Renal & Urology News - Jan-Feb 2020 Issue

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V O L U M E 19, I S S U E N U M B E R 1

Optimal mCRPC Drug Sequences Emerging Studies zero in on which agents are best used first

BY JODY A. CHARNOW PHARMACEUTICAL companies have greatly expanded the drug armamentarium for treating metastatic castrationresistant prostate cancer (mCRPC) in the past decade. Medical researchers have been exploring how best to use these medications, notably the sequence in which patients should receive the drugs to experience the best outcomes. They appear to be making progress.

“Optimal treatment sequencing is really starting to come into focus for patients with mCRPC,” Benjamin Maughan, MD, PharmD, Assistant

Professor of Genitourinary Medical Oncology at the Huntsman Cancer Institute of the University of Utah in Salt Lake City, told Renal & Urology News. “There seems to be 2 separate types of differentiating factors: clinical parameters and molecular parameters that are guiding treatment sequencing.”

For instance, in the prospective randomized CARD trial, which was published recently in the New England Journal of Medicine, Dr Maughan noted that the clinical factor of “shortterm duration of clinical benefit” from first novel hormone therapy (NHT)

Initial AS Can Be Safe for SRMs UNIVERSAL INITIAL active surveillance (AS) for patients with small renal masses (SRMs) using predefined progression criteria can safely delay or avoid treatment for most patients with initial maximum tumor diameters less than 3 cm, according to study findings presented at the 20th annual meeting of the Society of Urologic Oncology in Washington, DC.

Researchers report their experience with a novel management approach.

In a poster presentation, investigators led by Eric Kauffman, MD, of the Roswell Park Comprehensive Cancer Center in Buffalo, New York, reported their initial experience with a novel SRM management approach that includes a universal AS recommendation for all patients with SRMs who did not have progression at presentation and AS management using specific prospectively applied progression criteria for converting to treatment.

The study included 123 patients with SRMs who had more than 3 months of follow-up and were initially managed with AS. The initial median maximum tumor diameter was 2.2 cm (range 0.93.9 cm). The primary study outcome continued on page 9

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CHEMOTHERAPY FIRST IMPROVES OUTCOMES IN mCRPC CASES Upfront docetaxel followed by either abiraterone or enzalutamide is associated with better 3-year cancer-specific and overall survival than the opposite sequence in men with metastatic castration-resistant prostate cancer, according to a new study.

First-line docetaxel followed by abiraterone or enzalutamide

First-line abiraterone or enzalutamide followed by docetaxel

100

100

80

87.4%

82.4%

80

60

60

40

40

20

20

0

0

64.1%

determined that the sequence of NHT (abiraterone or enzalutamide)-taxane (cabazitaxel) is superior to an NHTNHT sequence. The PROfound trial presented at the European Society for Medical Oncology (ESMO) 2019 congress is a good example of a study using

PLND Extent Varies Widely

By Facility

BY JODY A. CHARNOW WIDE FACILITY-LEVEL variation exists in the extent of pelvic lymph node dissection (PLND) during radical prostatectomy in men with high-risk prostate cancer (PCa) despite lack of an apparent survival benefit associated with more extensive PLND, according to a recently published study.

Using the National Cancer Data Base, David F. Friedlander, MD, MPH, of the University of California San Diego, and colleagues studied 13,652 men with a high predicted probability of 10-year survival and who underwent radical prostatectomy. Of these, 11,284 (82.7%) had no/limited PLND (0-9 lymph nodes), 1601 (11.7%) had received a standard PLND (10-16 lymph nodes), and 767 (5.6%) underwent extended PLND (17 or more lymph nodes).

Compared with standard PLND and no/limited PLND, extended PLND was not significantly associated with improved survival at a median follow-up continued on page 9

60.8%

■ 3-year cancer-specific survival rate ■ 3-year overall survival rate

Source: Andrews J, Ahmed M, Karnes R, et al. Systemic treatment for metastatic castration resistant prostate cancer (m-CRPC): Does sequence matter? Presented at the Society of Urologic Oncology 20th Annual Meeting held December 4 to 6 in Washington, DC. Poster 73.

molecular features to clarify optimal sequencing, Dr Maughan said. The trial showed that a sequence of NHT (abiraterone or enzalutamide) followed by olaparib, an inhibitor of poly-ADP ribose polymerase (PARP), an enzyme continued on page 9

IN THIS ISSUE 2

Racial differences in PCa gene expression tests reported

10

Kidney stones common in patients with primary gout

18

Multidisciplinary PCa clinics may promote optimal care

18

Updated guidelines for managing advanced RCC released

21

Risk factors for reoperation after radical cystectomy identified

21

Cytoreductive nephrectomy found beneficial in mRCC

22

Cannabis smoking may increase erectile dysfunction risk

Managing conflicts of interest is vital for maintaining patient trust PAGE 23

2 Renal & Urology News

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Racial Differences in PCa Gene Tests Identified

BY JOHN SCHIESZER COMMERCIAL gene expression tests that guide treatment decisions for prostate cancer (PCa) may be less accurate at predicting disease progression risk in black men than white men, according to a new study published in Cancer Epidemiology, Biomarkers, & Prevention.

“Because African-American men tend to have a high risk of aggressive prostate cancer, we expected the gene expression patterns to follow this trend, with higher risk of progression indicated for African-American compared to European-American patients,” study author Travis A. Gerke, ScD, a­ ssistant

member at Moffitt Cancer Center in Tampa, Florida, told Renal & Urology News. “We were surprised to find that this trend was not apparent. In fact, genes from one of the tests implied lower risk for the African-American patients.”

When a man is diagnosed with lowor intermediate-risk PCa, c­ ommercially

available tests are commonly used to measure gene expression in the tumor, Dr Gerke said. Black men have a 70% greater risk of PCa and are more than twice as likely to die from the disease compared with white men. Three tests recommended by the National Comprehensive Cancer Network

www.renalandurologynews.com JANUARY/FEBRUARY 2020

(NCCN) for predicting outcomes among men with low- or intermediaterisk PCa—OncotypeDX Prostate, Prolaris, and Decipher—were developed and validated in predominantly European-American cohorts, Dr Gerke said.

Black men are underrepresented across many areas of public health research, and prognostic biomarker discovery in PCa is no exception. The

researchers examined whether gene expression patterns differed by race for the genes included in the OncotypeDX Prostate, Prolaris, and Decipher tests.

Dr Gerke and his colleagues used the gene expression panel NanoString to compare the expression of 60 genes included in the commercial tests in tumor samples from 327 patients. The samples were from 95 black and 232 white patients. The analysis showed

that 48% of the genes included in the panels were expressed at different levels in black vs white men. This finding was not entirely surprising due to the known racial differences in disease aggressiveness.

