Renal & Urology News - Sept/Oct 2018 Issue by Haymarket Media

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VO L UME 17, IS SUE NUMBE R 5

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Study: Apalutamide Preserves HRQoL BY JODY A. CHARNOW APALUTAMIDE treatment preserves health-related quality of life (HRQoL) while lowering the risk of metastasis among men with asymptomatic highrisk non-metastatic castration-resistant prostate cancer (nmCRPC), according to a new study. It also delays the decrease in HRQoL associated with symptomatic progression. “It is critical to delay the onset of metastasis in patients with nmCRPC,” lead investigator Fred Saad, MD, FRCS, Professor and Chairman of Urology at the University of Montreal Hospital Center,

IN THIS ISSUE 18

Acetaminophen-ibuprofen combo shows promise for nocturia

Pre-diabetes found to increase overactive bladder risk in women

Prazosin may decrease PCa relapse risk after radiotherapy

Bladder bacteria associated with LUTS severity in men

End-stage renal disease possibly linked to kidney stones

Doctors need to ensure patients understand information given to them. PAGE 31

told Renal & Urology News. “These data from the pivotal SPARTAN study found apalutamide, in combination with current standard of care, can prolong median metastasis-free survival, while preserving HRQoL, which is a significant advance for patients with nmCRPC and for clinicians who treat them.” He and his colleagues analyzed data from the SPARTAN randomized, placebo-controlled phase 3 trial in which 1207 asymptomatic men with nmCRPC at high risk of metastases were randomly assigned to receive apalutamide (806 men) or placebo

Benefit extends to symptomatic progression

APALUTAMIDE MAINTAINS physical and other aspects of wellbeing, data show.

(401 men) in addition to androgen deprivation therapy. The trial demonstrated that apalutamide recipients had significantly improved metastasis-free survival compared with men in the placebo arm. The median follow-up for overall survival was 20.3 months. Based

on the SPARTAN trial, the FDA on February 14 approved apalutamide for the treatment of patients with nmCRPC. Dr Saad’s team evaluated HRQoL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) continued on page 25

Nocturia Increases Fall Risk Annual PSA Screening Cuts PHILADELPHIA—Nocturia is asso- Among patients with fall tendency with an increased risk of falls, and documented falls (falls leading to a PCa Mortality ciated researchers from Germany and Belgium medical diagnosis), the average of numBY JODY A. CHARNOW ANNUAL PSA screening is highly effective at decreasing the risk of death due to prostate cancer (PCa) or any cause, new data suggest. In a retrospective cohort study of 400,887 men under age 80 years who had PSA testing at Kaiser Permanente Northern California, Paul F. Alpert, MD, of the University of California Medical Center in San Francisco, found that PSA screening every 12 to 18 months decreased PCa mortality and all-cause mortality risk by a significant 64% and 24%, respectively, among men aged 55 to 74 years, compared with continued on page 25

reported at the International Continence Society’s 2018 annual meeting. An analysis of data from 4.85 million people enrolled in the German statutory health insurance system in 2014-2015 found a 13% increased risk of falls among patients with nocturia compared with those who did not have nocturia, investigator Martin C. Michel, MD, of Universitätsmedizin Mainz, told conference attendees. The proportion of patients with falls was 50.3% and 44.4% among those with and without nocturia, respectively.

ber of drug prescriptions for patients with nocturia was 14 for those on micturition-related medications and 11.8 for those who were not. By comparison, patients without nocturia had an average of 9.8 prescriptions. Individuals with documented falls were not older than the general population and did not have more comorbidities, but on average received 1 additional drug, Dr Michel’s team reported. Of the 4.85 million individuals in the study population, 157,076 (3.24%) had continued on page 25

NOCTURIA: ‘A LEGITIMATE STAND-ALONE PROBLEM’

Alan J. Wein, MD, offers insight into a common ailment. PAGE 28

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Dramatic Rise in AKI Incidence Rates Reported INCIDENCE RATES of acute kidney injury (AKI) have risen dramatically in Ireland, with inpatients at highest risk of experiencing AKI, according to a new study. In a retrospective cohort study of new entrants into the country’s health system, the incidence rates of AKI from 2005 to

2014 increased significantly from 6.1% to 13.2% per 100 patient-years among men and 5.0% to 11.5% per 100 patient-years among women. Stage 1 AKI accounted for the greatest growth in incidence: from 4.4% in 2005 to 10.1% in 2014. Compared with 2005, patients who entered the health system in 2014 had

between 4.5-, 5.2-, and 4.1-fold greater odds of Stage 1, 2, and 3 AKI, respectively, after adjusting for changing demographic and clinical profiles, a team led by Austin G. Stack, MD, of University Hospital Limerick in Limerick, Ireland, reported online ahead of print in Nephrology Dialysis Transplantation.

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“Our study has shed new light not only on the overall pattern of AKI incidence over time but also on important trends according to the severity of AKI,” the authors wrote. “Of particular interest is the finding that the greatest absolute increases in AKI incidence were accounted for by increases in AKI Stage

www.renalandurologynews.com SEPTEMBER/OCTOBER 2018

1 from 4.4 to 10.1%, while the growth in Stage 2 (from 0.60 to 1.46%) and Stage 3 (from 0.46 to 0.81%) were less impressive.” The finding suggests that greater attention should be given to these “minor” AKI events and their determinants, according to the investigators. Incidence rates increased in all clinical settings (the location of patients when renal testing was performed) during the observation period, but

was greatest among inpatients than those in emergency department, outpatient clinic, and general practice (GP) settings. Compared with GP patients (reference), inpatients, emergency department patients, and outpatients had significant 19-, 6-, and 4.4fold increased odds of a first AKI, in adjusted analyses, respectively. “Our analysis would suggest that targeting of locations where AKI is

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most likely to occur would be a primary goal,” the investigators noted. “Through early detection strategies including electronic alert systems and adoption of early treatment interventions, it is likely than many AKI events could be prevented and more effectively managed.” For the study, Dr Stack’s team obtained data from Ireland’s National Kidney Disease Surveillance System,

Renal & Urology News 3

which is used to monitor trends and outcomes of chronic kidney disease in the Irish health system. The final study cohort included 451,646 patients, of whom 40,786 (9%) experienced a first AKI. The AKI group was significantly older than the no-AKI group (mean 67.5 vs 44.8 years). The investigators defined AKI using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. ■

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Surgical Overtreatment of PCa Reportedly in Decline INVESTIGATORS at the University of California, Los Angeles, report that surgical overtreatment of prostate cancer (PCa) at their institution is in decline. Decreased rates of overdiagnosis, better patient selection for surgery, or change in referral pattern may be among the reasons for the trend,

according to Amirali Salmasi, MD, MS, and colleagues at UCLA’s David Geffin School of Medicine. In a review of 1283 men who underwent radical prostatectomy (RP), Dr Salmasi’s team found that the frequency of overtreatment—defined as the presence of insignificant PCa in RP

specimens—decreased significantly from 15% in 2009 to 3% in 2016, according to a paper published online ahead of print in Urologic Oncology. The investigators defined insignificant PCa as a tumor with a Gleason score no higher than 6, a tumor diameter of 10 mm or less as a surrogate for

tumor volume less than 0.5 cc. The odds of overtreatment decreased by a significant 12% annually during the study period. On multivariable analysis, patients with a PSA density of 0.15 or greater had significant 70% decreased odds of insignificant PCa than those with a PSA density below 0.15. A biopsy Gleason score of 3+4 was associated with significant 85% decreased odds of insignificant PCa compared with a score of 3+3. In addition, the study showed that black patients had significant 87% decreased odds of insignificant PCa compared with white men. The authors commented that “it is difficult to parse out the exact reasons for this finding, but it may be due to inherent biology, access to care or other unknown reasons.”

Big drop in RP use for insignificant disease from 2009 to 2016 observed. Results also showed that pathologic evidence of advanced disease (T3a or higher with or without lymph node involvement) at the time of surgery remained unchanged, according to the investigators. The incidence of advanced disease was 33% in 2009 and 37% in 2016. The authors concluded that surgical overtreatment of insignificant PCa “has declined in a long-term trend that appears to be maintained.” Dr Salmasi’s team said the decline probably has a multifactorial explanation. The decrease in overtreatment may reflect lower rates of overdiagnosis of early-stage PCa. Another possibility is improved risk stratification and patient selection for surgery. The investigators pointed out that the proportion of patients with biopsy-proven Gleason score 3+3 cancer who underwent RP decreased from 52% in 2009 to 13% in 2016. The decreased rate of surgical overtreatment also could be due to improved risk stratification using multi-parametric magnetic resonance imaging and genomic testing. “It also is likely that changes in the referral pattern to our tertiary centers may have influenced our surgical cohort in that more advanced patients are likely to be referred to our center.” ■

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www.renalandurologynews.com

Contents

SEPTEMBER/OCTOBER 2018

SEPTEMBER/OCTOBER 2018 ■ VOLUME 17, ISSUE NUMBER 5

Urology 10

ONLINE

this month at renalandurologynews.com Clinical Quiz Test your knowledge by taking our latest quiz at renalandurologynews.com/ run-quiz

HIPAA Compliance Read timely articles on various issues related to keeping protected health information secure.

Drug Information Search a comprehensive drug database for prescribing and other information on more than 4000 drugs.

Novel Drug Combination Eases Nocturia An acetaminophen-ibuprofen formulation demonstrated short-term efficacy and safety in the treatment of nocturia symptoms. Use of Post-RP High-Dose Radiotherapy Increasing The trend is occurring despite an absence of supportive randomized studies. Data Support AUA Guidelines for SRMs A recent prospective study confirmed the effectiveness of nephron-sparing approaches such as partial nephrectomy.

Hearing Loss in the Elderly Associated With Gout Large study of Medicare patients showed that those with gout had a significant 44% increased risk of hearing impairment.

Bladder Bacteria, LUTS Severity Linked in Men Lower urinary tract symptom severity in men is associated with detectable bacteria in urine obtained via catheter.

Higher Caffeine Intake May Decrease Death Risk in CKD Compared with individuals in the bottom quartile of caffeine consumption, those in the top quartile had a 25% decreased risk of death, a study found.

News Coverage Visit our website for daily reports from Kidney Week 2018 in San Diego, October 23–28.

Advancements Bode Well for nmCRPC Management Novel imaging and tumor biomarker assays are likely to define non-metastatic castrationresistant prostate cancer more accurately, according to the authors of new review.

CALENDAR American Society of Nephrology Kidney Week 2018 San Diego October 23–28 Large Urology Group Practice Association (LUGPA) Annual Meeting Chicago November 2–3 2019 Canadian Uro-Oncology Summit Toronto January 10–12 Genitourinary Cancers Symposium San Francisco February 14–16 European Association of Urology 34th Congress Barcelona, Spain March 15–19 American Urological Association Annual Meeting Chicago May 3–6.

