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European Urology Today

EAU19 Congress News 34th Annual Congress of the European Association of Urology Barcelona, 15-19 March 2019

Plenary Session addresses BCa in young female patients Patient case discussions and surgical aspects By Erika de Groot “Bladder cancer (BCa) is generally considered as a disease of the elderly with a median age approximately 65 to 70 years at diagnosis. But approximately, one to two per cent of patients will be under 40 years of age. At Bern University in Switzerland, we have had 39 patients under the age of 50 and 16 patients under 40 from 2007 to 2017. ” So stated Prof. Fiona Burkhard (CH) as she kick-started “Plenary Session 01 Bladder cancer in the young patient: Unique aspects”, chaired by herself and Prof. Morgan Rouprêt (FR). Prof. Burkhard introduced the case of a 34-year-old female presenting with macrohaematuria at a different hospital. The patient had an initial

transurethral resection of the bladder (TURB) with a pT1G3, followed by a re-resection when muscleinvasive disease was found. She is a painter with one child, and has a smoking history of 10 pack-years. Prof. Burkhard shared that “the first question the patient asked me was ‘I would like to have second child. Would that be possible?’” The initial step is preoperative assessment, in which oncological aspects (tumour location) are prioritised over preserving fertility. Following this, specific surgical aspects are considered: nerve-sparing, organ-sparing, and the type of diversion to be offered to the patient. Then, if the patient is pregnant, the focus shifts to care during pregnancy and delivery. The introduction was followed by the lecture, “Fertility in the young female patient with bladder cancer: Surgical aspects” by Dr. Jo Cresswell (GB). She stated that it is not uncommon to see young female patients wanting to have children; however, for a number of young women who have/will undergo radical cystectomy (RC) or have BCa, sexual function and fertility may also be of importance.

Dr. Cresswell emphasises preservation of sexual function

Dr. Cresswell also discussed pelvic organ-sparing cystectomy, which includes uterine-sparing to preserve fertility; ovarian-sparing to avoid early menopause; and vaginal- and nerve-sparing to preserve sexual function.

On Saturday, live surgery got underway at EAU19! The EAU Section of Uro-Technology (ESUT), in cooperation with the EAU Robotic Urology Section (ERUS) and the EAU Section of Urolithiasis (EULIS) held an ambitious, all-day session dedicated to surgical cases. By using live feeds from up to four operating theatres simultaneously, as well as pre-recorded cases and expert moderation, delegates could experience a seamless surgical programme with demonstrations of all the latest tech. Live procedures included 3D laparoscopic partial nephrectomy; en-bloc bipolar bladder tumour resection; 4K laparoscopic radical prostatectomy and Lithovue single-use ureteroscopic lithotripsy.

She also cited the EAU Guidelines (2018): “In women, standard RC includes removal of the bladder, entire urethra and adjacent vagina, uterus, distal ureters and regional lymph nodes... Data regarding pelvic organ-preserving radical cystectomy for female patients remains immature.” One of the current Guidelines recommendations – offering sexualpreserving techniques to preserve sexual function since the majority will benefit – was rated “weak”. However, Dr. Creswell foresees this changing.

“I think it’s time to pay attention to vaginalsparing and ovarian-sparing surgery, and to put more focus on sexual function,” she stated. Careful assessment of the vagina is needed, and bladder-neck urethral biopsies should be considered pre-operatively. For uterine-sparing surgery with the objective of preserving fertility in selected patient cases, improved urinary function should also be taken into account.

Guidelines Session: Omitting biopsy in case of normal MRI mpMRI before biopsy for biopsy-naïve patients recommendation now in EAU Guidelines By Loek Keizer

(FR) offered a “balanced” viewpoint to aid discussion.

The EAU Guidelines Office, led by Prof. James N’Dow (GB) uses the Annual EAU Congress to launch its annually-updated guidelines. The Guidelines Controversies sessions, two of which took place on Saturday at EAU19, are a way to highlight the latest additions and changes.

“Hold fire, not end-fire” Prof. Moore strongly argued that standard biopsy in men with a negative MRI can have unfortunate results. “Side-effects of biopsy are common,” Moore pointed out, “and current treatment rates are much higher than recommended. Even active surveillance has morbidity and cost associated with it.”

The chairs of each Guidelines panel and independent experts explore the evidence base for new recommendations and involve the audience in the decisions through voting and discussion. The Prostate Cancer panel, led by Prof. Nicolas Mottet (FR) wanted to highlight changes in its recommen-dations on MRI imaging and the way it affects the decision to proceed with a biopsy. Prof. Caroline Moore (GB) and Dr. Sigrid Carlsson (USA) debated the pros and cons of foregoing biopsy after MRI, while Dr. Olivier Rouvière

Sunday, 17 March 2019

disease that might impact his life and be happier to forego the biopsy.” “In the UK, the discussion is reasonably well-framed about not detecting all cancer. A drive for maximum diagnosis can be a real problem. I think we will see people being sued for these harms. We can already see the beginnings of a backlash against overdiagnosis.”

“Five-year detection rates of significant cancer in men with negative MRI and no TRUS biopsy are low [5%]. I recommend that we hold fire, rather than end-fire.” Dr. Carlsson voiced her concerns on mpMRI being able to adequately detect all tumours: the technology might have a high enough sensitivity to detect, but there is massive inter-observer variability. The learning curve and the variance in each centre’s MRI capabilities also proved a challenge. Carlsson suggested several possible treatment pathways that could serve urologists and patients in future. Addressing the concerns about MRI quality, Moore later told EUT Congress News that while there is increased confidence in MRI, there is also still a lot of discussion about its quality. “During the session, James N’Dow asked if we had enough long-term data. I think it’s not long-term data we need, it’s quality assurance across the board.”

Prof. Moore at the Guidelines Controversies session

Involving the patient It was emphasised at the session that the patient should also be involved in the decision to perform biopsy if the MRI is negative. Moore: “Discussion with the patient is important and I’m pleased to see that in the 2019 EAU Guidelines. It’s a recognition that this is a preferencesensitive decision. A man might prefer greater certainty at the expense of side-effects and cost. Or he might be very confident in the fact we’re not missing the sort of

“Many good centres can do MRI. What we haven’t shown is that every centre can be a good centre. I think we can get there and that it’s mainly a training issue,” Moore concluded.

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Genomics in diagnosis and treatment ESOU-ERUS-ESUT joint meeting discusses new modalities in onco-urology By Patricia Chang

Congress News . . . . . . . . . . . . . . . . . . . . . . 1 Congress highlights . . . . . . . . . . . . . . . . . 2-3 Complications of laparoscopy . . . . . . . . . . . 4 Spina bifida patients and QoL . . . . . . . . . . . 5 HPV and penile cancer pathogenesis . . . . . . 8 Adolescent varicocele . . . . . . . . . . . . . . . . 10 Risk-based follow-up for testis cancer . . . . . 11 The OPEN trial . . . . . . . . . . . . . . . . . . . . . . 13 SCO: Interview with Prof. Stenzl . . . . . . . . . 14 Theranostics and functional imaging . . . . . 15 Neoadjuvant therapy in localized disease . . 17

Prof. Maurizio Brausi (IT), Prof. Evangelos Liatsikos (GR), and Dr. Henk van der Poel (NL) chaired the Joint Meeting of the EAU Section of Oncological Urology (ESOU), the EAU Robotic Urology Session (ERUS), and the EAU Section of Uro-Technology (ESUT), also featuring speakers from ECCO, EORTC GUCG, ESMO, ESSO, ESTRO and EUOG. This session was a highlight of the second day of EAU19 in Barcelona.

Involving patients Mr. Ian Banks (IE) represented the European Cancer Organisation (ECCO) and focussed on the need to improve the quality of cancer care. “We’re not talking about optional requirements, but essential requirements,” said Banks. Cancer patient outcomes in Europe can improve through the adoption and the implementation of these requirements.

On behalf of the European Uro-Oncology Group (EUOG), Prof. Susanne Osanto (NL) discussed the genomics of bladder cancer. “What is changing currently is the fact that we can detect tumours in part based on genomic alterations,” said Osanto. “It illustrates that for various types of tumours like lung, breast, colorectal melanoma, and squamous carcinoma you can now classify tumours based on what you know about RNA and DNA and proteomics,” added Osanto.

The message is that patients should be part of the multi-disciplinary team. Patients want to return to how their lives were before cancer struck, and increasingly they are demanding better quality, rather than quantity, of life.

This breakthrough insight into the genomics of single cells of cancers is a result of next generation sequencing. The Illumina sequencing platform is widely used. Genomics should be done before surgery to identify those who are likely to benefit from it.

A bladder-sparing protocol is not a single event, but a collaboration between urology, radiology and oncology. Neo-adjuvant chemotherapy (NACHT) is an important component. There are 15 randomised trials in the literature in over 3,000

On behalf of the European SocieTy for Radiotherapy & Oncology (ESTRO) Prof. Peter Hoskin (GB) shared his insights on bladder-sparing protocols in the treatment of muscle-invasive bladder cancer.

patients which show that (NACHT) gives a significant survival advantage, i.e. a 13% improvement in survival. There is also a statistically significant improvement in survival after ten years of follow-up. An important step is deciding which patients to select on the basis of genetic biomarkers. Genetic signatures will help in selecting patients that have very good quality of life after bladder preservation with very few events in terms of frequency of leaking. Prof. Aristotelis Bamias (GR), from the European Society for Medical Oncology (ESMO), pointed out that NACHT has been a long-term standard for urologists and oncologists. Several cisplatin-based combinations show significant efficacy in this setting, according to Bamias. “The combination of NACHT and cystectomy is a very good surrogate for survival,” said Bamias. Patients who have no microscopically residual disease in specimens after NACHT are effectively cured. The NACHT setting is therefore a very nice model for experimentation with potential biomarkers for the selection of patients.

EAU19: Poster and video presentations . . . 18 Interview: New Membership Office chairs . . 19 Failure of focal therapy for PCa . . . . . . . . . 20 Novel targeted therapies for penile cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

ESIU-ESUI highlight hot topics on imaging PI-RADS, radio-guided surgery and award updates

Complicated stones in children . . . . . . . . . 23

By Erika de Groot

European Urology Today

Updates on PI-RADS (Prostate Imaging Reporting and Data System) and radio-guided surgery were the hot topics of the session “Prepare for the future: Prevent, detect, strike back!”. This Joint Meeting of the EAU Section of Infections in Urology (ESIU) and the EAU Section of Urological Imaging (ESUI) was chaired by Prof. Georg Salomon (DE) and Prof. Dr. Florian Wagenlehner (DE).

Editor-in-Chief Prof. M. Wirth, Dresden (DE) Section Editors Prof. T. E. Bjerklund Johansen, Oslo (NO) Mr. Ph. Cornford, Liverpool (GB) Prof. O. Hakenberg, Rostock (DE) Prof. P. Meria, Paris (FR) Dr. G. Ploussard, Paris (FR) Prof. J. Rassweiler, Heilbronn (DE) Prof. O. Reich, Munich (DE) Dr. F. Sanguedolce, London (GB) Dr. Z. Zotter, Budapest (HU)

In his lecture, “PI-RADS: Past, present and future -what’s next in PI-RADS v3.0”, Prof. Dr. Jurgen Futterer (NL) enumerated suggestions and improvements needed for PI-RADS v2.0. These included: improvement of transition zone lesion detection; quantification of apparent diffusion coefficient (ADC); biparametric prostate magnetic resonance imaging (MRI) without Dynamic Contrast Enhanced (DCE) imaging; and retrieval of as much clinical information as possible, especially in patients under active surveillance.

Founding Editor Prof. F. Debruyne, Nijmegen (NL)

Regarding follow-up and biopsy, Prof. Futterer suggested implementing recommendations into PI-RADS v3: • Score 1 (very low likelihood of cancer): No biopsy, no follow-up • Score 2 (low likelihood of cancer): No biopsy, follow-up, multiparametric MRI if PSA increases • Score 3 (intermediate likelihood of cancer): If prostate specific antigen density (PSAD) < 0.15, follow-up; if PSAD > 0.2, MRI-guided biopsy

Onsite Reporting and Editing E. de Groot L. Keizer J. Tidman P. Chang Marketing Communication J. Bloemberg M. van Gurp L. Stuart-Young Advertising M. van der Krieke F. Strating

No part of European Urology Today (EUT) may be reproduced without written permission from the Communication Office of the European Association of Urology (EAU). The comments of the reviewers are their own and not necessarily endorsed by the EAU or the Editorial Board. The EAU does not accept liability for the consequences of inaccurate statements or data. Despite of utmost care the EAU and their Communication Office cannot accept responsibility for errors or omissions.

By Jen Tidman “Share. Care. Cure.” This, the mission of the European Reference Networks (ERNs), was emphasised during the eUROGEN Speciality Session at EAU19.

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Disclaimer

ERNs are the largest healthcare innovation in Europe; virtual cross-border networks involving expert teams, collaborating via the Clinical Patient Management System (CPMS) to share knowledge and treat >30 million patients with >8,000 rare or complex conditions.

EUT Congress News

During his presentation “Early biochemical recurrence: Will radio-guided surgery become state of the art?”, he stated: “PSMA-RGS provides exact localization. You don’t need to do frozen section analysis, and you might even detect additional lesions. Additionally, the surgical guidance provides more security, especially in areas urologists don’t usually navigate to during surgery.” Prof. Maurer also mentioned the drawbacks of PSMA-RGS: it may not be necessary in “easy” cases; logistical issues (e.g. facilities, certifications); regulations on the use of PSMA-ligands; and the still unknown benefit of salvage lymph node dissection (SLND). ESUI Vision Award Dr. Giorgio Gandaglia (IT) received the coveted ESUI Vision Award for his lecture “A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized

doctors have enough experience to tackle cases alone. “The more information you have available, the better the care delivered,” he said. He reported that based on early data, eUROGEN is expected to positively impact >100,000 patients having >60,000 procedures yearly. Michelle Battye (GB), eUROGEN Manager and session co-chair, noted that a priority objective of the ERN is to help smaller population countries, and stressed that

eUROGEN is the urological ERN, covering rare conditions and diseases across paediatric, functional and oncological urology. Currently it involves 29 healthcare providers from 11 EU countries, with additional Affiliated Partners joining now and a call for further full members to follow. eUROGEN Network Coordinator, Prof. Wout Feitz (NL) co-chaired the special session and emphasised the importance of ERNs for conditions where very few

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Radio-guided surgery Will prostate-specific membrane antigen radio guided surgery (PSMA-RGS) become state-of-the-art? Assoc. Prof. Tobias Maurer (DE) said that the data points to “yes”. Assoc. Prof. Maurer discusses the benefits of PSMA-RGS

Prostate Cancer Diagnosed with Magnetic Resonance Imaging Targeted and Systematic Biopsies”. The objectives of his study were to assess the accuracy of available tools in predicting lymph node invasion (LNI) and to develop a novel model for men diagnosed via MRI-targeted biopsies. Currently, available models predicting LNI are characterised by suboptimal accuracy and clinical net-benefit for patients diagnosed via MRI-targeted biopsies. Dr. Gandaglia stated that a novel nomogram specifically focused on men undergoing multiparametric MRI (mpMRI) should be used in order to identify those at higher-risk of LNI who should be considered for an ePLND. He added that adoption of this model using a 7% cut-off to identify candidates for ePLND could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.

eUROGEN ERN: Opportunities to join in 2019

Lay-Out/Printing D. Blom G. Smit EUT Editorial Office PO Box 30016 6803 AA Arnhem The Netherlands T +31 (0)26 389 0680 communications@uroweb.org

• Score 4 (high likelihood of cancer): MRI-guided biopsy • Score 5 (very high likelihood of cancer): MRI-guided biopsy

eUROGEN is not a project; it’s a new and unique form of cooperation in healthcare at European level. “This is the beginning of an iterative process,” she said. Vijay Sangar (GB), the lead for Workstream 3 on rare cancers, noted that another eUROGEN goal is to educate and train existing clinical teams and future clinicians. He emphasised that collaborative research is essential given the low patient numbers in some countries. Being part of an ERN removes barriers between Member States, facilitating funding applications, recruitment, and infrastructure change. Giovanni Mosiello (IT) demonstrated how CPMS has already been used to make suggestions for the treatment of a male infant with severe cloacal exstrophy in order to improve his standard of care and, ultimately, his quality of life.

Co-chairs Mrs. Michelle Battye and Prof. Wout Feitz

If you would like to learn more, eUROGEN has a stand at the EAU19 exhibition, within the EAU booth, where you can ask questions and get CPMS demonstrations and training. Sunday, 17 March 2019


‘Forgotten’ ureteral stents: Whose responsibility? Nightmare session offers legal implications, possible solutions for rare but critical occurrence By Loek Keizer EAU19 had an animated start on Saturday with Plenary Session 2; a ‘nightmare session’ on stones. Mr. Bertie Leigh (GB), veteran consultant solicitor, challenged some of Europe’s best stone surgeons on the troubling cases they presented. A nightmare session is based around disastrous cases. It particularly highlights the ethical and legal implications for the treating urologist, beyond the immediate medical effects of the treatment. It should be noted that the case presenters were not the urologists involved in the case in question, but they were tasked with defending the procedure against Mr. Leigh’s intense questioning.

accidentally left a stent in a patient. Between five and ten percent of the audience raised their hands.

ten of which will become encrusted, with increased risk of infection and obstruction.”

Assistant Prof. Kaloyan Davidoff (BG) presented a case from a German-speaking country, in which a 32 year-old Albanian woman had an emergency caesarian section and sustained ureteric injury. The urologist placed a JJ stent. The patient returned at four, six and eight months with a urinary tract infection, visible haematuria and pain.

“As a urologist, you might think ‘it’s not my job’, but it most definitely IS your job to monitor your patients’ stents,” Osther emphasised. He offered a variety of possible approaches beyond a card register: an electronic registry that warns the urologist when placed stents are set to expire, and closer involvement of the patient, equipping him or her with wristbands or smartphone apps. (As with all good shows, Prof. Osther finished on a song: an ode to the gentle urologist with a self-penned Ureter Song.)

Experts from the EAU’s urolithiasis section (EULIS) gave additional information about ongoing research and current practice for each case. Mr. Leigh joined the Annual EAU Congress for the third time, having previously grilled kidney and bladder cancer specialists at EAU17 and EAU18 respectively.

It was only 14 months after the childbirth that she was referred back to the urologist who found the severely encrusted stent. In the end, a combination of punch lithotripsy, URS and laser lithotripsy were used to dismantle the stent. Three SWL sessions were then required to completely remove the remains of the stent. The patient had endured constant bladder pain and recurrent urinary infections, and complained that she had not bonded properly with her child. The case was further complicated by the fact that the patient did not speak German.

The forgotten stent As the nightmare session got underway, cochairman Mr. Tim O’Brien (GB) polled the audience to see how many of those present had ever

Former EULIS Chairman Prof. Palle Osther (DK) added some background information to the complications and procedures in this illustrative case: “13 out of 100 ureteral stents will be forgotten,

Prof. Davidoff reponds to Mr. Leigh’s cross-examination

Cross-examination Mr. Leigh’s subsequent cross-examination of Prof. Davidoff and his case yielded many interesting questions that the urologist must consider around stent use. Further discussion with the panel members and the audience offered insights in current practice around the world.

