruction’36

‘The method for stricture evaluation is maximum flow rate<14 mL/s or endoscopic or radiographic examination’52

‘The abnormal narrowing of a duct’51

‘(Stricture) would result from repeated urethra trauma’40

‘These strictures may be the consequence of an inflammatory response to repeated microtrauma, and are often more frequent in patients who perform CISC longer than 1 year’35

Table 1 continued.

False passage ‘A false passage in the urethra is formation of an epithelialized tract created when the catheter is inserted against the urethral wall rather than guided through the urethral lumen and into the bladder vesicle’45

‘This is rare and occurs when a catheter has been inserted aggressively through a weak part of the urethra’36

‘Urethral false passage may occur in men with persisting urethral strictures, detrusor sphincter dyssynergia, and enlarged prostate. The false passage may occur at the site of the external sphincter, just distal to the prostate, or at peno-scrotal level (…)’35

‘Occurs when a catheter is placed into an area outside the opening of the urethra; commonly occurs when there is an obstruction in the urethra’51

‘False passages are also considered classical complications and often occur in case of urethral stricture’40

Epididymis-orchitis

‘Male patients with orchitis, a scrotal abscess, prostatitis, and epididymitis are likely to develop urethral damage’48

‘An inflammation of the epididymis, the cord-like structure along the back of the testis’51

‘Epididymo-orchitis (it is easier to diagnose and should be suspected at the onset of an inflammatory and/or painful scrotum)’40

Urethral/ epithelial damage

Urethral irritation

‘Number of epithelial cells on the catheter after removal’20

‘Recurrent modifications of the urethral wall but no development of a false passage’18

‘Measured through friction force and reported stickiness of the catheter, measured with an electronic dynamometer twice daily’19

‘Epithelial cells after catheter withdrawal as an indicator for urethral friction and trauma’41

‘Counting the cells on the catheter surfaces’56

‘The reason may be that a great number of patients might only have mucosal irritation symptoms, which indicate a very slight urethral trauma that cannot be detected by laboratory tests’13

CAUTI: catheter-associated urinary tract infection.

supplied by Ontario:51 'An inflammation of the epididymis, the cord-like structure along the back of the testis'. Another article implied that epididymo-orchitis might increase the risk of urethral damage.48 All three definitions/ explanations are tabulated in Table 1.

The term ‘epithelial damage’ or ‘urethral damage’ was mentioned in 10 articles, and defined in five articles with explanations.18-20,41,56 The number of epithelial cells after catheter removal seems to be an indicator of damage to the urethra,41,56 or the friction force exerted by the catheter.19 The damage is not followed by the formation of false passage (Table 1).18

Urethral irritation emerged as the least common complication in the context of urethral trauma, secondary to IC. Out of the articles, 11 measured this complication, but only two provided descriptions.11,16 Secretariat11 offered a basic definition, while Vaidyanathan et al.16 stated that this outcome was ascertained through urethral cytology. Urethral irritation, particularly as caused by IC, is frequently cited in review articles. A singular original research article, Ye et al.13 included elucidations regarding this outcome, highlighting it as a distinct indicator of urethral trauma. The term ‘urethral irritation’ surfaced in six articles,13,34,37-39,49 none of which extended further explanations. Comprehensive definitions and descriptions of urethral inflammation and irritation are available in Table 1

EVOLUTION OF COMPLICATIONS IN URETHRAL TRAUMA RESEARCH

The complications mentioned in the literature have evolved. From 1990–2010, most articles referred to various urethral trauma complications, albeit with scarce provision of definitions. The most mentioned complications throughout the publication history were ‘urethral complication’, ‘urethral trauma’, and ‘epithelial damage’. There are just as many publications between 2011–2020 compared to 1990–2010, and an increase in the number of complications with accompanying definitions. There was, however, the increase in reference to ‘false passage’, ‘haematuria’, ‘stricture’, and ‘epididymo-orchitis’, as examples. However, more can and must be done to simplify and clearly define the frequency and description of complications associated with IC.

In an analysis of original articles, when considering the frequency of complications, and their descriptions in relation to the study duration, the short-term studies of 1–10 days typically tracked one complication. In contrast, studies with durations of 1–6 months tended to investigate multiple types of complications. Notably, no single study covered as many as six types of complications,16 contrary to what was previously mentioned. Studies of 1 year duration typically reported two or three complications, indicating a varied approach to data measurement. Long-term studies, particularly those extending beyond 5 years, examined up to four different complications. This suggests an increasing complexity in outcome measurement correlating with longer study durations.

DISCUSSION

A key finding of this scoping review confirms that there is no unified definition of IC complications within the literature, but rather demonstrates the variation in definitions used. Considering this, the authors support the proposal made during a recent expert roundtable discussion, that to promote clarity and consistency, in both evidence and clinical practice, there is a need to establish a consensus definition for ICACs and associated endpoints. This should not only include symptoms or complications that can be observed and measured, but also consider the individual’s perceived/experienced symptoms that may not

always manifest with a physical sign that can be measured.

The term ‘urethral trauma induced by IC’ is also unclear. While several studies attempted to define this term, significant differences exist between them, e.g., "urethral injury can result from improper, difficult, or traumatic, repeated catheterisation,"29 and "IC can cause bruising and trauma to the urethral mucosa."36 Urethral trauma can refer to the friction force applied by the catheter during insertion or removal, damage to the lining of the urethra, or haematuria. Additionally, most definitions of urethral trauma do not include the type of catheter, the catheter material, or the handling of the catheter as a contributing factor to the trauma. As such, a more uniform and standardised definition of urethral trauma is needed.

It is important to note that most catheterisation trauma-related complications were reported in study durations of 1–6 months, or up to 1 year duration. Furthermore, the extent of traumatic damage to the urethral tissue lining caused by catheterisation is not well-documented.

Several questionnaires focused on patients’ experience but did not address the full range of long-term catheter complications that may provide a better understanding of their connection with complications (e.g., result from the catheter material, high friction force, improper handling of the catheter, etc). Further research is required to establish the mechanistic cause of the pathophysiology of catheter-induced urethral trauma, particularly in light of improvements with newer catheter materials, e.g., integrated amphiphilic surfactant.66

LIMITATIONS

The authors acknowledge a limitation in their search strategy, in that the focus was only on hydrophilic catheters. This exclusion may have narrowed the scope of their findings, as different materials and coatings could influence complication rates and patient experiences. The impact of catheter composition warrants further investigation, and should be considered in future research.

The authors’ review did not address potential variations in complication rates or patient experiences between individuals based on gender, or with and without perineal sensation; nor did it explore differences among patients who can void voluntarily versus those who cannot, or between individuals who catheterise themselves versus being catheterised by someone else. Although data on these distinctions may be scarce, acknowledging the possibility of divergent outcomes among these patient populations is important for a comprehensive understanding of the field. Future research should investigate whether these factors significantly impact patient outcomes.