Nephrology

Job Board Be sure to check our latest listings for professional openings across the United States.

Renal & Urology News 5

Hyperuricemia Prevalence Increasing Men and women had 45% and 47% increased odds of hyperuricemia, respectively, in 2014 compared with 2006, Irish researchers reported.

At the end of the day, I enjoyed doing this study

more than any I have ever done due to the possibility that it may have an actual tangible impact on practice. See our story on page 26

Departments 6

From the Medical Director How the federal ESCO program might affect dialysis care is unclear.

News in Brief Gout patients have a lower colorectal cancer prevalence.

Ethical Issues in Medicine Informed consent discussions need to be meaningful.

Practice Management Are patient portals right for your medical organization?

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FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Is ESCO the Future of Dialysis Care?

ince January 2017, some 10% of the 550,000 dialysis patients in the United States have been managed by 37 ESRD Seamless Care Organizations (ESCOs) participating in the Comprehensive ESRD Care (CEC) Model. The CEC Model was designed by the Centers for Medicare and Medicaid Services (CMS) to identify, test, and evaluate new ways to improve care for Medicare beneficiaries with ESRD. The first round of the ESCO project is expected to end by 2020. Through ESCO, CMS partners with health care providers, including nephrologists, as well as dialysis organizations, to test the effectiveness of this new payment and service delivery model in providing beneficiaries with what is expected to be a patientcentered approach with a higher quality of patient care. The ESCO model builds on the Accountable Care Organization (ACO) experience. As CMS states on its website, the model encourages dialysis providers “to think beyond their traditional roles in care delivery and supports them as they provide patientcentered care that will address beneficiaries’ health needs, both in and outside of the dialysis clinic.” It is generally believed that improved outcomes, such as lower hospitalization rates, along with reduced cost, may determine the fate of ESCO beyond 2020. If CMS decides ESCO will be the prevailing dialysis management model of the future, it is possible that CMS and other dialysis stakeholders will partner with practicing dialysis companies, nephrologists and investigators to examine the utility of more innovative models of transition to dialysis that are more gradual, such as incremental dialysis whereby initial treatment may be once or twice treatments a week and dialysis frequency increases gradually over time. If an objective of ESCO is to provide better care for less money, incremental dialysis may become an important cornerstone of ESCOs and other ACO-based integrated CKD care models. Under ESCO, we may also see greater use of home dialysis but stagnant growth of conventional in-center hemodialysis (HD). It is important to note that 600 to 800 new dialysis centers open each year in this country. How ESCOs might impact net income of nephrologists is unclear. Under ESCO, dialysis companies may gain more leverage vis-à-vis nephrologists’ payments. What matters, however, is how innovations springing from the ESCO model can improve dialysis patient experience and adherence to treatment regimens, decrease mortality and hospitalization, and preserve residual kidney function longer. Kam Kalantar-Zadeh, MD, MPH, PhD Professor & Chief, Division of Nephrology & Hypertension University of California Irvine School of Medicine Orange, California

Medical Director, Urology

Medical Director, Nephrology

Robert G. Uzzo, MD, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman Department of Surgery Fox Chase Cancer Center Temple University School of Medicine Philadelphia

Kamyar Kalantar-Zadeh, MD, MPH, PhD Professor & Chief Division of Nephrology & Hypertension University of California, Irvine School of Medicine Orange, Calif.

Urologists

Nephrologists

Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City

Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, N.C.

R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto

David S. Goldfarb, MD Professor, Department of Medicine Clinical Chief New York University Langone Medical Center Chief of Nephrology, NY Harbor VA Medical Center

Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD, FACS Chief Executive Officer Inova Health System Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology CCLCM (ret.) Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California Irvine

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center, Memphis Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc.

James M. McKiernan, MD John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology Columbia University College of Physicians and Surgeons, New York City

Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto

Kenneth Pace, MD, MSc, FRCSC Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto

Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center Detroit

Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J.

Renal & Urology News Staff Editor

Jody A. Charnow

Web editor

Natasha Persaud

Production editor

Kim Daigneau

Group art director, Haymarket Medical

Jennifer Dvoretz

Production manager

Krassi Varbanov

Director of production Circulation manager National accounts manager Editorial director

Louise Morrin Boyle Paul Silver William Canning Kathleen Walsh Tulley

General manager, medical communications

Jim Burke, RPh

CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 17, Number 5. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2018.

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Advancements Bode Well for nmCRPC Management BY JOHN SCHIESZER EMERGENCE OF MORE sensitive imaging modalities and novel tumor biomarker assays combined with new therapies promise to improve management approaches for men with nonmetastatic castration-resistant prostate cancer (nmCRPC) who experience rising PSA levels, according to a new review published in European Urology. A key component of managing these patients is earlier detection of metastatic disease, which might be possible with the current progress being made in positron emission tomography (PET) and multiparametric and whole-body magnetic resonance imaging, as well as the development of sensitive assays for measuring circulating tumor cells. Identification of “molecularly detectable residual disease” from circulating tumor material or bone micrometastases in patients with nmCRPC “could help stratify nmCRPC patients based on the risk of

noted that this update preceded FDA approval of enzalutamide in this setting. In a discussion of the benefits and risks of treating nmCRPC rather than mCRPC, the authors observed that an “unmet need in clinical trials for nmCRPC is evaluating not only the clinical benefits of an intervention,

but also the additional benefit derived from pursuing such interventions at the nmCRPC stage rather than at a later time point.” For their review, the authors conducted a literature search up to July 2018. The review included clinical trials and clinical practice guidelines

Review highlights potential of novel imaging and tumor biomarker assays. relapse and for treatment intensification,” Joaquin Mateo, MD, PhD, from the Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and colleagues wrote. Although observation might be an option for selected patients, the review noted, the novel anti-androgen medications enzalutamide and apalutamide could be appropriate treatment for nmCRPC patients with a PSA doubling time of 10 months or less. In the landmark phase 3 randomized, controlled PROSPER and SPARTAN trials, treatment with enzalutamide and apalutamide demonstrated increased metastasis-free survival among nmCRPC patients with a PSADT of 10 months or less. The agents also have been shown to increase time to detectable metastases by bone scan and computed tomography (CT) scans. The FDA approved enzalutamide and apalutamide for nmCRPC on July 13 and February 14, respectively, based on the findings from the PROSPER and SPARTAN trials, respectively. Dr Mateo and his coauthors pointed out that a 2018 National Comprehensive Cancer Network (NCCN) guideline update includes the option of using apalutamide as systemic therapy for patients with a PSADT of 10 months or less. They

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from NCCN, European Association of Urology, Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence, European Society for Medical Oncology, and Prostate Cancer Clinical Trials Working Group. Tomasz M. Beer, MD, Deputy Director of the Knight Cancer Institute and

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Professor of Medicine at Oregon Health and Sciences University in Portland, Oregon, said the new review provides a solid summary of the current state of knowledge. Still, many unanswered questions remain. “I do think that there is enough evidence to evolve the standard of care, but I would note that it is not 1 standard of care for all patients,” he told Renal & Urology News. “The PROSPER and

SPARTAN trials demonstrated an improvement in metastases-free survival but have not demonstrated overall survival.” Overall survival may be similar if patients with nmCRPC are treated early or when they have the first signs of metastatic CPRC, Dr Beer said, adding that the PROSPER and SPARTAN trials only included men with a shorter PSADT.

In addition, adverse effects vary from patient to patient and treatment costs are an important consideration, he pointed out. “So I think that the review does a fine job, and it needs to be understood as discussing a new standard of care that can be deployed in nmCRPC, but need not be deployed in every patient. There is room for individualizing therapy decisions in this setting,” Dr Beer said.

Amar Kishan, MD, Assistant Professor in the Department of Radiation Oncology at the University of California, Los Angeles, agrees with Dr Beer. “The new PET-imaging technologies, including fluciclovine and especially prostatespecific membrane antigen-based imaging, will likely allow us to identify metastases in many of these men. What to do with that information is unclear,” Dr Kishan said. n

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Hearing Loss in the Elderly Associated With Gout GOUT IS ASSOCIATED with an increased risk of hearing loss in elderly individuals, new study findings suggest. In retrospective study of claims data from 1.71 million Medicare patients aged 65 years and older, the incidence rate of new hearing impairment cases was 16.9 per 1000 person-years among

patients with gout compared with 8.7 per 1000 person-years for among those without gout, Jasvinder A. Singh, MD, and John D. Cleveland, B:8” MD, of the University of Alabama in T:7.5” Birmingham, reported in BMJ Open (2018;8:e022854). S:7” After adjusting for demographics, medical comorbidities

and common cardiovascular and gout medications, gout was associated with a significant 44% increased risk of hearing impairment. “To our knowledge, this study is among the first to describe an association of gout with hearing loss in older adults,” Drs Singh and Cleveland wrote.

New hearing impairment developed in 89,409 of the 1.71 million patients. Patients who experienced hearing impairment during follow-up were older than those who did not (76.5 vs 75.2 years). Gout is a chronic inflammatory arthritis characterized by hyperuricemia and urate crystal formation that subsequently result in inflammation and oxidative stress, the authors observed. “These processes could be one of the potential explanations of the association.” With respect to study limitations, the authors noted that their study findings are only generalizable to individuals aged 65 years and older. The investigators did not have access to laboratory measures, including serum urate, or markers of inflammation or oxidative stress, limiting assessment of whether these mechanisms underlie the association between gout and hearing impairment. ■

Suicide Risk Up After PCa Diagnosis MEN ARE AT ELEVATED risk of suicide following a prostate cancer (PCa) diagnosis, according to the findings of a new meta-analysis T:10.375”

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published in Prostate Cancer and Prostatic Diseases. In a meta-analysis of 8 observational studies that included 1,281,393 men with PCa and 842,294 matched men who did not have PCa, a team led by Shusheng Wang, MD, of Guangdong Provincial Hospital of Chinese Medicine in Guangzhou, China, found an overall 2-fold increased risk of suicide among men diagnosed with PCa during the first year compared with PCafree men. The risk was particularly elevated during the first 6 months after diagnosis. Men aged 75 years or older at diagnosis had a 51% higher risk of risk of suicide than PCa-free men, whereas patients younger than 65 years at diagnosis had a non-significant 37% increased risk. The investigators found no significant increase in risk beyond 12 months after diagnosis. ■

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Renal & Urology News 13

News in Brief

Please visit us at www.renalandurologynews.com for the latest news updates from the fields of urology and nephrology