Further discussion led to Prof. Osther referencing the hospital’s responsibility, or even in some cases the existence of a national stent database that monitors placement and removal. Solutions offered by the panel and the audience included co-signed forms, the suggestion that every new stent also include a distinctive wristband for the patient, and the creation of stent guidelines, for instance from an international body such as the EAU.

“Did you make a serious effort to contact the patient?” Mr. Leigh asked. “Did you explicitly and adequately inform the gynaecologist or GP? Is a language barrier, or a claim of patient ignorance, really sufficient to escape blame for this negligence?”

The nightmare session continued with two further cases: severe sepsis following ureteroscopy and bowel injury as a result of percutaneous nephrolithotomy. Both cases were discussed and subjected to questions of legality asked by Mr. Leigh to each case presenter.

Day 2 Award Gallery

Our Secretary General Prof. Chris Chapple opens the EAU19 Exhibition

Best Booth Award 2019: Coloplast. From left to right: K. Russell, J. Mahoney, A. Bournot, S. Achour, N. Dampeyrou, MJ. Landre

Best Paper on Fundamental Research: T. Mitchell (Great Shelford, United Kingdom)

Best Paper on Fundamental Research: S. Turajilic (London, United Kingdom)

Best Paper on Clinical Research: G. Gandaglia (Milan, Italy)

Best Paper on Clinical Research: A. Territo (Barcelona, Spain)

Best Scientific Paper in European Urology: J. Bosschieter (Amsterdam, The Netherlands) Sponsored by ELSEVIER

Best Scientific Paper Fundamental Research in European Urology: Y. Deruyver (Leuven, Belgium) Sponsored by ELSEVIER

Best Scientific Paper Clinical Research in European Urology: M. Liss (San Antonio, United States of America) Sponsored by ELSEVIER

Best Scientific Paper on Robotic Surgery in European Urology: B. Bochner (New York, United States of America) Sponsored by VATTIKUTI FOUNDATION

First Prize Best Abstract (Non-Oncology): K. Monastryrskaya (Bern, Switzerland)

Third Prize Best Abstract (Non-Oncology): N. Watkin (London, United Kingdom)

First Prize Best Abstract (Oncology): L. Mertens (Amsterdam, The Netherlands)

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Second Prize Best Abstract (Oncology): C. Bravi (Milan, Italy)

Second Prize Best Abstract (Non-Oncology): M. Elbaset (Mansoura, Egypt)

During the opening of the Exhibition, Prof. Chris Chapple was also presented with his portrait on behalf of the EAU History Office

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Complications of laparoscopy due to technique Decision-making on early re-exploration Prof. Riccardo Autorino Dept. of Urology Virginia Commonwealth University Richmond (US) ricautor@gmail.com The role of minimally invasive surgical techniques in urology has exponentially grown over the past two decades, and laparoscopic and robotic-assisted procedures are well established in the armamentarium of most urologic surgeons1. Thus, one needs to be familiar with the perioperative management of patients undergoing these procedures and be aware of potential complications, some of which require surgical re-exploration. The decision-making process leading to a second surgical procedure which is necessary to manage a severe complication following a primary procedure certainly presents a challenging scenario for both the patient and the surgeon. Different factors are considered in this process and different options need to be explored in a timely fashion. An uncommon event The literature on the rate of surgical re-exploration after urologic laparoscopic and robotic procedures remains sparse and it is mainly drawn from series more broadly focusing on ’complications’ (see Table 1). In general, reported rates are low (range 0-2.4%) and therefore the need for surgical exploration can be regarded as uncommon, as in most cases conservative or non-surgical measures can be adopted successfully. On the other hand, the decision to proceed to surgical re-exploration is mostly dictated by severe and possibly life-threatening clinical scenarios. Therefore, it is of utmost importance to identify those situations in which secondary surgery is needed, to avoid disastrous consequences. In some cases, imaging techniques can be of assistance, in others clinical symptoms and laboratory results might prompt the decision to take the patient back to the operation room. Only few series have specifically looked at the outcomes of surgical re-intervention after urologic laparoscopy (see Table 2)2-5. Bhayani et al. defined an ’early’ re-exploration that occurred within the first 10 hours after the primary procedure3. Postoperative bleeding certainly represents the most frequently occurring and important indication for a ’take back’ to the OR after a laparoscopic or robotic procedure. This can be prevented by some important intraoperative measures, including meticulous dissection and careful control of vessels during the procedure, which can be accomplished by using various measures (clips, ultrasonic or bipolar energy, suturing, haemostatic agents). Moreover, since the pneumoperitoneum may mask intraoperative venous bleeding, it is good practice to lower insufflation pressure and carefully inspect the abdomen before ending the procedure6. However, even when no specific technical error is made, a bleeding can still occur. Manage postoperative haemorrhage A step-by-step approach can be used to detect and manage postoperative haemorrhage (see Figure 1). Clinical and laboratory findings are usually highly suggestive, and imaging (CT scan) should be obtained only if haemodynamic stability can be achieved by initial conservative measures. Otherwise, the decision for immediate surgical exploration can be made. This may consist of laparoscopic exploration, if the

bleeding is not profuse. Otherwise, exploratory laparotomy should be pursued4. Another way to manage a bleeding is emergency angiography (see Figure 2), as reported for laparoscopic radical prostatectomy7, but, more frequently, after minimally invasive partial nephrectomy8.

Table 2: Series specifically looking at re-exploration after laparoscopic urologic surgery: literature overview Reference Yayacioglu 2002

N of cases 9

Re-exploration Indication for re-exploration (n) rate, % 0.7 Ileus (2), urinoma (2), mesenteric hernia (1), SBO (1), rectus muscle hematoma (1), duodenal perforation (1), thrombosis renal artery (1) 0.8 Bleeding (9)

Type of re-explorative procedure (n) Laparoscopic (4) or open (5)

Other main indications for early re-exploration are bowel-related events. During a transperitoneal Bhayani 2006 9 Laparoscopic (5) or procedure, a bowel injury may occur at any time from open (4) access to closure. It has been estimated that the risk Gong 2007 3 0.3 Bleeding (3) Laparoscopic (3) of bowel injury after laparoscopic radical Wszolek 2014 14 0.7 Suspicious of bowel injury (3), Laparoscopic (12) or nephrectomy is 0.8%9. The most common causes are bleeding (3), pelvic collection (4), open (2) access-related and thermal damage via anastomotic dehiscence (2) electrocautery. When bowel injury is not recognised, the patient may present with signs of sepsis and acute abdomen 1-2 days after surgery. The diagnosis can be Prostate Surgery. Eur Urol. 2016; 69(2):334-44. confirmed by a CT scan. Major thermal injuries might 6. Breda A, Finelli A, Janetschek G, Porpiglia F, Montorsi F. Complications of laparoscopic surgery for renal masses: 11. Coelho RF, Palmer KJ, Rocco B, et al. Early complication require bowel resection, whereas non-thermal prevention, management, and comparison with the open rates in a single-surgeon series of 2500 robotic-assisted injuries can usually be repaired with direct closure experience. Eur Urol. 2009; 55(4):836-50. radical prostatectomies: report applying a standardized bysuturing6. Proper access techniques should be implemented during any laparoscopic procedure, to 7. Park YH, Lee JH, Kim HH. Severe bleeding after grading system. Eur Urol 2010; 57:945–52 avoid both vascular and organ injury10. laparoscopic radical prostatectomy: successful 12. Lim SK, Kim KH, Shin TY, Hong SJ, Choi YD, Rha KH. Active monitoring During laparoscopy, it is imperative that the surgeon actively monitors the location of the instruments which may potentially injury the viscera. The same applies to the robotic surgeon at the console, who relies on the bedside assistant. Moreover, it is always important to check the integrity of the thermal insulation of laparoscopic and robotic instruments. Other bowel-related events, such as ileus, intestinal obstruction and intestinal ischaemia, may be secondary to an unrecognised bowel injury, an internal hernia, or a port site hernia and/or dehiscence (see Figure 3). The incidence of a port-site hernia is less than 1%11, and they generally occur at the larger incision sites. However, port-site hernias have also been described through 5-mm ports and 8-mm robotic ports12. It has been suggested that blunt obturators reduce the incidence of trocar hernias13. Signs of a trocar hernia are abdominal pain, ileus or subileus, nausea and vomiting. The diagnosis can be confirmed by CT scan with oral contrast media. Laparoscopic exploration, hernia reduction and resection of necrotic intestine might be required. In conclusion, any minimally invasive urologic surgeon should be familiar with the potential complications that might require early surgical re-exploration. Thanks to the implementation of sound laparoscopic techniques, these events are nowadays uncommon. However, one needs to be aware that careful postoperative monitoring and timely diagnosis and management are key to achieve good outcomes.

management with transarterial embolization. J Endourol. 2008; 22(12):2687-9. 8. Shin J, Han K, Kwon JH, et al. Clinical results of transarterial embolization to control postoperative vascular complications after partial nephrectomy. J Urol. 2018 Nov 2. pii: S0022-5347(18)44051-7. doi: 10.1016/j. juro.2018.10.022. 9. Bishoff JT, Allaf ME, Kirkels W, Moore RG, Kavoussi LR, Schroder F. Laparoscopic bowel injury: incidence and clinical presentation. J Urol. 1999; 161(3):887-90. 10. Sotelo RJ, Haese A, Machuca V, et al. Safer Surgery by Learning from Complications: A Focus on Robotic

A rare case of interparietal incisional hernia from 8 mm trocar site after robot-assisted laparoscopic prostatectomy. Hernia. 2014;18(6):911-3 13. Leibl BJ, Schmedt CG, Schwarz J, Kraft K, Bittner R. Laparoscopic surgery complications associated with trocar tip design: review of literature and own results. J Laparoendosc Adv Surg Tech A 1999;9: 135–40.

Sunday 17 March 10.30-12.00: Thematic session 5 Complications of laparoscopy due to technique

Figure 1: Management algorithm for management of postoperative bleeding (adapted from ref. 4)

References 1. Autorino R, Porpiglia F, Dasgupta P, et al. Precision surgery and genitourinary cancers. Eur J Surg Oncol. 2017; 43(5):893-908. 2. Yaycioglu O, Ramakumar S, Kavoussi LR, Jarrett TW. Early repeated exploration after laparoscopic urologic surgery: comparison of clinical, radiologic, and surgical findings. Urology. 2002; 59(2):190-4. 3. Bhayani SB, Link RE, Makarov DV, Jarrett TW, Kavoussi LR. Exploration for hemorrhage following laparoscopic renal surgery: intraoperative findings. J Urol 2006; 175(6):2137-9. 4. Gong EM, Zorn KC, Gofrit ON, et al. Early laparoscopic management of acute postoperative hemorrhage after initial laparoscopic surgery. J Endourol. 2007; 21(8):8728. 5. Wszolek MF, Canes D, Moinzadeh A, Sorcini A. Laparoscopy for the detection and treatment of early complications from minimally invasive urologic surgery. J Endourol. 2014; 28(10):1197-201

Figure 2: 69yo gentleman who underwent a robotic radical prostatectomy for localized intermediate risk prostate cancer (PSA 5.1 ng/ml; GS 3+4; prostate volume 30 cc). During recovery in the PACU, blood pressure went down, patient became tachycardic, and presented abdominal distention and tenderness. Hb dropped from 11.6 g/dL (immediately after surgery) to 7.9 g/dL (3 hours later). Decision was made to take patient back to the OR, without imaging. An exploratory laparotomy was performed within 5 hours from the end of the first surgery. It was not possible to find a clear source of significant bleeding, packing was performed, and abdomen was left open with ABThera in place. Patient was taken to interventional Radiology, as he was still clinically instable. An arteriogram and Gelfoam embolization of the anterior division of the right internal iliac artery were performed and allowed to stop the bleeding.

Table 1: Re-exploration rates after laparoscopic and robotic procedures: literature overview Reference Fahlenkamp 1999 Vallancien 2002 Yaycioglu 2002 Colombo 2007 Hruza 2010 Rosevear 2006 Liapis 2008 Coelho 2010 Tanagho 2013 4

Technique Lap

Retro Robotic

EUT Congress News

Procedure Various

Study period No of cases 1992-98 2,407

Re-exploration rate, % 0.8

Various Various Various oncological Radical prostatectomy Various Various Radical prostatectomy Partial Nephrectomy

1992-01 1993-00 1997-06 1999-08 1996-04 1995-07 2002-09 2007-11

2.4 0.7 2 0.3 0.4 1.1 1 0.2

1,311 1,226 1,867 2,200 911 600 2,500 886

Figure 3: 72 yo gentleman who underwent a hand assisted laparoscopic right radical nephrectomy for a large renal mass. The specimen was extracted through a 15 cm infraumbilical midline incision. Patient developed postoperative ileus and on postoperative day 4 a CT confirmed dehiscence of the midline incision for a large fascial defect, which led to “take back” on postoperative day 5 for secondary closure.

Sunday, 17 March 2019


Spina bifida patients: Long-term follow-up and quality of life 60% of patients still report issues with urinary incontinence in adulthood Anna Bujons Tur, MD, PhD, FEAPU Head of Pediatric Urology Unit Urology Department of Fundació Puigvert Barcelona abujons@ fundacio-puigvert.es As the long-term survival of individuals with complex congenital and paediatric diseases has improved, more patients with spina bifida (SB) are living into adulthood. Historically, SB patients were not expected to survive into adulthood, but thanks to improvements in surgical and multidisciplinary care, 70–80% are now doing so, compared with only 20–30% 40 years ago. On the other hand, these patients may continue to face lifelong issues related to their condition, including urinary incontinence, recurrent urinary tract infections, chronic kidney disease, impaired mobility and difficulties with health and sexual function. Hydrocephalus can be associated with cognitive impairments, such as dysfunctions in attention and executive functions. There is a risk of pressure ulcers and often a need for tendon and bone surgery to correct various congenital or early-onset deformities in the lower extremities and spine. One of the greatest challenges is to establish transition care for this population. Sexual life in adulthood is an important aspect of quality of life, and poses a considerable challenge for people with SB.

Quality of life Despite the advances that have been achieved, 60% of patients still report issues with urinary incontinence in adulthood, as well as neurogenic bowel, with negative consequences for their quality of life. Urinary incontinence is easier to correct than faecal incontinence, and improved purgative actions (laxatives, transanal irrigation, Malone antegrade continence enema) can improve quality of life. Patients should bear in mind that if they have an enlarged bladder or a continent reservoir, they will be at greater risk of presenting lithiasis, may experience reservoir perforation, and also have a higher likelihood of bladder cancer at a much younger age than the general population. Sexual and reproductive disorders in spina bifida While sexual life in adulthood is an important component of the quality of life, it is a considerable challenge for people with SB. Nevertheless, this topic has received limited attention in the literature. Baby with Spina Bifida

Patients with SB show an increasing interest in their sexuality when they reach adolescence, and paediatric and transition urologists must pay due attention to their worries and concerns. The ability to have sexual intercourse and achieve orgasm may be negatively affected by reduced or absent motor and sensory function. Additionally, presence of paralysis of the lower extremities complicates and adversely affects the process of development and testing of sexuality.

Sexual dysfunction in patients with SB is related to the neurological defect. Shurtleff classified patients into three groups according to the level of spinal injury, whereby patients with a lesion below L1 have normal sexual function, those with a lesion between L3 and L5 display variable sexual function and those Urinary tract disorders in spina bifida About 90% of patients with SB are born with normal with a lesion above L2 have no sexual response7. This renal function. However, most of them will suffer division has been maintained in subsequent deterioration of kidney function throughout their lives. publications8,9. Renal failure is the most frequently quoted cause of Men with a spinal defect between T11 and L2 usually severe morbidity in patients with SB. Renal damage do not have reflex or psychological erections. The can start early, within the first six months, and penile sensation depends on the level of the spinal historically renal failure resulted in death in up to injury, with 33% of patients with a lesion at L2 or 20% during the first year of life and remained a higher reporting intact penile sensation. PDE5 common cause of death at all ages2. Over time, various advances have been made in management of inhibitors have proven to be successful in treating erectile dysfunction in this context, enabling up to the neurogenic bladder, and there is now improved 75% of male patients to achieve antegrade understanding of the ’safe’ bladder. ejaculation. Infertility can be caused by the impossibility of penetration, retrograde ejaculation, Pro-active approach ductal obstruction or a defect in spermatogenesis. In recent years, a more proactive approach to managing the neurogenic bladder in children with SB Twenty percent of patients with myelomeningocele and normal bladder function have normal ejaculation; has gained currency. Prophylactic treatment has however, there may be failure of spermatogenesis. replaced watchful waiting. Several studies have shown that early prophylactic treatment with clean Sexual function in women with SB intermittent catheterisation and anticholinergic Puberty in girls with SB is earlier and more medication may prevent the need for bladder augmentation, improve bladder function and preserve pronounced than in boys, taking place at between 6 and 9 years of age, a year and a half sooner than in kidney function. the general population10. Special attention to bladder function is required The literature contains limited data on sexual function during the first 6 years of life and during puberty, in women with SB. As in men, sexual dysfunction as changes are most pronounced during these periods3. varies depending on the level of the injury. About 90% of women with spinal injuries at L3 or lower report Bladder dysfunction of patients with SB, especially intact sexual sensation, and 40% of these patients state that they achieve orgasm. Only 12.5% with lesions those with high-pressure bladder irrigation, may worsen during growth stages, especially puberty. above L3 report orgasmic sensation, and only 50% of Patients who already have clean intermittent those with lesions above L2 report intact vulvar catheterisation and receive anticholinergics may sensation. Some studies show that women affected by myelomeningocele may have erogenous zones in the then require surgical interventions such as injection periumbilical area and the nipples and are of botulinum toxin or bladder augmentation to improve low compliance and protect the upper consequently able to derive sexual pleasure and even urinary tract. Patients who experience difficulties in achieve orgasm in the absence of genital sensation. manual dexterity or alterations in limbs usually undergo appendicovesicostomy at the time of Lack of sensitivity is a very important factor in sexual enlargement to facilitate self-catheterisation4,5,6. relationships. The alteration of sensitivity in the area

called the “saddle”, which comprises the perineum, external and internal genitalia, inner side of the thighs and anus, can cause disturbances in arousal. Urinary continence is another important factor in sexual relationships and contacts. In the series of Gatti et al., continent SB patients were between 3.5 and 2.4 times more likely to be sexually active compared with incontinent patients11. When we conducted a study of 125 women with SB, 46.8% reported that urinary incontinence had been a sexual limitation, a further 29% had dyspareunia and a third complained of having no pleasure sensation12. Pregnant women with SB Women with SB have the same fertility as the general population. Several published series, however, report that they have an increased risk (4%) of having children with SB13. This risk can be reduced if folic acid supplements are administered from 3 months before pregnancy to week 12 of pregnancy. It is recommended that controls with urinalysis and renal function tests are periodically performed on pregnant women with SB because they may suffer from recurrent acute pyelonephritis. Patients with enterocystoplasty have a false positive proteinuria due to secretion of mucus from the intestinal segment. A uric acid blood test is recommended to detect pre-eclampsia. Caesarean delivery is more common in women with SB than in the general population due to bladder augmentation12,13. Impact of spina bifida on quality of life The health implications of a diagnosis of SB are very significant: hydrocephalus, alterations in mobility, spasticity, contractions, deformity, scoliosis, epilepsy, renal alterations, hypertension, urinary and faecal incontinence, constipation, alterations in sexual function, cognitive disorders, difficulties in school integration, social, psychological, obesity, chronic pain, etc. Patients are exposed to multiple surgeries throughout their lives (neurosurgical, orthopaedic, and urological) and there are significant impacts on quality of life14. Quality of life studies show that children with SB who have a significant physical disability (including problems with continence) have a worse quality of life14,15. The disease and chronic disability imply a major impact on all aspects of functioning and, therefore, quality of life. In addition to motor and sensory problems, there are issues of adaptation, psychological problems and low self-esteem16. Social isolation may sometimes occur due to low mobility, low self-esteem and urinary and faecal incontinence.