What did stand out, however, was that the risk predictions provided by Prolaris and Decipher based on the risk scores were not significantly different between black and white patients. In addition, the

Renal & Urology News 3

OncotypeDX scores provided more favorable risk prediction for black vs white men. “Our study suggests that gene expression patterns for the 3 commercially available tests vary by race, and further research is needed to determine whether these variations associate with lessened risk prediction accuracy in African American patients,” Dr Gerke said.

“Caution is currently warranted when applying biomarker panels of prostate

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PCa gene tests

continued from page 3

cancer prognosis in clinical decisionmaking in African-American men.”

This analysis is the first to evaluate race-specific expression patterns of established prognostic genes in 3 commercially available panels on a single-gene expression platform. The study, however, is limited by a lack

of f­ollow-up data for comparing outcomes, the investigators noted.

Simpa Salami, MD, MPH, Assistant Professor of Urology at the University of Michigan in Ann Arbor, said the disparity in PCa outcomes is indisputable.

“While some believe it is solely due to socioeconomic factors/lack of access or biological differences, I believe that it is a combination of both,” Dr Salami said.

“While the usefulness of biomarkers in

assessing the aggressiveness of low-grade prostate cancer is highly debatable, this study highlights the limitations of using such tests in a one-size-fits-all approach.”

If PCa biology is truly different between black and white men, Dr Salami added, one would expect that biomarkers for predicting such biology would be different.

“This study indicates that we must exercise caution when applying tests

­developed in one population to another, he said.”

Daniel A. Barocas, MD, MPH, Associate Professor of Urology at Vanderbilt University in Nashville, Tennessee, said the study is important because it raises a relevant question. “I think what they have done is taken us one step forward and said what is the differential expression between African-American men and European-American men,” he said. ■

www.renalandurologynews.com JANUARY/FEBRUARY 2020

Renal & Urology News 5

RC+PLND Safe After Pembro Neoadjuvant Therapy NEW DATA support the safety of radical cystectomy and pelvic lymph node dissection (PLND) following neoadjuvant treatment with the checkpoint inhibitor pembrolizumab for muscle-invasive bladder cancer (MIBC), Alberto Briganti, MD, of San Raffaele Hospital in Milan, Italy,

and colleagues reported in European Urology.

The data are from a prospective ­assessment of perioperative outcomes among 68 patients with cT3bN0 MIBC or less enrolled in the PURE01 trial. Patients received 3 cycles of ­ pembrolizumab 200 mg every

3 weeks and subsequently underwent either open or robot-assisted radical c­ ystectomy (52 and 16 patients, ­respectively) plus extended PLND. Previously published results from the phase 2 PURE-01 trial showed that the treatment was ­associated with a pathologic response rate as high as 42%. Of

the 68 ­patients, 31 (46%) ­received an orthotopic neobladder.

Complications A total of 52 patients (77%) experienced complications of any grade, whereas 47 (69%) and 22 (32%) experienced grade 2 or higher complications and readmission at 90 days, respectively. Highgrade complications (Clavien-Dindo 3a or higher) were observed in 23 patients (34%). The most frequent complications were fever and ileus, which occurred in 35 (52%) and 21 (31%) of patients, respectively. No patient died during the 90 days following surgery.

“The current study represents the first prospective evidence supporting the surgical safety of radical cystectomy and pelvic lymph node dissection in patients with nonmetastatic bladder cancer who received neoadjuvant immunotherapy with pembrolizumab,” the authors wrote.

Dr Briganti’s team collected data on perioperative outcomes systematically and prospectively at surgery and during hospitalization as well as at 90 days after surgery during patients interviews conducted by medical doctors and ­according to European Association of Urology (EAU) guidelines.

Limitations With regard to study limitations, the authors noted that their results were obtained from analyses of a relatively small cohort of patients who met inclusion criteria of a prospective phase 2 trial and might not be generalizable to other settings. Dr Briganti’s team also pointed out that their findings “cannot be translated to patients receiving concomitant chemotherapy and immunotherapy, where ongoing trials are assessing the role of combination therapies in the neoadjuvant setting.”

The authors acknowledged that the rate of adverse events they observed in their study might be in the higher range of what is reported in the literature, but this discrepancy can be explained by factors not directly related to pembrolizumab therapy. For example, they noted that they relied on a prospective data collection system based on EAU guidelines for reporting complications, whereas the majority of available studies did not use a standardized approach to collect perioperative data at 90 days. “This might result in an underestimation of the inci­ dence and severity of complications, in particular when considering minor events or complications that occurred after hospital discharge.” ■

6 Renal & Urology News

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Contents

JANUARY/FEBRUARY 2020

Urology 18

ONLINE

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

18

21

22

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.

News Coverage Visit our website for daily reports on the latest developments in clinical research.

Guidelines for Advanced RCC Updated A combination of axitinib and pembolizumab is recommended as initial therapy for patients with favorable-risk advanced clear cell renal cell carcinoma.

Post-RC Reoperation Risk Factors ID’d Increasing BMI and a history of COPD are associated with an increased likelihood of reoperation within 30 days, investigators reported.

Cannabis Use Increases ED Risk in Men In a meta-analysis, cannabis smokers had 3.8-fold increased odds of erectile dysfunction compared with nonusers.

VOLUME 19, ISSUE NUMBER 1

CALENDAR European Association of Urology Annual Congress 2020 Amsterdam, The Netherlands March 20–24 National Kidney Foundation 2020 Spring Clinical Meetings New Orleans March 25–29 American Urological Association Annual Meeting Washington, DC May 15–18 ERA-EDTA 57th Congress Milan, Italy June 6–9 Canadian Urological Association 75th Annual Meeting Victoria, British Columbia, Canada June 27–29 International Continence Society 50th Annual Meeting Las Vegas August 26–29

Nephrology 14

Oral Drug May Transform Anemia Therapy Robert Provenzano, MD, discusses results from phase 3 trials of roxadustat, an agent that has shown superiority to epoetin alfa.

16

CKD Risk Lower With Moderate Alcohol Use Compared with never-drinkers, individuals who had 2 to 7 drinks per week had a significant 20% decreased risk of incident CKD.

16

Rising FGF23 Found to Up Risk of KRT Each 1 standard deviation increase in mean natural log-transformed FGF23 in the past was significantly associated with a 1.9-fold increased risk for incident kidney replacement therapy.

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

Multidisciplinary PCa Clinics May Promote Optimal Care Clinics that provide patients with an opportunity to consult with various specialists facilitate adherence to evidence-based national guidelines, study findings suggest.

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20

Anemia, Hyperuricemia Linked in Chronic Kidney Disease Among individuals with CKD, the presence of anemia was significantly associated with 2.3-fold increased odds of hyperuricemia in adjusted analyses.

Personally, I’ve always felt uncomfortable

not treating anemia in CKD patients. I believe anemia is not asymptomatic.