This review spans a considerable timeframe, during which the terminology used in the literature may have evolved. For instance, terms like ‘microhaematuria’ might also appear as ‘microscopic haematuria’ or ‘non-visible haematuria’. Although the authors have made efforts to account for this variability, it is possible that not all synonymous terms were captured in their search strategy. This may have affected the comprehensiveness of their search results, and should be considered when interpreting the findings.

CONCLUSION

In conclusion, there is no single, universally accepted definition of urethral trauma associated with catheter use. Definitions vary widely, encompassing a range of symptoms, assessment methods, and potential complications. This diversity in definitions not only reflects the complexity of the complications associated with intermittent catheterisation, but also underscores the need for a standardised approach for defining, measuring, and reporting complication outcomes, to improve patient outcomes and standards of care.

With the emergence of new catheter technologies, it is important for the field of urology to establish unified definitions for these urethral complications to support ongoing research, education for patients and healthcare professionals alike, and clinical practice. The

expert roundtable discussed the particular challenge in defining UTI symptoms, as there can be an overlap between symptoms of a UTI and of urethral trauma. This situation poses a challenge for future researchers to address, and the authors call on the international expert communities to include all stakeholders including patients, healthcare professionals, users, and industry, to drive a consensus and support by establishing clear definitions for ICACS, and aligning clinical practice for the treatment of CAUTIs.7

RECOMMENDATIONS

Based on this scoping review and multiple definitions of complications, the authors recommend that researchers or investigators, and healthcare providers be as detailed as possible when describing the specific type of catheter-related complication. This is particularly important when discussing what type of definition is being used regarding UTIs, since there are multiple definitions. Investigators should include all types of complications that occur, rather than focusing on just one specific complication. The literature is also lacking with regard to other variables that may impact intermittent catheterisation complications. These variables should include patient-related factors, such as the person’s frequency and compliance at performing catheterisation, whether they are independent when performing catheterisations, gender, pre-existing urethral problems (false passage, stricture), and type of catheter being used. This information would be extremely helpful in improving patient compliance, decreasing complications, and helping to assess current catheters and promote further advances in catheter design.

The authors also recognise the need for validated outcome measures for assessing the patient experience related to IC. Given the importance of patient-centred care, there is a need for the development and validation of tools that accurately capture how much patients feel bothered by the IC process. Researchers should prioritise efforts to develop and validate such measures, to better understand and address patient needs and concerns.

References

1. Lapides J et al. Clean, intermittent self-catheterization in the treatment of urinary tract disease. J Urol. 1972;107(3):459-6.

2. Mattelaer JJ, Billiet I. Catheters and sounds: the history of bladder catheterisation. Paraplegia. 1995;33(8):429-33.

3. European Association of Urology (EAU). EAU guidelines on neurourology. 2023. Available at: https:// uroweb.org/guidelines/neurourology. Last accessed: 22 March 2024.

4. Ginsberg DA et al. The AUA/SUFU guideline on adult neuruogenic lower urinary tract dysfunction: treatment and follow-up. J Urol. 2021;206(5):1106-13.

5. Consortium for Spinal Cord Medicine. Bladder management for adults with spinal cord injury: a clinical practice guideline for health-care providers. J Spinal Cord Med. 2006;29(5):527-73.

6. Newman D et al. Insights from an expert roundtable discussion: navigating intermittent catheterisation-associated complications. EMJ. 2023;8(3):3848.

7. Tricco AC et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med. 2018;169(7):467-73.

8. Salameh A et al. Prevention of urinary tract infections in patients with spinal cord injury. CMAJ. 2015;187(11):807-11.

9. Agwu NP et al. Review article: urethral catheters and catheterization techniques. NJM. 2022;31(5):497-508.

10. Medical Advisory Secretariat. Hydrophilic catheters: an evidencebased analysis. Ont Health Technol Assess Ser. 2006;6(9):1-31.

11. Fader M et al. Coated catheters for intermittent catheterization: smooth or sticky? BJU Int. 2001;88(4):3737.

12. Ye D et al. Catheters for intermittent catheterization: a systematic review and network meta-analysis. Spinal Cord. 2021;59(6):587-95.

13. Ivaz SL et al. Intermittent selfdilatation for urethral stricture disease in males: a systematic review and meta-analysis. Neurourol Urodyn. 2016;35(7):75963.

14. Feng D et al. Outcomes comparison of hydrophilic and non-hydrophilic

catheters for patients with intermittent catheterization: an updated meta-analysis. Asian J Surg. 2020;43(5):633-5.

15. Vaidyanathan S et al. Urethral cytology in spinal cord injury patients performing intermittent catheterisation. Paraplegia. 1994;32(7):493-500.

16. Perrouin-Verbe B et al. Clean intermittent catheterisation from the acute period in spinal cord injury patients. Long term evaluation of urethral and genital tolerance. Paraplegia. 1995;33(11):619-24.

17. Waller L et al. Clean intermittent catheterization in spinal cord injury patients: long-term followup of a hydrophilic low friction technique. J Urol. 1995;153(2):345-8.

18. Waller L et al. The importance of osmolality in hydrophilic urethral catheters: a crossover study. Spinal Cord. 1997;35(4):229-33.

19. Biering-Sørensen F et al. Urethral epithelial cells on the surface on hydrophilic catheters after intermittent catheterization: crossover study with two catheters. Spinal Cord. 1999;37(4):299-300.

20. Wyndaele J et al. Evaluation of the use of Urocath-Gel catheters for intermittent self-catheterization by male patients using conventional catheters for a long time. Spinal Cord. 2000;38(2):97-9.

21. Vapnek JM et al. A prospective randomized trial of the LoFric hydrophilic coated catheter versus conventional plastic catheter for clean intermittent catheterization. J Urol. 2003;169(3):994-8.

22. Cindolo L et al. Standard versus hydrophilic catheterization in the adjuvant treatment of patients with superficial bladder cancer. Urol Int. 2004;73(1):19-22.

23. Bagi P et al. Safety of a new compact male intermittent catheter: randomized, cross-over, single-blind study in healthy male volunteers. Urol Int. 2011;86(2):17984.

24. Cardenas DD et al. Intermittent catheterization with a hydrophiliccoated catheter delays urinary tract infections in acute spinal cord injury: a prospective, randomized, multicenter trial. PM R. 2011;3(5):408-17.

25. Spinu A et al. Intermittent catheterization in the management of post spinal cord injury (SCI) neurogenic bladder using new hydrophilic, with lubrication in close

circuit devices--our own preliminary results. J Med Life. 2012;5(1):21-8.