It is essential that sexual function is routinely evaluated in these patients during follow-up clinic visits. Transition programmes could provide anticipatory guidance including sexual education to adolescent patients with SB. References 1. Skokan AJ, Kovell RC. Advances and challenges in transitional urology: caring for adolescents and young adults with lifelong complex genitourinary conditions. Curr Urol Rep. 2018;19(4):26. 2. Rendeli C, Ausili E, Tabacco F, Caliandro P, Aprile I, Tonali P, et al. Assessment of health status in children with spina bifida. Spinal Cord. 2005;43(4):230–235. 3. Goldwasser B, Barrett DM, Webster GD, Kramer SA. Cystometric properties of ileum and right colon alter bladder augmentation, substitution or replacement. J Urol. 1987;138:1007–1008. 4. Lottman H, Traxer O, Aigrain Y, Melin Y. Posterior approach to the bladder for implantation of the 800 AMS artificial sphincter in children and adolescents: techniques and results in eight patients. Ann Urol. 1999;3(5):357–363. 5. Caim MP, Casale AJ, King SJ, Rink RC. Appendicovesicostomy and new alternatives for the Mitrofanoff procedure: Results in the last 100 patients at Riley Children´s hospital. J Urol. 1999;162:1749–1752. 6. Khoury JM, Timmons SL, Corbel L, Webster GD. Complications of enterocystoplasty. Urology. 1992;40(1):9–14. 7. Shurtleff DB, Hayden PW, Chapman WH, Broy AB, Hill ML. Myelodisplasia problems of long-term survival and social function. West J Med. 1975;122(3):199–205. 8. Cass AS, Bloom BA, Luxenberg M. Sexual function in adults with myelomeningocele. J Urol. 1986;136(2):425– 426. 9. Sandler AD, Worley G, Leroy EC, Stanley SD, Kalman S. Sexual function and erection capability among young men with spina bifida. Dev Med Child Neurol. 1996;38(2):823–829. 10. von Linstow ME, Biering-Sørensen I, Liebach A, Lind M, Seitzberg A, Hansen RB, Biering-Sørensen FJ. Spina bifida and sexuality. Rehabil Med. 2014;46(9):891–897. 11. Gatti C, Rossi C, Ferratti A, Casolari E, Casadio G, Scire G. Predictors of successful sexual partering of adults with spina bífida. J Urol. 2009;182:1911–1916. 12. Bujons, A. Aspectos ginecologicos sexualidad femenina. En: Garat JM, Miguelez C. Espina bifida y sexualidad. Ed. Bayer Schering Pharna. Barcelona, 2009; p. 107-117 13. Laurence KM, Beresford A. Continence, friends, marriage and children in 51 adults with spina bifida. Dev Med Child Neurol Suppl. 1995;35:123–128. 14. Lassmann J, Garibay Gonzalez F, Melchionni JB, Pasquariello PS Jr, Snyder HM 3rd. Sexual function in adult patients with spina bifida and its impact on quality of life. J Urol. 2007;178(4 Pt 2):1611–1614. 15. Bomalaski MD, Teague JL, Brooks B. The long-term impact of urological management on the quality of life of children with spina bifida. J Urol. 1995;154:778–781. 16. Papua L.Relationship between the clinicalneurophysiologic pattern, disability, and quality of life in adolescents with spina bifida. J Child Neurol. 2004;9:952–957. 17. Lavigne JV, Faier Routman J. Correlations of psychological adjustment to pediatric physical disorders: a metaanalytic review and comparison with existing models. J Dev Behav Pediatr. 1993;4:117–123.

Sunday 17 March 10.30-12.00: Thematic Session 10 Paediatric urology update 2019 Figure 1 and 2 : Bujons et al. Incontinence and sexual female limitation

Sunday, 17 March 2019

EUT Congress News

5


Booth

#D38

Pioneering in Energy-based Technologies HIFU

Prostate Cancer

6

EUT Congress News

ESWL & LASER Urinary Stones

Sunday, 17 March 2019


吀栀攀 䰀漀渀搀漀渀 倀爀漀猀琀愀琀攀 䤀洀愀最椀渀最 愀渀搀 䘀漀挀愀氀 吀栀攀爀愀瀀礀 䴀愀猀琀攀爀挀氀愀猀猀 倀爀攀猀攀渀琀攀搀 戀礀 倀爀漀昀攀猀猀漀爀 䠀愀猀栀椀洀 唀⸀ 䄀栀洀攀搀 䐀爀 䌀氀愀爀攀 䄀氀氀攀渀 唀渀椀琀攀搀 䬀椀渀最搀漀洀

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䤀 倀

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ERUS19 16th Meeting of the EAU Robotic Urology Section

Robotic Live Surgery

Creating consensus in robotic urology

䠀愀渀搀猀ⴀ漀渀 眀椀琀栀 䴀刀䤀Ⰰ 䈀椀漀瀀猀礀 ☀ 䘀漀挀愀氀 吀栀攀爀愀瀀礀

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䠀愀渀搀猀ⴀ漀渀 眀椀琀栀 䴀刀䤀Ⰰ 䈀椀漀瀀猀礀 ☀ 䘀漀挀愀氀 吀栀攀爀愀瀀礀

㔀ⴀ㘀 䄀瀀爀椀氀 ㈀ ㄀㤀

In conjunction with: Junior ERUS-YAU Meeting European School of Urology (ESU) Courses ESU/ERUS Hands-on Training in Robotic Surgery

Leadership skills courses for urologists and nurses YUO and EAUN offer Leadership for Medical Professionals Courses in Barcelona Do you wish to refine your management and leadership skills or sharpen your decision-making abilities? Do you want to improve your leadership communication skills?

11-13 September 2019, Lisbon, Portugal An application has been made to the EACCME® for CME accreditation of this event

Then the EAU Young Urologists Office (YUO) may have the right programme for you in Barcelona during the Annual EAU Congress. On During the Annual EAU Congress to be held in Barcelona two courses will be offered to young urologists and nurses. The EAUN Leadership Course will be Sunday, 17 March from 12.30 to 15.30 hrs., while for urologists the Leadership for Medical Professionals Course will be on Monday 18 March from 08.30 to 11.30 hrs. Young urologists The YUO is working on its Personal Development Programme where courses will focus on management and communication skills, leadership, finances, etc. The first part of this programme is a course on Leadership for Medical Professionals, designed for young (under 45 years) urologists and related health professionals who have the potential to be future leaders in national and international urology. To ensure that the course is sustainable, a follow-up will be provided after the congress. The participants of the course will be getting new and practical information for use in practice. Also the aim of the follow-up is to ensure a better connection of theory and practice. Applicants should have: • A letter of motivation stating the applicant’s interest for the course

Sunday, 17 March 2019

䌀漀洀洀甀渀椀挀愀琀椀漀渀 椀渀 琀栀攀 䌀氀椀渀椀挀㨀 䘀漀挀愀氀 吀栀攀爀愀瀀礀 瘀猀⸀ 圀栀漀氀攀 䜀氀愀渀搀

刀攀最椀猀琀攀爀 漀渀氀椀渀攀 䀀 眀眀眀⸀昀琀洀愀猀琀攀爀挀氀愀猀猀⸀挀漀洀

www.erus19.org

· · ·

䐀愀礀 伀渀攀

• • •

Recommendation letter from the applicant’s immediate superior or supervisor Proven fluency in English Readiness to submit essay-type articles in preparation for the course

The YUO board will review all applications on a first-come, first-served basis and selected participants will come from countries across Europe. Nurses During the interactive course Nurses in a leadership role: Cultivating your leadership we will guide you in finding your role as leader, especially when the ultimate responsibility is not yours. The programme will focus on leadership, effectiveness and communication in relation to patients, teams, colleagues, surgeons and other superiors. There is room to reflect on your preferred leadership style and to exchange your personal experiences with peers from all over Europe. So bring a case of a challenge you are currently facing in your hospital! How to join? Participants will come from countries across Europe. For both courses a small token fee of €62.50 will be required to ensure attendance by selected applicants. Please send an email to Angela Terberg, at a.terberg@uroweb.org, clearly stating that you are interested in the EAUN leadership course or in the YUO leadership course.

EUT Congress News

7


The role of HPV in penile cancer pathogenesis Time to start a vaccination programme for boys? Prof. Maximilian Burger Caritas St. Josef Medical Center, University of Regensburg, Regensburg (DE)

Table 1: Number of all cancer cases attributable to HPV by region, cancer sites and sex8 Region

Cervix uteri

Vulva

Penile cancer

Anus male Anus female

Europe World

58,000 530,000

5,100 20,000

2,700 13,000

2,700 17,000

4,200 18,000

Head and Head and neck male neck female 11,000 2,800 30,000 7,500

All HPV related cancer 87,000 630,000

mburger@ caritasstjosef.de Epidemiological impact is impressive: they do affect 1% of ever sexually active men and women. High risk strains, namely type 16 and 18, lead to precancerous and malign lesions. They are seen as pivotal causes not only of penile cancer, but also of cervical, anal, vulvar and also oropharyngeal cancer8.

Why should you read these lines? This is just about penile cancer. And penile cancer isn’t exactly the malignancy we’re dealing with every day. Prostate, bladder and renal cell cancer - sure, that’s our regular trade. But penile cancer is comparatively rare. So, some 50% of penile cancers are related to HPV, And HPV? Well…. we’re urologists- not virologists. and HPV is even more relevant for cervical cancer. So, you could simply jump on to the next article in this newspaper. But should you? Around 70% are caused by HPV 16 and 18, even90% of anal cancer is related to HPV, and some 25% of vulvar cancers. HPV is even very relevant in head and No. Stick with me for three reasons. neck cancer. While smoking and alcohol are seen as 1. Penile cancer is a grave health burden and a the main risk factors, HPV is pivotal in oropharyngeal genuinely urological malignancy. 2. In contrast to many other cancers you can even squamous cell carcinoma. The types 16 and 18 are seen responsible for 85% of cases globally. And relate prevent it. 3. HPV goes way beyond penile cancer only - this is this to incidence rates; a recent analysis by de Martel and co-workers gives you good idea of the about preventing adolescent boys and girls from importance of HPV in cancer burden (Table 1)8. a variety of malignancies. Why is penile cancer important? To begin with, the incidence of penile cancer is not that low. Its annual incidence rate per 100,000 ranges globally from 0.7 in India to 8.3 in Brazil1. And it ranges even within Europe, from roughly 0.7 in e.g. the Netherlands, Germany or Italy to about 1.5 in e.g. some areas of Spain. In the UK an increase of 20% has been suggested, from 1.1 in 1979 to 1.3 in 20091,2. If treated early and right, outcome is fairly good; organ sparing surgery may allow preservation and 5-year disease specific survival in over 90%. In contrast, delayed treatment confers poor prognosis and 5-year disease specific survival drops to some 30% in case of pelvic lymph-node metastasis1. In contrast to other urological malignancies, treatment outcome has not improved largely over recent years; 5-year survival remained some 60% over the last twenty years and even decreased significantly in the US3. So, we need to be aware of this cancer - it is important and we can progress. That is, if we are aware of it and its current treatment standard as defined by Oliver Hakenberg and his panel of the respective EAU guidelines.

included 26 trials of 2vHPV and 4vHPV with almost 75,000 participants. Vaccination is highly certain to lower the incidence of cervical intraepithelial neoplasia (CIN) grade 2 and worse from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN graded 3 and worse from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10) in adolescent girls and women aged 15 to 2611. In contrast, it is moderately certain that incidence rates of CIN grade 2 are similar between unvaccinated women and women vaccinated aged 24 to 45 (RR 1.04 (0.83 to 1.30))12. A trial randomising 14,000 women to 4vHPV vs. 9vHPV found antibody responses to HPV-6, 11, 16, and 18 to be similar in both arms; disease related to HPV-31, 33, 45, 52, and 58 in a prespecified susceptible population was 0.1 per 1,000 personyears in the 9vHPV group and 1.6 per 1,000 personyears in the qHPV group13. So, efficacious vaccination is possible with different agents.

But the age of vaccination does matter decisively. The effect will be much greater in younger, i.e. teenage, years. Also, fewer doses need to be applied. A non-inferiority trial assessed immunogenicity following four different regimes of 9vHPV in some 1,500 girls and So, here’s the bad news: HPV related cancer burden is boys aged 9 to 14. A 2-dose regime of 9vHPV vaccine separated by 6 or 12 months resulted in an tremendous - and this goes way beyond penile immunogenicity 4 weeks after the last dose noninferior cancer. And here’s the good news: there is a very to a 3-dose regimen in a comparative cohort of some good chance to prevent HPV related cancer in girls and boys. Harald zur Hausen was awarded with a 300 girls and young women aged 16 to 2615. Nobel prize for his research on HPV leading to the Is HPV vaccination safe? development of a vaccine, which actually does work. What about the second demand: is HPV vaccination safe? Yes. Very much so. The Cochrane systemic Why should we consider HPV vaccination? We hope HPV-related cancer can be prevented in the review found a similar risk of serious adverse later lives of young girls and boys if they are between control and HPV vaccines in women of all vaccinated prior to sexual activity. Vaccines have been ages (RR 0.98 (0.92 to 1.05))13. And the same is true for the trials of 9vHPV. Pain at the injection site seems available for over 10 years now starting in 2006 with the only adverse event of relevance9. a quadrivalent vaccine (4vHPV, Gardasil®, Merck) aiming at HPV types 6,11,16 and 18, followed by a bivalent vaccine aiming at HPV types 16 and 18 And what about the third demand: is it used? No. And (2vHPV, Cervarix®, GSK) and a nonvalent vaccine that’s the problem. A full coverage of HPV vaccination (9vHPV, Gardasil9®, Merck) aiming at 9 HPV types, i.e. in girls would protect girls and heterosexual men. Herd immunity would work. But only if utilisation was 6, 11, 16, 18, 31, 33, 45, 52 and 589. All of these are What does penile cancer have to do with HPV? approved in girls age 9 and up; 4vHPV and 9vHPV are much higher than it is to date. A very recent analysis A lot. Or a little more precisely: half of it. Did you note also approved in boys aged 9 and up. from the Netherlands assessed HPV-prevalence in the marked local variation in incidence? One core STD-clinics from 2009 to 2015. The percentage of factor of this phenomenon is the varying prevalence vaccinated women increased from 2% in 2009 to 37% Three basic demands of HPV infection. There are generally two main Vaccination is only good if three basic demands are in 2015. Among all women, the HPV16/18 prevalence pathways of penile cancer suggested. One is chronic fulfilled: it is effective, it is safe and - last but not least decreased from 23% prevaccination to 15% in 2015 inflammation potentially associated with phimosis or - it is used. (adjusted prevalence ratio [aPR] 0.62, ptrend < 0.01). lichen sclerosis leading to a slow accrual of genetic Among heterosexual men, the HPV16/18 prevalence alterations in its wake. Losses of alleles in the regions So, let’s start with the first demand: is HPV vaccination decreased from 17% prevaccination to 11% in 2015 9p21 and 17p are typically coding the tumour effective? Yes. This has been shown by numerous (aPR 0.52, ptrend < 0.01). But HPV16/18 was not different suppressor genes p16 and p53. The other is an studies adding to the trials leading to approval of the in unvaccinated women. So, the decreasing HPV16/18 infection with the human papilloma virus (HPV) vaccines. E.g. one study analysed geometric mean prevalence among heterosexual men suggests herd leading to a rather abrupt acquisition of genetic titers in approx.. 1,100 women and 1,400 men aged 16 protection from girls-only vaccination. But the lacking damage mainly via the HPV oncogenes E6 and E7, to 26 following vaccination with 9vHPV finding more herd effects among unvaccinated women suggests again inactivating p16 and p534,5. HPV-infected cells than 99.5% of subjects seropositive at month 7 for underutilisation16. And the same phenomenon is INK4a 10 demonstrate marked accumulation of p16 due to each vaccine HPV type . The vaccination effect found throughout Europe - more or less. Vaccination excessive cell division caused by oncoproteins E6 and seemingly lasts. Seropositivity 5 years after vaccination coverage rates vary decisively according to a recent E7 binding to the tumour suppressor proteins p53 and with 9vHPV ranged from 76 to 99% in a long-term survey, from e.g. 23% below age 20 in Poland to 69% at age 11 in Finland, but are largely not thought to Rb, respectively5. follow-up of 150 subjects of another study11. provide solid herd immunity17. So- there is more than an opportunity to start vaccinating boys. There is an The immunohistochemical expression of p16INK4a has And is there clinical efficacy beyond seropositivity? obligation! been suggested as a surrogate marker for HPV Yes, there is. A recent Cochrane systematic review infection. So - HPV infection is almost causative for penile cancer and is found in roughly 50% of cases according to a recent meta-analysis of some 50 studies including some 4,000 patients6. Some prognostic meaning has been suggested, e.g. Matthias May and co-workers report advantageous cancer specific survival of HPV-associated primary invasive squamous cell cancer7. The current EAU guidelines recommend inclusion of the HPV status in the pathology report1. Why is HPV-related cancer important? HPV is the most common sexually transmitted infection; most adults may be infected at some point in their lives. While most infections will resolve spontaneously, some cause benign and malign lesions. More than 40 HPV strains have been identified in the genital regions. Those strains are classified as “low risk” and “high risk”. Low risk strains, namely type 6 and 11, lead to genital warts; condylomata acuminata are all related to HPV.

8

EUT Congress News

“It is our obligation to start vaccinating boys now.”