Short Takes Melatonin Fails to Ease Nocturia in MS Patients

accounted for 16% more than the

Low-dose melatonin may be an inef-

ish general population, Katri Saarela,

fective therapy for nocturia in adult

of the National Institute for Health and

patients with multiple sclerosis (MS),

Welfare in Helsinki, and colleagues

according to a new study.

reported online ahead of print in the

expected cancer incidence in the Finn-

European Journal of Epidemiology. The

Melatonin is known to regulate circadian rhythm and decrease

incidence of kidney and bladder cancer

smooth muscle activity such as in the

was, respectively, 42% and 17% higher

bladder, Marcus J. Drake, MD, of the

than expected for the general popula-

University of Bristol in Bristol, UK, and

tion. Dr Saarela’s team found a small

colleagues explained in BMC Neurol-

but significantly decreased incidence of

ogy (2018;18:107). In a double-blind,

prostate cancer.

placebo-controlled trial, Dr Drake’s in the signs or symptoms of nocturia

Low-Dose Aspirin Does Not Compromise RARP Outcomes

between patients who took 2 mg per

Continuation of low-dose aspirin does

night of sustained-release melatonin

not compromise surgical outcomes

or placebo at bedtime.

among men undergoing robot-assisted

team found no significant difference

radical prostatectomy (RARP),

Kidney Cancer Incidence Higher in Type 2 Diabetics

researchers reported online ahead of

Kidney and bladder cancer are

Gagan Gautam, MS, MCh, and col-

print in the Journal of Endourology.

among the malignancies that occur with

leagues at the Max Institute of Cancer

higher incidence among individuals with

Care in New Delhi, India, divided RARP

type 2 diabetes, new data suggest.

patients into a non-aspirin group and

Out of 428,326 patients with type

low-dose aspirin (75 mg per day)

2 diabetes identified using the Finnish

group. The investigators found no sig-

National Diabetes Register, investiga-

nificant difference between the groups

tors found 74,063 cases of cancer

in bleeding-related complications and

over 4.48 million person-years. This

overall 90-day complication rates.

Obese RP Patients Fare Worse Obese patients have higher rates of biochemical recurrence following radical prostatectomy for prostate cancer than overweight or normal-weight patients, according to a recent study. Shown here are the percentages of men who experienced biochemical recurrence by weight group. 35

30.9%

30 25 20

18.6%

17.8%

Overweight

Normal weight

15 10 5 0

Obese

Source: Yu YD, Byun SS, Lee SE, Hong SK. Impact of body mass index on oncological outcomes of prostate cancer patients after radical prostatectomy. Sci Rep. 2018;8:11962.

Physically Demanding Jobs Linked to Lower PCa Risk M

en who have physically demanding jobs may be at lower risk of prostate cancer (PCa) than those who do not, according to a recent report. A case-control study examining data from the Nordic Occupational Cancer Study found that men with low, medium, and high cumulative exposure to perceived physical workload (PPWL) had 10%, 12%, and 7% lower risk of PCa, respectively, than those with no PPWL exposure, Jorma Sormunen, MD, of the University of Tampere and Tampere University Hospital in Tampere, Finland, and colleagues reported in the Asian Pacific Journal of Cancer Prevention. Adjustment for socioeconomic status did not substantially change results. The authors concluded that their study corroborates earlier research showing that lack of physical activity and a sedentary lifestyle seem to be associated with an elevated risk of PCa compared with any level of physical activity. The study population consisted of 239,835 PCa cases and 1,199,175 controls from Finland and Sweden. The average age at PCa diagnosis was 72.2 years.

Colorectal Cancer Prevalence Lower Among Gout Patients G

out patients have a lower prevalence of colorectal cancer, a study of US veterans suggests. Among 581 gout patients and 598 osteoarthritis patients without gout who had documented colonoscopies, the 10-year prevalence of colorectal cancer was significantly lower among the gout patients (0.8% vs 3.7%), Anastasia Slobodnick, MD, from the Section of Rheumatology, VA New York Harbor Health Care System, and colleagues reported online ahead of print in the Journal of Clinical Rheumatology. Differences in colorectal cancer prevalence remained significant after stratifying for non-steroidal anti-inflammatory drug use. In a sub-analysis, the significantly lower prevalence of colorectal cancer among gout patients compared with osteoarthritis patients persisted among those who underwent diagnostic colonoscopy (0.5% vs 4.6%), but not screening colonoscopy (0.9% vs 1%).

RC Surgical Site Infection Risk Higher in Women S

urgical site infections among patients undergoing radical cystectomy (RC) are more likely among women than men, according to a new Canadian study published online ahead of print in Urologic Oncology. In a historical cohort study involving 9275 RC patients, a team led by Rodney H. Breau, MD, of the Ottawa Hospital Research Institute in Ottawa, Ontario, found that, on multivariable analysis, female sex was independently associated with significant 21% increased odds of SSI compared with male sex. The researchers identified patients using the American College of Surgeons’ National Surgical Quality Improvement Program database (2006 to 2016). SSI occurred in 1277 (13.7%) patients: 308 female patients (16.4%) and 969 male patients (13.1%). Women who experienced SSI had a significantly greater risk of other complications, including wound dehiscence, septic shock, and need for reoperation.

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■ ICS 2018, Philadelphia

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International Continence Society 2018 48th Annual Meeting

Novel Drug Combination Eases Nocturia A prolonged action acetaminophen-ibuprofen formulation shows promise in a phase 2 trial IN A PHASE 2 TRIAL, a novel prolonged action formulation of an acetaminophen-ibuprofen combination demonstrated short-term efficacy and safety in the treatment of nocturia symptoms, according to researchers. Both drugs inhibit prostaglandins, which have been shown to have a role in modulating detrusor muscle tone and micturition and thus represent a potential therapeutic target in the treatment of nocturia, investigators noted. The double-blind trial, which enrolled 86 patients with nocturia, compared low, medium, and high doses of the 2-drug therapy (Paxerol) with placebo for 2 weeks. The primary outcomes were average number of nocturnal voids (ANV) and nocturia quality of life (NQOL) scores. Patients in the 4 study arms were not significantly different with regard to demographic and baseline voiding characteristics. Investigator

Pre-Diabetes Ups OAB Risk in Women PRE-DIABETES IS associated with an increased risk of overactive bladder (OAB) in women, new data suggest. Even modestly elevated fasting plasma glucose (FPG) and HbA1c are independently associated with an increased likelihood of OAB in women. Among women, an FPG of 110 to 125 mg/dL was associated with

Mahyar Kashan, MD, of Downstate College of Medicine in Brooklyn, New York, presented study findings. Compared with placebo recipients, patients treated with any Paxerol dose experienced significant decreases in the

Decreased number of nightly voids and improved sleep quality reported. average number of nocturnal voids. All study arms had a decrease in NQOL scores (reflecting improvement), but significantly larger reductions occurred in those receiving a medium and high dose of the pharmacotherapy. Duration of first uninterrupted sleep increased (DFUS) in all 4 groups, with a

significantly larger increase in the highdose treatment arm versus placebo. “We found no significant difference in total hours of nightly sleep in the Paxerol groups compared with placebo, and overall there were no severe adverse events and none of the adverse events that we found were thought to be related to the study drug,” Dr Kashan told attendees. The significant decrease in ANV in all of the Paxerol arms, combined with the significant improvement in NQOL scores in the medium and high dose Paxerol arms compared with placebo, “suggests that the effects in the medium- and high-dose groups have a positive subjective impact in patients’ perception of their voiding symptoms,” Dr Kashan said. In addition, the high-dose Paxerol group demonstrated a significant increase in DFUS without an associated change in total hours of nightly sleep, “suggesting

that patients found an improvement in their quality [of sleep] without a change in their total duration [of sleep].” Adrian Wagg, MB, BS, Capital Health Research Professor in Healthy Ageing at the University of Alberta in Edmonton, a co-moderator of the nocturia session at which Dr Kashan presented the study findings, said he is concerned about the potential long-term renal effects of the new therapy, “particularly where it’s being used for nocturnal polyuria, which primarily affects older people who have diminished renal function to start with.” The mechanism of action of these drugs primarily relates to the kidney reducing nocturnal polyuria, he said. Certainly, with long-term ibuprofen use, there is always a concern about renal toxicity or renal impairment, he said. “It might all right for short-term use, [but] we need to be cautious about long-term use.” ■

OAB Risk Linked to Visceral Fat EXCESS ABDOMINAL visceral fat is a risk factor for overactive bladder (OAB), investigators concluded. In a study involving 190 patients, OAB was most strongly associated with the ratio of visceral fat volume (VFV) to total abdominal fat volume (TAV), Tomohiro Matsuo, MD, of Nagasaki University Hospital in Japan, and colleagues reported. Of the 190 patients (mean age of 60.4 years), 90 (47.4%) met OAB criteria. The investigators used computed tomography to calculate VFV, TAV,

visceral fat area (VFA), subcutaneous fat area (SFA), and subcutaneous fat volume (SFV). The OAB group had a significantly higher mean body weight than the non-OAB patients (57.6 vs 54.5 kg), but the mean body mass index (BMI) was not significantly different (22.9 and 22.2 kg/m2). The OAB group also was significantly older (mean 67.4 vs 54.2 years). The OAB group had significantly higher mean VFA than the non-OAB group (112.1 vs 73.8 cm2) as well as a

significantly greater mean VFA/SFA ratio (1.07 vs 0.53), VFV (3167 vs 1860.8 cm3), VFV/SFV ratio (1.55 vs. 0.52), and VFV/TAV ratio (49.7 vs 32.5). On multivariable analysis, a VFV/TAV ratio above 0.591 was an independent risk factor for OAB. It was associated with significant 4.7-fold odds of OAB compared with a ratio below 0.591. “Together, these results suggest that an accumulation of visceral fat, which triggers metabolic syndrome, increases the risk of OAB,” Dr Matsuo’s team concluded in their study abstract. ■

significant 46% increased odds of OAB compared with an FPG less than 100 mg/dL (reference), Yoshitaka Aoki, MD, PhD, and colleagues from the University of Fukui in Fukui, Japan, reported. An HbA1c of 5.5% to 5.9% was associated with significant 31% increased odds of OAB compared with an HbA1c less than 5.5% (reference). The investigators found no significant association between FPG or HbA1c and OAB in men. ■

Nocturnal Polyuria Common in Men with LUTS MORE THAN HALF of men with lower urinary tract symptoms (LUTS) have nocturnal polyuria (NP), and it is severe in about 10% of cases, investigators reported. The findings are from a prospective study of 162 men with LUTS who completed both the International Prostate Symptom Score (IPSS) questionnaire and frequency volume chart (FVC) for