26. DeFoor W et al. Results of a prospective randomized control trial comparing hydrophilic to uncoated catheters in children with neurogenic bladder. J Pediatr Urol. 2017;13(4):373.e1-373.e5.

27. Davis NF et al. Long-term outcomes of urethral catheterisation injuries: a prospective multiinstitutional study. World J Urol. 2020;38(2):473-80.

28. Cohen AJ et al. Multicenter urethroplasty outcomes for urethral stricture disease for patients with neurogenic bladder or bladder dysfunction requiring clean intermittent catheterization. Transl Androl Urol. 2021;10(5):2035-42.

29. Stensballe J et al. Hydrophiliccoated catheters for intermittent catheterisation reduce urethral micro trauma: a prospective, randomised, participant-blinded, crossover study of three different types of catheters. Eur Urol. 2005;48(6):978-83.

30. Hakansson, MA et al. Health care utilization and complications rates among users of hydrophiliccoated catheters. Urologic Nurs. 2015;35(5):239-47.

31. De Ridder DJMK et al. Intermittent catheterisation with hydrophiliccoated catheters (SpeediCath) reduces the risk of clinical urinary tract infection in spinal cord injured patients: a prospective randomised parallel comparative trial. Eur Urol. 2005;48(6):991-5.

32. Robinson J. Urinary catheterisation: assessing the best options for patients. Nurs Stand. 2009;23(29):40-5.

33. Wyndaele JJ et al. Neurological patients need evidence-based urological care. Neurourol Urodyn. 2010;29(4):662-9.

34. Di Benedetto P. Clean intermittent self-catheterization in neurourology. Eur J Phys Rehabil Med. 2011;47(4):651-9.

35. Mangnall J. Key considerations of intermittent catheterisation. Br J Nurs. 2012;21(7):392, 384, 396-8.

36. Dellimore KH et al. A scoping review of important urinary catheter induced complications. J Mater Sci Mater Med. 2013;24(8):1825-35.

37. Li L et al. Impact of hydrophilic catheters on urinary tract infections in people with spinal cord injury: systematic review and metaanalysis of randomized controlled

trials. Arch Phys Med Rehabil. 2013;94(4):782-7.

38. Nazarko L. Intermittent selfcatheterisation and catheter fixation. Br J Community Nurs. 2013;18(7):322, 324-5.

39. Biardeau X, Corcos J. Intermittent catheterization in neurologic patients: update on genitourinary tract infection and urethral trauma. Ann Phys Rehabil Med. 2016;59(2):125-9.

40. Shamout S et al. Outcome comparison of different approaches to self-intermittent catheterization in neurogenic patients: a systematic review. Spinal Cord. 2017;55(7):629-43.

41. Rognoni C, Tarricone J. Healthcare resource consumption for intermittent urinary catheterisation: cost-effectiveness of hydrophilic catheters and budget impact analyses. BMJ Open. 2017;7(1):e012360.

42. Wilson M. Intermittent selfcatheterisation in the context of multiple sclerosis and spinal injury. BJNN. 2017;13(6):278-81.

43. Theron F et al. Best practice recommendations for bladder management in spinal cord-afflicted patients in South Africa. S Afr Med J. 2019;109(2b):12569.

44. Engberg S et al. Current evidence related to intermittent catheterization: a scoping review. J Wound Ostomy Continence Nurs. 2020;47(2):140-65.

45. Orlandin L et al. Difficulties of patients and caregivers in performing clean intermittent catheterization: scoping review. ESTIMA - Braz J of Enterostomal Ther. 2020;DOI:10.30886/estima. v18.907_IN.

46. Prieto JA et al. Intermittent catheter techniques, strategies and designs for managing long-term bladder conditions. Cochrane Database Syst Rev. 2021;10(10):Cd006008.

47. Kanti SPY et al. Recent advances in antimicrobial coatings and

material modification strategies for preventing urinary catheterassociated complications. Biomedicines. 2022;10(10):2580.

48. Hedlund H et al. Hydrophilic versus non-coated catheters for intermittent catheterization. Scand J Urol Nephrol. 2001;35(1):49-53.

49. Bermingham SL et al. Intermittent self-catheterisation with hydrophilic, gel reservoir, and noncoated catheters: a systematic review and cost effectiveness analysis. BMJ. 2013;346:e8639.

50. Health Quality Ontario (HQO). Intermittent catheters for chronic urinary retention: a health technology assessment. Ont Health Technol Assess Ser. 2019;19(1):1153.

51. Liao X et al. Effects of hydrophilic coated catheters on urethral trauma, microtrauma and adverse events with intermittent catheterization in patients with bladder dysfunction: a systematic review and meta-analysis. Int Urol Nephrol. 2022;54(7):1461-70.

52. Webb RJ et al. Clean intermittent self-catheterisation in 172 adults. Br J Urol. 1990;65(1):20-3.

53. Wyndaele JJ, Maes D. Clean intermittent self-catheterization: a 12-year followup. J Urol. 1990;143(5):906-8.

54. Sutherland RS et al. Clean intermittent catheterization in boys using the LoFric catheter. J Urol. 1996;156(6):2041-3.

55. Giannantoni A et al. Intermittent catheterization with a prelubricated catheter in spinal cord injured patients: a prospective randomized crossover study. J Urol. 2001;166(1):130-3.

56. Campbell JB et al. Complications associated with clean intermittent catheterization in children with spina bifida. J Urol. 2004;171(6 Pt 1):2420-2.

57. Cardenas DD, Hoffman JM. Hydrophilic catheters versus noncoated catheters for reducing

the incidence of urinary tract infections: a randomized controlled trial. Arch Phys Med Rehabil. 2009;90(10):1668-71.

58. Sallami S et al. Clean intermittent catheterization following urethral stricture surgery using a low friction catheter versus conventional plastic catheter: a prospective, randomized trial. UroToday International Journal. 2011;DOI:10.3834/uij.19445784.2011.04.07.

59. Woodbury MG et al. Intermittent catheterization practices following spinal cord injury: a national survey. Can J Urol. 2008;15(3):4065-71.

60. Lauridsen SV et al. European Association of Urology Nurses Evidence-based Guidelines for Best Practice in Urological Health Care Catheterisation Urethral intermittent in adults Dilatation, urethral intermittent in adults Evidence-based Guidelines for Best Practice in Urological Health Care Catheterisation Urethral intermittent in adults Dilatation, urethral intermittent in adults. 2013.

61. Humphreys O et al. A biomimetic urethral model to evaluate urinary catheter lubricity and epithelial micro-trauma. J Mech Behav Biom Mat. 2020;108:103792.