See our story on page 14

24

Departments 8

From the Medical Director Twice-weekly hemodialysis gaining acceptance

10

News in Brief Study challenges routine testing for VUR prophylaxis

23

Ethical Issues in Medicine When and how to manage conflicts of interest

24

Practice Management The value of educating medical students on healthcare economics

8 Renal & Urology News

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FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Twice-Week Hemodialysis Is Gaining Acceptance

B

ack in August 2012, I wrote a provocative editorial in this space titled, “How About Twice-Weekly Hemodialysis?”

This was the first time the topic of dialysis provided less frequently than 3 times a week was brought up in the 21st century. I argued that because kidney function worsens gradually, dialysis treatment should be gradual and incremental, starting with 1 to 2 hemodialysis (HD) treatments a week.

The 2012 editorial encountered some mixed reactions, including from colleagues who were interested to know more about twiceweekly dialysis, but also from colleagues who found the idea unacceptable and even repulsive. I explained back then that during my trips to Mexico, India, China, and other Latin American and Asian countries, I was intrigued by the large numbers of patients with end-stage renal disease who underwent HD less frequently, usually twice a week. In 2014, several colleagues and I published the first consensus paper on twice-weekly and incremental HD in the American Journal of Kidney Disease. The paper included 10 eligibility criteria for transition to a twice-weekly regimen. At the same time, my team at the University of California Irvine (UCI) started the first incremental dialysis transition program in the United States using these criteria. Today, at any given time, up to a third of all dialysis patients treated at UCI have been on a twice-weekly schedule. Meanwhile, a large number of landmark studies have been published suggesting favorable outcomes associated with incremental dialysis, including longer preservation of residual kidney function and greater quality of life and patient centeredness. Interestingly, in our UCI program, all patients have survived the twice-weekly dialysis regimen, and most have successfully transitioned to thrice-weekly or more frequent regimens from 3 months to 3 years after initiation of incremental dialysis.

In July 2019, President Donald Trump signed an Executive Order launching the “Advancing American Kidney Health Initiative,” which is expected to support incremental dialysis because it is patient-centered and offers financial advantages. Today, the incremental dialysis model we introduced at UCI is being used in many of the 7000 dialysis units across the nation. Even dialysis facilities in Western Europe—where twice-weekly HD met with harsh criticism and resistance—have incorporated this approach. Still, incremental dialysis is in its infancy, and additional studies including controlled trials with home dialysis are needed. Meanwhile, we should be committed to offering patients the dialysis regimen they prefer.

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, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine Orange, CA

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

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

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

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

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center Memphis

Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD Chief Executive Officer Inova Health System Falls Church, VA Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology (ret.)

Cleveland Clinic Lerner College of Medicine Cleveland Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology UC Irvine School of Medicine Orange, CA 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 Kenneth Pace, MD, MSc Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Vancouver, Canada

Edgar V. Lerma, MD 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. Denver Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Associate Professor of Medicine Wayne State University School of Medicine Detroit Vice President of Medical Affairs, DaVita Healthcare Denver Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital Teaneck, NJ

Renal & Urology News Staff Editor

Jody A. Charnow

Web editor

Natasha Persaud

Production editor Group creative director, medical communications Production manager Vice president, sales operations and production Director of audience insights National accounts manager Editorial director, Haymarket Oncology

Kam Kalantar-Zadeh, MD, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine Orange, California Twitter/Facebook: @KamKalantar

Kim Daigneau Jennifer Dvoretz Brian Wask Louise Morrin Boyle Paul Silver William Canning Lauren Burke

Vice president, content, medical communications Kathleen Walsh Tulley General manager, medical communications President, medical communications Chairman & CEO, Haymarket Media Inc.

James Burke, RPh Michael Graziani Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 19, Number 1. 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 © 2020.

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Emerging drug sequences continued from page 1

involved in DNA repair, was superior to a sequence of NHT-NHT in patients with DNA repair deficits, particularly BRCA1 and BRCA2 genomic alterations.

Other sequences need to be explored, he said, but the optimal sequences for hormone therapies and chemotherapies are becoming clearer, Dr Maughan said.

Improved progression-free survival In another presentation at the ESMO 2019 congress, Carlo Cattrini, MD, of the Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre in Madrid, and colleagues reported findings from the PROREPAIR-B study demonstrating significantly longer progression-free survival among men with mCRPC who received abiraterone or enzalutamide upfront compared with those who received first-line docetaxel (10.8 vs 8.3 months). Overall

PLND facility variation continued from page 1

of 83.3 months, Dr Friedlander’s group reported in Annals of Surgical Oncology.

The risk adjusted facility-level predicted probabilities of no/limited, standard, or extended PLND ranged from 17.8% to 96.3%, 3.3% to 53.3%, and 0.01% to 52.6%, respectively. “To our knowledge, our paper is the first to demonstrate facility-level variation in predicted probabilities of various PLND extents, with most facilities favoring no/limited PLND,” the authors wrote.

The finding is striking, they noted, given that American Urological Association guidelines recommend PLND for patients with intermediate- or highrisk disease and European Association of Urology guidelines recommend extended PLND in high-risk cases.

The finding of no survival benefit with more extensive PLND is c­ onsistent

Initial AS safe for SRMs continued from page 1

was p ­ rogression-free survival (PFS).

Progression criteria for recommending treatment at presentation or during AS were absence of benign tumor biopsy histology plus any of the following: presence of a maximum tumor diameter greater than 4 cm; a tumor growth rate greater than 5 mm per year; maximum tumor diameter greater than 3 cm plus a tumor growth rate of 3 mm or greater per year; high-risk biopsy

Renal & Urology News 9

No survival difference Some studies, however, have not found a difference in outcomes related to mCRPC drug sequencing. In a retrospective study of treatment sequences in

real-world practice published in Clinical Genitourinary Cancer in 2019, Kazutaka Okita, MD, of Hirosaki University School of Medicine in Hirosaki, Japan, and colleagues found no significant difference in OS among men with mCRPC treated with abiraterone first followed by enzalutamide, or the reverse sequence, abiraterone or enzalutamide first followed by docetaxel, or the reverse sequence, or docetaxel first followed by cabazitaxel.

In Dr Maughan’s view, sufficient evidence exists to include mCRPC treatment sequences in practice guidelines based on both molecular and clinical characteristics. “However, these guidelines should take into consideration the quality of the evidence,” he said. “I believe that the guidelines should provide a general guide but leave flexibility to allow the providing clinician to use any sequence. The data to date are not strong enough to endorse a single, specific sequence as the only option that should be considered for any given patient.” ■

Academic medical centers were more likely than other types of facilities to perform extended PLND. These centers tend to have greater interdisciplinary collaboration and may have tumor boards and the presence of multiple specialties, he explained. “As a result,”

he said, “specialists may be able to collaborate with one another, either preoperatively or postoperatively, and discuss contemporary literature guiding clinical and surgical practice, including the performance of pelvic lymphadenectomy.”