Conclusion HPV vaccination is effective and safe - but boys need to support the girls here. To protect them - and themselves. The German Robert-Koch-Institute recommends all girls and boys to be HPV vaccinated aged 9 and 14 with 2 doses 5 months apart to be finished prior to first intercourse. And this is not asked too much. The data and circumstances we see are more than an opportunity to start vaccinating boys now. They are an obligation! And it’s decisively on us urologists to live up to this. Let’s raise awareness and promote HPV vaccination among ourselves, other health care providers and parents now. References: 1. Hakenberg OW et al. EAU Guidelines on Penile Cancer. EAU Guidelines. Edn. presented at the EAU Annual Congress Copenhagen 2018. ISBN 978-94-92671-01-1. 2. Arya, M., et al. Long-term trends in incidence, survival and mortality of primary penile cancer in England. Cancer Causes Control, 2013. 24: 2169. 3. Verhoeven RH, Janssen-Heijnen ML, Saum KU et al (2013) Population-based survival of penile cancer patients in Europe and the United States of America: no improvement since 1990. Eur J Cancer 49(6):1414–1421 4. Hakenberg OW, Dräger DL, Erbersdobler A, Naumann CM, Jünemann KP, Protzel C: The diagnosis and treatment of penile cancer. Dtsch Arztebl Int 2018; 115: 646–52. DOI: 10.3238/arztebl.2018.0646 5. May M, Brookman-May SD, Ecke TH, Burger M. Molecular characterization of penile cancer: Literature review of new prognostic markers and potential therapeutic targets. Urologe A. 2018 Apr;57(4):398-407. 6. Olesen TB, Sand FL, Rasmussen CL, Albieri V, Toft BG, Norrild B, Munk C, Kjær SK. Prevalence of human papillomavirus DNA and p16INK4a in penile cancer and penile intraepithelial neoplasia: a systematic review and meta-analysis. Lancet Oncol. 2019 Jan;20(1):145-158. 7. Gunia S, Erbersdobler A, Hakenberg OW, Koch S, May M. p16(INK4a) is a marker of good prognosis for primary invasive penile squamous cell carcinoma: a multiinstitutional study. J Urol. 2012 Mar;187(3):899-907. 8. de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017 Aug 15;141(4):664-670. 9. Vorsters A, Arbyn M, Baay M, Bosch X, de Sanjosé S, Hanley S, Karafillakis E, Lopalco PL, Pollock KG, Yarwood J, Van Damme P. Overcoming barriers in HPV vaccination and screening programs. Papillomavirus Res. 2017 Dec;4:45-53. 10. Castellsagué X, Giuliano AR, Goldstone S, Guevara A, Mogensen O, Palefsky JM, Group T, Shields C, Liu K, Maansson R, Luxembourg A, Kaplan SS. Immunogenicity and safety of the 9-valent HPV vaccine in men. Vaccine. 2015 Nov 27;33(48):6892-901. 11. Guevara A, Cabello R, Woelber L, Moreira ED Jr, Joura E, Reich O, Shields C, Ellison MC, Joshi A, Luxembourg A. Antibody persistence and evidence of immune memory at 5years following administration of the 9-valent HPV vaccine. Vaccine. 2017 Sep 5;35(37):5050-5057. 12. Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018 May 9;5:CD009069. 13. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. 14. Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, Moreira ED Jr, Ngan Y, Petersen LK, Lazcano-Ponce E, Pitisuttithum P, Restrepo JA, Stuart G, Woelber L, Yang YC, Cuzick J, Garland SM, Huh W, Kjaer SK, Bautista OM, Chan IS, Chen J, Gesser R, Moeller E, Ritter M, Vuocolo S, Luxembourg A; Broad Spectrum HPV Vaccine Study. N Engl J Med. 2015 Feb 19;372(8):711-23. 15. Iversen OE, Miranda MJ, Ulied A, Soerdal T, Lazarus E, Chokephaibulkit K, Block SL, Skrivanek A, Nur Azurah AG, Fong SM, Dvorak V, Kim KH, Cestero RM, Berkovitch M, Ceyhan M, Ellison MC, Ritter MA, Yuan SS, DiNubile MJ, Saah AJ, Luxembourg A. Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women. JAMA. 2016 Dec 13;316(22):2411-2421. 16. Woestenberg PJ, Bogaards JA, King AJ, Leussink S, van der Sande MA, Hoebe CJ, van Benthem BH; Medical Microbiological Laboratories and the Public Health Services. Assessment of herd effects among women and heterosexual men after girls-only HPV16/18 vaccination in the Netherlands: A repeated cross-sectional study. Int J Cancer. 2018 Nov 13. doi: 10.1002/ijc.31989. [Epub ahead of print] 17. Sheikh S, Biundo E, Courcier S, Damm O, Launay O, Maes E, Marcos C, Matthews S, Meijer C, Poscia A, Postma M, Saka O, Szucs T, Begg N. A report on the status of vaccination in Europe. Vaccine. 2018 Aug 9;36(33):49794992.

Sunday 17 March 10.30-12.00: Thematic Session 04, Penile cancer

Sunday, 17 March 2019


ESU courses and HOT courses at day 3 of EAU19 Listed below is a collection of must-attend ESU courses and Hands-on Training (HOT) courses categorised according to topics. Boost your know-how and fine-tune your skills tomorrow, 17 March. Topics

ESU Courses

Speakers

Time

Rooms

Female urology

ESU Course 20: Advanced vaginal reconstruction

D. Pushkar (RU)

08:30 – 11:30

Green room 16

Male LUTS

ESU Course 38: Management of BPO: From medical to surgical treatment, including setbacks and operative solutions

V.A.C. Ramani (GB)

14:30 – 17:30

Green room 21

Neurogenic and non-neurogenic voiding dysfunction

ESU Course 25: Chronic pelvic pain in men and women

E.J. Messelink (NL)

08:30 – 11:30

Green room 22

ESU Course 31: Practical neuro-urology

F. Cruz (PT)

12:00 – 14:00

Green room 21

Prostate cancer

ESU Course 22: Metastatic prostate cancer

K. Pummer (AT)

08:30 – 11:30

Green room 14

ESU Course 24: Surgery or radiotherapy for localised and locally advanced prostate cancer

R.J.A. Van Moorselaar (NL) 08:30 – 11:30

Green room 21

ESU Course 27: Oligometastatic prostate cancer

R. Karnes (US)

12:00 – 14:00

Green room 16

ESU Course 33: Prostate cancer update: 2018-2019

F. Montorsi (IT)

12:00 – 14:00

Green room 23

ESU Course 36: Focal treatment in prostate cancer

E. Barret (FR)

14:30 – 17:30

Green room 14

ESU Course 39: Prostate cancer imaging: When and how to use it

J. Walz (FR)

14:30 – 17:30

Green room 22

Renal tumours

ESU Course 23: Advanced course on laparoscopic renal surgery

R. Bollens (FR)

08:30 – 11:30

Green room 13

Urethral strictures

ESU Course 40: Advanced course on urethral stricture surgery

R. Inman (GB)

14:30 – 17:30

Green room 23

Urolithiasis

ESU Course 21: Update on stone disease

A. Patel (GB)

08:30 – 11:30

Green room 15

ESU Course 37: Advanced endourology in the non-standard patients with urolithiasis

G. Kamphuis (NL)

14:30 – 17:30

Green room 13

ESU Course 26: Surgical anatomy for laparoscopic and robotic assisted radical prostatectomy and cystectomy

J-U. Stolzenburg (DE)

08:30 – 11:30

Green room 23

ESU Course 29: Laparoscopy for beginners

X. Cathelineau (FR)

12:00 – 14:00

Green room 14

ESU Course 30: Basic penile scrotal surgery and first steps in endourology

R. Sancez Salas (FR)

12:00 – 14:00

Green room 13

ESU Course 28: New perspectives in the management of upper tract tumours

S. Shariat (AT)

12:00 – 14:00

Green room 15

ESU Course 32: Management and outcome in invasive and locally advanced bladder cancer

B. Malavaud (FR)

12:00 – 14:00

Green room 22

ESU Course 34: Laparoscopic and robot-assisted laparoscopic radical cystectomy

N.P. Wiklund (SE)

14:30 – 17:30

Green room 16 Green room 15

Urological surgery

Urothelial tumours

ESU Course 35: How will immunotherapy change the multidisciplinary management of urothelial bladder cancer

A. Necchi (IT)

14:30 – 17:30

Topics

HOT Courses

Speakers

Time

Rooms

Laparoscopy

HOT 11: ESU/ESUT Hands-on Training Course in Basic laparoscopy

09:00 – 10:00

Green room 6

HOT 12: ESU/ESUT Hands-on Training Course in Basic laparoscopy

10:30 – 11:30

Green room 6

HOT 13: ESU/ESUT Hands-on Training Course in Basic laparoscopy

12:00 – 13:00

Green room 6

HOT 14: E-BLUS Exam

13:30 – 14:00

Green room 6

HOT 18: E-BLUS Exam

14:00 – 14:30

Green room 6

HOT 19: E-BLUS Exam

14:30 – 15:00

Green room 6

Diagnostics and follow-up

HOT 15: ESU/ESFFU Hands-on Training Course in Urodynamics

H. Hashim (GB)

09:00 – 12:00

Green room 7

HOT 22: ESU/ESUI Hands-on Training Course in Prostate MRI reading for urologist

C. Moore (GB)

13:00 – 16:30

Green room 9

HOT 20: ESU/ESUI Hands-on training Course in Urological ultrasound

V. Scattoni (IT)

09:30 – 11:00

Greem room 8

HOT 21: ESU/ESUI Hands-on training Course in Urological ultrasound

V. Scattoni (IT)

11:30 – 13:00

Green room 8

REGISTER NOW WCE 2019 29 October - 2 November

ABU DHABI, UAE

What is the SIU?

Held in conjunction with:

ENDOUROLOGICAL SOCIETY

Join us in the spectacular city of Abu Dhabi, UAE, for the 37th World Congress of Endourology, the world’s foremost meeting dedicated to minimally invasive urologic surgery. Assembling today’s global leaders in endourology, WCE 2019 will provide unparalleled opportunities to expand your education, enhance your skills and exchange ideas.

THE SIU is

130

DIFFERENT COUNTRIES

THE SIU is

10,000 MEMBERS and counting.

Learn more and register today at

www.WCE2019.com

Come and visit us at booth E50 to learn more about SIU and our latest programmes and activities.

www.siu-urology.org

Sunday, 17 March 2019

EUT Congress News

9


Testicular development and adolescent varicocele Diagnosis, treatment and outcome Prof. Gunter De Win, Adolescent and Reconstructive Urologist University Hospital Antwerp (BE) University College London Hospitals, London, Uk

A varicocele is a tortuous dilatation of the testicular veins in the spermatic cord. It occurs mostly at the left side. Medical literature reveals a prevalence of up to 20% in adolescents and a similar incidence in adults. In man who present with fertility problems there is an increased prevalence up to 40%1. Although the presence of varicocele is considered to be one of the main correctable causes of male infertility, only 60% of adult patients with a varicocele will show improvement in semen parameters after varicocelectomy and only 50% of men will ultimately father a child2-3. Do varicoceles cause progressive testicular damage if left untreated? Is repair in adulthood ineffective to restore a normal testicular function? Detection and treatment of varicocele in the pubertal period might therefore be suggested. However, only 20% of adolescent varicocele patients develop fertility issues later in life4. The clinical significance of an adolescent varicocele for future fertility later in life is an interesting topic for an ongoing controversial debate. A national screening programme to detect varicoceles during puberty was started in Belgium in 1987. An extensive patient survey conducted 14 years after the option to treat for unilateral leftsided varicoceles didn’t show any difference in paternity rate between the treated and untreated in those patients who desired to have children (78% vs 85%)5. An observational Turkish survey which only included bilateral varicoceles and unilateral varicoceles with >20 TAI (testicular atrophy index) favoured treatment with paternity rates of 77.3% vs 48.4%. However, the follow-up in the untreated group was much shorter than the follow up in the Belgian study. Also, there was no difference in both study arms concerning men who considered themselves having fertility problems6. Furthermore, if extrapolated, the infertility probability in non-operated varicocele patients reaches 87% which is much higher than the estimated infertility prevalence in the general population7. A retrospective Israeli study in serviceman tried to evaluate the effect of preventive surgery during adolescence, surgery at the time when infertility occurs or surveillance and compared the paternity rates to healthy controls. Paternity in surveillance patients compared to healthy controls was 71% vs 76%. Although borderline statistically significant, the paternity rate in non-operated adolescent varicocele patients was only 5% lower than healthy controls. Surprisingly, the preventive surgery group had a 3% better fertility rate than the healthy controls (79% vs 76%). Treatment, when fertility issues occurred, showed a lower fertility rate (58%). This fertility rate was lower than that of adolescent varicocele patients that were followed up conservatively (71%)8. The authors warn about over-utilisation of surveillance, however, in my interpretation of this study, the benefit of preventive surgery was very limited. Because paternity was clearly better in the bigger surveillance group (95.2% of patients) compared to the patients treated at the time infertility problems arose (1.4% of patients) one should consider that probably other more important factors (microdeletions of Y chromosome, environmental factors, smoking,…) than the presence of the varicocele explained the low fertility rate in the treated patients . Currently, there are no RCT’s available to evaluate the effect of adolescent varicocele and future paternity. As paternity is a difficult to measure long-term parameter, most studies evaluating the effect of varicocele treatment use surrogate parameters like testicular volume, testicular volume difference or standard semen analysis as a proxy measure for future fertility. Early studies showed a high incidence of ipsilateral smaller testis and a lower sperm concentration which 10

EUT Congress News

evaluating paternity before we can make stronger guidelines.

both seemed to improve after treatment. In most of these studies, the subjects happened to be its own control (before and after treatment). These studies didn’t include a control group with healthy adolescents without a varicocele so generalisation of these findings is difficult.

All these future studies have to take into account the normal variations in rapid pubertal development, calculate testicular volumes in a standardized way and classify each varicocele patient based on well-defined parameters. References

The EAU Guidelines propose a few indications for varicocele treatment during adolescence with a weak strength rating: symptomatic varicoceles, pathologic sperm quality in older adolescence, varicoceles associated with another pathology Fig. 1: The impact of PRF in Tanner V adolescents on sperm DNA fragmentation affecting fertility and varicoceles with a persistent small testis multiplies length, width and height by 0.71. However, (size difference of > 2ml or 20%). These indications most published studies still use the 0.52 factor. For are mostly based on observational studies. use in primary practice, a formula using a simple measurement of the width of the testis with a Several parameters to select which adolescent centimetre ruler matching ultrasound values has even varicocele patients need treatment have been been proposed17. suggested in the past. In most studies, no difference was found between the grade of varicocele and adolescent sperm parameters9,10. Furthermore, semen As in 20% of adolescent boys varicoceles are analysis during pubertal development is hampered by detected, no clear selection criteria during ethical issues and the lack of normal values. We have adolescence exist and many boys and parents are afraid of future fertility issues, there is probably a to take into account the natural history of semen clear overtreatment. Furthermore, surgery can induce analysis parameters which also can normalise hydrocele formation (12-28%), testicular atrophy, without intervention, just as a result of further damage to the vas and also persistence of the pubertal development11. varicocele and recurrence is possible. And only 20% varicocele patients present with fertility issues. Still, “We must work together to develop ofmany infertile patients present with an untreated varicocele and treatment during at the time of fertility more multicentre studies based issues often doesn’t solve the problem. This can be on standardized indications and due to the fact that fertility is not just due to the including pubertal development as varicocele itself, but maybe other factors (such as Y abnormalities) can play an important well as long term studies evaluating chromosome role18.

paternity before we can make stronger guidelines.”

A recent review showed that varicocele treatment during adolescence doesn’t have an impact on sperm motility and normal sperm cells but improved sperm concentration. However, also before treatment sperm concentration was within the normal range, so the consequences for future paternity are not clear12. Studies of hormonal abnormalities have shown mixed results. A meta-analysis evaluating postoperative reduction in testicular asymmetry showed an overall average catch up growth of 76.4%13. One study in Tanner 5 adolescents showed that a testicular volume differential of greater than 20% doubles the odds of a lower total motile sperm count but if the total volume of both testes is 30 ml or more, the total motile sperm count is normal14. Current guidelines suggest persistent left testicular hypotrophy of more than 20% or > 2 ml as a criterion for treatment. However, as recently shown, testicular asymmetry is a natural phenomenon during pubertal development. One-fifth of healthy adolescents without a varicocele have a 20% atrophy index or 2ml volume difference in favour of the right testicle in Tanner stage 315. One measurement of hypotrophy isn’t enough because a spontaneous catch-up growth has been shown in up to 71%16. An important left-sided varicocele can also have an impact on the right testicle and so left-sided hypotrophy can disappear resulting in a lower total testicular volume but no difference between left and right. Bilateral loss of testicular volume can decrease the value of ipsilateral asymmetry. This phenomenon can only be detected by follow up with up to dated testicular growth charts. Therefore age-matched controls and longitudinally developed growth charts are necessary to evaluate the effect of varicoceles on testicular growth. Before developing these, a consensus on how to measure testicular volume has to be made as well. The most correct formula to calculate sonographic testicular volume is the Lambert Formula which

We definitely need better selection criteria to select those adolescents that can benefit from varicocele treatment. The reason that, so far, no good selection criteria for adolescent treatment are found is that too often varicoceles are studied as a whole group or according to their grade of testicular hypotrophy of the left side and all of these are no reliable parameters during pubertal development. Also, the rapidly changing pubertal development is often not taken into account. Most studies only focus on Tanner 5 adolescence. Non-invasive peak retrograde flow measurement (PRF), the highest peak in cm/s at the level of the pampiniform plexus in supine position was introduced in 2009 and progressive testicular asymmetry was seen when this value was above 38.4cm/s with a combination of testicular atrophy index of 20%19,20. A peak retrograde flow above 30 cm/s is associated in one study with lower % motile sperm and morphologic characteristics in Tanner V adolescents21. More studies and especially RCT’s are necessary to evaluate the impact of PRF on future fertility and paternity. Pilot studies suggest an impact of high sperm DNA fragmentation rate on miscarriage in adult subfertile couples. We studied the impact of PRF in Tanner V adolescents on sperm DNA fragmentation and found that the presence of a varicocoele with a high PRF (> 38.4 cm/s) tends to increase both total and vital DNA fragmentation as compared to healthy controls and varicocele with a low PRF22, see Fig. 1. Measuring DNA fragmentation, as a functional parameter for sperm quality, can maybe solve the problem of unclear outcomes with standard semen analysis. When currently making decisions to treat, we must remember that most of these patients present with an asymptomatic, unilateral varicocele which was incidentally noticed by a primary care provider, one measurement of testicular volume and asymmetry is not sufficient and probably only a minority will really benefit from the offered procedure. We must work together to develop more multicentre studies and long term studies

1. Gorelick JI, Goldstein M. Loss of fertility in men with varicocele. Fertil Steril 1993;59(3):613–6. 2. Shamsa A, Nademi M, Aqaee M, Fard AN, Molaei M. Complications and the effect of varicocelectomy on semen analysis, fertility, early ejaculation and spontaneous abortion. Saudi J Kidney Dis Transpl 2010;21:1100–5. 3. Dubin L, Amelar RD. Varicocelectomy: 986 cases in a twelve-year study. Urology 1977;10(5):446–9. 4. W.H.O. The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril 1992; 5. Bogaert G, Orye C, De Win G. Pubertal screening and treatment for varicocele do not improve chance of paternity as adult. J Urol 2013;189(6):2298–303. 6. Çayan S, ahin S, Akbay E. Paternity Rates and Time to Conception in Adolescents with Varicocele Undergoing Microsurgical Varicocele Repair vs Observation Only: A Single Institution Experience with 408 Patients. In: Journal of Urology. 2017. 7. Kurtz MP. What Can we Learn (and What Can’t we Learn) from Observational Studies of Adolescent Varicocele Treatment? J Urol 2017; 8. Verhovsky G, Neheman A, Rappaport YH, et al. Varicocele Management Strategies and Resulting Paternity Rates in a Cohort of Young Adults. Urology 2018; 9. Mori MM, Bertolla RP, Fraietta R, Ortiz V, Cedenho AP. Does varicocele grade determine extent of alteration to spermatogenesis in adolescents? Fertil Steril 2008;90(5):1769–73. 10. Diamond D a., Zurakowski D, Bauer SB, et al. Relationship of Varicocele Grade and Testicular Hypotrophy to Semen Parameters in Adolescents. J Urol 2007;178(4):1584–8. 11. Chu DI, Zderic SA, Shukla AR, et al. The natural history of semen parameters in untreated asymptomatic adolescent varicocele patients: A retrospective cohort study. J Pediatr Urol 2017; 12. Afshar K, Locke JA, Noparast M, Afshar K. Treatment of varicocele in children and adolescents: A systematic review and meta-analysis of randomized controlled trials. J Pediatr Urol 2017; 13. Li F, Chiba K, Yamaguchi K, et al. Effect of Varicocelectomy on Testicular Volume in Children and Adolescents: A Meta-analysis. Urology 2012;i. 14. Kurtz MP, Zurakowski D, Rosoklija I, et al. Semen parameters in adolescents with varicocele: Association with testis volume differential and total testis volume. J Urol 2015; 15. Vaganée D, Daems F, Aerts W, et al. Testicular asymmetry in healthy adolescent boys. BJU Int 2018; 16. Van Batavia JP, Woldu SL, Raimondi PM, et al. Adolescent varicocele: Influence of Tanner stage at presentation on the presence, development, worsening and/or improvement of testicular hypotrophy without surgical intervention. J Urol 2010;184(4 SUPPL.):1727–32. 17. Sotos JF, Tokar NJ. Appraisal of testicular volumes: volumes matching ultrasound values referenced to stages of genital development. Int J Pediatr Endocrinol 2017; 18. Bogaert G, van den Heijkant M, Albersen M. Varicocele in Children and Adolescents: A Challenge for Diagnosis and Treatment Indications [Figure presented]. Eur. Urol. Suppl. 2017; 19. Kozakowski KA, Gjertson CK, Decastro GJ, Poon S, Gasalberti A, Glassberg KI. Peak retrograde flow: a novel predictor of persistent, progressive and new onset asymmetry in adolescent varicocele. J Urol 2009;181(6):2717–22; discussion 2723. 20. Van Batavia JP, Badalato G, Fast A, Glassberg KI. Adolescent varicocele-is the 20/38 harbinger a durable predictor of testicular asymmetry? J Urol 2013;189(5):1897–901. 21. Verim S, Uguz S, Celikkanat S, et al. Prognostic predictors of fertility in young adult patients with varicocele: Peak retrograde flow velocity and reflux grade. J Ultrasound Med 2016;35(6):1241–50. 22. Peak Retrograde Flow in Varicoceles influences sperm DNA integrity in Adolescents, De Win G, Stuer S, Coeck E, De Wachter S, De Neubourg D, Punjabi U ESHRE,Annual Conference Barcelona 2018, Human Reproduction, Volume 33, Issue suppl_1, 1 July 2018, Pages i1–i541.