62. Lundgren J et al. The importance of osmolality for intermittent catheterization of the urethra. Spinal Cord. 2000;38(1):45-50.

63. Bardsley A. Intermittent selfcatheterisation in women: reducing the risk of UTIs. Br J Nurs. 2014;23(Suppl 18):S20-9.

64. Heard L, Buhrer R. How do we prevent UTI in people who perform intermittent catheterization? Rehabil Nurs. 2005;30(2):44-5, 61.

65. Pollard D et al. Evaluation of an integrated amphiphilic surfactant as an alternative to traditional polyvinylpyrrolidone coatings for hydrophilic intermittent urinary catheters. Biotribology. 2022;32:100223.

Ureterocutaneous Fistula in the Setting of Recurrent Gluteal Abscesses: A Case Report

Authors: *Catherine F. Alapatt,1 Young Son,1 Benjamin A. Fink,1 Brian Thomas,1 Sean Coulson,1 Shawon Akanda,1 Jacob Thatcher,1 Thomas Mueller2

1. Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA

2. New Jersey Urology, L.L.C., Voorhees, USA

*Correspondence to alapat38@rowan.edu

Disclosure: The authors have declared no conflicts of interest.

Received: 13.12.22

Accepted: 05.02.24

Keywords: Gluteal abscess, ureteral fistula, ureterocutaneous fistula.

Citation: EMJ Urol. 2024;12[1]:68-73. https://doi.org/10.33590/emjurol/10304254.

Abstract

Ureteral fistulas are a rare occurrence that can arise from iatrogenic trauma, radiation, malignancy, and inflammation. Treatment options of urinary tract fistulas are handled on a case-by-case basis, and can necessitate a surgical approach. The authors present the case of an 85-year-old female patient with a ureterocutaneous fistula, where conservative management with percutaneous nephrostomy is a viable alternative to surgical intervention.

Key Points

1. This article describes the approach in management of a fistula for a patient unwilling to undergo surgery. It offers serial percutaneous nephrostomy catheter exchange as a viable surgery alternative for patients with ureterocutaneous fistulas, who are otherwise unwilling, or unable, to undergo surgery.

2. The importance of this article is highlighted in the rarity of its presentation, as well as its management. Ureterocutaneous fistulas, as presented in this case report, are not common occurrences, and management can require surgery.

3. The authors hope that clinicians will accept their approach as a possible method of management for these types of fistulas. They also recommend that clinicians continue to take an individualised approach with fistulas, as every case is unique, and requires special considerations.

INTRODUCTION

Ureteral fistulas are a rare occurrence, and are most commonly the result of iatrogenic trauma, although other causes include radiation, malignancy, and inflammation.1,2 Treatment of urinary tract fistulas often depends on their severity and location, with some fistulas

requiring conservative therapy, whereas surgical repair can also be utilised in refractory cases.3 Multiple complications can result from fistulas, such as electrolyte imbalances, and commonly hyperchloremic metabolic acidosis with hypokalaemia in the setting of enterovesical fistula.4 Elevated creatinine and uraemia with normal kidney function can also occur

secondary to fistula, due to the reabsorption of these products.5

Radiation fistulas are frequently difficult to manage, as intervention must be performed after a 3–6-month period to allow for the greatest success. If treated prematurely, there is a risk that the inflammation in the affected areas has not diminished.1 Iatrogenic trauma has also been cited as a potential cause for ureteral fistula development in patients.6 Conservative measures are the first line of treatment for uncomplicated ureteral fistulas, including watchful waiting before moving on to ureteral stent, or percutaneous nephroureteral stent placement. When necessary, surgical options include the excision of fistula with anastomosis or grafting.1

Ureterocutaneous fistulas are rare, and seldom discussed in literature. Reported here is a case of ureterogluteal fistula with concurrent presacral abscess secondary to previous pelvic radiation history and potential iatrogenic trauma.

CASE PRESENTATION

An 85-year-old female presented to the emergency department (ED) with vaginal pain, subjective fevers, and clear discharge from her

left buttock for 2 days’ duration. The patient’s past medical history included a known draining, presacral abscess involving the left gluteal muscle, and Stage IIb cervical cancer diagnosed 11 years prior to initial presentation that was treated with cisplatin and radiation. Additionally, this was complicated by retroperitoneal fibrosis causing extrinsic compression of bilateral ureters, requiring bilateral nephroureteral stents. The patient also had a history of chronic urinary tract infections (UTI) with extended spectrum β-lactamases Klebsiella. On presentation, the patient’s blood pressure was 112/58 mmHg, pulse of 80 beats/minute, respiratory rate of 16 breaths/minute, a temperature of 37 °C, and oxygen saturation of 98%. The patient’s creatinine was 1.71 mg/dL, and she had a white blood cell count of 5.7x103 uL, and a lactate of 3.5 mg/dL. Urinalysis displayed 3+ protein, 4+ blood, positive nitrites, 4+ leukocytes, and many bacteria, suggestive of UTI. A CT scan of the abdomen and pelvis without contrast was performed, revealing a 6.0x5.4x3.0 cm presacral abscess involving the left gluteus maximus muscle, with fistulous communication to the skin surface, in addition to bilateral severe hydronephrosis (Figure 1). In the ED, the patient was started on empiric vancomycin and aztreonam, and admitted for gluteal abscess with extension and acute kidney injury.

CTAP is without contrast in transverse plane (left panel) showing a 6.0x5.4x3.0 cm presacral abscess (arrow) involving the left gluteus maximus muscle. Sagittal plane CTAP without contrast (right panel) displaying presacral abscess with fistulous communication to the skin (arrow).

CTAP: CT of the abdomen and pelvis.

Figure 1: CT of the abdomen and pelvis.

During the patient’s admission, wound fluid creatinine measured 55.00 mg/dL, with serum creatinine 1.16 mg/dL, and lactate 1.80 mg/dL, leading to suspicion of a ureteral fistula. As the gluteal abscess was draining clear fluid on presentation, General Surgery recommended extending the drainage site to improve the abscess; however, the patient refused intervention initially. Urine cultures also revealed Klebsiella pneumonia, requiring initiation of ceftazidime and avibactam per Infectious Disease. The Klebsiella infection was believed to be due to a suspected fistula. As a result of the continued infection, General Surgery deferred to Urology and Interventional Radiology. A cystoscopy with bilateral retrograde pyelogram for bilateral nephroureteral stent exchange was performed per the patient’s extensive history of UTIs and chronic stents. A cystogram and retrograde ureterogram were also performed, but did not reveal any ureteral or bladder extravasation indicative of a fistula at the time. During this time, the patient was continued on meropenem for management of the gluteal abscess and gram-negative UTI. On Day 6 in the hospital, interventional radiology performed a CT-guided aspiration and catheter placement of the left presacral collection. The CT-guided aspiration was delayed, as the patient was not agreeable until then to any drainage or incision, despite advice from the managing team. Cultures from the collected abscess also showed Klebsiella pneumonia, along with Candida glabrata, for which anidulafungin was added.