R. Jeffrey Karnes, MD, Chair of the Division of Community Urology at the Mayo Clinic in Rochester, Minnesota, who was not involved in the new study but has conducted research on PLND during radical prostatectomy, commented that “latent variables are at play” that might influence how PLND extent is interpreted, such as how surgeons submit lymph nodes for pathologic examination. For example, if nodes are submitted in packets based on where they were removed (such as from right external iliac vs right pelvic regions), the former may result in a larger node count, he said.

In addition, there might be inter- and

i­ntra-pathologic variations in how nodes are counted.

Further, Dr Karnes pointed out that the number of nodes removed does not necessarily correlate with PLND extent, which is related more to regions of dissection. For example, surgeons could remove a lot of nodes from the external iliac region yet miss critical areas (such as near the internal/hypogastric region), he said, adding that there are mapping studies for PLND in prostate cancer that highlight critical areas to dissect.

Dr Karnes also said he is unclear how the investigators came up with the number of nodes that defined extended vs standard dissection. Although they performed a sensitivity analysis, they did not present the numbers used to establish the cut points. They also did not determine if the number of nodes removed resulted in a higher rate of detecting positive nodes. ■

­ istology; tumor stage greater than h cT3a stage; or symptoms.

During a median follow-up of 30 months, 35 patients (29%) met at least 1 progression criterion.

Patients with a maximum tumor diameter less than 2 cm, 2.1-3.0 cm, and greater than 3.0 cm had 3-year PFS rates of 83%, 75%, and 45%, respectively, Dr Kauffman and his colleagues reported. The metastasis-free survival rate was 100% regardless of whether patients progressed or not. Of the 35 patients who progressed while on AS,

28 (80%) converted to treatment (27 with surgery and 1 with ablation). Only 1 (1%) of 88 patients who did not progress converted to treatment because of anxiety or other causes. In addition, 61% of resected tumors had adverse renal cell carcinoma (RCC) pathology (high-grade tumors and/or stage pT3a disease).

The AS protocol can differentiate aggressive and indolent tumors for treatment selection by avoiding removal of benign tumors “and enriching resection for adverse RCC pathology,” the investigators concluded in their study abstract.

Dr Kauffman’s group noted that the risk of metastasis for patients with SRMs on AS is low and frequently outweighed by treatment-related morbidity or mortality.

The current literature on AS for SRMs, they pointed out, is confounded by highly selected patients with SRMs who were unfit for treatment. Consequently, treatment rates and standardized progression criteria for triggering treatment for healthier patients with SRMs are not well defined. ■

survival (OS) between the treatment sequences, however, did not differ significantly (31.3 vs 29.9 months, respectively).

First-line chemotherapy superior At the Society of Urologic Oncology’s 20th annual meeting this past December in Washington, DC, Jack R. Andrews, MD, and colleagues at Mayo Clinic in Rochester, Minnesota, reported on a study demonstrating that upfront chemotherapy with docetaxel for mCRPC followed by abiraterone or enzalutamide if chemotherapy fails is associated with superior cancer-specific and overall survival compared with the opposite treatment sequence (see chart on the cover).

In a 2019 paper published in Lancet Oncology, a team led by Kim N. Chi, MD, of the Vancouver Prostate Centre in Vancouver, British Columbia, reported on a phase 2 randomized trial showing that men with newly diagnosed mCRPC experience slower PSA progression if they receive abiraterone plus prednisone with prior research. “Our follow-up could have been longer, ideally, but, at the end of the day, we did find that despite this v­ ariation, there really is no difference in overall survival with ­different extents of pelvic lymph node dissection,” Dr Friedlander told Renal & Urology News.

At most facilities, prostate surgery is performed with no or limited PLND.

first followed by enzalutamide rather than the reverse sequence.

“Our trial is the first, to our knowledge, to show an advantage to using a sequencing strategy of both drugs: the treatment sequence of abiraterone plus prednisone followed by enzalutamide

Recent studies may provide guidance on which drugs should be used upfront. had a longer time to PSA progression than did the opposite sequence,” Dr Chi and colleagues wrote.

10 Renal & Urology News

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News in Brief

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

Short Takes Urothelial Cancer Therapy Approved

ultrafiltration—was significantly

The FDA has granted accelerated

gait speed and 0.05 m/s additional

approval to enfortumab vedotin-ejfv

slowing per year, according to the

(Padcev, Astellas Pharma) for patients

researchers.

associated with a 0.02 m/s slower

with locally advanced or metastatic has progressed on platinum-based

NAC Improves Survival In High-Grade UTUC

­chemotherapy and immunotherapy.

Neoadjuvant chemotherapy (NAC)

The drug targets the cell adhesion

prior to surgery for high-risk upper

molecule Nectin-4, which is highly

tract urothelial carcinoma (UTUC)

expressed in urothelial cancers. It

improves survival, according to study

is the first antibody-drug conjugate

findings published online in Annals of

­approved for treating advanced uro-

Surgical Oncology.

urothelial cancer whose disease

thelial cancer.

the study included 74 patients with high-grade UTUC: 37 who received

Predialysis fluid overload is associ-

underwent initial surgery (no-NAC

ated with slower gait speed and gait

group). The 3-year disease-free and

speed decline over time, investiga-

overall survival rates were 78.4% and

tors reported in Nephrology Dialysis

86.5%, respectively, in the NAC group

Transplantation.

compared with 51.4% and 62.2%,

NAC followed by surgery and 37 who

Christopher Carlos, MD, of the

respectively, in the no-NAC group,

University of California, San Francisco,

Lingxiao Chen, MD, of Central South

and colleagues measured predialysis

University, Changsha, Hunan, China,

gait speed at baseline and at 12 and

and colleagues reported. On multi-

24 months in a group of 298 dialysis

variate analysis, the NAC group had a

patients. Each 1 liter of predialysis

significant 75% decreased risk of dis-

fluid overload—as ascertained using

ease progression and 78% decreased

bioimpedance or volume of ­delivered

risk of death.

Nocturia Prevalence in the US The estimated prevalence of nocturia (1 or more urination episodes per night) is high among men and women aged 20 years or older who participated in the US National Health and Nutrition Examination Survey from 2005 to 2016, according to a recent study. Shown below are the proportions of men and women who reported nocturia according to age group.

100

100

84.7%

82.7%

60

80

70.2% 56.8%

40

20

20

20-39

68.9%

74.3%

60

40

0

study of Brazilian patients with primary gout found that more than one-third of them suffer from nephrolithiasis, according to a report in Advances in Rheumatology.

Leonardo Santos Hoff, MD, and colleagues at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo studied 123 patients (mean age 62.9 years, 93.5% male) with primary gout. Of the 123 patients, 43 (35%) had nephrolithiasis, including 23 (18.7%) with asymptomatic nephrolithiasis (detected only by ultrasonography), 7 (6%) with asymptomatic nephrolithiasis (detected by ultrasonography and a positive clinical history), and 13 (10%) had a history of kidney stones.