3 days. Silvia Bassi, MD, of Azienda Ospedaliera Universitaria Integrata Verona in Italy, and colleagues found that 54.9% of patients had NP, defined as nocturnal polyuria index (NPi) greater than 33%, Severe NP, defined as an NPi greater than 50%, was present in 9.9%. NP prevalence varied by age group. It was 64.7%, 48.5%, and 56.4% among

men aged less than 65 years, 65 to 74 years, and 75 years or older, respectively, according to the investigators. Severe NP was present in 2.9%, 6.0%, and 17.7%, respectively. NP was significantly associated with higher median IPSS domain 7 (nocturia) and total IPSS scores, but did not influence IPSS domain 2 (frequency) and domain 8 (bother) scores, according to the investigators. ■

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Prazosin May Lower PCa Relapse Risk After RT PRAZOSIN, an alpha-blocker commonly used to manage acute lower urinary tract symptoms among men receiving radiation therapy (RT) for prostate cancer (PCa), may decrease the likelihood of recurrent cancer, according to investigators. A team of Australian researchers led by Shailendra Anoopkumar-Dukie, PhD, of Griffith University in Southport, Queensland, based those findings on a retrospective study of 303 men with PCa who had received RT from 1998 to 2017. In that study, 147 men received prazosin, a quinazoline alpha-blocker and 72 received tamsulosin, a non-quinazoline alpha-blocker, to treat lower urinary tract symptoms. Another 84 men naïve to treatment with alpha-blockers served as controls. The 2- and 5-year rates of biochemical relapse were significantly lower

Study: TVS Use for SUI Declining USE OF TRANSVAGINAL sling (TVS) procedures for stress urinary incontinence (SUI) has been in decline following warnings from the Food and Drug Administration (FDA) and Health Canada about complications associated with transvaginal mesh, researchers reported. Joseph R. Labossiere, MD, and colleagues at the University of Toronto identified 120,999 women who underwent SUI surgery from 1994 to 2016. From 2000 to 2009, the annual rate of TVS procedures increased from 19 to 129 per 100,000 population. The annual rate declined after 2009 to 60 procedures per 100,000 population in 2016, according to Dr Labossiere and his colleagues. “These data suggest that the regulatory warnings had a significant effect on how patients and physicians approach surgical management of SUI,” Dr Labossiere’s team concluded in their study abstract. ■

among prazosin-treated patients (2.7% and 8.8%, respectively) compared with tamsulosin recipients (15.2% and 25%) and controls (22.6% and 34.5%), Dr Anoopkumar-Dukie’s

team reported in a poster presentation. Prazosin-treated patients had a 3.9 times lower relative risk of biochemical relapse compared with controls. “To our knowledge, this is the

rovide an argument for first study to p the use [of] prazosin in the treatment of prostate cancer as an adjunct treatment option,” Dr Anoopkumar-Dukie and colleagues concluded. ■

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Bladder Bacteria, LUTS Severity Linked in Men LOWER URINARY tract symptom (LUTS) severity in men is associated with detectable bacteria in urine obtained via catheter, according to a new study that investigators say demonstrated for the first time that collection of catheterized urine is the most appropriate way to sample male bladder microbiota. Petar Bajic, MD, of Loyola University Medical Center in Maywood, Illinois, and colleagues studied 28 men undergoing surgery for benign prostatic enlargement (BPE)/LUTS and 21 undergoing non-BPE/LUTS surgery. They stratified men by International Prostate Symptom Score (IPSS). Paired voided/catheterized urine specimens were collected for expected quantitative urine culture (EQUC) and 16S ribosomal RNA gene sequencing. Lower urinary tract microbiota (LUTM) were detected in catheterized urine of 22.2% of men with mild LUTS, 30% of those with moderate LUTS, and 57.1% of those with severe LUTS, the investigators reported online ahead of print in European Urology Focus.

Bacteria in urine obtained by catheter is associated with increasing IPSS. Bacteria were present in the catheterized urine of 19 men. Of these, 4 men (21.1%) were in IPSS categories less than 8, 3 (15.7%) were in categories 8–19, and 12 (63.2%) in categories greater than 19. Increased IPSS category was associated with significant 2.2-fold higher odds of detectable bacteria in catheterized urine. Nearly all voided urine specimens showed detectable bacteria, so investigators found no association between bacteria in voided urine and increasing IPSS. “For the first time, we have successfully applied EQUC and 16S sequencing to male catheterized urine and associated the presence of bacteria with increasing IPSS,” the authors wrote. Many patients with detectable microbiota in both voided and catheterized urine showed unique organisms in their voided samples. “This indicates that most voided urine microbiota is sampled from the urinary tract distal to the bladder and that the male bladder is a relatively low-biomass environment,” they stated. “This observation confirms for the first time that collection of catheterized urine is the most

appropriate method of sampling male bladder microbiota.” Men in the BPE/LUTS surgery group were significantly older than those in the non-BPE/LUTS surgery group (mean 64.3 vs 56 years), and they had a higher proportion of patients with hypertension (64.3% vs 23.8%).

In a discussion of study limitations, the authors noted that the patients undergoing BPE/LUTS surgery and non-BPE/LUTS surgery were not matched with respect to age or hypertension. “As BPE/LUTS is a disease of the elderly, most patients with mild LUTS were younger overall,” they

wrote. “The difference in hypertension is likely attributable to the difference in age alone.” Dr Bajic and colleagues pointed out, however, that patients with and without identifiable microbiota in their bladders did not differ significantly in any baseline characteristics. ■

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LDR Brachytherapy Beneficial In High-Risk PCa LOW-DOSE-RATE brachytherapy (LDR-BT), primarily as a boost in conjunction with external beam radiation therapy and androgen deprivation therapy, is highly effective in treating cT3a and cT3b high-risk prostate cancer, according to study findings published in Brachytherapy.

The treatment is associated with excellent biochemical control and survival, data show. The study, by Manuj Agarwal, MD, of the University of Maryland School of Medicine in Baltimore, and colleagues, included 99 men with a median age of 69.4 years. The men received either

definitive LDR-BT or LDR-BT boost after EBRT from 1998 to 2007. About 86% received ADT. The median follow-up was 7 years. The 7-year rate of freedom from biochemical failure (FFBF), prostate cancer-specific survival, and overall survival were 65.2%, 90.1%, and

77.9%, respectively, Dr Agarwal’s team reported. Patients who received LDR-BT boost achieved a 7-year FFBF rate of 73.5%. “LDR-BT boost implantation of patients should be strongly considered for cT3 patients given the merits of trimodality care,” the authors concluded. ■

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ESRD Risk Linked to Recurrent Kidney Stones PATIENTS WHO who have recurrent symptomatic kidney stones are at higher risk of end-stage renal disease (ESRD) than those who experience incident symptomatic kidney stones, investigators concluded. In addition, patients with asymptomatic stones and bladder stone formers have an

increased all-cause mortality risk compared with non-stone formers. “Recurrent stone formers might accrue incremental kidney injury with each stone event,” a research team led by Andrew D. Rule, MD, of Mayo Clinic in Rochester, Minnesota, reported online ahead of print in the

American Journal of Kidney Diseases. “Therefore, treatments to prevent kidney stone recurrence may be beneficial for delaying CKD [chronic kidney disease] progression, especially because kidney stone events are associated with reductions in glomerular filtration rates and increases in proteinuria.” T:6.875”

Dr Rule and his collaborators conducted a historical matched-cohort study that included 6,984 stone formers and 28,044 non-stone formers matched by age and sex. All were residents of Olmsted County, Minnesota. Investigators used ICD-9 codes to identify residents’ first documented urinary

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stones in the county from January 1, 1984 to December 31, 2012. Following a review of medical charts, the investigators categorized subjects into 5 mutually exclusive categories: incident symptomatic kidney (first stone event during the study period), recurrent symptomatic kidney (first stone event before 1984 or residency in Olmsted County, with recurrence in the county during the study period),

asymptomatic kidney stone only (incidentally detected), bladder stone only, and miscoded (no urinary stone). Over a mean follow-up of 12 years, ESRD developed in 65 stone formers (0.93%) and 102 non-stone formers (0.36%), Dr Rule’s team reported. Compared with non-stone formers, recurrent symptomatic kidney, asymptomatic kidney, and miscoded stone formers had a T:6.875” significant 2.3-fold,

3.9-fold, and 6.1-fold increased risk of ESRD, respectively, after adjusting for baseline diabetes, hypertension, chronic kidney disease, dyslipidemia, gout, and obesity. The investigators observed no increased ESRD risk among incident symptomatic kidney and bladder stone formers. They identified ESRD events (initiation of maintenance dialysis or kidney transplantation) using the US Renal Data System database.

“The higher risk for ESRD in recurrent symptomatic compared with incident symptomatic kidney stone formers suggest that stone events are associated with kidney injury,” the authors concluded. In addition, asymptomatic kidney stone formers and bladder stone formers had a significant 40% and 37% increased risk of all-cause mortality risk, respectively, compared with nonstone formers. n

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Use of Post-RP High-Dose Radiotherapy Increasing USE OF HIGH-DOSE and very-highdose radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer is increasing despite an absence of randomized studies supporting this postoperative treatment, according to a new study. From 2003 to 2012, the use of highdose RT (greater than 6660 cGy) after

RP increased from 29.9% to 63.5%, a team led by John Christodouleas, MD, of the University of Pennsylvania in Philadelphia, reported online ahead of print in Prostate Cancer and Prostatic Diseases. The use of very-high-dose radiotherapy (greater than 7020 cGy) T:6.875” increased from 4.5% to 10.8%.

“This change in practice may be exposing patients to excess toxicity without cancer control benefits,” Dr Christodouleas and his colleagues concluded. Patients diagnosed at community centers were less likely to be treated with high-dose radiation therapy compared

with those at academic or comprehensive centers, the study found. By 2012, approximately 2 out of 3 post-RP patients were treated with radiation doses greater than 6660 cGy and 1 out of 9 were treated with doses above 7020 cGy. “This observation is consistent with our hypothesis that radiation dose creep occurred in the absence of level I evidence,” the authors noted. Dr Christodouleas’ team explained that in postoperative RT for prostate cancer, dose escalation cannot be achieved without increasing dose to normal tissues because most cells within the clinical target volume are part of normal/uninvolved nearby organs. “As such, dose escalation in this setting invariably increases risks of toxicities,” they wrote. “The clinical benefits of dose escalation, however, are not clear.”

Trend is occurring despite an absence of good supportive trial evidence.