On Day 9 in the hospital, the patient’s presacral drain was exchanged by Interventional Radiology due to dislodgement. During exchange, contrast was seen collecting in the presacral space, as well as the distal left ureter and urinary bladder, suggestive of a fistulous tract with the distal left ureter (Figure 2). Due to this fistulous tract, the patient’s left nephroureteral stent was removed, and converted to a left percutaneous nephrostomy (PCN) catheter. This was done to decrease drainage output to the affected area, and promote healing. The patient was ultimately discharged with a left PCN and gluteal drain, due to the refusal to undergo any further invasive interventions; continued high output; and instructed to follow-up with Urology as an outpatient.

Approximately 9 months after initial presentation, the patient returned to the ED with a chief complaint of PCN displacement. The patient mentioned she had experienced some drainage from the initial gluteal site, and had mild left flank pain. Urinalysis revealed no bacteria growth, creatinine was 0.82 mg/dL, and the patient had a white blood cell count of 7.8x103 uL. On examination, no fluid was identified in the gluteal abscess drain. CT abdomen and pelvis without contrast showed resolution of bilateral hydronephrosis, and the fluid collection previously found in the left presacral space was no longer present. An antegrade nephrostogram showed extravasation to a gluteal abscess drain, revealing a persistent presacral abscess and fistula of the left ureter (Figure 3). The patient was instructed to undergo routine nephrostomy catheter exchange in 4–6 weeks as an outpatient to manage the persistent fistula of the left ureter.

DISCUSSION

Ureterocutaneous fistulas are rare, and while iatrogenic is most common, cases involving non-surgical trauma, calculous disease, and granulomatous inflammation have been reported.7 Due to the often post-surgical aetiology, ureteral injuries are diagnosed with delay, and usually only become apparent once the patient becomes symptomatic.8 Continuous drainage from the fistula can be seen in patients with ureterocutaneous fistulas similar to the described case.9 If a ureterocutaneous fistula is suspected, fluid and serum creatinine levels should be obtained. If the creatinine level in the fluid is at least 18% or more than the serum creatinine levels, this potentially signifies urinary leak.10 A urologic CT and fistulography can be used as an imaging modality for fistula diagnosis.9

The fistula in this case was most likely a complication of several processes, including the inflamed collection, prior radiation, stent placement, and gluteal abscess drain placement. Prior radiation for cervical cancer in this patient possibly induced obliterative endarteritis, leading to tissue hypoxia, denervation, and fibrosis of the tissue. The vascular insult to the ureter caused mucosal breakdown, which weakened the area, making it susceptible to the initial formation of the fistula.11,12 The fistula resulted from the chronic inflammatory state, concomitant

Figure 2: Interventional radiology study of injected contrast into the presacral region.

This reveals the collection of contrast in presacral space (thick arrow), as well as collection within the left distal ureter (thin arrow) and urinary bladder, suggestive of a fistulous tract between the ureter and presacral space.

Figure 3: Antegrade nephrostogram showing contrast extravasation at the level just below the iliac crest to the abscess.

with a presacral abscess at presentation, and the radiation-induced tissue injury. These issues, in tandem, prevented the fistula from resolving. A ureterocutaneous fistula is rare in nature, as radiation is a risk factor, and unique in the structures that it affects. Radiation, however, can induce many other rare types of fistulas, including ureteroarterial fistulas and ureterovaginal fistulas.

Nearly half of fistulas can be attributed to radiation. Previous literature reports 0.3–3.0% are secondary to brachytherapy, 0.6% are related to external beam radiotherapy, and 2.9% are related to combination therapy.13 There is no current evidence that states that radiation-induced fistulas differ in outcomes when compared to abscess-induced fistulas. However, of the urinary complications that occur from radiation therapy, urinary fistulas are the most difficult to manage, and often require surgical intervention.12 The treatment of ureterocutaneous fistulas is well-described in literature. Conservative management can lead to the spontaneous resolution of fistulae in 35.7% of patients.14 Similarly to the treatment of fistulas and abscesses in general, intervention aims to divert the urine away from the fistula, and promote abscess healing. Nephroureteral stent placement is the first preferred method of treatment for ureteral fistulas, with a success rate of 63.0% for patients with uterovaginal fistulas.15 If access cannot be obtained, percutaneous nephrostomy tube placement is often employed for urinary diversion. Surgical excision is also used in the case of ureterocutaneous fistulas, to close off the affected area. If the patient was amenable to surgery in this case, the team would have first visualised the bladder and ureters with a cystoscopy. A stent would then have been inserted to the level of the fistula. Afterwards, a fistulectomy would be attempted, with surgical excision of the fistula. A waterproofing interposition layer would be placed, before finally closing the area. In providing a waterproofing layer, the opening to the skin is closed off,

References

1. Avritscher R et al. Fistulas of the lower urinary tract: percutaneous approaches for the management of a difficult clinical entity. Radiographics. 2004;24(Suppl 1):S217-36.

minimising recurrent infections. Alternative surgical approaches include simple stitches to close the area without the introduction of an interposition layer. This approach has greater efficacy in smaller fistulas. In larger fistulas with unhealthy skin, waterproofing provides the best benefit. Occasionally, larger fistulas require possible ureteric reconstruction with stent placement.16 A systematic review demonstrated that any type of waterproofing technique used to close a fistula of the urinary tract has extremely high success rates.17

The major takeaway from this case report is that conservative PCN replacement is a viable treatment method for patients with a ureterocutaneous fistula who are unwilling to undergo procedures. It is a suitable method that can show adequate management of this specific issue when surgery is not achievable. This can be applied in future cases where patients are not amenable to surgery, or if there are significant comorbidities that make surgery an impractical option. However, as these cases are rare, and often involve prior iatrogenic trauma, the authors find that management must be personalised for each patient.

CONCLUSION

Presented here is the first reported case of a ureterocutaneous fistula with gluteal abscess formation, in a female with prior retroperitoneal radiation and subsequent fibrosis treated solely with a PCN tube. After the discovery of fistula formation to a gluteal abscess, serial PCN exchange, carried out approximately every 4–6 weeks, has been used to mitigate urine flow through the fistula. This has allowed for a resolution of the patient’s gluteal abscess, and decreased drainage through the sinus tract 9 months after initial presentation.

2. Partin AW et al., “Chapter 129: Urinary Tract Fistulae,” Partin AW et al. (eds.), Campbell Walsh Wein Urology (2020) 13ᵗʰ edition, Amsterdam: Elsevier.