“The prevalence of nephrolithiasis in primary gout is high, and many patients are asymptomatic,” the authors concluded. “Therefore, patients should be screened for this condition either with ultrasonography or [computed tomography].”

After propensity score matching,

Fluid Overload Tied to Slower Gait Speed

80

Kidney Stones Common in Patients with Primary Gout A

40-59 Men

60+

0

20-39

40-59

60+

Women

Source: Soysal P, et al. Trends and prevalence of nocturia among US adults, 2005-2016. Int Urol Nephrol. 2019; published online ahead of print.

Study: Radium-223 Superior for PCa Bone Metastases T

reatment with bone-targeted alpha-emitting but not beta-emitting radioisotopes is associated with a significant improvement in overall survival and symptomatic skeletal event (SSE)-free survival among patients with bone metastases from castration-resistant prostate cancer (CRPC), according to a new study published in JAMA Oncology.

In a meta-analysis of data from 6 randomized clinical trials that included 2081 patients with bone metastases from CRPC, Gwénaël Le Teuff, PhD, of Institute Gustave Roussy in Villejuif, France, and colleagues found that, compared with no radioisotope use, treatment with the alpha emitter radium-223 was associated with a significant 30% decreased risk of death, whereas use of the beta emitter strontium-89 did not confer a significant survival benefit. In addition, radium-223 treatment was associated with a significant 35% decreased risk of SSEs, whereas strontium-89 treatment did not result in a significant decrease in the risk of SSEs.

VUR Prophylaxis Does Not Warrant Routine Testing R

outine blood test monitoring of complete blood count (CBC), serum electrolytes, or creatinine is not warranted for young children receiving long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) for recurrent urinary tract infections (UTIs), investigators concluded in a paper published in Clinical Pediatrics.

Milan Dattaram Nadkarni, MD, of Wake Forest University in Winston-Salem, North Carolina, and colleagues analyzed data from the prospective randomized, placebo-controlled RIVUR trial, which enrolled 607 children aged 2 to 71 months who had vesicoureteral reflux (VUR) diagnosed after symptomatic UTIs. In that trial, investigators randomly assigned 302 patients to receive TMP-SMZ and 305 to receive placebo, and followed up with patients for 24 months.

“In conclusion, our study did not reveal any adverse effect of TMP-SMZ prophylaxis on CBC, serum electrolytes, and creatinine,” the authors concluded.

14 Renal & Urology News

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Oral Drug May Transform Anemia Therapy Robert Provenzano, MD, is Associate Professor of Medicine at Wayne State University School of Medicine in Detroit and Vice President of Medical Affairs at DaVita Healthcare in Denver. Dr Provenzano has conducted extensive research on the management of anemia in patients with kidney disease. At Kidney Week 2019 in Washington, DC, he and other investigators presented findings of phase 3 clinical trials showing that roxadustat was superior to epoetin alfa at improving hemoglobin levels in hemodialysis patients regardless of iron status, with a lower risk of major cardiovascular events.

What is the basis for how roxadustat works?

Dr Provenzano: Roxadustat is a fascinating drug from a physiologic perspective. It builds on the work of this year’s Nobel Prize winner in physiology or medicine on the cellular sensing mechanism for oxygen. Billions of years ago, the earth had no oxygen. When plants began producing oxygen, which can be toxic, animals had to adapt. The HIF [hypoxia-inducible factor] system is what evolved to enable single-cell animals to survive. Under low oxygen conditions or when inhibited by roxadustat or another stabilizer, the HIF alpha subunit remains stable and allows translation of the appropriate genes that physiologically increase erythropoietin levels, improves iron absorption through the gut, and moves iron from the circulation into the bone marrow.

Instead of a pharmacologic approach where we hammer patients with synthetic erythropoietin, inhibiting HIF is a more elegant approach using a system that has evolved over billions of years.

What were the key findings from the phase 3 trials you and others presented?

Dr Provenzano: In the OLYMPUS trial,1 which enrolled non-dialysis CKD patients, roxadustat increased hemoglobin levels compared with placebo regardless of iron-repletion status or inflammation, and it was as safe as placebo. In incident dialysis patients [the HIMALAYAS study] we were able to

show not only that it was effective, it was effective irrespective of iron status and required administration of less iron than the epoetin alfa control arm.2 We also saw that it worked in inflamed patients. A good number of kidney patients are inflamed. A huge home run.

We learned from the TREAT and CHOIR studies that if hemoglobin levels get too high, they can increase the incidence of stroke, myocardial infarction, and other cardiovascular events.

In the HIMALAYAS trial, we looked at major adverse cardiovascular events (MACE), defined as all-cause mortality, stroke, and myocardial infarction, and MACE+, which included MACE as well as hospitalization for unstable angina or congestive heart failure.

Roxadustat was significantly safer with regard to MACE and MACE+ than using epoetin alfa. And there was a trend toward lower mortality.

In the ROCKIES study,3 we looked at prevalent dialysis patients and found remarkable efficacy. Roxadustat outperformed epoetin alfa, and patients required less rescue therapy such as blood transfusion or IV iron. When we looked at MACE and MACE+ and mortality, we did see an improved signal for MACE+. So roxadustat was not any worse and maybe a little bit better.

Do you think HIF inhibitors, if approved for use in the United States, will increase treatment of anemia in patients with nondialysis CKD?

Dr Provenzano: We basically don’t treat anemia in the CKD population today in the United States. Payers want nephrologists to deliver value, but it’s hard to deliver value in the CKD population. There’s not much that can forestall progression of kidney disease.

ESAs are inconvenient to administer in these patients. Therefore, that population is left untreated. But if I can manage their anemia with a pill and no iron, it’s a game changer. If it forestalls worsening of their kidney function, it’s a home run. In the OLYMPUS trial, the roxadustat group had slower progression of CKD compared with placebo. If this delays dialysis initiation, patients have more time to get a transplant. That is critical.

Personally, I’ve always felt uncomfortable not treating anemia in CKD patients. I believe anemia is not asymptomatic. If a normal hemoglobin level is 14 (g/dL), and patients have a hemoglobin of 10, treating that hemoglobin of 10 may have benefits. Patients may feel slightly better so they might stay at work. If they’re employed, they’ll be less depressed, which has been shown to decrease hospitalization rates. Logistics matter when delivering kidney care.

Delivering IV erythropoietin to a CKD patient is really difficult. And giving them IV iron, which is required, is very

difficult. I just think this is one of the most exciting times in our field.

A large study presented at Kidney Week revealed a 23.3% prevalence of severe anemia (hemoglobin levels below 10 g/ dL) among patients with CKD patients not on dialysis. Should a finding such as this prompt nephrologists and payers to reconsider the clinical management of anemia in this patient population?

Dr Provenzano: Yes. We need to construct appropriate trials that look at this population and determine the impact of anemia management on quality of life, sense of well-being, employment, [progression] to dialysis, and potential cardiovascular events.