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Although some retrospective studies suggest dose-escalated postoperative radiation therapy may improve biochemical control, there have been no randomized trials to support it, the authors pointed out. For the study, the investigators analyzed data from 13,195 men (mean age 64 years (range 25 to 89 years) in the National Cancer Data Base (NCDB) who had pT2–3, N0, M0 prostate cancer and received radiation therapy following RP. Of these patients, 9.7%, 48.1%, and 33.6% of patients had Gleason scores of 6, 7, and 8–10, respectively. Gleason scores were not available for 8.5%. With regard to study limitations, the authors noted that the NCDB only captures cases in which postoperative radiation therapy was used as part of the first course of therapy. Patients treated with postoperative RT because of late postoperative biochemical recurrences may have different patterns of care, they explained. In addition, the investigators said they could not distinguish between patients receiving adjuvant therapy and salvage therapy as part of the first course of therapy. “If these patients are treated differently and their relative proportions are changing over time, changes in dosing may be obscured or magnified.” ■

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Apalutamide and HRQoL

Nocturia ups fall risk

and EQ-5D-3L questionnaires, which patients filled out at baseline and during treatment. FACT-P is a 39-item questionnaire developed and validated specifically for patients with prostate cancer (PCa). FACT-P has 5 subscales (physical wellbeing, social and family wellbeing, emotional wellbeing, functional wellbeing, and PCa. The scores from these subscales can be added together to arrive at a single overall score, which ranges from 0 to 156. Higher FACT-P total and subscale scores indicate a higher HRQoL. The EQ-FD-3L has 5 items that ask patients to rate their perceived health state at the

nocturia. Of 11,695 individuals with a tendency to fall, 5403 had documented falls, the investigators found. Falls were associated with a 28% greater expenditure for hospital stay and medications. “The presence of nocturia is associated with greater health care costs in patients with a tendency to fall,” Dr Michel said. “In terms of polypharmacy, reducing the overall number of drug treatments per person could be an attempt to reduce drug-drug interactions and possibly stabilize persons with fall tendencies.” The Belgian study, a single-center retrospective pilot study conducted at a tertiary referral hospital, found that 125 (28%) of 447 reported incident in-hospital falls from January 1, 2015 to December 31, 2015 were associated with nocturnal toileting, according to investigator Ronny Pieters, MSc, RN, of Ghent University Hospital, who presented study findings. Thirty-nine falls were associated with daytime toileting.

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Delayed decrease in HRQoL seen with symptomatic progression. time they are filling out the questionnaire. The questions ask about mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Scores range from 0 to 3, with 1 indicating no problems, 2 indicating some problems, and 3 indicating extreme problems. Group mean scores for patient-reported outcomes show that overall HRQoL was maintained from baseline after start of treatment with apalutamide until treatment cycle 29 for those who remained on therapy, the investigators reported online ahead of print in Lancet Oncology. During a median treatment duration of 16.9 months, “mean changes from baseline in the FACT-P subscales were similar in both study arms, indicating that the addition of apalutamide to androgen deprivation therapy did not result in a decrease in HRQoL.” The researchers also stated: “Findings from the EQ-5D-3L health utility index indicated that patients believed their abilities to walk about, wash and dress themselves, and perform their usual activities were maintained after initiation of study treatment.” Patients who received apalutamide had a similar HRQoL after development of metastasis as those in the placebo group. “Amongst men in this patient population,” Dr Saad said, “maintaining quality of life is an important endpoint. … The results published are extremely reassuring because as clinicians, we can positively alter the course of one’s prostate cancer journey, while preserving HRQoL.” ■

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Annual PSA screening continued from page 1

no prior screening, according to study findings published online ahead of print in Urology. The study found no survival benefit for PSA screening at any interval for men younger than 55 years. Among men aged 70 to 74 and 75 to 79 years, a screening interval of 12 to 18 months decreased the risk of PCa mortality by a significant 67% and 52%, respectively. For the study, Dr Alpert sorted the study population into 6 groups based on PSA testing intervals: 12 to 18, 18 to 24, 2 to 3 years, 4 to 9 years, and no prior PSA test. He also categorized the patients into 7 age groups: younger than 50, 50 to 54, 55 to 59, 60 to 64, 65 to 69, 70 to 74, and 75 to 79. Of the 400,887 men in the study, 8542 had a biopsy-proven PCa diagnosis during the 5-year study period (1998 to 2002). Over 12 to 16 years of follow-up, 770 men died from PCa, 2512 died from other causes, and 5260 remained alive. “This is the first study to evaluate various screening intervals and age groups, showing that yearly screening is the interval of choice,” Dr Alpert wrote. In an updated statement on PCa screening released in May, the United States Preventive Services Task Force recommends that men aged 55 to 69 years make an individual decision

The hospital services with the most reported incident falls were geriatrics (74 falls), rehabilitation (55), gastroenterology (34), hematology (30), and neurology (30), according to the investigators. Of the 447 falls, 242 (54%) occurred from 8:00 PM to 7:59 AM. The most-reported mechanisms of fall were loss of balance (26%) and slipping (25%). Most patients (58%) suffered no injuries from their falls. Pieters and his colleagues said the proportion of falls associated with nocturnal toileting in 2015 (28%) is probably an underestimate. They noted, for example, that approximately 20% to 25% of incident falls are not reported in incident reports. The investigators observed that urine production in healthy individuals is lower at nighttime compared with daytime. Consequently, it would be expected that the prevalence of incident falls associated with going to the toilet to be lower at nighttime than daytime. Their study showed, however, that the majority of falls associated with toileting happened at nighttime (76% vs 24%).

about PCa screening with their clinician. The task force recommends against routine screening for men aged 70 years and older. Two large randomized prospective studies came to different conclusions about the effect of PSA screening on PCa mortality. In the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, investigators found no significant difference in PCa mortality between men who underwent annual PSA testing for 6 years and

Prostate cancer death risk reduced by 64% among men aged 55 to 74. those who received usual care (control arm). The control group, however, was “highly contaminated,” as more than half of the men had prior PSA screening, “making the lack of findings difficult to interpret,” Dr Alpert noted. The European Randomized Study of Screening for Prostate Cancer (ERSPC), in which men were assigned to PSA screening every 4 years or to a control arm, found a 21% decrease in PCa mortality in the screened men compared with controls. However, an analysis of the Göteborg subset of the ERSPC,

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These new studies add to growing evidence of the potential adverse consequences of nocturia. In a paper published recently in PLoS One (2017;12:e0169690), investigators in Korea reported on a population-based study of 92,660 men demonstrating that increasing nocturia frequency was associated with increasing risk for falls.

German researchers found a 13% higher risk of falls among nocturia patients. In adjusted analyses, individuals who had 1 or 2 nocturia episodes per night had significant 1.4-fold increased odds of falls, whereas those who had 3, 4, and 5 or more episodes per night had significant 2-fold increased odds. In a subgroup analysis, the adjusted odds for falls increased significantly increased in all age groups as the frequency of nocturia increased, the investigators reported. ■

which used a 2-year screening interval, found a 44% decrease in PCa mortality. “This suggests that the choice of a shorter screening interval may have led to more powerful results,” Dr Alpert wrote. Data from the National Cancer Institute show that the PCa death rate decreased by 51% from 1993 to 2014, the same period in which widespread PSA screening was performed, Dr Alpert noted. “Although this does not prove a causal relationship, it is highly suggestive, and the improvements in radiation therapy and chemotherapy in this time period cannot account for the magnitude of this change,” he wrote. Jim C. Hu, MD, MPH, the Ronald Lynch Professor of Urologic Oncology and Professor of Urology at Weill Cornell Medical College in New York, said the new study was “high quality,” with findings similar to those of the ERSPC. He noted, however, that the study was retrospective, and findings do not appear to be adjusted for variables such as race, income, education, body mass index, and comorbidities. Only a randomized controlled trial, which balances all unmeasured confounders, can zero in on the best frequency with which screening should be performed. This is unlikely to be performed in the United States because of strong preferences by doctors and patients alike, he said. ■

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Preventing Prostate Biopsy Infections Alcohol needle washing and pre-biopsy rectal cultures for targeted prophylaxis are among the strategies BY JOHN SCHIESZER RECENT STUDIES may improve urologists’ ability to decrease the risk of infectious complications from prostate biopsies. A study by Matthew N. Simmons, MD, PhD, and colleagues showed that prophylaxis with a combination of ciprofloxacin and ceftriaxone in conjunction with isopropyl alcohol needle washing can significantly reduce the incidence of sepsis following prostate biopsy compared with a ciprofloxacingentamicin regimen. The needle washing technique is quick and inexpensive and can be incorporated easily into existing biopsy protocols, the authors reported in Urology.1 A systematic review and meta-analysis by Bhavan Prasad Rai, MSc, and colleagues, which was published in Prostate Cancer and Prostatic Diseases,2 found that fosfomycin can significantly lower the rate of urinary tract infections (UTIs) and antimicrobial resistance compared with quinolone-based regimens. In another systematic review and meta-analysis, investigators led by Matthew J. Roberts, MBBS, PhD, reported in the World Journal of Urology3 that targeted antibiotic prophylaxis based on rectal cultures prior to biopsy can decrease the risk of infectious complications. Origin of the idea “I spent many years during my doctorate doing molecular cloning and plating out bacteria,” related Dr Simmons, of Urology Specialists of Oregon in Bend. “I considered bacterial inoculation/ sterilization from that perspective and figured that fecal matter inside the core biopsy needle could be the main source of infection. I reviewed the literature and saw little addressing that possibility, and came up with the cleaning method described in the paper.” He and his colleagues had been using a gentamicin/ciprofloxacin regimen, but then changed to ciprofloxacin/ceftriaxone in 2014 after reviewing the current evidence, Dr Simmons said. For their study, the investigators enrolled 829 consecutive patients scheduled to undergo prostate biopsy and divided them into 3 groups based on prophylactic regimen: ciprofloxacin plus gentamicin (group 1), ciprofloxacin plus ceftriaxone (group 2),

and ciprofloxacin plus ceftriaxone and needle washing (group 3). The incidence of post-biopsy sepsis was 3.8%, 2%, and 0%, respectively. All prostate biopsy patients at his practice now receive ceftriaxone/ciprofloxacin and undergo needle washing. So far, only 1 post-biopsy infection occurred in 350 consecutive patients undergoing prostate biopsy. The washing technique may seem simple and trivial, but it appears to be highly effective, he stated. “At the end of the day, I enjoyed doing this study more than any I have ever done due to the possibility that it may have an actual tangible impact on practice,” Dr Simmons told Renal & Urology News. “In this clinic, we have reduced our biopsy infection rate to less than 1%. I have not had to admit a patient for post-biopsy sepsis for 3 full years, and that is golden.”