3. He Z et al. Conservative treatment of patients with bladder genital tract fistula: three case reports. Medicine (Baltimore). 2020;99(31):e21430.

4. Murakami K et al. Severe metabolic acidosis and hypokalemia in a patient with enterovesical fistula. Clin Exp Nephrol. 2007;11(3):225-9.

5. Chan YH et al. A veno-caliceal fistula related to ureteric stricture in a kidney allograft masquerading as renal failure. Am J Kidney Dis. 2007;49(4):547-51.

6. Oyelowo N et al. Iatrogenic ureterocutaneous fistula and incisional hernia following laparotomy. PAMJ Clin Med. 2020;3:170.

7. Yu NC et al. Fistulas of the genitourinary tract: a radiologic review. Radiographics. 2004;24(5):1331-52.

8. Gayer G et al. Urinomas caused by ureteral injuries: CT appearance. Abdom Imaging. 2002;27(1):88-92.

9. Tang C et al. A case of ureterocutaneous fistula after nephrectomy. Urology. 2020;136:e16-9.

10. Kumar Regmi S et al. Drain fluid creatinine-to-serum creatinine

ratio as an initial test to detect urine leakage following cystectomy: a retrospective study. Indian J Urol. 2021;37(2):153-8.

11. Narayanan P et al. Fistulas in malignant gynecologic disease: etiology, imaging, and management. Radiographics. 2009;29(4):1073-83.

12. Chorbińska J et al. Urological complications after radiation therapy-nothing ventured, nothing gained: a narrative review. Transl Cancer Res. 2021;10(2):1096-118.

13. Uro Today. ESOU 2019: fistulae: nightmare complications of surgery and radiotherapy. Available at: https://www.urotoday. com/conference-highlights/ esou-2019/esou-2019-prostatecancer/109773-esou-2019how-to-deal-with-nightmarecomplications-of-surgery-andradiotherapy-fistulae.html. Last accessed: 1 May 2022.

14. Hattori Y et al. Effective secondary reconstruction of refractory urethrocutaneous fistula after metoidioplasty using folded superficial circumflex iliac artery perforator flap. Plast Reconstr Surg Glob Open. 2020;8(3):e2716.

15. Al-Otaibi KM. Ureterovaginal fistulas: the role of endoscopy and a percutaneous approach. Urol Ann. 2012;4(2):102-5.

16. Mukherjee S et al. Spontaneous ureterocutaneous fistula secondary to obstructed ureteric stone. Urology. 2020;138:e5-7.

17. Choudhury P et al. ‘Waterproofing layers’ for urethrocutaneous fistula repair after hypospadias surgery: evidence synthesis with systematic review and meta-analysis. Pediatr Surg Int. 2023;39(1):165.

Incidental Zinner Syndrome in Nigeria: A Case Report

Authors:

*A.O. Takure,1,2 B.A. Adewumi,3 O.E. Fatade,4 A.O. Adeyinka4,5

1. Department of Surgery, College of Medicine, University of Ibadan, Nigeria

2. Division of Urological Surgery, Department of Surgery, University College Hospital (UCH), Ibadan, Nigeria

3. Department of Obstetrics and Gynaecology, University College Hospital (UCH), Ibadan, Nigeria

4. Department of Radiology, University College Hospital (UCH), Ibadan, Nigeria

5. Department of Radiology, College of Medicine, University of Ibadan, Nigeria

*Correspondence to augusturoendo@gmail.com

Disclosure: The authors have declared no conflicts of interest. The authors report that informed written consent has been obtained from the patient for publication of this case report and any accompanying images.

Received: 05.06.23

Accepted: 15.01.24

Keywords: Asymptomatic, case report, hepatitis, Nigeria, Zinner syndrome (ZS).

Citation: EMJ Urol. 2024;12[1]:74-79. https://doi.org/10.33590/emjurol/11000010.

Abstract

Zinner syndrome (ZS) is a rare urogenital condition characterised by the triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ipsilateral ejaculatory duct obstruction, resulting from malformation during early embryogenesis of the mesonephric (Wolffian) duct.

The authors present a 35-year-old male who was being evaluated for chronic hepatitis B virus infection. He was referred to the urology outpatient clinic on account of incidental ultrasound finding of solitary right kidney. General physical examination revealed a healthy-looking young male with a flat abdomen and no palpable enlarged organs. Digital rectal examination revealed normal sized prostate with no palpable pararectal masses. MRI of the pelvis revealed a triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ipsilateral ejaculatory duct obstruction.

The clinical diagnosis was asymptomatic ZS. He is on yearly follow-up at the urology outpatient clinic for lower urinary tract symptoms, pelvic pain, painful ejaculation, features of infertility, and pelvic ultrasound. If any of these symptoms occur, he will be treated with an α-adrenergic receptor blocker, drainage of the seminal vesicle cyst, and appropriate treatment for infertility. He is also on active surveillance for viral hepatitis by the gastroenterology team.

In conclusion, prompt referral and comprehensive radiological imaging investigations of patients with unilateral agenesis of the kidney will lead to increased identification and report of patients with ZS. There is paucity of literature reports on ZS in the authors’ environment, and this case report, to the best of the authors’ knowledge, is the first from Nigeria.

Key Points

1. The presence of a solitary kidney on incidental ultrasound evaluation should raise a high index of suspicion for Zinner syndrome (ZS).

2. CT scan and MRI are very important in establishing the diagnosis of ZS.

3. The association of infertility and ZS is not fully understood. Further study with close monitoring of ZS is likely to identify the exact cause of infertility, to provide appropriate pre-emptive treatment.

INTRODUCTION

Zinner syndrome (ZS) is a rare urogenital anomaly characterised by a triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst, and ipsilateral ejaculatory duct obstruction, which was first described in 1914 by Zinner.1 It arises from the abnormal embryological development of the mesonephric ducts occurring during the first trimester, and usually presents between the second and fourth decade of life, when there is an increase in the size of the seminal vesicle.2,3 Symptomatic patients often respond well to open surgical excision, transurethral deroofing, or laparoscopic excision of the seminal vesicles.4,5

The literature search did not reveal any publication from the authors’ environment; hence, the authors present this case report of asymptomatic ZS discovered in an asymptomatic chronic hepatitis B (HB) virus infection in a young male Nigerian, which, in the course of evaluating the liver by ultrasound, revealed a solitary right kidney. MRI further identified ipsilateral renal agenesis, ipsilateral cystic seminal vesicle, and ipsilateral ejaculatory duct cyst. In addition, teratozoospermia was observed in the seminal fluid analysis.