Sunday 17 March 10.30-12.00: Thematic Session 10 Paediatric urology update 2019

Sunday, 17 March 2019


Risk-based follow-up for testis cancer A joint recommendation by the EAU and ESMO intermediate prognosis metastatic disease (according to IGCCCG) achieving a complete remission with or without surgery (for seminoma this includes residual lesions < 3cm or residual lesions > 3cm that are PET negative).

Dr. Richard Cathomas Deputy Head Medical Oncology Cantonal Hospital Graubünden (CH)

richard.cathomas@ ksgr.ch Follow-up is an integral and important part of testis cancer management. This is especially the case for patients diagnosed with stage I disease and treated with active surveillance but also for all other patients in complete remission after adjuvant or curative treatment. Until recently, several different and varying recommendations existed in parallel. In 2018, however, the same recommendations based on a consensus conference of testis cancer specialists were adopted and published by EAU and ESMO1,2. The results are presented in this short article. Follow-up in the first 5 years after diagnosis and treatment The primary aim of follow-up for testis cancer patients in the first five years is the timely diagnosis of recurrent disease in order to be able to treat the patient with curative intent with the least aggressive therapy. Later on, the focus shifts to detection and treatment of long-term toxicities. An adequate follow-up relies on a profound knowledge about testicular cancer with regards to histology, stage, primary treatment and treatment success. The follow-up has to be tailored to each individual patient and the schedule has to be acceptable for the patient, the physician as well as the health care system in order to achieve good compliance. The interval of follow-up visits and the tests to be performed at each visit depend on the risk of relapse in general and on the likely site of relapse in particular. Prospective literature about follow-up is scarce, only one randomised trial has been published regarding the implications of different follow-up schedules and the respective use of imaging and tumour markers. Therefore, all guidelines regarding follow-up rely on information from case series or therapeutic trials. For a long time most recommendations included tight schedules with extensive imaging using computed tomography (CT) scans (up to 15 CT scans over 5 years!). With the recognition of the risk of ionizing radiation associated with repeated CT scanning and more accurate risk assessment, all guidelines have over the past years markedly reduced the number of CT scans advised. Moreover, an MRI of the abdomen can replace CT in centres with experience. Relapse risk Table 1 provides an overview of relapse risk within the first 2 years and between 2-5 years after diagnosis, based on data from prospective trials and large retrospective analyses. Based on these results it becomes clear that relapse risks are highly varied and depend on exact diagnosis and chosen initial treatment. For a simple follow-up, the consensus panel decided to create three major groups with similar risk and localisation of relapse. Three major follow-up groups are defined: 1. Patients with seminoma stage I (irrespective of treatment) 2. Patients with nonseminoma stage I on active surveillance 3. All patients having received either adjuvant treatment or curative chemotherapy for good and

It is important to note that patients not achieving a complete remission or presenting with poor prognosis disease should be followed up individually in specialised centres. Tables 2-4 show the schedules of minimal recommendations for follow-up of the three different groups based on the consensus group discussion and votings1,2. Generally, an MRI of the abdomen can be used instead of CT in experienced centres. Regarding the use of ultrasound of the contralateral testis a majority of the consensus members recommend no regular ultrasound, not in case of negative biopsy nor if no contralateral biopsy has been performed.

Table 2: Recommended minimal follow-up for seminoma stage I on active surveillance or after adjuvant treatment (carboplatin or radiotherapy) Modality Tumor markers Chest X-ray Abdominopelvic CT/MRI

YEAR 1 2 times 0 2 times

YEAR 2 2 times 0 2 times

YEAR 3 2 times 0 At 36 months

YEAR 4+5 once At 60 months

After 5 years Further management according to survivorship care plan

Table 3: Recommended minimal follow-up for non-seminoma stage I on active surveillance Modality Tumor markers Chest X-ray Abdominopelvic CT/MRI

YEAR 1 4 times * 2 2 times

YEAR 2 4 times 2 At 24 months***

YEAR 3 2 times 1 (if LVI+) At 36 months **

YEAR 4+5 1-2 times At 60 months if LVI+ At 60 months **

After 5 years Further management according to survivorship care plan

* In case of high risk (LVI+) a minority of consensus group members recommends 6 times ** Recommended by 50% of consensus group members *** In case of high risk (LVI+) a majority of consensus group members recommends an additional CT at 18 months

Follow-up longer than 5 years after diagnosis Follow-up for relapse for more than five years is generally not recommended. Therefore no regular imaging or tumour marker measurement is necessary. Very late relapse (VLR) after 5 years is a rare event occurring in approximately 0.5% of patients according Table 4: Recommended minimal follow up after adjuvant treatment or complete remission for advanced to a population-based analysis. Most patients with disease (excluded: poor prognosis and no remission) VLR are diagnosed due to symptoms, elevated tumour markers can be found in both seminomatous and Modality YEAR 1 YEAR 2 YEAR 3 YEAR 4+5 After 5 years non-seminomatous germ cell tumours in up to 50% Tumor markers 4 times 4 times 2 times 2 times Further of patients. Patient education about relapse symptoms +/- doctor visit management and physician awareness is a very important part of according to Chest X-ray 1-2 Once Once Once survivorship management. The early use of imaging survivorship Abdomino1-2 times At 24 months At 36 months At 60 months and tumour markers in case of suspicion of relapse is care plan** pelvic CT/MRI encouraged. Thorax CT * * * *

“Adoption of EAU/ESMO recommendations is highly recommended”

*same time points as abdomino-pelvic CT/MRI in case of pulmonary metastases at diagnosis ** in case of teratoma in resected residual disease: patient should remain with uro-oncologist

The aim of follow-up after more than five years after diagnosis shifts to detection of late side effects of treatment. This includes cardiovascular disease, metabolic syndrome (arterial hypertension, impaired glucose tolerance, hyperlipidaemia, obesity), impaired renal function, neuropathy, ototoxicity as well as hypogonadism and secondary malignancies It is recommended to use a survivorship care plan. Moreover psychological and social support may be required over time. Testis cancer survivors should regularly be advised to adapt their lifestyle in order to control additional risk factors (e.g. non-smoking, weight control, regular physical exercise). Conclusions The joint EAU/ESMO recommendations for follow-up as published in 2018 provide the clinician with an easy to use, safe and convenient schedule of follow-up for patients with testicular cancer. Adoption of these recommendations is highly recommended. References 1. Albers P et al. EAU guidelines on testicular cancer, European Association of Urology 2018; www.uroweb.org. 2. Honecker F et al. ESMO consensus conference on testicular germ cell cancer: diagnosis, treatment and follow-up. Ann Oncol 2018;29:1658-1686.

Sunday 17 March 10.30-12.00: Thematic Session 09 Testis cancer: Surgery is back again

Table 1: Overview of relapse rate depending on initial stage, histology and treatment Histology

Initial Stage

Therapy

Seminoma

I

Surveillance

Relapse rate 12-31%

Seminoma Seminoma Seminoma Seminoma Non-Seminoma Non-Seminoma Non-Seminoma Non-Seminoma Non-Seminoma

I I IIA/B IIB-III good prognosis I, low risk I, high risk I I, high risk IIA-III good prognosis

Adj. Carboplatin Adj. RT 20 Gy RT 30/36Gy 3xBEP/4xEP Surveillance Surveillance Adj. RPLND Adj. 1x BEP 3xBEP/4xEP

5% 4% 5-15% 8 -12% 15% 45-50% 8-10% 3 -4% 8-12%

Sunday, 17 March 2019

Relapse rate > 2 years 3-5% 1% > 3 years 1% 1% 2% <2% 1% <2% <2% <1% <2%

Main area of relapse Abdomen Abdomen Outside RT field Outside RT field Abdomen, Lung Abdomen, Lung Abdomen, Lung Lunge Abdomen, Lunge Abdomen, Lunge EUT Congress News

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Today’s European Urology Events Surgery-in-Motion

March 17th 10.30 – 12.30 eURO Auditorium 2

Aims and objectives: The Surgery-in-Motion session is dedicated to novel treatment strategies in BPO. Experts in the field will provide explanations and video demonstrations of various surgical techniques and discuss why they do it “their way.” Questions from the audience are welcome.

10:30 - 10:40 Welcome and introduction Alexander Bachmann, Vienna (AT) Jim Catto, Sheffield (GB) Alexandre Mottrie, Aalst (BE) Peter Schatteman, Aalst (BE) 10:40 - 10:48 Natural history of ‘BPH’ and prostate conditions for surgery Alexander Bachmann, Vienna (AT) 10:48 - 11:28 Enucleation techniques Moderator: Alexander Bachmann, Vienna (AT) 10:48 - 10:58 HoLEP Peter Schatteman, Aalst (BE) 10:58 - 11:08 ThuLEP Andrea Gross, Hamburg (DE) 11:08 - 11:18 Green-LEP Fernando Gomez Sancha, Madrid (ES) 11:18 - 11:28 Bipolar enucleation Thomas Herrmann, Frauenfeld (CH) 11:28 - 11:52 Vaporisation techniques Moderator: Peter Schatteman, Aalst (BE)

11:28 - 11:36 Greenlight Laser Alexander Bachmann, Vienna (AT) 11:36 - 11:44 REZUM Alexander Bachmann, Vienna (AT) 11:44 - 11:52 Bipolar Plasmavaporisation (‘Button’ or Mushroom) Bogdan Geavlete, Bucharest (RO) 11:52 - 12:00 New immediate ablative techniques: Aqua-ablation Moderator: Peter Schatteman, Aalst (BE) Speaker: Thorsten Bach, Hamburg (DE) 12:00 - 12:16 Mechanically deobstructing techniques and others Moderator: Alexander Bachmann, Vienna (AT) 12:00 - 12:08 Urolift Henry Woo, Sydney (AU) 12:08 - 12:16 Temporary implantable Nitinol Device (iTIND), Francesco Porpiglia, Turin (IT) 12:16 - 12:21 Closing remarks Alexander Bachmann, Vienna (AT) Jim Catto, Sheffield (GB) Alexandre Mottrie, Aalst (BE) Peter Schatteman, Aalst (BE)

europeanurology.com eufocus.europeanurology.com euoncology.europeanurology.com

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EUT Congress News

Sunday, 17 March 2019


Designing a randomised trial on peno-bulbar urethroplasty OPEN Trial wins third prize for best non-oncological abstract at EAU19 Prof. Nick Watkin Urology Department St. George’s University of London

It is notoriously difficult to randomize between surgical procedures, but with Rob’s pragmatism, and a meticulous trial design, it was approved to begin in 2013. The OPEN trial (open vs endoscopic urethroplasty) recruited in over one third of UK urology units. But it was not easy to randomize: one has to remember that the eligible patients had usually had a failed urethrotomy already and may have had a preconception that urethroplasty might be better.

Rob Pickard (1961-2018) Prof. Pickard trained at the Royal London Hospital and was appointed to Newcastle Freeman Hospital as a Consultant Urological Surgeon in 1996. He was Senior Lecturer and became Professor of Urology at Newcastle University in 2009.

nick.watkin@nhs.net

“Recurrence within 24 months was less frequent and occurred later after urethroplasty, and urethroplasty also resulted in a better improvement in maximum urinary flow rate.” To put this into context, at that time, ten times as many DVIU/dilations were performed compared with urethroplasty. This was despite the presumption from non-randomised case-series that urethroplasty (both anastomotic and buccal graft augmentation) had a medium term successful outcome of 90-95%, whereas in contrast DVIU had a 40-60% revision rate at 3-4 years. Of course, the scientific evidence was relatively weak. Case series were usually retrospective in nature, with no standard protocol, follow up incomplete, but most importantly, the definition of success was poorly defined. The objective measure of success most commonly relied on a flow rate (usually over 15ml per second) and very little else. The PROM score When Professor Rob Pickard and I discussed the idea of a trial comparing DVIU with urethroplasty over a coffee at the 2009 BAUS meeting, it was Rob who immediately recognized the importance of the need for a randomized trial. Not only that, he felt that we had to focus on the patient’s symptoms more than an arbitrary measure of urinary flow rate. At the time, there was no symptom score that was validated for urethral strictures and outcome. So before we could consider the trial, we and colleagues in the UK Urethral Surgeons Group set about to design and validate a Urethral Stricture Surgery Patient Reported Outcome Measure (USS-PROM). This was the first of its kind and two landmark papers were published in European Urology in 2011 and 2013. The PROM has been widely adopted internationally, and translated into several languages. It is now common for urethroplasty outcomes to be reported with the measure of change in the PROM score. Whilst this project was in development, the UK Urethral Surgeons, chaired by Prof. Tony Mundy, developed a National Urethroplasty Database, a set of best practice guidelines and galvanized a group of like-minded surgeons who would be able to support a National Trial. The OPEN trial The necessary steps had been taken for the protocol to be submitted. Rob, as Chief Investigator worked in Newcastle and closely with colleagues in Aberdeen (in particular Prof. Luke Vale, Ms. Sonya Carnell, Dr. Jing Shen, Mr. Graeme Maclennan, and Ms. Beatriz Goulao), who had been recognized for their skill and knowledge in surgical randomized trial design and recruitment. Sunday, 17 March 2019

Implications The OPEN Trial set out to provide direct comparative evidence of effectiveness and cost-effectiveness of open urethroplasty and endoscopic urethrotomy for 222 men with recurrent bulbar urethral stricture. The results of the trial showed that both procedures provided rapid symptom relief and equivalent improvement in health-related quality of life. In absolute terms, the scores reduced from 13 (out of a maximum of 24) to 7. Recurrence within 24 months was less frequent and occurred later after urethroplasty, and urethroplasty also resulted in a better improvement in maximum urinary flow rate. It did however cost more than urethrotomy and had a low chance of being considered cost-effective over the long-term. The recurrence rate at 2 years was 20% for the urethroplasty group and 37% in the urethrotomy group. In this study, recurrence was defined as a need for re-intervention or decline in symptoms or flow to pre-treatment baseline levels.

Prof. Pickard was instrumental in setting up the OPEN trial and the PROM score that made it possible to measure patients’ symptoms. The results of his work are presented at EAU19 by his co-Chief Investigator Prof. Watkin.

outcome. We also want to look into the factors that drive patient choice of differing surgical procedures. Will this trial change practice? At the very least, it’s thought provoking. There is something for every viewpoint. Better, more informed decision-making should be assumed in future guidelines. I am not sure the rates of procedures will necessarily change.

Rob Pickard passed away on 24 July, 2018 after being diagnosed with glioblastoma multiforme two and a half years earlier. He is survived by his wife Rebecca and two children. Based on the full obituary on BAUS.org.uk

active on the guidelines panel and at many EAU scientific meetings. There are few people in the urological community who don’t recognize his name and the contributions with which he has been closely involved.

I first heard that we won the third prize for nononcological abstract at EAU19 in the first weeks of 2019 and naturally I was very pleased and alerted the trials team. But then my thoughts turned to Rob who had given so much of his short time left to get the project completed and soon to be published. Rob was a great advocate of European urology and was very

What does this mean for current practice? We now have high-level evidence of the benefit of two very different procedures. Our data will help clinicians worldwide to provide more accurate information on the comparative benefit of urethroplasty and urethrotomy for their male patients with recurrent bulbar urethral stricture. At present it appears that either procedure is likely to give substantial symptom benefit without risking significant harms. The duration of that benefit is longer with urethroplasty but at the expense of a longer operation and recovery time. Patients, informed by their clinician, will need to balance these factors in the light of their individual circumstances, values and preferences to decide which procedure to undergo. The higher cost of urethroplasty will concern those funding the procedure. Healthcare systems choosing to provide a urethroplasty service may need to work with clinician groups to ensure sufficient sites and provision of urologist training are available to men needing to access a service that will enable clinicians to counsel patients about the choice of treatment. As is often the case, the data falls between the extremes of published poorer quality evidence, with urethroplasty recurrence rates higher and urethrotomy rates lower than previously reported. The fact that symptom scores are similarly improved at two years was probably not expected but may go some way to explain why many patients are ready accept repeat urethrotomy. Perhaps we have focused too much on flow rates and not considered the degree of bother that a patient has. Further research What further research can we conduct? The most obvious project is to continue follow up out to 5 years and possibly 10 years. Will the curves separate over a longer period of surveillance? There is certainly the enthusiasm in the trial team to look into this, but the patients are increasingly hard to track and we know that there is a drop off in patients’ willingness to remain as “trial participants”.