Fosfomycin more effective Dr Rai said he and his colleagues were not surprised that fosfomycin was more effective at preventing UTIs and lower the rate of antimicrobial resistance. “There is a trend towards increasing quinolone resistance globally and hence alternate antibiotics are likely to be more effective,” said Dr Rai, a Consultant Urologist and Robotic Surgeon at James Cook University Hospital, Middlesbrough, UK. The meta-analysis included 5 studies comparing fosfomycin and non-fosfomycin prophylaxis in men undergoing TRUS-guided prostate biopsy. In these studies, 1,447 men received fosfomycin and 1,665 patients received quinolone-based prophylaxis. The researchers found no significant differences in adverse event rates between the 2 cohorts. “I think it’s important to review our antibiotic practices,” Dr Rai said. Benefit of rectal cultures In the rectal culture study, Dr Roberts’ team analyzed the effectiveness of targeted antibiotic prophylaxis (TAP) compared with empiric prophylaxis regimens on rates of post-biopsy infectious complications. They identified 15 studies (8 retrospective and 7 prospective) with 12,320 participants. Infectious complication incidence rates were 3.4% among those receiving

empiric regimens compared with 0.8% among TAP recipients. “Our meta-analysis confirmed that targeted prophylaxis resulted in less infectious complications and essentially removed antimicrobial resistance as an influential factor,” said Dr Roberts, a urology resident and lecturer in the Faculty of Medicine at The University of Queensland, Australia. “These findings were similar to our previous report from 2014, but with more studies and patients. The findings were unsurprising and reflective of why many urology departments have incorporated a targeted prophylaxis approach.”

Transperineal vs transrectal biopsy Dr Roberts stated that it may be preferable to perform transperineal biopsy rather than transrectal biopsy because the former is associated with

significantly fewer infections. When transrectal biopsy is only method available, delaying the procedure until risk factors (such as recent overseas travel to areas of high antibiotic resistance, antibiotic use in last 6–12 months, and immunosuppression) resolve or are reduced is worth considering, as are adjunct antiseptic methods such as rectal and needle disinfection, according to Dr Roberts. n REFERENCES 1. Simmons MN, Neeb AD, Johnson-Mitchell M. Reduced risk of sepsis after prostate biopsy using a cephalosporin-fluoroquinolone antibiotic regimen and isopropyl alcohol needle washing. Urology. 2018;115:102-106. 2. Noreikaite J, Jones P, Fitzpatrick J, et al. Fosfomycin vs. quinolone-based antibiotic prophylaxis for transrectal ultrasound-guided biopsy of the prostate: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2018;21:153-160. 3. Scott S, Harris PN, Williamson DA, et al. The effectiveness of targeted relative to empiric prophylaxis on infectious complications after transrectal ultrasound-guided prostate biopsy: a meta-analysis. World J Urol. 2018;36:1007-1017.

Urine Culture Prior to Prostate Biopsy May be Unnecessary ROUTINE OFFICE URINE CULTURES performed on asymptomatic men prior to prostate needle biopsy (PNB) may be unnecessary, a new study suggests. In a prospective observational study, investigators led by Jay D. Raman, MD, FACS, of Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania, found that fewer than 5% of asymptomatic men had positive office cultures prior to PNB. The study, published in International Urology and Nephrology, included 150 asymptomatic men who had urine cultures obtained 14 days prior to PNB. Positive cultures were not treated and antibiotic prophylaxis prior to PNB included ciprofloxacin 500 mg the night before and morning of the biopsy. The study showed that only 6 men (4%) had evidence of asymptomatic bacteriuria with more than 10,000 CFU/mL on office urine culture. Infectious complications developed in only 4 men (2.7%) following biopsy, (2 with sepsis and 2 with culture-positive UTIs). In all 4 cases, the causative pathogen was quinolone-resistant Escherichia coli. Post-biopsy infectious complications did not develop in any of the 6 patients who had preoperative positive urine cultures. “Our study confirmed that preoperative urine culture in asymptomatic men without urinary tract symptoms is unnecessary before prostate biopsy, Dr Raman told Renal & Urology News. “This was not a surprise, but reaffirmed that this test is unnecessary and omitting this is prudent for reducing unnecessary costs.” Consulting with local antibiograms to assess for microbial sensitivities, coupled with rectal swab cultures when feasible and topical rectal antiseptic at time of biopsy, could help reduce the risk of infections dramatically, Dr Raman said. n

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Nocturia: ‘A Legitimate Stand-Alone Problem’ In March, the FDA for the first time approved a medication for the treatment of nocturia due to nocturnal polyuria in adults. For some perspective on nocturia, Renal & Urology News sat down with Alan J. Wein, MD, PhD (Hon), Founders Professor and Emeritus Chief of Urology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. At the American Urological Association (AUA) 2018 Annual Meeting in San Francisco, Dr Wein was a member of a faculty that gave an instructional course titled, “Nocturia: Advances in Diagnosis and Management.” Is there a take home message from the various presentations at this year’s AUA annual meeting?

Dr Wein: The main message coming out of the meeting is that nocturia is a legitimate stand-alone problem that is associated with a number of negative things, such as increased mortality, increased falls and fractures, depression, increased sleepiness during the day, decreased attention to work, increased number of sick days, which may or may not be cause and effect. Nocturia is the most common urinary tract symptom. With men who have bladder outlet obstruction secondary to prostatic enlargement, it’s also the thing that bothers them the most. If you look at the totality of people who have lower urinary tract symptoms, the minority have urinary incontinence; the majority have some element of nocturia.

One of the studies presented at this year’s AUA annual meeting (Drangsholt S et al. Poster MP27-14) concluded that nocturia treatment is modest at best. What are your thoughts?

Dr Wein: Medications used to treat people with OAB and BPH have little effect on nocturia. If you have patients who have OAB, which is urgency with or without incontinence, and usually with frequency and nocturia, and you treat those people with OAB medications, then you’ll improve their frequency by about 20%, you’ll improve their urinary incontinence episodes—if they have

urgency incontinence—anywhere from 40% to 70%, and you’ll improve their urgency episodes by 25% to 50%. But you won’t have much of an effect on their nocturia. At best, if they get up 3 times a night, you’ll decrease their nocturia to 2, 2.5 episodes a night, but only if they have severe urgency associated with their waking to void. Meta-analyses looking at the effect of antimuscarinics and nocturia show that the difference between drugs and placebo was 0.2. So at best there is a modest effect of OAB drugs on nocturia. If you look at the individual studies, that’s really what the difference is. In some studies, there is no difference at all. The situation also applies to medications for BPH. The placebo effect in nocturia is extra ordinarily high. The lowest I’ve ever seen is 20%, the highest, 40% to 50%. Now there’s an FDA approved medication in the US (Noctiva, formerly AV002) to treat nocturia that’s due to nocturnal polyuria —50% of people get 50% better. Within that population who gets better, everything improves. First uninterrupted sleep period is lengthened past 4 hours, which is sort of the magic number according to the sleep experts. They get up fewer total times a night. Quality of life gets better. You can use it in people who do or don’t have overactive bladder or BPH.

When should doctors prescribe the new drug?

Dr Wein: Let’s say a 65-year-old man comes to the office complaining of

hesitancy, decreased stream, and urgency, and he says the daytime symptoms don’t bother him, but the nighttime urination, getting up 4, 5 times a night, is a major problem for him. In these cases, I think the drug can be used first line. But if the man says all the urinary symptoms bother him, he urinates 9 or 10 times a day, his stream is poor and he gets up frequently at night to urinate, the average urologist most likely would treat him for BPH, so they would give him an alpha blocker or a 5-alphareductase inhibitor. If the man comes back and says he’s actually doing a lot better during the day but still gets up 3 times a night, then the new drug can be used as second-line therapy while continuing first-line therapy. So I think the drug will be used as both first-line and second-line therapy depending on the severity of complaints.

With congestive heart failure or peripheral edema of any cause, fluid is retained outside of the vascular system. When patients lie down at night, this accumulated fluid enters the vascular system, increasing blood pressure and renal blood flow, which increases the amount of urine produced. If patients lie down in the late afternoon, a lot of that fluid returns to the vascular system. That fluid is urinated out before they go to sleep at night. The number of times during a 24-hour period that they urinate doesn’t change, but the urination distribution changes, so they do it more when they’re awake when it’s less bothersome than when they go to bed and try to go to sleep, when it becomes more bothersome. This works for anyone with lower extremity lymphedema. Sleep apnea is a quick hit, as is better control of diabetes and hypertension.

What are some other ways to manage nocturia?

What underlying causes of nocturia are underappreciated?

Dr Wein: There are a lot of quick hits that physicians can do for somebody who has nocturia. One such quick hit is to have patients with congestive heart failure lie down for an hour, hour and a half, at about 4 o’clock in the afternoon.

Dr Wein: The most startling cause is sleep apnea. Doctors just don’t think to ask patients about sleep apnea when they complain about nocturia. Sleep apnea causes hypoxia, resulting in pulmonary vasoconstriction. This leads to increased right atrial pressure that stimulates secretion of atrial natriuretic peptide, which then causes inhibition of arginine vasopressin and promotes salt and water excretion. If you give patients a CPAP mask, and the patient uses it successfully, it’ll improve the nocturia right away, the first night. Are there areas of nocturia research that need more attention?

Medications used to treat OAB and BPH have little effect on nocturia. —Alan J. Wein, MD

Dr Wein: One unexplored clinical question is whether antidiuretic drugs work as well in patients who do not have nocturnal polyuria. One of the definitions of nocturnal polyuria is the output of 33% of 24-hour urine production at night. Suppose somebody makes a lot of urine during the day, but less than 33% of their urine output at night. Does the drug work less well in those patients, and, if so, how much less? Another area that needs to be explored is whether the negative associations with nocturia, such as increased falls and fractures, cardiac disease, and increased mortality are the cause or result of nocturia. n

www.renalandurologynews.com SEPTEMBER/OCTOBER 2018

Renal & Urology News 29

Data Support AUA Guidelines for SRMs A prospective study confirmed the effectiveness of nephron-sparing approaches for small renal masses BY JODY A. CHARNOW A NEW PROSPECTIVE study has validated and strengthened recent American Urological Association (AUA) guidelines recommending that nephron-sparing approaches such as partial nephrectomy, ablation, and active surveillance (AS) be preferred in the management of small renal masses (SRMs), according to researchers at Johns Hopkins University in Baltimore. “This study fills a major gap identified by the AUA [guidelines] committee by critically evaluating the statements in a prospective fashion, thereby strengthening the evidence behind the guidelines,” first author Ridwan Alam, MD, MPH, a urology resident, told Renal & Urology News. “While careful and expert patient selection remains crucial in the evaluation and management of SRMs, nephron-sparing approaches,

including AS, have increasingly become accepted as the mainstay of treatment.” Dr Alam and colleagues compared the effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablation, and AS for SRMs among