What are the possible adverse effects of roxadustat?

Dr Provenzano: The drug stimulates approximately 3800 different genes.

This has raised concerns of unintended consequences. What are we going to see long term? That is a question with all new drugs that enter the market, especially drugs used in a chronically ill population such as kidney patients.

We see that it lowers cholesterol, so that’s a positive unintended benefit. We see that it delays progression. That’s a positive unintended consequence. But when you look at patients who have super-high HIF levels, such as patients with pulmonary fibrosis or polycythemia vera, we see no safety issues. I feel pretty confident that the lower HIF dose that we’re administering to treat anemia is going to be relatively safe. ■

Disclosures Dr Provenzano is on the editorial advisory board of Renal & Urology News. He also is Vice President of Medical Affairs at DaVita Healthcare and is on the board of directors for Nephroceuticals.

He receives study funding from FibroGen, AstraZeneca, and Astellas.

REFERENCES

I just think this is one of the most exciting times in our field. ­—Robert Provenzano, MD

1. Fishbane S, El-Shahawy MA, Pecoits-Filho R, et al.

OLYMPUS: A phase 3, randomized, double-blind, placebo-controlled, international study of roxadustat efficacy in patients with non-dialysis-dependent (NDD) CKD and anemia. Presented at Kidney Week 2019 in Washington, DC. Abstract TH-OR023.

2. Provenzano R, Besarab A, Leong R, et al.

HIMALAYAS: A phase 3, randomized, open-label, active-controlled study of the efficacy and safety of roxadustat in the treatment of anemia in incidentdialysis patients. Presented at Kidney Week 2019 in Washington, DC. Abstract TH-OR021.

3. Fishbane S, Guzman NJ, Pergola PE, et al. ROCKIES: An international, phase 3, randomized, open-label, active-controlled study of roxadustat for anemia in dialysis-dependent CKD patients. Presented at Kidney Week 2019 in Washington, DC. Abstract TH-OR022.

www.renalandurologynews.com

JANUARY/ FEBRUARY 2020

Renal & Urology News 15

Hospitalizations Up for Prostate Biopsy Infections INFECTION RATES following prostate biopsy have remained stable since 2007, but visits to emergency departments and hospital and intensive care unit (ICU) admissions for post-biopsy infections continue to increase, according to a new study. In addition, use of targeted prophylaxis remains limited.

Investigators led by Jim C. Hu, MD, of New York Presbyterian Hospital, Weill Cornell Medical College, New York, used 2001-2015 data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine 30-day infection rates and emergency department visits and hospital and ICU admissions for infection following prostate biopsy. The study included 274,858 biopsies. At the time of biopsy, patients had a mean age of 74 years.

The overall rate of post-biopsy infections increased from 5.9% in 2001 to 7.2% in 2007, but remained stable through 2015, Dr Hu and his colleagues reported in Urology. Still, from 2001 to 2015, the rate of emergency department visits for post-biopsy infections increased from 0.2% to 0.5%. The rate of hospital admissions increased from 0.5% to 1.3%, and the rate of ICU admissions rose from 0.1% to 0.3%.

Rectal swab use for targeted prophylaxis is low but increasing, study finds.

In addition, compared with surgeons who perform only 1 prostate biopsy per year, those who performed 25 or more biopsies per year had significant 35% decreased odds of post-biopsy infection and 50% decreased odds of hospitalization for post-biopsy infection.

“In the absence of an unforeseen confounding effect, our data suggest there is a component of surgeon volume contributing to infectious risks,” the authors wrote. “While the underlying reason for this association is unknown, technical skill, familiarity with prophylaxis protocols, office workflow, and post biopsy management are hypothetical contributing factors that deserve further exploration.”

Use of rectal swabs for targeted prophylaxis remains low (1.8% of biopsies in 2015), but did increase significantly from the 0.2% rate in 2001, according to the investigators.

“Taken together, our findings on prostate biopsy patterns of care inform physicians, policy makers, and payers in terms of formulating incentives or policies to encourage the uptake of strategies to combat the increasing incidence of post-biopsy infectious complications,” Dr Hu’s team concluded.

In cautioning that their findings must be interpreted in the context of the study design, the authors pointed out that their use of Medicare data only allows them to access a proportion of prostate biopsy volume by surgeons. “However, it is very likely that biopsy volume in the elderly is strongly

correlated to prostate volume irrespective of age,” they noted.

The investigators said their use of Medicare claims data “may underestimate the true incidence of infectious complications that do not receive a diagnosis code, such as minor or self-limited prostatitis, cystitis and epididymitis.” ■

16 Renal & Urology News

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CKD Risk Lower With Moderate Alcohol Use Consuming 2 to 7 drinks per week is associated with a 20% lower risk of CKD vs no alcohol intake ­ ltration rate (eGFR) below 60 mL/ fi min/1.73 m2 accompanied by a 25% or greater eGFR decline, a kidney-­diseaserelated hospitalization or death, or end-stage renal disease. They defined 1 drink as a 4-ounce glass of wine, a 12-ounce beer, or a 1.5-ounce shot of hard liquor. Current drinkers were more likely to be men and to be white, results showed. They also were more likely to have higher income and education levels. During a median follow-up of 24 years, incident CKD developed in 3664 participants.

Previous research has shown that moderate alcohol consumption, defined as up to 1 drink per day for women and up to 2 drinks per day for men, is associated with a decreased risk of coronary heart disease (CHD). This may be due to alcohol increasing high-density lipoprotein cholesterol, which could increase transport rate of l­ipoproteins

Rising FGF23 Found to Up Risk of KRT

i­ ncident KRT (either maintenance dialysis initiation or a kidney transplant) in adjusted analyses, Dr Mehta’s team reported in the American Journal of Kidney Disease.

The investigators used group-based trajectory modeling for 1163 patients who survived beyond their fifth annual study visit without reaching the KRT outcome. They identified 3 distinct trajectory groups of FGF23 change over time: stable, slowly increasing, and rapidly increasing (mean group slope of 0.03, 0.14, and 0.40 per year, respectively, in natural log-transformed FGF23). Of the 1163 patients, 354 reached the KRT outcome during a median follow-up of 3.2 years.

Compared with a stable FGF23 trajectory, slowly and rapidly increasing FGF23 trajectories were associated with 3.6- and 21.4-fold increased risks for incident KRT, respectively, in fully adjusted models.

Potential mechanisms by which FGF23 increases may lead to CKD progression are not completely understood, but prior research suggests that FGF23 excess may increase fibroblast activation during kidney injury and result in profibrotic signaling, the authors pointed out. FGF23 also might indirectly impact CKD progression by stimulating phosphaturia and promoting nephrocalcinosis, resulting in renal tubular damage and tubulointerstitial fibrosis, they noted. ■

INCREASING LEVELS of fibroblast growth factor 23 (FGF23) are independently associated with an elevated risk for incident kidney replacement therapy (KRT), according to investigators.