PATIENT INFORMATION

The patient was a 35-year-old, single factory worker, who first presented to the Urology

outpatient clinic of the University College Hospital (UCH), Ibadan, Nigeria. He was the third of three children in a monogamous family setting. There was no family history of a similar medical condition, and he did not smoke or drink alcohol.

The patient was referred to Urology for evaluation of an incidentally noted congenital solitary right kidney during ultrasound evaluation of the liver, for the workup of chronic HB.

At the presentation, there were no upper or lower urinary tract symptoms, nor deep pelvic pain. There was no history suggestive of hypertension, diabetes, peptic ulcer, or bronchial asthma. There was no history of previous surgery and blood transfusion. He had been a patient of the Gastroenterology unit for 12 years on account of incidental HB surface antigen detection during a screening in school. He had remained asymptomatic on follow-up. HB e-antigen, HB e-antibody, and HB core immunoglobin M were all negative, and liver function test results were within normal limits.

Examination revealed a young man who was afebrile, not pale, anicteric, well hydrated, and with no demonstrable pitting pedal oedema. Vital signs were within normal limits. Chest, cardiovascular, abdominal, and external genitalia examinations were essentially normal. The digital rectal examination revealed a normal-sized prostate, and no other extra-rectal masses were felt.

The complete blood count, electrolyte urea, creatinine, and liver function tests were essentially normal. However, the semen analysis revealed teratozoospermia.

The abdominopelvic ultrasound scan showed a normal urinary bladder and prostate, with dilatation of both the left ejaculatory duct and left seminal vesicle (Figure 1).

Figure 1: B-mode ultrasound images of patient with asymptomatic Zinner syndrome, showing left dilated ejaculatory duct and left seminal vesicle.

The abdominal axial and coronal T1-weighted (T1W) MRI Fast Imaging Employing Steady-state Acquisition (FIESTA) images showed a normally located right kidney, and absent left kidney. The intestine was in the left renal bed, with the psoas muscle seen (Figure 2). Both pelvic axial T1W MRI and T2-weighted (T2W) MRIs showed cystic left seminal vesicles and a dilated left ejaculatory duct that were hyperintense on T1W images, and hypointense on T2W images, respectively (Figure 3).

The patient has remained asymptomatic and is currently on yearly follow-up with pelvic ultrasound to assess the growth rate of the seminal vesicle, as well as seminal fluid analysis for his fertility status.

The patient expressed surprise and was happy that his clinical diagnosis was identified, and promised to keep his appointment at the urology outpatient surgical clinic.

DISCUSSION

The triad of unilateral renal agenesis, ipsilateral obstruction of the ejaculatory duct, and ipsilateral seminal vesicle cyst, is referred to as ZS. The incidence of ZS is low. Sheih et al.6 reported that the incidence of seminal vesicle cystic dilatations in patients with ipsilateral renal agenesis or dysplasia was 0.0046% (13 in 28,000) among children in Taipei. Furthermore, van den Ouden et al.4 reported a pooled case of 52 cases of ZS before 1998.

Figure 2: Fast Imaging Employing Steady-state Acquisition (FIESTA) MRI sequences.

A) Axial

B) Coronal

Scans show a normally sited right kidney with empty left renal bed; a bowel loop is noted as hyperintense structure surrounded by fat, just lateral to the left psoas muscle.

Figure 3: Pelvic axial MRI of dilated structure and adjacent beaded structures posterior to the urinary bladder.

A) T1W MRI showing hyperintense dilated structure and adjacent beaded structures posterior to the urinary bladder, all consistent with seminal vesicle cyst and ejaculatory duct dilatation.

B) T2W MRI showing the same structures, now hypointense.

T1W: T1-weighted; T2W: T2-weighted.

In a systematic review of 214 cases of ZS between 1999–2020, Liu et al.7 reported that 80.8% of patients were symptomatic, with equal prevalence of right and left renal agenesis.

ZS is very rare among Africans. In their pooled study, van den Ouden et al.4 reported that only two patients (4%) were African. It is not surprising that only two cases have been reported from Africa to date.8,9

A B

A B

From these reports, it seems that there are racial differences in the reported incidence of ZS. In Ethiopia, Beyene et al.9 reported that a heightened sexual activity may have contributed to presentation in their case report. This has not been corroborated by other authors. The authors need to investigate this further in any new cases of ZS in Africa.

This geographical question could be answered by screening preschool children and adults for renal agenesis with abdominal ultrasound, before entry into secondary schools or tertiary institutions. This may likely increase the reporting of ZS in Nigeria, and across Africa. Of note is the presentation of incidental solitary right kidney in this case report, picked up on ultrasound. This is the first case report from Nigeria that was asymptomatically discovered while evaluating this index patient for asymptomatic chronic HB infection. Further evaluation of the patient was based on a high index of suspicion for ZS. With this case report from Nigeria, the authors hope to raise clinicians’ level of awareness, and encourage them to thoroughly evaluate any case of ipsilateral renal agenesis in order to identify the full spectrum of congenital anomalies in such patients. This may translate into higher incidence of a condition that has seemingly been underreported or misdiagnosed in Nigeria.

A study in China, where ZS is also rare, discovered genetic features in the 14 cases reported. The mutated genes were BMP4, RPGRIP1L, SEC63, SETD2, AGFG1, FLT1, and ZNF141. 10 The authors cannot categorically state that there is a genetic impact on ZS from this case report. However, they could explore this possibility by screening for the mutated genes in their patient, to determine genetic features in patients with ZS in Africa.

The aetiology of ZS is believed to result from the developmental arrest of the mesonephric (Wolffian) ducts during the fifth week of embryogenesis. This is particularly obvious since the mesonephric duct in males develops to form half of the trigone, the urinary bladder neck, urethra, seminal vesicle, vas deferens, epididymis, and epididymal heads, under the influence of testosterone and Müllerian duct inhibitory factor. Thus, the outcome of such disturbances includes ipsilateral renal agenesis, dilatation of the distal ureter, cystic dilatation of the seminal vesicle,

and obstruction of the ejaculatory duct on the affected side.4,11

The clinical presentations of ZS are variable and non-specific, often leading to diagnostic challenges.10,12 Many patients tend to become symptomatic between the second and fourth decade of life, when there is an increase in the size of the seminal vesicle to >5 cm.3

Some common presentations in ZS include lower urinary tract symptoms, such as urinary frequency and pelvic pain.12,13 The indications for surgical intervention are recurrent urinary tract infections,14 and haematospermia.15 ZS is a recognised cause of painful ejaculation and male infertility.16,17 The patient in this case report had a significant percentage of abnormal sperm cells, despite good sperm concentration and motility; therefore, he should be closely monitored.18 The complete blood count, electrolytes, urea, and creatinine, as well as liver function test, and serum prostate-specific antigen, were essentially normal.