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Editorial Board Editors M.P. Wirth, Dresden O.W. Hakenberg, Rostock D. Castro-Diaz, Santa Cruz de Tenerife B. Wullich, Erlangen

Editorial Committee A. Briganti, Milan S. Egawa, Tokyo S. Madersbacher, Vienna M.S. Michel, Mannheim V. Mirone, Naples R. Mundy, London J. Nordling, Herlev M. Porena, Perugia J.J. Rassweiler, Heilbronn H. Rübben, Essen A. Stenzl, Tübingen J. Stolzenburg, Leipzig Y. Sun, Shanghai Language: English ISSN 0042–1138 (print) e-ISSN 1423–0399 (online)

Urologia Internationalis offers many benefits to authors: Cost-effective publishing No submission fee, free online color figures, no page limit, no publication fee for papers of 3 printed pages or less. Rapid review A fast review process of less than 30 days after submission. Quality The journal stands out both for its efficient submission process and the excellent picture quality. Each article is fully copyedited by highly trained staff and monitored throughout every stage of its production. Impact Inclusion in all the major abstracting and indexing services including Journal Citation Reports, PubMed/MEDLINE, Biological- Abstracts, Embase Submission Guidelines for authors at

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Previously, free grafts of foreskin, or scrotal skin flaps had recognized medium to long-term complications that included re-stricture, hair ingress and diverticular formation. These factors often weighed against the decision to offer urethroplasty, when Direct Visualisation Internal Urethrotomy (DVIU), or urethral dilation, remained the alternatives. The latter choices were simpler to perform, more widely available, and had a shorter less complex recovery. Both patients and specialists would often choose these procedures and it was not common for there to be a discussion of urethroplasty.

However, for Rob, another challenge had faced him. A dizzy spell on holiday in late 2015 led to a diagnosis of an incurable brain tumour that forced him to retire from clinical practice a few months later. Rob asked me to take over as Acting Chief Investigator, but importantly he continued to be involved with the trial follow-up, data analysis and writing of the scientific papers. Rob lived to know that the first paper was ready for submission to The Lancet, before he sadly passed away last summer only a couple of weeks later. (see inset)

Sensitivity

As the objective for our trial began to be formulated in 2008-09, peno-bulbar urethroplasty was gaining popularity with the recognition of the reliability and versatility of buccal mucosal grafts. This was certainly the case in UK practice, but probably also internationally. These grafts were increasingly used for augmentation of the strictured urethra.

Apart from his work on OPEN, Pickard also developed the ANTIC, SUSPEND and CATHETER clinical trials, leading the innovation and implementation of non-invasive urodynamic and home uroflowmetry devices. At the 2016 BAUS meeting, he was awarded the Silver Cystoscope for his outstanding contribution to training in urology.

Thirty months later, the trial closed for entry, having successfully recruited, and follow-up continued to the end of 2017.

We certainly need to look at strategies to reduce the costs of urethroplasty without reducing successful EUT Congress News

13


From the EAU Scientific Congress Office

Stenzl takes on new role, focuses on scientific pursuits SCO Chairman imparts vision for urology in Europe & beyond We interviewed esteemed and internationally-known Prof. Dr. Arnulf Stenzl (DE), current Chairman of the EAU’s Scientific Congress Office (SCO) and recentlyelected Adjunct Secretary General - Executive Member Science. Prof. Arnulf Stenzl has been the Chairman of EAU’s SCO since 2012, taking responsibility for the continuous development and improvement of the EAU’s Annual Congresses. He is currently head of the Department of Urology at the Eberhard Karls University of Tübingen in Germany; Managing Director of the Inter-University Center for Medical Technologies Stuttgart – Tübingen; and has other academic positions in Graz and Innsbruck, Austria; at the University of California, Los Angeles (UCLA); and in Bern, Switzerland. Throughout his career, Prof. Stenzl received numerous accolades such as Honorary Member of the Bristol Urological Institute (Bristol, UK), and Werner-Stähler Memorial Prize, Southwest German Association of Urology in 2007, 2009, 2010 and 2011, to name a few. He has won almost 20 urologyrelated awards including those for best abstract at various congresses. A highly-respected and distinguished scientist, Prof. Stenzl serves on the editorial board of close to 20 urology-related scientific journals and has coauthored over 651 papers since 1984. He is also patent owner of notable inventions in the field of urology such as the C-Trap, an implantable device that treats urinary incontinence (Patent AT00/00001) and the implantable incontinence device (Patent A290/99). Prof. Stenzl is a member of many associations and committees such as the German urological association Deutsche Gesellschaft für Urologie e.V. (DGU), Swiss Urological Association, Austrian Association of Experimental Surgery, and many more.

In this edition of the EAU19 Congress Newsletter, he shares his aspirations for urologists and the field, as well as, what his roles in the EAU entail. What are your main responsibilities as SCO Chairman? I oversee the review process of thousands of abstracts submitted for an annual EAU congress. For the upcoming EAU19 congress in Barcelona, 5,500 abstracts were submitted – a record-breaking number compared to previous EAU congresses. The proposals for topics of the Plenary and Thematic sessions for the upcoming meetings are created with the help of the SCO. Together with the Scientific Congress Committee, the annual congress’ Scientific Programme – from the Plenary, Thematic to the Poster sessions – is composed. Additionally, the SCO works together with the Video Congress Committee to evaluate and approve video submissions. What are the most rewarding aspects of your role as SCO Chairman? To work with respected, highly-regarded experts in various fields related to urology is fascinating. At SCO meetings, the best people European urology has to offer are sitting in one room discussing and shaping the future of this field in Europe. To be part of this and to further set incentives so that sciences related to urology eventually lead to more high-level abstract submissions; to motivate the most talented young people to choose urology and the young urologists to apply themselves to urologic science and evaluate it; to help revolutionise ground-breaking studies that encourage more collaborations and knowledgesharing. These are truly fulfilling for me as Chairman.

member of the SCO then its Chairman. On a national level, I became a board member of the Austrian uro-oncology section and later, of the DGU. And it was during this time that I became more inspired to help I aim to encourage the younger generation to pursue accelerate the level of European urology and expand careers in the field of urology and to further delve into its reach beyond the continent. scientific work. I encourage them to connect and What do you wish to achieve with this new role? collaborate with colleagues within and beyond My goals for this role include achieving the pinnacle Europe as they have the potential to be the frontrunners, the next-in-line leaders in this field and for urology; motivating the most talented and skilled to get into urology; creating networks within Europe; its subspecialties. increasing the number of participants in various sections of the EAU; and boosting the number of What attracted you to this position? attendees of EAU congresses and meetings. Within a span of over 15 years, I first served as a further increase the level of science and technology in urology; to make urology a leading medical and scientific field in Europe.

You have just been elected as Adjunct Secretary General - Executive Member Science. Congratulations! What are your main tasks and objectives? Thank you. In this new role, I plan to maintain and

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Shock wave treatment with DUOLITH® SD1 »ultra« for erectile dysfunction and urological pain therapy Significant improvement of erectile function1 Stabilisation in advancement of penis curvature2 Significant improvement of pain3 Non-invasive therapy

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No reported side-effects No anaesthesia required 1 2 3

Chung et al. BJU international, 2015, 115, 46-49 Palmieri et al. European Urology, 2009, 56 (2), 363-370 Zimmermann et al. European Urology, 2009, 56, 418-424

STORZ MEDICAL AG · Lohstampfestrasse 8 · 8274 Tägerwilen · Switzerland · www.storzmedical.com

Sunday, 17 March 2019


Theranostics: The future of functional imaging PSMA, a promising molecule for imaging and therapy in advanced prostate cancer Dr. Andrea Farolfi Nuclear Medicine, S. Orsola University Hospital Bologna (IT)

Prof. Stefano Fanti Nuclear Medicine, S. Orsola University Hospital Bologna (IT)

The possibility to combine a diagnostic biomarker with a therapeutic agent is called ’theranostics’, derived from the Greek words therapeia (therapy) and gnosis (knowledge). This concept has been known since 1946 when radio-iodine was first used by Seidlin and colleagues for imaging and therapy of thyroid adenocarcinoma. Currently evidence suggests that a PSMA-targeting combined approach may not only provide a more accurate diagnosis, but also a realistic option to treat patients with advanced prostate cancer. During the last few years prostate-specific membrane antigen (PSMA) ligands for imaging and therapy have drawn the attention of the scientific community. PSMA is a type II carboxypeptidase-associated transmembranous glycoprotein with folate hydrolase activity. It has been demonstrated that PSMA is over-expressed in prostate cancer cells as well as in other cancers (thyroid, breast, kidney and others) and benign conditions. Therefore PSMA is neither a prostate cancer specific nor a neoplastic specific biomarker. Imaging A variety of PSMA ligands for PET as well as SPECT imaging have been introduced into the clinic over the recent years. To date most literature deals with 68 Ga-PSMA-11. However, data from prospective multicentre trials are not yet available for PSMA ligands and none of these tracers has been approved by EMA or FDA. Staging In primary prostate cancer, studies focusing on the localisation and extent of the disease found that PSMA is not very sensitive for lesions within the prostate, especially in case of a lower Gleason score1,2. Nevertheless, combining PSMA PET with MRI showed promising results3,4. Regarding nodal staging, several studies have compared PSMA PET to lymph node histopathology and in a systematic review by Corfield et al. sensitivity ranged from 33 to 99%, while median specificity ranged from 82 to 100% in high-risk patients5. Biochemical recurrence Many studies demonstrated the higher detection rate of PSMA PET compared to direct competitors such as choline or fluciclovine PET during early biochemical recurrence. In a systemic review on the role of the existing imaging techniques such as TRUS, CT, mpMRI and PET with different radiotracers in patients with early recurrent prostate cancer, de Visschere et al. found that PSMA PET shows higher detection rates than any other imaging modality, especially in the range of low PSA values (< 0.5 ng/ml)6. Castration-resistant prostate cancer The monitoring of systemic disease might become an application for PSMA imaging even if conventional cross-sectional imaging by either CT or MRI and bone scan (BS) is still the recommended staging modality in patients with castration-resistant prostate cancer (CRPC). Nevertheless, the introduction of PSMA PET for patients with CRPC as a staging modality may provide higher sensitivity and specificity compared to morphological imaging and BS, but also raises many questions. Firstly, a higher sensitivity would result in a shift from men who were previously found to have non-metastatic castration resistant prostate cancer (nmCRPC) according to BS into a mCRPC disease state, which would significantly influence treatment Sunday, 17 March 2019

Figure: 68-year old man with Gleason score 6 metastatic CRPC. Previous treatments included radical prostatectomy, ADT, docetaxel, abiraterone and 223radium. In April 2017, PSA was 412 ng/mL and Hb 8 g/dL with subsequent 11C-choline (April 2017) and 68Ga-PSMA PET/CT (June 2017) showing diffuse bone involvement. Thus the patient was referred to Heidelberg (DE) for one cycle of 225 Ac-PSMA-617 in July 2017. After two months (September 2017) PSA was 3 ng/mL and Hb 10 g/dL and 68Ga-PSMA PET/CT revealed a remarkable decrease in PSMA uptake.

decision making, resulting in earlier treatment and, secondly, exclude certain treatment options. Therapy Radio guided surgery Since 2014, the Technical University of Munich (TUM) has described the PSMA-radio guided surgery concept. This novel method to detect metastatic prostate cancer lesions in an intra-operative setting mainly consists of the intravenously administration of PSMA labelled with SPECT isotopes followed by surgery. In the operating theatre, a gamma probe, which provides live acoustic and visual feedback of the count rate, is employed to locate the target lesions. The possibility to reach an immediate confirmation of metastases removal by ex-vivo gamma probe analysis is a major benefit of this technology. Maurer et al. found a sensitivity of 84% and an accuracy of 93% using 99mTc-PSMA-I&S in a retrospective study with 31 prostate cancer patients with biochemical recurrence after primary radical prostatectomy7.

“PSMA is neither a prostate cancer specific nor a neoplastic specific biomarker.” Radio ligand therapy In a theranostic intent, PSMA-directed imaging is essential to demonstrate PSMA-positive metastatic disease and adequate PSMA expression in target lesions. Additionally, current evidence suggests that a PSMA-targeting combined approach may not only provide a more accurate diagnosis, but is also a realistic option to treat CRPC patients, e.g. by employing ligands such as β-emitting isotopes, Auger emitters or α-emitting isotopes. Since 2015, an increasing number of studies report very encouraging results on the safety and efficacy of PSMA RLT in over 700 patients, representing over 1,000 administered cycles. These studies have used variable administered activity, treatment intervals and the number of cycles. Universally these therapies are performed under compassionate use dispensation according to the Declaration of Helsinki. This is typical for patients who have exhausted the available therapies, including second generation ADTs or chemotherapy. β-emitting isotopes The first small molecule inhibitor used for endoradiotherapy in men was 131I-MIP-10958. However, 177Lutetium (177Lu) has gained popularity as the therapeutic radionuclide of choice due to its β-emitting desirable physical properties. In a systemic review, von Eyben et al. compared the efficacy and side-effect profile of PSMA targeted therapy with 177Lu (12 studies and 669 patients) to the available third-line treatments in CRPC9. Overall, following 177Lu-PSMA therapy 44% of patients had a maximum decline of PSA of ≥ 50% and a median overall survival (OS) of 14 months. Although this study has limitations, including heterogeneous

patient characteristics with the potential for selection bias and the retrospective nature of prior studies, it poses a clinical equipoise to commence phase II/III trial to compare the efficacy and side effect profile of this treatment. In the first prospective phase II study, Hofman et al. reported on the safety and efficacy of PSMA radio ligand therapy in 30 patients with CRPC10.Their cohort involved heavily pre-treated patients with 87% having received ≥ 1 line of prior chemotherapy (80% docetaxel and 47% cabazitaxel) and 83% having received prior abiraterone and/or enzalutamide. In this study > 50% PSA reduction was achieved in 57% of patients. The most common toxicities include grade 1 xerostomia in 87%, grade 1-3 fatigue in 56% and grade 3-4 thrombocytopenia in 27% (approximately half of which was probably related to progressive marrow infiltration by disease). More importantly, improvement in pain and quality of life was reported. Median PSA progression free survival (PFS) and OS were 7.6 months and 13.5 months, respectively. α-emitting isotopes About one third of the patients do not respond to radio ligand therapy with 177Lu-labelled PSMA ligands. Furthermore, diffuse red marrow infiltration, especially after extensive previous chemotherapy, is likely to induce higher grade haematological toxicity during 177Lu-PSMA ligand therapy. It has been demonstrated in patients with neuroendocrine tumours that targeted alpha therapy with 213 Bi-DOTATOC could break radio-resistance to beta particle emitters while simultaneously reducing haematological toxicity in the setting of diffuse red marrow infiltration. Therefore, PSMA ligands labelled with the alpha emitter 225Actinium (225Ac) have been applied to patients with diffuse bone marrow involvement or resistance towards therapy with 177 Lu-PSMA ligands (see Figure). A study in 40 patients with advanced to final stage disease by the Heidelberg group included follow-up of PSA response and radiological PFS at six months11. Furthermore, a Swimmer-Plot analysis was used for intra-individual comparison of the duration of tumour control by treatment with PSMA-ligands and the other treatment modalities given before radio ligand therapy. A PSA decline > 50% was observed in 63% and any PSA response in 87% of the patients. The median duration of tumour control was 9.0 months, whereas five patients had long-term responses of more than two years. These preliminary results of 225 Ac-PSMA ligand therapy in patients with advanced to final disease stages are promising. However, earlier xerostomia was the main reason to discontinue therapy or to refuse additional administrations. Therefore, additional efforts should address this side effect which reduces the quality of life of these patients. In this respect more knowledge about the non-specific uptake of small molecule PSMA ligands in the salivary glands may pave the way to new preventive strategies for the prevention of salivary gland dysfunction.

To conclude, PSMA is a promising molecule for both imaging and therapy in advanced prostate cancer patients; nevertheless, further studies are needed to investigate its role and to determine the impact of its side effects and its overall strategy outcome. References 1. Fendler WP, Schmidt DF, Wenter V, et al. 68Ga-PSMA PET/CT Detects the Location and Extent of Primary Prostate Cancer. J Nucl Med. 2016;57(11):1720-1725. doi:10.2967/jnumed.116.172627 2. Uprimny C, Kroiss AS, Decristoforo C, et al. 68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44(6):941-949. doi:10.1007/s00259-017-3631-6 3. Rhee H, Thomas P, Shepherd B, et al. Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer. J Urol. 2016;196(4):1261-1267. doi:10.1016/j. juro.2016.02.3000 4. Eiber M, Weirich G, Holzapfel K, et al. Simultaneous 68Ga-PSMA HBED-CC PET/MRI Improves the Localization of Primary Prostate Cancer. Eur Urol. 2016;70(5):829-836. doi:10.1016/j.eururo.2015.12.053 5. Corfield J, Perera M, Bolton D, Lawrentschuk N. 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET) for primary staging of high-risk prostate cancer: a systematic review. World J Urol. 2018;36(4):519-527. doi:10.1007/s00345-018-2182-1 6. Visschere PJLD, Standaert C, Fütterer JJ, et al. A Systematic Review on the Role of Imaging in Early Recurrent Prostate Cancer. European Urology Oncology. 2018;0(0). doi:10.1016/j.euo.2018.09.010 7. Maurer T, Robu S, Schottelius M, et al. 99mTechnetiumbased Prostate-specific Membrane Antigen-radioguided Surgery in Recurrent Prostate Cancer. Eur Urol. April 2018. doi:10.1016/j.eururo.2018.03.013 8. Maresca KP, Hillier SM, Femia FJ, et al. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J Med Chem. 2009;52(2):347357. doi:10.1021/jm800994j 9. von Eyben FE, Roviello G, Kiljunen T, et al. Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review. Eur J Nucl Med Mol Imaging. 2018;45(3):496-508. doi:10.1007/s00259-017-3895-x 10. Hofman MS, Violet J, Hicks RJ, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 07 2018. doi:10.1016/S1470-2045(18)30198-0 11. Kratochwil C, Bruchertseifer F, Rathke H, et al. Targeted Alpha Therapy of mCRPC with 225Actinium-PSMA-617: Swimmer-Plot analysis suggests efficacy regarding duration of tumor-control. J Nucl Med. January 2018. doi:10.2967/jnumed.117.203539

Sunday 17 March 08.00-10.23: Plenary Session 3 Imaging in prostate cancer: Is it time to change paradigms?

EUT Congress News

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EAU Edu Platform

The online learning platform for GU cancers

PROSTATE CANCER

KIDNEY CANCER

uroonco.uroweb.org

BLADDER CANCER

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Innovators in Bladder Cancer website Launching in March 2019! The Innovators in BC website is a science-based, international forum providing the latest scientific and clinical information to urologists, oncologists and uro-oncologists managing BC.

Innovators in BC aims to provide an accessible scientific resource to facilitate: • sharing up-to-date information in the field • assisting the optimisation of daily clinical practice • supporting peer-to-peer learning by facilitating the sharing of content

To register for access, please visit the Ipsen Booth: E38 in Hall 8.1

Hot topics

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HEX-ES-000005 l February 2019

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Sunday, 17 March 2019


Neoadjuvant therapy in localised disease Who is going to benefit? Dr. Maria C Mir Maresma Attending Urologic Oncologist Fundacion Instituto Valenciano Oncologia (FIVO) Valencia (ES)

of inactivation of the von Hippel–Lindau tumoursuppressor gene (VHL). Over the last decade, treatment for metastatic RCC (mRCC) has focused on targeting the VEGF signalling pathway with receptor tyrosine kinase inhibitors, such as sunitinib, or monoclonal antibodies that block VEGF, such as bevacizumab. Although VEGF pathway blockade is effective in many patients, it is associated with development of resistance.