Rupal Mehta, MD, of Northwestern University’s Feinberg School of Medicine in Chicago, and colleagues used serial FGF23 measurements and FGF23 trajectories to evaluate the association between FGF23 levels and KRT risk among 1597 patients (case-cohort analytic sample) in the Chronic Renal Insufficiency Cohort Study. Patients had up to 5 annual measurements of carboxy-terminal FGF23.

FGF23 regulates phosphate homeostasis by stimulating urinary phosphate excretion and lowering 1,25-dihydroxy­ vitamin D levels, the investigators noted.

Of the 1597 patients in the casecohort analytic sample, 728 reached the KRT outcome and 859 experienced the composite outcome of KRT or death during a median follow-up of 6.3 years.

Each 1 standard deviation increase in mean natural log-transformed FGF23 in the past was significantly associated with a 1.9-fold increased risk for

New study findings are consistent with previous research showing a protective effect of moderate alcohol intake.

and lipoprotein lipase activity, thereby preventing CHD, Dr Rebholz and his colleagues explained. As CHD and CKD “share many risk factors and pathophysiology, it is p ­ ossible that

­ oderate alcohol consumption may m also reduce the risk of CKD.” The authors noted that the findings of their study echo those of previous research demonstrating an inverse association between alcohol intake and CKD risk, but these earlier investigations were conducted in select populations with limited generalizability. “The present analysis, which was conducted in a community-based cohort of black and white men and women from 4 US centers, helps to address this gap,” they stated.

The new study is not without limitations, however. Dr Rebholz’s team pointed out that alcohol intake was self-reported and thus subject to reporting bias and may have been under-reported. The investigators also acknowledged that they did not have baseline values for albuminuria and proteinuria, which would have been useful markers of kidney damage. ■

Drug for Upper Tract Urothelial Cancer Granted Priority Review THE FDA HAS granted priority review

The NDA is supported by the posi-

to a New Drug Application (NDA) for

tive results from the pivotal Phase 3

a mitomycin gel formulation to treat

OLYMPUS (Optimized DeLivery of

low-grade upper tract urothelial cancer

Mitomycin for Primary UTUC Study)

(UTUC). If approved, the product would

trial, a pivotal, open-label, single-arm

be the first non-surgical treatment

phase 3 clinical trial of the mitomycin

for malignancy, according to a press

gel. The trial enrolled 74 patients with

release from UroGen Pharma Ltd,

low-grade UTUC at clinical sites across

which is developing the gel.

the United States and Israel. Study par-

Priority review designation shortens

ticipants received 6 weekly instillations

the review period from the standard 10

of the gel administered via a standard

months to 6 months from the sub-

catheter. Four to 6 weeks following the

mission of the application, the press

last instillation, patients underwent a

release explained. The FDA grants

Primary Disease Evaluation (PDE) to

priority review to applications for drugs

determine complete response (CR), the

that, if approved, “would be significant

primary endpoint of the study.

improvements in the safety or effective-

The mitomycin gel demonstrated

ness of the treatment, diagnosis, or

a CR rate of 59% of patients. The

prevention of serious conditions when

durability of response was estimated to

compared to standard applications.”

be 89% and 84% at 6 and 12 months,

According to UroGen, the company is on track for a potential launch of the product by mid-2020. The FDA

respectively. The estimated median time to recurrence was 13 months.

The most commonly reported treat-

previously granted Orphan Drug, Fast

ment-related emergent adverse events

Track, and Breakthrough Therapy

(AEs) were ureteric stenosis (43.7%),

Designations to the mitomycin gel for

urinary tract infection (32.4%), hema­

treating low-grade UTUC.

turia (31.0%), and flank pain (29.6%). ■

© WESTEND61 / GETTY IMAGES

MODERATE CONSUMPTION of alcohol may decrease the risk of chronic kidney disease (CKD), according to a new study published in the Journal of Renal Nutrition.

In a prospective analysis of data from 12,692 participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study, a team led by Casey M. Rebholz, PhD, MS, of Johns Hopkins Bloomberg School of Public Health in Baltimore found that, compared with people who never drank alcohol, those who consumed 1 or fewer drinks per week, 2 to 7 drinks per week, 8 to 14 drinks per week, and 15 or more drinks per week had significant 12%, 20%, 29%, and 23% decreased risks of incident CKD, respectively, after adjusting for total energy intake, age, sex, race, and other potential confounders.

The investigators defined incident CKD as an estimated glomerular

18 Renal & Urology News

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Multidisciplinary PCa Clinics May Promote Optimal Care Goals include facilitated adherence to evidence-based national guidelines

BY JOHN SCHIESZER PATIENTS WITH prostate cancer (PCa) are more likely to receive appropriate care in a multidisciplinary (MultiD) PCa clinic where multiple specialists evaluate and advise patients, according to a new study.

A MultiD clinic provides men with PCa with an opportunity to consult with a radiation oncologist, a urologist, and a medical oncologist as necessary during the same visit to discuss treatment options and potential side effects.

MultiD clinic visits facilitate adherence to evidence-based national guidelines and may help eliminate some biases, study findings suggest.

“Despite previous studies on disparities in treatment for African-American men, in the MultiD clinic definitive therapy was appropriately delivered and active surveillance in elderly African Americans was accepted,” study investigator Deborah A. Kuban, MD, of The University of Texas MD Anderson Cancer Center in Houston, told Renal & Urology News. “While many of us who practice MultiD care always thought the above to be true, this study lends evidence to the principle.”

In the largest study of its kind, Dr Kuban and her colleagues compared 4,451 men with PCa receiving care at a MultiD clinic from 2004 to 2016 with 392,710 men in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with PCa from 2004 to 2015. The median ages were similar in the 2 cohorts; however, the SEER cohort was slightly older than the MultiD cohort (65 vs 62 years).

Greater use of active surveillance The study, which was published in Cancer, showed that black men who visited the MultiD clinic were more likely to receive definitive therapy compared with national trends. Overall, men with low-risk disease were more likely to choose active surveillance (AS) in the MultiD clinic compared with the SEER cohort. In 2015, the rate of AS among men with low-risk disease was 74% in the MultiD clinic patients compared with 54% in the SEER group. The tendency toward AS for patients with low-risk PCa is supported

by ­current National Comprehensive Cancer Network (NCCN) guidelines and national trends.

Among high-risk men, significantly more men were offered aggressive treatment in the MultiD clinic group compared with the SEER cohort. All men with high-risk disease received definitive treatment in the MultiD clinic group. However, approximately 20% of men with high-risk disease opted for non-definitive treatment in the SEER group. NCCN guidelines recommend men with high-risk PCa receive definitive treatment.

Multidisciplinary clinics could help decrease racial disparities in care.