Clinically significant CKD is nearly 11-fold more likely with RN than PN, data show. 638 patients. SRMs were defined as tumors 4 cm or small in diameter. The median follow-up time was 3 years, with 158 patients (24.7%) followed for at least 5 years. They analyzed data using the prospectively-maintained Delayed Intervention and Surveillance

Higher Caffeine Intake May Decrease Death Risk in CKD GREATER INTAKE OF caffeine is

between caffeine intake quartiles

associated with a decreased risk of

and CKD sages or urinary albumin-

death among individuals with chronic

creatinine ratio categories with respect

kidney disease (CKD), according to a

to all-cause mortality. “Consequently,

new study.

caffeine consumption appears to be

Compared with individuals in the first quartile of caffeine consumption (less than 28.20 mg/day), those in

safe through different stages of kidney disease,” the authors stated. The study included 4863 individuals

the second, third, and fourth quartiles

with CKD identified using the National

(28.20–103.00, 103.01–213.50,

Health and Nutrition Examination

and greater than 213.50 mg/day,

Survey (NHANES) 1999–2010. Of

respectively) had a 26%, 25%, and

these, 1283 individuals died during

25% decreased risk of death after

a median follow-up of 60 months.

adjusting for age, smoking status,

CKD was defined as an estimated

gender, race, CKD stage, and numer-

glomerular filtration rate of 15–60 mL/

ous comorbidities and other potential

min/1.73 m2 and/or a urinary albumin-

confounders, Miguel Bigotte Vieira,

to-creatinine ratio greater than 30

MD, of the Centro Hospitalar Lisboa

mg/g. Caffeine intake was evaluated

Norte in Lisbon, Portugal, and col-

by 24-hour dietary recalls at baseline.

leagues reported online ahead of print

“If these results are to be confirmed

in Nephrology Dialysis Transplantation.

by prospective studies, advising these

The study found no significant associa-

patients to drink more caffeine may

tion between caffeine consumption

reduce their mortality,” the authors

and either cardiovascular- or cancer-

concluded. “This would be a simple,

related mortality. In addition, the investi-

clinically beneficial and inexpensive

gators found no significant interactions

option in patients with CKD.” ■

for Small Renal Masses (DISSRM) database, which is supervised by Phillip Pierorazio, MD, the study’s senior author. Results showed that cancer-specific survival at 7 years was 98.8% in the PN group and 100% in all of the other groups, Dr Alam and his collaborators reported in BJU International. The AS group demonstrated significantly worse overall survival than the other groups, and this was likely due to older age and greater comorbidities at enrollment, according to the investigators. The estimated glomerular filtration rate (eGFR) was lowest among the RN patients but comparable among the other groups. In multivariable mixedeffects logistic regression, RN was associated with significant 10.9-fold increased odds of clinically significant chronic kidney disease (CKD), defined

as an eGFR below 45 mL/min/1.73 m2 (CKD stage 3B or higher), when compared with PN. Ablation and AS did not differ significantly from PN with respect to the risk of clinically significant CKD.

Long-Term Darbepoetin Use Safe

hemoglobin (Hb) level at the time of occurrence. For example, the proportion of patients with CV-related AEs was 7.1% among those with an Hb level below 11 g/dL at the time of event occurrence compared with 0.2% among those with an Hb leve of 13 g/dL or higher. The study identified no new safety concerns, Dr Tanaka and colleagues reported. In the effectiveness set, mean Hb levels remained in the 10.0–10.6 g/dL range during weeks 4–156. At 3 months after initial darbepoetin administration, the composite renal endpoint of either a 50% reduction in estimated glomerular filtration rate, initiation of dialysis, or renal transplantation occurred in 39.5% of patients with an Hb level of 11 g/dL or higher compared with 44.8% of those with an Hb level below 11 g/dL. An Hb level of 11 g/dL or higher vs less than 11 g/dL at 3 months after darbepoetin initiation was associated with a significant 27% decreased risk of the composite renal endpoint. The cumulative proportion of renal survival (no composite renal endpoints) was significantly higher among patients with an Hb level of 11 g/dL or higher compared a level below 11 g/dL. “This study demonstrated that a decrease in composite renal endpoints is associated with the achievement of target Hb levels being maintained by darbepoetin,” the authors wrote. ■

LONG-TERM DARBEPOETIN use is safe and effective for treating anemia in patients with chronic kidney disease (CKD) not on dialysis, according to a post-marketing surveillance study conducted in Japan. The study examined a safety analysis set of 5547 patients and effectiveness analysis set of 5024 patients. All patients were treated with darbepoetin and followed up for 3 years. In the safety analysis set, adverse events (AEs) and adverse drug reactions (ADRs) occurred in 44.4% and 7.1% of patients, respectively, Tetsuhiro Tanaka, MD, of the University of Tokyo Graduate School of Medicine, and colleagues reported online ahead of print in Clinical and Experimental Nephrology. The 7.1% incidence rate of ADRs was lower than that reported in pre-approval Japanese clinical trials (30.75%), according to the investigators. Cardiovascular (CV)-related AEs occurred in 12.6% of the overall population. The proportion of patients who presented with CV-related AEs was lower among patients with a higher

Quality of life Importantly, this is among the first studies to examine the effect of management strategy on quality of life (QoL) scores in this patient population, according to the investigators. Using the Short Form 12 questionnaire, the authors found that QoL was lowest among AS patients due to lower physical health scores. Mental health scores, however, were comparable among the groups, and, in fact, improved over time, possibly demonstrating increasing comfort with the chosen management strategy, according to Dr Alam. ■

30 Renal & Urology News

SEPTEMBER/OCTOBER 2018 www.renalandurologynews.com

Hyperuricemia Prevalence Increasing Men and women had 45% and 47% increased odds of hyperuricemia, respectively, in 2014 vs 2006 RESEARCHERS in Ireland have documented a substantial increase in the prevalence of hyperuricemia. From 2006 to 2014, the prevalence of hyperuricemia increased from 19.7% to 25.0% among men and from 20.5% to 24.1% among women, a team led by Austin G. Stack, MD, of University Hospital Limerick and the Health Research Institute at the University of Limerick, reported in PLOS One. After adjusting for baseline demographic characteristics and illness indicators, men and women had significant 45% and 47% increased odds of hyperuricemia, respectively, in 2014 compared with 2006. Hyperuricemia prevalence increased with age. In 2014, the prevalence was 18.6%, 20.2%, 27.7% and 43.0% among those aged 18 to 39, 40 to 59, 60 to 80, and older than 80 years, respectively. The corresponding percentages in 2006 were 13.7%, 16.5%, 24.1%, and 39.2%, respectively.

Larger Renal Tumors More Aggressive AS RENAL TUMOR SIZE increases, so does its aggressiveness, a study found. In a study of 2650 patients who underwent radical or partial nephrectomy for solid renal tumors, those with 2 cm, 3 cm, and 4 cm tumors had an estimated 18%, 24%, and 29% likelihood of aggressive histology, respectively, Bimal Bhindi, MD, and colleagues at Mayo Clinic in Rochester, Minnesota, reported online ahead of print in European Urology. The 10-year progression-free survival rates for indolent and aggressive malignant tumors were 90% and 71%, respectively. The 10-year cancer-specific survival rates were 96% and 81%. For any given tumor size, men were more likely than women to have aggressive histology. For 2, 3, and 4 cm tumors, the likelihood of aggressive histology was 21%, 28%, and 33%, respectively, for men compared with 13%, 17%, and 21%, respectively, for women. “These data have important implications for the initial counseling and management of patients with an incidentally

Hyperuricemia On the Rise A study conducted in Ireland found that hyperuricemia afflicted a significantly greater proportion of men and women in 2014 compared with 2006, as shown below. 25 20 15

n Men

n Women

25.0%

24.1%

20.5%

19.7%

10 5 0

2006

2014

Source: Kumar A U A, Browne LD, Li X, et al. Temporal trends in hyperuricaemia in the Irish health System from 2006–2014: A cohort study. PLoS One. 2018;13(5):e0198197.

Hyperuricemia prevalence generally increased with decreasing kidney function. In 2014, the prevalence was 25.1%, 54.8%, 67.7%, and 48.9% among individuals aged 18 to 39, 40 to 59, 60 to 80, and older than 80 years, respectively. The corresponding percentages in 2006 were 19.2%, 48.3%, 75.2%, and 59.2%.

detected, radiographically indeterminate renal mass,” the authors stated. The authors noted that strengths of their study included the use of a large and robust institutional database with long-term follow-up. The study was not without limitations, however. For example, as the study was observational, the investigators could not rule out selection bias. “Patients not represented in the cohort include those electing to undergo active surveillance, those with angiomyolipomas who did not proceed to surgery, poor surgical candidates, and those with metastatic disease who were managed with systemic therapy,” they wrote. Of the 2650 patients, 2350 (88.7%) and 300 (11.3%) had malignant and benign tumors, respectively, and 1860 (70.2%) and 790 (29.8%) had indolent and aggressive tumors, respectively. The patients had a median age of 63 years, and 37% were women. The vast majority of the malignant and benign tumor groups were white (96% and 94%, respectively). Patients had a median radiographic tumor size of 3.8 cm. High-grade clear-cell and high-grade papillary renal cell carcinoma (RCC), collecting duct RCC, translocationassociated RCC, and hereditary leiomyomatosis RCC were among the types of malignancies that the investigators considered aggressive. n

In multivariable analysis, individuals aged 40 to 59, 60 to 80, and more than 80 years had a significant 12%, 9%, and 27% increased risk of hyperuricemia, respectively, compared with those aged 18 to 39 years. Patients with an estimated glomerular rate (eGFR) of 60 to 89, 30 to 59, 15 to 29, and less than

15 mL/min/1.73 m2 had a 2.1, 8.0, 15, and 7.58 times increased risk of hyperuricemia, respectively, compared with individuals who had an eGFR of 90 mL/min/1.73 m2 or higher. Men had a significant 23% decreased likelihood of hyperuricemia compared with women. Other factors significantly associated with an increased risk of hyperuricemia included elevated white cell count and higher hemoglobin levels. The investigators determined hyperuricemia prevalence by analyzing data from 128,014 individuals aged 18 years or older in Ireland’s National Kidney Disease Surveillance Programme. Dr Stack’s group defined hyperuricemia as a serum uric level greater than 7 mg/dL in men and greater than 5.7 mg/dL in women. The investigators noted that their analysis was based on estimates derived from patients in Ireland’s health system and may not accurately reflect the true prevalence in the population. n

CKD Prevalence High Among Elderly Diabetics SOUTH KOREAN investigators who

Among patients with an eGFR of 60

studied a group of elderly patients with

mL/min/1.73 m2 or above, the progres-

type 2 diabetes found that they have a

sion rate to more than stage 3 CKD

high prevalence and progression rate

was 39.6% at the end of follow-up. In

of chronic kidney disease (CKD).