Immune checkpoints and immune checkpoint inhibitors in RCC Immune checkpoints and immune checkpoint inhibitors in RCC In addition to its well-characterised Immune checkpoints and immune checkpoint inhibitors in RCC

role in angiogenesis, VEGF is also believed to play a role in cancer immune evasion. Data from preclinical models and phase 1 studies suggest that anti-VEGF might enhance the antitumour activity of immune checkpoint blockade by improving T-cell infiltration, upregulating major histocompatibility complex class I expression, and reversing myeloid Expression of the immune checkpoint molecule immunosuppression. A phase 1 study programmed death-ligand 1 (PD-L1) on tumour cells Renal cell carcinoma (RCC) accounts for 3% of adult and/or tumour-infiltrating immune cells (IC) has been combining atezolizumab and malignancies and constitutes 95% of renal tumours. bevacizumab established the reported to suppress antitumour immunity and is Surgery continues to be the mainstay of treatment for associated with poor prognosis in mRCC. The combination to be well-tolerated in RCC. However, in case of locally advanced disease, RCC, with evidence of augmentation of importance of intact immune surveillance in resection can be challenging due to parenchymal antitumour immunity and encouraging controlling outgrowth of neoplastic transformation reconstruction, great vessel dissection and major has been known for decades14. Accumulating evidence antitumour activity compared with complications. historical experience with either single shows a correlation between tumour-infiltrating Kirsty Ross, and Rob J. Jones Clin. Sci. 2017;131:2627agent alone. lymphocytes (TILs) in cancer tissue and favourable 2642 Kirsty Ross, and Rob J. Jones Clin. Sci. 2017;131:2627Furthermore, up to 20-30% of patients undergoing prognosis in various malignancies15. In particular, the Kirsty Ross, and Rob J. Jones Clin. Sci. 2017;131:2627-2642 2642 Kirsty Ross, and Rob J. Jones Clin. Sci. 2017;131:26272642 Neoadjuvant therapy presence of CD8+ T-cells and the ratio of CD8+ nephrectomy for RCC present with chronic kidney ©2017 by Portland Press Ltd in advanced ©2017 by Portland Press Ltd ©2017 by Portland Press Ltd effector T-cells / FoxP3+ regulatory T-cells seems to disease disease (CKD). Another 30% develop CKD on ©2017 by Portland Press Ltd The use of neoadjuvant therapy has correlate with improved prognosis and long-term follow-up and this is the rationale for parenchymal evolved as a concept to improve the preservation. These patients carry a high risk of survival in many solid tumours. safety and complex resection in loco-regional axitinib and anti-PD-L1 therapy would make for a developing locally recurrent disease and systemic potential synergism, two phase Ib dose-finding advanced disease. Neoadjuvant studies are a unique progression. High-risk patients with no evidence of “Although VEGF pathway blockade opportunity to further investigate the way in which studies to evaluate safety, pharmacokinetics and disease following complete resection may therefore immune checkpoint inhibition works and to identify pharmacodynamics of avelumab, an anti-PD-L1 benefit from adjuvant and neo-adjuvant systemic is effective in many patients, it is monoclonal antibody, or pembrolizumab, an anti-PD1 predictors of treatment response. treatment strategies which primarily aim to prolong associated with development of monoclonal antibody, in combination with axitinib disease-free (DFS) and, ultimately, overall survival Currently, 11 clinical trials have been published on the were performed. The first results presented at ESMO (OS). The use of neoadjuvant therapy has evolved as a resistance.” neoadjuvant setting for RCC (either M0 or M1 patients 2016 were promising with objective response rates of concept to improve the safety and complex resection 67-70 % and acceptable toxicity profiles. included). One trial included bevacizumab, 2 in loco-regional advanced disease. Atezolizumab sorafenib, 2 pazopanib, 5 sunitinib and 1 axitinib. All drugs reported a median 1.5 cm tumour shrinkage, Table 2 summarises the ongoing clinical trials Overproduction of vascular endothelial growth Atezolizumab is a humanised engineered immunoregarding neoadjuvant treatment for RCC. They except for axitinib. Axitinib was the only TKI that factor globulin G1 monoclonal antibody that selectively include either single agents or combination in Aberrant angiogenesis and antitumour immune targets PD-L1 to block its interaction with PD-1 and the provided a 3 cm diameter decrease in size in M0 localised or locally advanced disease. locally advanced RCC. suppression are hallmarks of many cancers. Clear-cell co-stimulatory molecule B7.1 to reinvigorate tumourrenal cell carcinoma (RCC) is associated with a specific T-cell immunity. PD-L1/PD-1 inhibitors, Recent research on intratumoural immune Sunday 17 March hyperangiogenic state due to overproduction of including atezolizumab, have shown durable 08.00-10.15: Plenary Session 4 components after pretreatment of human renal cell vascular endothelial growth factor (VEGF) as a result responses in patients with previously treated mRCC. Renal Cell Carcinoma (RCC) carcinoma suggests a potential synergism for TKI with anti-PD-L1 therapy that could be exploited. Since Table 1: Summary of rationale for administration of neoadjuvant treatment for localised RCC PROS CONS • Decrease in size and stage. It results in decreased • Delay on curative treatment (surgery) progression surgical morbidity, it facilitates postoperative (in case of no response) recovery, allows partial nephrectomy (PN) • Toxicity due to treatment: it might increase • Early treatment of metastatic disease surgical morbidity • Test sensitivity to treatment • To study biomarkers

Table 2: Ongoing neoadjuvant localised/locally advanced RCC clinical trials Single agents NIVOLUMAB Phase 1 PI-Hopkins N = 30

PEMBROLIZUMAB Phase 1 PI-unknown N = 36

Combination agents DURVALUMAB+TREMELIMUMAB Phase 1 PI-Cleveland Clinic N = 45

SITRAVATINIB+NIVOLUMAB Phase 1 PI-MD Anderson N = 25 AXITINIB+AVELUMAB Phase 2 PI-Netherlands Cancer Institute N = 40 Other therapies VACCINE Phase 1 Rosswell Park N=4 Stereotactic Ablative Radiation Therapy Phase II UT Southwest N = 30 Sunday, 17 March 2019

M0 RCC Stage II-IV (cT2a-cT4NanyM0 or TanyN1M0) Dose: 3 mg/kg day 1 of each 2-week cycle x3 pre-nephrectomy Primary Endpoint: # adverse events (from first dose until 100 days post-surgery) Secondary endpoint: objective tumour response, objective tumour response timeframe, QoL, MFS, OS cT1bNxM0 Pembro 200 mg IV 3 week cycles x3 +SOC+ adjuvant pembro up to 1 y (17 cycles) Primary endpoint: # adverse events (up to 22 weeks), % of patients treated w/ 2-fold change from baseline in intratumoural lymphocytic infiltration cT2b-cT4 and/or N1M0, any histological subtype Neoadjuvant + adjuvant Primary Endpoint: DTL Secondary endpoint: EBL, LOS, OR time, ICU, blood transfusions, postoperative complications, % tumour-infiltrating CD8+ T-cells after treatment Locally advanced RCC Primary endpoint: % of patients achieving a point in time objective response (CR or PR) prior to surgery Secondary endpoint: # adverse events (12 weeks) Localised RCC N0M0 with intermediate/high-risk RCC and completely resectable primary tumours Primary endpoint: # patients w/ PR Secondary endpoint: # adverse events, RFS, OS (up to 10 y)

3 - 6 September 2019

Leading Continence Research and Education Call for Abstracts: 1 March - 1 April 2019 International Continence Society 49th Annual Meeting

www.ics.org/2019

Vaccine made from patient’s tumour cells and white blood cells cT2 or less N0M0 RCC To receive 3 intradermic injections of RCC cluster Primary endpoint: change in immune marker expression levels Secondary endpoint: # adverse events RCC IVC Thrombus (level II or more) Objective: to decrease local recurrence and likelihood of embolic complications Primary endpoint: safety (# grade 4 and 5 within 90d postop; RFS

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Don’t miss EAUN19’s poster and video presentations This year’s scientific and practical nursing posters and videos show exceptional quality Jason Alcorn, BSc MSc DNurs Hudd, Dip Uro Care LMU, FHEA EAUN Board Member Wakefield (GB)

j.alcorn@eaun.org Hello, I hope you are enjoying this year’s conference, here in Barcelona. Especially, have you had a look at the posters on display. If not, then you should go and have a browse. You never know, you may get inspired and come away with some ideas to improve practice. When talking about research, we very often focus on the big projects or that undertaken by our medical colleagues. Nursing research doesn’t get much time in the spotlight, this needs to change. If you have a poster in this year’s conference, have an idea for a project, or have undertaken a recent project, then let’s get it out there.

“The videos came up with a new word: explanimation (what a nice word!)” The posters this year are of exceptional quality and I would like to thank all the contributors for their hard work and allowing us to review their research. There are 24 posters on display for you to browse around this year. In this short article I am not going to take you through each poster in detail but, give you an overview. I am categorising these posters into three groups: cancer; benign urology; and expert guided posters. Its’s good to see a wide variety of research from all around the globe. We are proud to have work from here in Europe,

notably Spain, our hosts, as well as contributions from Pakistan, Israel and China.

within one week is enough when undertaking clean intermittent catheterisation.

In the benign poster offering, there are the themes of “In the expert guided poster education and practice related work. It is good to see men’s health being given some prominence in section, we find that there is a real Pakistan. The educative posters looked at the use of diversity of work, something for simulation workshops and videos aimed at both healthcare professionals and patients. The videos everyone here.” came up with a new word: explanimation (what a nice word!). Whereas, the remaining posters investigated the roles of the ‘Advanced Practice Nurse’ The cancer related posters seemed to be split into two camps. One of service development and the other of in Switzerland and the training of ‘Infirmary quality of health. The service development posters professionals’ in Spain. looked at various aspects. These were focussed on improvements, as you would expect. Two posters The practice posters had a range of contributions, featured the diagnostic pathway, whilst the remaining from catheters to measuring the degree of two looked at implementing a urology cancer complications in surgery to ostomy self-care. advanced nursing role and evaluating patient’s views Interestingly, one study looked at difficult reon a pre-treatment seminar school, specifically for catheterisation and whether using a guidewire following a catheter removal makes a difference, does radiotherapy. it, you’ll have to look at the poster to find out! Whereas, another study looking at catheters, The quality of health posters span the wide aspect of evaluates whether follow up with a telephone call health quality. This was from trying to identify the most effective tools to help men with self-examination for testicular cancer in Italy, to validating a needs assessment tool for muscle invasive bladder cancer patients in Denmark. However not to be outdone, prostate cancer was the focus of the remaining two posters. A longitudinal study looked at the quality of life of patients and their spouses and the final poster at optimising psychosocial support for At Herlev hospital in Copenhagen animated narratives for radical prostatectomy patients have prostate cancer patients been developed to help patients understand the treatment and help nurses to spend more time undergoing active on individual care surveillance.

16-18 March 2019, Barcelona In the expert guided poster section, we find that there is a real diversity of work, something for everyone here. What would our research be without the mention of our old enemy the ‘smoker’. Colleagues from Israel have looked at helping patients to stop smoking and create a ‘continuum’ from hospital to community to support these patients. Also, from Israel the role of the nurse in treating patients with erectile dysfunction, which is very important for our patients. Then we have an evaluation of a service from China, which looked at patient satisfaction on nursing care following ESWL. The final three posters looked at a structure for assessing and managing patients with symptoms who wish to die at home, which is a very topical issue at present. A study has then looked at how long does a patient need to recover from side effects after receiving BCG treatment. And finally, an interesting pilot from the UK which evaluated the ‘Living with and Beyond Cancer’ care package in New Zealand prostate cancer patients. There we have a brief run-down of the posters on display for your perusal. Lots of hard work, time and dedication have gone into these studies. The benefits of undertaking these make it well worth the effort. If you have an idea, come and discuss it with Corinne Tillier or Franziska Geese (ask for them at the EAUN Booth) and next year we could be looking at your poster. Saturday, 17 March, 14.15-16.00 Sunday, 18 March, 11.45-13.30 Sunday, 18 March 15.00-15.30 Poster and Video Sessions at the 20th International EAUN Meeting

URO 88 1.0 01/2019/A-E

me and o c e s a le P 26 t Booth D a s u it is v

The New Flexible Video-Cystoscope HD-VIEW The highest demands by definition BRILLIANT Camera chip in High-Definition yy EASY Atraumatic tip for gentle insertion yy FAST Suction valve for rapid bladder draining yy

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Sunday, 17 March 2019


“Building a sense of belonging” Interview with the incoming chairmen of the EAU Membership Office The EAU’s Membership Office can look forward to a new approach and renewed energy from its leadership, promising EAU members more acknowledgement for their contribution to the Association and a larger sense of belonging.

Prof. Pushkar (DP): I feel that, with 18,000 EAU members the Membership Office is becoming a crucial office within the Association. More so when Europe has no borders anymore, embracing its neighbouring countries.

Profs. Bernard Malavaud (Toulouse, FR) and Dmitry Pushkar (Moscow, RU) will, from EAU19 on, form a dual chairmanship of the EAU’s Membership Office. Prof. Malavaud will formally be its Chairman, with Prof. Pushkar serving as Vice-Chairman. We spoke to the two chairmen on the occasion of their appointment.

How will you be dividing the tasks and responsibilities between the Chair and Vice-Chair?

In your opinion, what is the role of the Membership Office within the EAU?

The two of us will convene in Barcelona to devise how the Membership Office work can best take advantage of our complementary inputs. Indeed, the objectives of reinforcing and structuring the benefits of EAU membership are in no way menial and will require multiple exchanges of ideas, interactions with the EAU’s Central Office and other external parties. No doubt, it will be an asset to have two senior officers of distinct perspectives and backgrounds, possibly Prof. Bernard Malavaud reinforced by a select few younger urologists.

Prof. Dmitry Pushkar

However, responsibilities cannot be divided and as Chair it will ultimately fall to me to embody and defend our collective vision to the Executive.

Is there anything you would like to say to the EAU’s members?

Prof. Malavaud (BM): Academic associations can succeed in their mission only through the strength and dedication of their members. Fostering the highest level of educational and scientific output, and dedication to its members are therefore two sides of the same coin for the EAU. In other words, the membership office is dedicated to maintaining and developing the human structure that will allow the other Offices to further promote the EAU mission statement: “to raise the level of urological care throughout Europe and beyond”. What are your ambitions for the Membership Office? BM: My ambition is to build among the EAU members the sense of belonging to a wide and powerful association that cares for them and acknowledges their unique individual contributions. To that end, we will use creative thinking to structure a programme that upholds the personal contributions of all EAU members from the junior resident to the highest-ranking officer, in the form of a gradation of benefits and individual recognition.

BM: ‘Dividing’ is a tricky word as it relates to division, which is a far cry from my previous relations with Prof. Dmitry Pushkar. It is a candid statement to say that I look forward to Dmitry’s support.

Your predecessor, Prof. Korneyev is one of the longest-serving EAU Board Members. How do you look back on his tenure?

However, as it is idiomatically said: “no tree grows to the sky”. I posit that after the rapid expansion driven by my predecessor comes a time when it is necessary to expand and personalise the benefits that all active members of the EAU may expect from their contributions. This may be particularly necessary when the traditional forms of rewarding membership and fidelity to our association are being beaten back by unlimited web access to scientific journals and guidelines and reduced industry support for congresses.

BM: Taking over from Prof. Korneyev, who brought the roster of EAU members to unprecedented heights is a daunting task and I must acknowledge my deepest thanks for his past leadership and the efficient structure that is handed over to me.

This is even more challenging when all international organisations in urology and major academic institutions now take advantage of social media and modern means of communication to enlarge their audience and followers.

DP: In light of the importance of the Office, the EAU has deemed that I may support and help Bernard. I am honoured and will perform to the best of my abilities in this role.

DP: The EAU is the fastest growing urological society with enormous educational and scientific opportunities. The Membership Office will do its best to deliver those opportunities to every member of the association. BM: There is! Your membership is valued and it is the ambition of this Membership Office to acknowledge and provide tangible evidence of your individual contribution to the EAU’s motto of “raising the level of urological care throughout Europe and beyond”.

Platinum Picture Perfect Please come to the European Urology booth #L04 and have your Platinum Postcard created and posted online. Daily from 10.00 to 18.00

europeanurology.com eufocus.europeanurology.com

euoncology.europeanurology.com

Sunday, 17 March 2019

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Failure of focal therapy for prostate cancer - what now? Prof. Dr. med. Roman Ganzer, FEBU Asklepios Hospital Bad Tölz Bad Tölz (DE) r.ganzer@ asklepios.com

Focal therapy (FT) in prostate cancer is an experimental treatment option for selected prostate cancer patients that comprises all subtotal, organpreserving treatment approaches of the prostate with the aiming at reducing potential side effects of radical treatment options whilst maintaining oncologic efficacy1,2. Current case series and one prospective randomised trial have demonstrated satisfying safety profile, favourable morbidity profile and acceptable short- and mid-term oncologic outcome1,3. There is no consensus on how to follow patients after FT. Since prostate specific antigen (PSA) is not a validated marker for post FT monitoring, the combination of imaging (such as multiparametric magnetic resonance imaging) and prostate biopsy have been recommended to be performed between 6 to 12 months after FT in most published studies. In current literature, around one quarter of patients will present with a positive follow-up biopsy4. There is no consensus how to proceed with these patients. Failure definition: There is no accepted failure definition following FT. In-field failure defines any positive control biopsy within a treated are, whereas out-field failure describes a positive biopsy outside the treatment zone. Independently insignificant versus significant cancer has to be included to guide any further treatment decision. There are no accepted definitions on post FT biochemical failure such as ASTRO or Stuttgart definition5.