MRI is the gold standard in the diagnosis of ZS. It is often performed in the coronal and transverse plane without contrast. The protocol commonly used is T1W turbo spine-echo (TSE), T2W TSE, and a T1W TSE fat-saturation. It often shows a multiloculated seminal vesicle cyst that is hypointense on T1W images, and appears bright on T2W images. The MRI features are renal agenesis and occasional situs inversus viscerum, as well as lobulated multiloculated cystic lesion of the seminal vesicle with saccular dilated enlarged ectopic ureter that opens into the cystic seminal vesicle. This is well appreciated in the T1W coronal view.19,20

Contrast-enhanced axial CT of the abdomen with coronal reconstruction shows ipsilateral renal agenesis, and lobulated multiloculated cystic seminal vesicle with saccular dilated, with or without enlarged ectopic ureter, that opens into the cystic seminal vesicle. The dilated seminal vesicle does not demonstrate contrast enhancement, which is in keeping with nonmalignant cyst.19,20

Abdominal ultrasound shows solitary kidney and empty contralateral renal bed with a retrovesical liquid mass. Transrectal ultrasound visualises retrovesical hypoechoic cyst with posterior enhancement and impure content

that compresses the urinary bladder, and protrudes into the bladder lumen.14,21 However, in environments with limited resources, abdominal CT or ultrasound scan are suitable alternatives to MRI.14,20

Seminal fluid analysis is also an important investigation in ZS, as about 45% of cases are documented with infertility.22 In some cases, cystoscopy may be necessary to exclude ipsilateral ejaculatory duct causing bladder outlet obstruction, as this may require aspiration.23

Observation with close follow-up is advocated for those who are asymptomatic, as in this case report. The duration of follow-up needed is variable, and the longest documented follow-up is that reported by Kelly et al.,24 where the patient was followed up for 14 years, and eventually had a successful laparoscopic excision of his

References

1. Zinner A. Ein fall von intravesikaler Samenblasenzyste. Wien Med Wochenshr. 1914;64:605.

2. Hevia Palacios M et al. Zinner syndrome with ectopic ureter emptying into seminal vesicle. Case Rep Urol. 2021;2021:8834127.

3. Bearrick EN, Husmann DA. Screening for Zinner syndrome in patients with a congenitally solitary kidney: lessons learned. J Urol. 2023;210(6):888-98.

4. van den Ouden D et al. Diagnosis and management of seminal vesicle cysts associated with ipsilateral renal agenesis: a pooled analysis of 52 cases. Eur Urol. 1998;33(5):433-40.

5. Seo Y et al. Congenital seminal vesicle cyst associated with ipsilateral renal agenesis. Yonsei Med J. 2009;50(4):560-3.

6. Sheih CP et al. Cystic dilatations within the pelvis in patients with ipsilateral renal agenesis or dysplasia. J Urol. 1990;144 (2 Pt 1):324-7.

7. Liu T et al. Zinner syndrome: an updated pooled analysis based on 214 cases from 1999 to 2020: systematic review. Ann Palliat Med. 2021;10(20):2271-82.

8. Abakar D et al. Zinner syndrome. Eur J Case Rep Intern Med. 2021;8(7):002628.

9. Beyene E et al. Zinner syndrome: a first case report from Ethopia. Radiol Case Rep. 2023;18(1):86-90.

increased seminal vesicle cyst. Other available treatment options of seminal vesicle cysts include open or robotic excision of the cysts.25,26

In cases with infertility and painful ejaculation, transurethral resection of ejaculatory ducts aid resolution of symptoms, and improve semen characteristics.4

CONCLUSION

This case report from Nigeria will increase the level of suspicion from ultrasound screening, encourage thorough evaluation of patients with solitary kidney, and reduce misdiagnosis and under-reporting of ZS. Asymptomatic patients should be closely followed up with imaging studies and laboratory tests, and appropriately treated when symptomatic.

10. Dai R et al. Clinicopathological and genetic features of Zinner’s syndrome: two case reports and review of literature. Front Urol. 2023;3:1257368.

11. Hannema SE, Hughes IA. Regulation of Wolffian duct development. Horm Res. 2007;67(3):142-51.

12. Sada F et al. Challenging clinical presentation of Zinner syndrome. Radiol Case Rep. 2023;18(1):256-9.

13. Pina-Vaz T et al. Zinner’s syndrome, a retrospective series of three cases: different strategies to the same problem. BMJ Case Rep. 2021;14(10):e242757.

14. Ibrahim A et al. Zinner’s syndrome: a rare diagnosis of dysuria based on imaging. Case Rep Urol. 2020;2020:8826664.

15. Canales-Casco N et al. Hematospermia as a rare form of presentation of Zinner syndrome. Urology. 2017;99:e15-6.

16. Rahoui M et al. An unusual cause of painful ejaculation in a young patient: Zinner syndrome. Ann Med Surg (Lond). 2022;10:79:103982.

17. Hofmann A et al. Zinner syndrome and infertility–a literature review based on a clinical case. Int J Impot Res. 2021;33(2):191-5.

18. Almuhanna AM et al. Zinner’s syndrome: case report of a rare maldevelopment in the male genitourinary tract. Urol Case Rep. 2021;39:101839.

19. Fiaschetti V et al. Zinner syndrome

diagnosed by magnetic resonance imaging and computed tomography: role of imaging to identify and evaluate the uncommon variation in development of the male genital tract. Radiol Case Rep. 2016;12(1):54-8.

20. Alarifi M et al. The association of renal agenesis and ipsilateral seminal vesicle cyst: Zinner syndrome case report. Case Rep Urol. 2019;2019:1242149.

21. Farooqui A et al. Massive seminal vesicle cyst with ipsilateral renal agenesis – Zinner syndrome in Saudi patient. Urol Ann. 2018;10(3):333-5.

22. Ostrowska M et al. Zinner syndrome–a rare cause of recurrent epididymitis and infertility. Clin Pract. 2021;11(4):942-6.

23. Kori R et al. Zinner syndrome mimicking bladder outlet obstruction managed with aspiration. Urol Ann. 2019;11(4):449-52.

24. Kelly NP et al. Long-term surveillance and laparoscopic management of Zinner syndrome. Case Rep Urol. 2021;2021:6626511.

25. Govorov A et al. Treatment of Zinner syndrome with robotassisted surgery. Eur Urol Open Sci. 2022;44(Suppl 4):S282.

26. Lim CY, Liu CL, Huang SK. Laparoscopic excision of huge seminal vesicle cyst in Zinner syndrome. Radiol Case Rep. 2023;18(6):2172-5.

www.emjreviews.com