addition, 30.2% progressed to albumin-

In a study of 190 patients aged 65 years or older (mean 70.4 years)

uria from normoalbuminuria, according to the researchers.

who had type 2 diabetes for a mean

The authors found that diabetes dura-

duration of 10.6 years, the baseline

tion of 10 years or more was associated

prevalence of CKD—defined as an esti-

with significant 3.46-fold increased odds

mated glomerular filtration rate (eGFR)

of CKD at baseline compared with a

below 60 mL/min/1.73 m2 and/or the

duration of less than 5 years.

presence of albuminuria—was 59.5%,

In an acknowledgement of study limi-

investigators from the CHA Bundang

tations, Dr Kim’s team noted that their

Medical Center in Seongnam led by

study sample was neither large nor

Soo-Kyung Kim, MD, reported online in

representative of the Korean popula-

the Diabetes & Metabolism Journal.

tion. In addition, the Modification of Diet

The study population, which consisted

in Renal Disease (MDRD) study equa-

of patients who visited a diabetes clinic

tion, which the investigators used to

at their institution, had a mean follow-up

calculate eGFR, has not been validated

duration of 64.5 months. From baseline

in patients older than 70 years, and

to the end of follow-up, the mean eGFR

no coefficient of the MDRD equation

decreased significantly from 65.7 to

has been published for Koreans. “This

52.7 mL/min/1.73 m . The annual rate of

limitation might render CKD prevalence

eGFR decline was 2.42 mL/min/1.73 m2.

results imprecise.” n

www.renalandurologynews.com SEPTEMBER/OCTOBER 2018

Renal & Urology News 31

Ethical Issues in Medicine Patients must understand care-related information physicians give them for valid informed consent to exist BY DAVID J. ALFANDRE, MD

Not just a legal formality My colleague was right: Medicine is complicated. But I continued to worry that physicians resisted promoting IC because they primarily believed it to be a legal formality that does not meaningfully benefit patients or physicians. If physicians believe IC is simply a bureaucratized exercise designed to meet specific legal requirements and not advance patient care, then they are right to be frustrated at the time and energy required to complete it. IC is so critical to the practice of medicine and protecting patients’ right to

their IC not just for discrete procedures, but for the range of medical care including a physical examination, changes in treatment plans, radiology and laboratory studies, and plans for follow-up. The risks, benefits, and amount of information documented or exchanged varies, but the process remains the same.

Need for transparency How can physicians help patients in a practical way become truly informed in decisions about care? Bioethicist Harold Brody, MD, has written extensively about improving disclosure in IC and believes that the current legal standards fall short in guiding clinicians to fulfill the ethical ideals of informed consent.2 Brody suggests a different approach. The physician should make his/her thinking sufficiently transparent enough that patients understand how a recommendation was made (i.e., by identifying the problem and the advantages and disadvantages of the medically reasonable options). He suggests that this standard “…requires the physician to engage in the typical patient-management thought process, only to do it out loud in language understandable to the patient.” Here’s an example from a nephrologist’s outpatient practice. Most physicians probably have had this sort of

Ideally, by making their thought processes transparent to patients, physicians can make their language understandable. participate in decisions about their care, that it was codified in law. IC is often believed to be a discrete event such as obtaining a required signature on a form for a specific procedure, but it is more generally seen as a process.1 For valid IC to occur, the physician is obligated to disclose all the relevant information about a proposed treatment or procedure to the patient, and the patient has to understand that information and be able to make a voluntary choice. Patients provide

conversation already in one form or another, but for those who have not, or at least not consistently, the intent is to demonstrate the discrete steps of disclosure and understanding in enabling an ethically strong IC process.

Sample conversation “I’m concerned that your blood pressure has been consistently elevated. I recommend that we go up on medication A because it will lower your blood

fter a case conference on informed consent, a skeptical colleague approached me and said, “Medicine is far too complicated. Patients will never really understand enough to make fully informed health care decisions. That expectation puts an unreasonable burden on physicians.” I’m glad he shared that comment with me. It belies the continuing challenges in providing informed consent (IC) and its role in improving care. There was no simple response to his claim, so in the end I responded in the simplest way I knew how. I asked him if he wanted his spouse or his brother to fully understand their care when they saw their physician.

Patients should know their physicians’ reasoning behind management recommendations.

pressure which can reduce your risk of stroke, heart attack, and progression of your kidney disease. Most patients do fine with this higher dose, but for patients who have side effects, they usually report X and Y. Serious side effects, which are extremely rare and for which I will monitor you, include Z. There are at least 2 alternatives that I can see to this approach. The first is to do nothing, which I don’t advise because it won’t reduce your risk of the health problems I mentioned. The second alternative is to start a new medication, but I think my recommendation is preferable because it will mean fewer pills for you, and because you are already tolerating medication A. What do you think about what I’ve said?” If the patient nods in agreement, the disclosure obligation likely has been met. To ensure patient understanding, the physician goes on: “What questions did you have? To make sure I haven’t made this too complicated, can you tell me in your own words why I made this recommendation? I don’t want this to feel like a test. Gauging your understanding helps me know if I need to clarify anything I’ve told you.” When physicians make patients’ care understandable to them, they

honor their basic obligation to respect patients’ autonomy, promote their participation in decisions about their care, and ultimately help them make the right decisions for themselves. If IC is important to the ethical practice of medicine, it is for this reason. Ideally, by making their thought processes transparent to patients, physicians can make their language understandable and better inform patients about their care. That is a burden we can probably all bear. ■ David J. Alfandre MD, MSPH, is a health care ethicist for the National Center for Ethics in Health Care (NCEHC) at the Department of Veterans Affairs (VA) and an Associate Professor in the Department of Medicine and the Department of Population Health at the NYU School of Medicine in New York. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the NCEHC or the VA. REFERENCES 1. Braddock CH 3rd, Edwards KA, Hasenberg NM, et al. Informed decision making in outpatient practice: time to get back to basics. JAMA. 1999;282:2313-2320. 2. Brody H. Transparency: informed consent in primary care. Hastings Cent Rep. 1989;19:5-9.

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Practice Management A

ccording to report released by the Office of the National Coordinator for Health Information Technology (ONCHIT) in April, only 52% of patients in a large survey said they were offered online access to their medical records as of 2017. Of those, approximately half said they viewed their records in the past year, totaling about 28% of people nationwide. Roughly one-third of respondents were using an electronic health device and 40% had a wellness app on their phone or tablet. In addition, according to the Pew Research Foundation, 96% of Americans own a cell phone and three-quarters own a computer. These findings suggest a gap in the way health care providers and patients use technology generally and how they incorporate it into their health care.

Who is using patient portals? In 2015, researchers at athenahealth, a company based in Watertown, Massachusetts that provides networkenabled services for health care and point-of-care mobile apps, investigated portal use and adoption and found a few interesting statistics, some of which debunked popular portal myths. First, small practices implement portals at about the same rate as larger

Associate Director of the Clinical and Translational Science Institute at Wake Forest School of Medicine in WinstonSalem, North Carolina, said portal use has grown at the clinic where he works (which has a high number of low-income patients), but remains somewhat low. A 2016 in the Journal of Medical Internet Research penned by Dr Miller and colleagues reported on a study of lowincome primary care practices in North Carolina. After interviewing clinical personnel at the practices, they found most implemented portals because they were mandated. The providers also had low expectations for portal use. In addition, they expressed concerns portals would create more work, confuse patients, and alienate those not using them. Dawn Paulson, Director of Informatics at the American Health Information Management Association, is generally a fan of portals, but she said they are not necessarily for everyone. A healthy person who only sees a doctor when they have a cold has little need for it. People with chronic conditions, however, will be the “heavy hitters” on the portals. “People who have chronic illnesses are very in tune to their health care,” she said. “Even before portals, they would come in the office with three-ring binders with their health records in them.”

Nearly all patient portals should allow patients to view lab and test results, request prescription refills, and schedule appointments. groups. Next, 30-somethings’ use is highest, but people in their 60s are about as likely to use them as those in their 40s. Portal adoption does not trail off steeply until patients are in their 70s. And older patients sign in and use portals more frequently than younger ones. In 2018, almost 40% of athenahealth’s portal users are aged 55 years or older. Income levels may have a slight impact on whether or not people are using portals. David Miller, MD, MS,

Emily Lord, Product Marketing Manager at athenahealth, said portals empower patients to be more active in their health care; improve patient/provider communication; and save patients time and hassle by letting them pay bills and view health information online. It can also provide an edge for providers in a consumer-driven market. “Providing patients with the convenience they have come to expect in their interactions with other industries, such as banking,

Health care providers have a number of factors to consider when deciding to implement patient portals BY TAMMY WORTH

Patient use of portals may be increased if staff members explain how they work.

will increasingly become a competitive advantage when it comes to attracting and retaining patients,” she said. Dr Miller said people have looked at whether portals improve outcomes, and the data are “messy.” Many portal users are already engaged patients with greater resources. Overall, though, he said they are beneficial and can be an important tool for managing care.

Encouraging use If portals can improve patient care, but uptake is low, what can providers do to increase usage? Dr Miller suggests taking the effort to build portal usage out of the hands of physicians. “If they put it on the doctors it generally doesn’t work,” he said. “Clinics that have higher uptake are ones that empower the front desk and nurses to explain it to the patients.” A multi-pronged approach appears to be the most effective in encouraging use. This includes making it part of a routine patient visit by discussing it during check in or intake. Paulson said providers have a higher success rate with sign up and usage if they have a nurse sit down and show a patient how to use the portal. Different portals come with a range of features, but nearly all of them should allow patients the basics: viewing lab and test results, requesting

prescription refills, and scheduling appointments. The ONCHIT report found about 85% of patients used the portal for lab results, 62% either refilled a prescription or made an appointment, and nearly half sent a message to their provider. Another feature many physicians have been hesitant to put in place is the ability to email or send messages through the portal. Many worry, as Dr Miller did, about “opening the floodgates and ending up with hundreds of emails a day.” This capacity, however, has ended up saving him time. He can respond to electronic notes much more quickly than having to pick up a phone or relay a message to a nurse, who then must call a patient, he said. The more tools a portal has, the more likely patients are to use it, Paulson said. She recommends using OpenNotes, which allows patients to see a provider’s notes placed in the health record. “That’s what people want to see,” she said. “It gives a more complete record and gives a bigger, better picture of what the patient’s condition is. We will see patient engagement skyrocket as more information is made available to them.” ■ Tammy Worth is a freelance medical journalist based in Blue Springs, MO.