Failure management: There are several potential options on how to proceed in case of clinically significant recurrence after FT but no guideline recommendations. More importantly, there are important questions to be answered in the failure situation after FT: • what kind of salvage treatment should be offered? • is 2nd line FT treatment an option? • what are the complication rates of any salvage treatment option? • does initial FT compromise erectile function, continence and safety in case of salvage treatment? – If so, to what extent? • what is the safety profile and functional outcome of salvage treatment after FT in comparison to initial radical treatment? Salvage treatment options: Possible options in case of recurrence are active surveillance, focal re-treatment with the same technology, whole gland ablation with different technologies, salvage radiotherapy (sRT) as well as salvage radical prostatectomy (sRP). There is only scarce evidence in the literature to all of these options. In a recent review by Marra et al. only 4 studies included outcome of salvage treatment following FT after screening 390 manuscripts (67 patients, study quality was low, all retrospective)6. Salvage treatment was initiated 3-48 months after FT. Salvage cryotherapy was investigated in 1 study, sRP in 3 studies. The biochemical recurrence rate was 32.8%, the positive surgical margin rate after sRP 20%. Continence was preserved in 56.7% of patients, potency was poorly reported with only 4.4% and 5.9% of patients having erections spontaneously or with medical assistance, respectively. Eight Clavien 3 complications occurred in 12 patients after sRP. Re-do treatment: One salvage option is using the same technology that was used of initial FT treatment. Interestingly, re-do HIFU is considered as part of the FT concept and not as salvage treatment in some series: a total of 122/599 (20.2%) patients in a recently published multicenter FT HIFU study were re-treated with HIFU7. Although there are only few data in the literature, re-treatment

seems to be associated with increased urinary leak and worsening of erectile function8,9. Salvage Radiotherapy (sRT): 3. sRT has been described as a salvage option after whole gland ablation failure but not in FT series. After whole gland ablation sRT showed to be an effective option which seems to be associated with worsening 4. of erectile function compared to pre-treatment status10. Salvage radical prostatectomy (sRP): In a retrospective matched pair analysis Nunes-Silva et 5. al. compared oncological and functional outcome of 22 patients undergoing salvage robotic radical prostatectomy (sRALP) following FT with 44 patients following primary RALP for prostate cancer11. There 6. were comparable complication rates and continence rates at 1 und 2 years in both groups. However, patients in the sRALP group showed statistically significant inferior potency outcome as well as biochemical-free survival rates. The RAFT trial 7. (ClinicalTrials.gov NCT03011606) is currently ongoing in the UK and hopefully will provide prospective evidence of sRALP after FT using different energy sources. 8.

Conclusion: There is only limited evidence to answer the question to what degree prior FT impacts safety, oncologic and functional outcome of salvage treatment options in case of recurrence. There are no comparative data to prove superiority of any salvage option (re-do focal ablation, whole gland ablation, radiation and radical prostatectomy). Date from few retrospective series indicate that sRP is feasible and safe. However, patients undergoing FT have to be informed that future sRP might be associated with inferior erectile function and biochemical-free survival compared to RP in the primary setting. Future ongoing trials such as the RAFT trial are important to provide solid evidence for these open questions.

9.

10.

11.

Multicenter Phase II Study on Focal Therapy (Hemiablation) of the Prostate with High Intensity Focused Ultrasound. J Urol, 199: 983, 2018 Azzouzi, A. R., Emberton, M., investigators, P. C. M. s.: Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer - Authors’ reply. Lancet Oncol, 18: e188, 2017 van der Poel, H. G., van den Bergh, R. C. N., Briers, E. et al.: Focal Therapy in Primary Localised Prostate Cancer: The European Association of Urology Position in 2018. Eur Urol, 74: 84, 2018 Blana, A., Brown, S. C., Chaussy, C. et al.: Highintensity focused ultrasound for prostate cancer: comparative definitions of biochemical failure. BJU Int, 104: 1058, 2009 Marra, G., Gontero, P., Walz, J. C. et al.: Complications, oncological and functional outcomes of salvage treatment options following focal therapy for localized prostate cancer: a systematic review and a comprehensive narrative review. World J Urol, 2019 Guillaumier, S., Peters, M., Arya, M. et al.: A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer. Eur Urol, 74: 422, 2018 Berge, V., Dickinson, L., McCartan, N. et al.: Morbidity associated with primary high intensity focused ultrasound and redo high intensity focused ultrasound for localized prostate cancer. J Urol, 191: 1764, 2014 Blana, A., Rogenhofer, S., Ganzer, R. et al.: Morbidity associated with repeated transrectal high-intensity focused ultrasound treatment of localized prostate cancer. World J Urol, 24: 585, 2006 Holtzman, A. L., Hoppe, B. S., Letter, H. P. et al.: Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound. Int J Radiat Oncol Biol Phys, 95: 465, 2016 Nunes-Silva, I., Barret, E., Srougi, V. et al.: Effect of Prior Focal Therapy on Perioperative, Oncologic and Functional Outcomes of Salvage Robotic Assisted Radical Prostatectomy. J Urol, 198: 1069, 2017

References 1. Valerio, M., Ahmed, H. U., Emberton, M. et al.: The role of focal therapy in the management of localised prostate cancer: a systematic review. Eur Urol, 66: 732, 2014 2. Ganzer, R., Hadaschik, B., Pahernik, S. et al.: Prospective

Sunday 17 March 10.30-12.00: Thematic Session 02 Focal therapy

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STEPS Sessions To Evaluate luate ProgresS Progres in the management of o urological cancers

Interactive, Insightful and Independent Education Learning from Experts in Onco-Urology Applications now open! Visit Ipsen booth E38 during EAU19 to learn more

What is STEPS? STEPS, or “Sessions To Evaluate ProgresS in the management of urological cancers”, is a programme specifically designed for recently specialised onco-urologists who want to learn directly from worldleading experts in bladder, prostate, renal and testis cancers. The CME-accredited programme is a fundamental part of the EAU/ESOU strategic partnership with Ipsen. It is founded on our shared commitment to the education of young urologists. Bringing together a multinational group of medical professionals across several areas of expertise, and with different experiences, allows the fellows to see a variety of new treatment possibilities. It can highlight the pitfalls and solutions provided by diverse approaches. It also opens the door to creating international ties among medical practitioners, and a networking opportunity that can prove invaluable to the careers of young clinicians. “STEPS connects younger urologists from different countries – it’s very interactive with lots of new information and data discussed” STEPS fellow 2018

To date, 20 different internationally recognised experts, supported by the ESOU Board, have inspired 158 fellows from 30 countries – and our objective is to continue supporting STEPS to help improve the management of all patients with urological cancers. Who should apply? Recently specialised clinicians with a firm interest in the management of urological cancers, who: - Can demonstrate support from their Head of Department

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21


Are novel targeted therapies on the horizon? Session on targeted therapy in penile cancer management Philippe E. Spiess Dept. of GU Oncology Moffitt Cancer Centre Tampa, Florida (US)

survival for the study cohort remained disappointing. The safety profile for dacomitinib remained quite favourable, with only 10.7% of patients exhibiting grade 3 toxicity and no patient requiring discontinuation of therapy as a result of intolerable side effects. A novel element in this study was the correlation of specific gene mutations among treatment responders. In another study by Necchi et al., panitumumab (an anti-EGFR monoclonal antibody) was evaluated for advanced penile squamous cell carcinoma when surgery and chemotherapy had failed5.

Disclosures: The presenter serves as the vice-chair of the NCCN© panel on bladder and penile cancer

Although based on a study cohort of only 11 patients, panitumumab was reported to elicit 2 complete We aim to define the considerations of targeted responses within a patient population at high therapy in the management of penile cancer. It is likelihood of rapid cancer progression. Recent critical to be aware of recent publications which research efforts in penile cancer have been geared to would indicate a rise in the incidence of penile cancer elucidating actionable targets, with a recent review in certain parts of the world. Recently, attention was highlighting that this work remains in its infancy with drawn to a lack of significant improvement in survival most noted genetic mutations carrying causative or rates over the past two decades as evaluated in prognostic value6. registry data in Europe and North America. This has led some to believe that current systemic therapies “Advances in our understanding of employed in the management of advanced penile cancer have mostly been ineffective in altering the the molecular pathways and driving natural history of this disease.

Figure 2: Recent significant genomic studies in penile cancer

As is often seen with responders to checkpoint immunotherapy, several of the patients had durable responses for up to 5 years. In addition, there are some exciting immune mediated therapies being explored, including the isolation and potential re-injection of tumour infiltrating lymphocytes alone or in combination as well as intralesional tumour vaccination in combination with immune boosting through HPV-related systemic vaccination.

mutations implicated in penile A recent publication by Joshi et al. evaluated the squamous cell carcinoma will with predictors of survival within the United States all likelihood result in additional National Cancer Database Registry and found that Novel targeted therapies onthethe horizon? strongest determinants of survival among a cohort of personalised therapeutic options on patients targeted therapy in penile cancer management Session 1,123 penile cancer was undergoing an being integrated in our treatment inguinal lymph node dissection (ILND), age at diagnosis and clinical staging nodal status . armamentarium.”

In conclusion, at present there is some scepticism on the efficacy of current systemic therapies for advanced penile cancer whereby there is a significant need and effort to enhance the targeted therapies utilised in these patients. An area of particular enthusiasm pertains to the adoption of immunotherapies either alone or combination. Advances in our understanding of the molecular pathways and driving mutations implicated in penile squamous cell carcinoma will with all likelihood result in additional personalised therapeutic options being integrated in our treatment armamentarium. References: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

1

Philippe E. Spiess Most notably, neither receiving perioperative Dept. of GU Oncology chemotherapy nor radiotherapy were identified as Moffitt Centre predictorsCancer of survival. In a subsequent paper by Chipollini et al., the lack(US) of improvement in overall Tampa, Florida

Joshi, JAMA Oncology Chipollini, European Urology Chipollini, J Urol Necchi, BJU Int Necchi, Clin GU Cancer Chipollini, IJMS 2017 Jacob, J Urol Azzizi, Clin GU Cancer Udager, Annals of Oncology Massarelli E, JAMA Oncology

There are ongoing prospective studies which may bear fruit in identifying novel systemic therapies and actionable mutations. A study by Jacob et al. on survival was seen with the administration of Sunday 17 March genomic profiling of refractory metastatic penile and neoadjuvant or adjuvant systemic therapy when 10.30-12.00: Thematic Session 04 non-penile cutaneous squamous cell carcinoma controlling for other variables in a multivariate Cox Penile cancer highlighted the truly divergent molecular © regression model2. characteristics of these tumours and hence cautioned that effective systemic therapies must be developed to This same group determined that delaying the time to their unique tumour phenotypes and likely driving undergoing an ILND from time of diagnosis using mutations7. It is similarly essential to consider that We aim to define theforconsiderations of penile targeted the management of penile cancer. It is established clinical indications surgery (i.e. high most tumourstherapy are believedin to be related to the risk pathological characteristics of the primary tumour human papillomavirus (HPV, 50-70%), with a study by critical to be aware of recent publications which would indicate a rise in the incidence of penile or biopsy proven inguinal lymph node metastasis) for Azizi et al. demonstrating the favourable prognostic of UROGENITAL CANCER TREATMENT 3 monthsin or longer resulted in adverse patientworld. mTOR signalling upregulation positive to a lack of significant cancer certain parts of the Recently, attentionamong wasHPVdrawn AT A GLANCE outcomes providing an impetus for referring or penile tumours as assessed in a tissue microarray and improvement in survival rates over the past two decades as evaluated in registry data in Europe PA S T, P R E S E N T A N D F U T U R E treating physicians to proceed with surgical review of the literature8. 3 management this timeline . and North within America. This has led some to believe that current systemic therapies employed in the Prognostic value of immune factors management of advanced penile cancer have mostly been ineffective in altering the natural One exciting and rapidly evolving area of research “Recent research efforts in penile in penile cancer portends to the prognostic value history of this disease. of immune factors in the tumour cancer have been geared to microenvironment of penile squamous cell 34TH ANNUAL EAU CONGRESS, BARCELONA actionableby targets, carcinoma. The frequent expression of of survival within the United States Aelucidating recent publication Joshi with et al. evaluated the predictors AN IPSEN SPONSORED SATELLITE SYMPOSIUM programmed death ligand 1 (PD-L1) in both a recent Cancer review highlighting that National Database Registry and found that the strongest determinants of survival among primary and metastatic penile squamous cell CHA IR E D BY P R OFE S S OR LU I S M A R T Í NE Z -P I ÑE I R O (S PA I N) this work remains in its infancy carcinoma offers potential opportunities for a cohort of 1,123 penile cancer patients was undergoing an inguinal lymph node dissection S AT U R D AY 1 6 M A R C H immunotherapeutic approaches9. In a1 recent with most noted genetic mutations (ILND), age at diagnosis and clinicalphase staging nodal status. Most notably, neither receiving 2 clinical trial, a combination of immune carrying causative or prognostic Dr María Ribal (Spain) checkpoint blockade usingidentified nivolumab and as a predictors of survival. perioperative chemotherapy nor radiotherapy were In a tumour-specific vaccine for patients with incurable value.” Challenging paradigms in advanced prostate cancer: A new era subsequent paper by Chipollini et al., lackcancer of improvement in overall survival was seen with HPVthe 16 related was explored10. Although The treatment landscape for prostate cancer is constantly evolving to improve patient outcomes. Dr Ribal provided overview of how treatments for prostate cancer have changed over time, with a specific focus most of these tumours were oropharyngeal the administration of neoadjuvant or adjuvant systemic therapy when controllingon androgen foranother deprivation therapies (ADTs). The latest key clinical trials and data supporting the use of ADT Emerging novel targeting therapies tumours, the results, although preliminary, were 2 in prostate cancer were summarised, including evidence that explores the use of ADT as a backbone therapy variables a multivariate Cox model. This same group determined forthat delaying the The group of in Necchi et al. reported an open labelregression quite impressive with overall response rates of combination treatments. 33% including complete responses in 8%. phaseto 2 trial using first-line therapy with orally time undergoing an ILND from time of diagnosis usingseen established clinical indications for Professor Marc Oliver Grimm (Germany) administered dacomitinib (a pan HER tyrosine kinase What made these results all the more exciting is surgery (i.e. high risk pathological characteristics of thehasprimary The proven changing landscape in advanced Renal Cell Cancer that this combination approach been trialledtumour or biopsy inhibitor) for locally advanced or metastatic penile 4 management squamous cell carcinoma . The authors reported in a high-risk study population with patients often inguinal lymph node metastasis) for 3 months or longer resulted in adverse patient outcomes Treatment with both tyrosine kinase receptors (TKIs) and immunotherapies have been shown to improve some significant tumour regression in a subset of failing prior platinum-based chemotherapy or providing an impetus for referring ormultiple treating management patient outcomes, and should be adapted into the treatment landscape for advanced renal cell carcinoma lines ofphysicians systemic therapy. to proceed with surgical patients. Unfortunately overall and progression-free (aRCC). Prof Grimm discussed the development of these two therapies and the latest clinical evidence 3

Disclosures: The presenter serves as the vice-chair of the NCCN panel on bladder and penile cancer

within this timeline.

exploring combination treatment of TKIs and immunotherapies, and how this could potentially improve patient outcomes. Understanding the evolution of the treatment landscape for aRCC is important in order to better understand how the approach to treatment sequencing and selection, based on individual patient characteristics, can impact patient outcomes. Professor Yair Lotan (USA)

Blue light flexible cystoscopy: Improving the patient experience Non-muscular-invasive bladder cancer management has a significant impact on urology services due to its high risk of recurrence. Clinical guidelines support the use of photodynamic diagnosis to improve detection, particularly in high risk tumours. Prof Lotan presented recent evidence with blue-light flexible cystoscopy (BLFC) outpatient surveillance that demonstrated superior outcomes versus white light where, most notably, every third patient with carcinoma in situ was only detected with BLFC. Study participant anxiety levels were also lower. Prof Lotan also described clinical scenarios where BLFC could be employed and identified service design considerations.

CBZ-ALL-001441 FEBRUARY 2019

Figure 1: Recurrence-free (A) and disease specific (B) survival after groin dissection in entire cohort

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Sunday, 17 March 2019


Complicated stones in children and safe solutions Technical advances allow for careful approach in paediatric population M. Selcuk Silay Chairman Dept. of Paediatric Urology Istanbul Gelisim University & Istanbul Memorial Hospital Istanbul (TU)

The incidence of paediatric stone disease is increasing not only in the east but also in the western world1. Some of the children suffering from stone disease present with a complicated form, due to size, location, anatomical factors or related to the type of the stone (cystine, xanthine, etc.). Due to the recurrent nature of paediatric stones, achieving a stone-free state after surgery is of utmost important and therefore, complicated stones in children should be approached carefully by dedicated stone experts. One of the most important improvements in the last decade has been the technical advances of the instruments which are suitable for use in paediatric population. Various types and sizes of novel instruments including different nephroscopes (mini,

Figure 1: Different sizes of nephroscopes used for percutaneous nephrolithotomy in children

ultramini, micro, etc.) (see Figure 1), different sizes and characteristics of ureteroscopes (flexible ureteroscopy (fURS), ultrathin ureteroscope (URS), etc.) and many other advancements in supplementary equipment (laser devices, stone retrieval baskets, etc.) changed the course of the outcomes in paediatric calculi2. It is obvious that open stone surgery has almost disappeared and the vast majority of paediatric stones can be managed with endoscopic treatment options. Personalised stone management In order to deal with complicated stones in children, the surgeon needs to select the best treatment option for the patient from all the technical equipment he has. Personalised management is the key to success of each procedure. Another strategy to deal with complicated stones is the combined approaches such as laparoscopy/ robot-combined flexible URS or laparoscopy/ robot-combined percutaneous nephrolithotomy. These approaches are useful especially in some very rare situations including spinal abnormalities, anatomical malformations, ectopic kidneys, retrorenal colon, or failed endoscopic treatments27. This way, the procedures can be completed in a single session without the necessity of an auxiliary procedure. Figure 2 demonstrates laparoscopic pyeloplasty combined antegrade flexible URS in a 7-month-old infant with ureteropelvic junction obstruction and symptomatic lower pole kidney stone. Complex renal stones such as staghorn stones, large renal stones and cystine stones represent a challenge in children. The operative time increases which may also increase the complications. A new strategy to decrease the operative time for complex stones is the use of high power laser devices for fragmentation. Bujons et al. demonstrated the effectivity of 70W laser (3.5J pulse, 20 pulse/s frequency) for stones with a mean size of 4.4 cm in 35 children35. The overall stone-free rate was 78% and it increased up to 85% after secondary procedures.

Figure 2: A: CT demonstrating left lower pole stone and left UPJ construction in a 7-month-old infant. B: Demonstration of using 2 different endoscopic systems at the same time; one for laparoscopy and one for antegrade flexible URS. C: Laparoscopic view of retrieval of the kidney stone by fURS via basket catheter. D: Closure of renal pelvis after laparoscopic Anderson-Hynes pyeloplasty combined with antegrade fURS.

Tips in handling complex stones If you want to handle complex stones in children here are some tips which might be useful: 1. Acquire experience in adult stone cases, and then move to paediatric cases. This is safer. 2. Always start paediatric cases with a mentor. This will make you more comfortable. 3. Get experienced in both access techniques (eye of the needle & triangulation) Even access to a 2 cm stone in the renal pelvis can be challenging in infants and smaller children due to high mobility and the small size of the kidney. 4. Have all the equipment (miniperc, microperc, flexible URS, ultrathin URS, access sheath, etc.) at your institution in order to increase your chance to realise a stone-free status in children. You never know which one you need after you start the procedure. 5. If you have high-power laser at your institution, you are lucky and you can use it in hard stones such as cystine stones. This will decrease

operating time. 6. It is not recommended for a low-volume centre to perform complex cases in children As a conclusion, modern-day endoscopic devices related to miniaturisation of the instruments and advancements in technology, significantly improved the outcomes of paediatric stone disease treatment in the last decade. Complex stones in children can now be treated by using combined approaches or with miniaturised instruments. However, surgical experience and individualised treatments are key to success in the treatment of challenging cases in children. Future technical improvements are also awaited and will soon improve the efficiency of the current endourological procedures. Sunday 17 March 10.30-12.00: Paediatric urology update 2019 Thematic Session 10

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EAU19 Report - Highlights from Day 2  

The latest urology news and backgrounds directly from the EAU19 venue in Barcelona.

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