Among men in the MultiD clinic, black men had significant 17%, 41%, and 52% increased odds of receiving brachytherapy, external beam radiotherapy, and radical prostatectomy, respectively, compared with white men, the investigators reported. Black race in the SEER cohort was associated with an increased use of brachytherapy/ brachytherapy boost and EBRT, but the magnitude of this association was less pronounced.

Anthony D’Amico, MD, PhD, Chief of Genitourinary Radiation Oncology at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, said these findings are important because they show how personalized medicine for PCa is evolving.

“Multidisciplinary clinics not only bring together expertise from all the specialists involved in the care of prostate cancer permitting a discussion of all appropriate options, but also often provide the opportunity for both pathology and radiology review. All this contributes to optimizing the personalization of the treatment approach, which should lead to better cancer control outcomes,” Dr D’Amico said.

Amar U. Kishan, MD, Chief of Genitourinary Radiation Oncology at the University of California, Los

Angeles, California, said he agrees that these clinics are important in guiding appropriate treatment recommendations. “The authors report several key findings, including that men with lowrisk disease who were seen in the multidisciplinary clinic were significantly more likely to receive non-definitive therapy when compared with men from a large population registry, and, moreover, the trend to offer non-definitive therapy among low-risk patients was more marked over time and began to accelerate earlier in men seen at the multidisciplinary clinic,” Dr Kishan said.

Dr Kishan added that the new findings should be interpreted with some caveats.

“The analysis has several limitations, which the authors acknowledge, including the lack of detailed information about the general health status of the men in the population registry as well as the fact that men seen in the multi-disciplinary status may have significantly greater resources to pursue treatment than men in the population registry,” Dr Kishan said.

Any intervention that helps increase the delivery of guideline-concordant care will help improve overall outcomes for men with PCa, including not only cancer control outcomes, but quality of life outcomes, he added. The MultiD approach also may help mitigate racial disparities that are related to non-standard treatment recommendations. “These findings are important, and hopefully can help encourage the development of more multi-disciplinary clinics across the country,” he said.

‘Big fan of MultiD’ Judd W. Moul, MD, Professor of Surgery and the Director of the Duke Prostate Center at Duke University Medical Center in Durham, North Carolina, said the investigation by Dr Kuban and her collaborators is an excellent study and clinically relevant.

“This new paper from MD Anderson is the largest publication to date on the topic. I am a big fan of MultiD,” Dr Moul said. “We do a true MultiD clinic every Friday at Duke and have been doing it since 2004 and patients love being able to see a urologist and medical oncologist and radiation oncologist at same time.” ■

Guidelines for Advanced RCC Updated A RECENTLY UPDATED consensus statement from the Society for Immunotherapy of Cancer (SITC) recommends a combination of axitinib and pembrolizumab as initial therapy for patients with favorable-risk advanced clear cell renal cell carcinoma (aRCC), according to a report in the Journal of ImmunoTherapy of Cancer.

The updated recommendations, developed by the SITC’s Cancer Immunotherapy Guidelines Renal Cell Carcinoma Subcommittee, “are meant to provide guidance to clinicians with the most up-to-date data and recommendations on how to best integrate immunotherapy into the treatment paradigm for patients with advanced RCC.” For patients with intermediate- or poor-risk clear cell aRCC or whose disease has a sarcomatoid component, the society recommends ipilimumab plus nivolumab or axitinib plus pembrolizumab as upfront treatment. Anti-PD-1 monotherapy is recommended as initial therapy for patients with non-clear cell aRCC. Patients were categorized

Revised position paper includes a treatment algorithm for advanced RCC. as having favorable-, intermediate-, and high-risk disease based on criteria established by the International Metastatic RCC Database Consortium.

The updated recommendations are based on current FDA approvals for first-line therapy. The paper includes an algorithm to guide management of patients with aRCC. Treatment decisions, however, should be made on a case-by-case basis, according to panel members.

“The final selection of therapy should be individualized based on patient eligibility and therapy availability based on the treating physician’s discretion,” Brian I. Rini, MD, of the Cleveland Clinic Taussig Cancer Center, and coauthors wrote.

The subcommittee recommends central nervous system imaging for all patients, with bone imaging considered for symptomatic patients. ■

20 Renal & Urology News

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ACP Issues Testosterone Therapy Guideline Treatment should be limited to men with low testosterone accompanied by sexual dysfunction TESTOSTERONE replacement therapy (TRT) should only be prescribed to men who have age-related low testosterone levels with sexual dysfunction, according to a new evidence-based clinical practice guideline from the American College of Physicians (ACP), published in the Annals of Internal Medicine.

Discussions with patients should include the potential benefits, harms, costs, and patient preferences.

Clinicians should reevaluate symptoms within 12 months and periodically thereafter and discontinue treatment if there is no improvement. The guideline, which points out that the testosterone level at which to initiate TRT is not clear, does not address testosterone monitoring or hypogonadism diagnosis.

In the systematic review, ACP’s Clinical Guidelines committee examined 38 randomized controlled trials lasting at least 6 months as well as 20 long-term observational studies. They evaluated clinical

Fast Potassium Correction In the ED Critical QUICKLY NORMALIZING serum potassium levels in hyperkalemic patients visiting the emergency department (ED) might cut their death risk.

In a review of 114,977 ED visits to Stony Brook University hospital in New York during 2016 to 2017, 1033 patients (mean age 60 years; 58% male) presented with a serum potassium level of 5.5 mEq/L or higher. In-patient mortality (8.5% vs 0.8%) and hospital admission (80% vs 39%) rates were significantly higher in hyperkalemic than normokalemic patients, respectively, according to results published in the American Journal of Emergency Medicine.

In the hyperkalemia group, patients whose serum potassium level normalized to less than 5.5 mEq/L within 3 to 8 hours had a significantly lower death risk (6.3% vs 12.7%) than those whose serum potassium level remained persistently elevated, Adam J. Singer, MD, and colleagues reported. Normalization of potassium level were associated with a significant 53% lower mortality risk.

The team accounted for patient age,

outcomes using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system for sexual function, physical function, quality of life, energy/vitality, depression, cognition, serious adverse events, and major adverse cardiovascular events.

TRT should not be started to improve vitality, cognition, or physical function.

Analyses showed that global sexual function improved by 35% and erectile function by 27% with testosterone therapy compared with no treatment.

“The evidence shows that men with age-related low testosterone may experience slight improvements in sexual and erectile function,” ACP President

comorbidities, serum creatinine, and initial potassium level. Hospital and intensive care unit admission rates and length of stay appeared similar between groups.

Only 60% of patients presenting with hyperkalemia received treatment in the ED. Similar proportions of patients who did and did not experience potassium normalization received treatment.

It is unclear why some patients were resistant to therapy.

The authors stated that their study is the first showing that ED patients presenting with hyperkalemia have a lower mortality risk when their potassium levels normalize while still in the ED, compared with those whose potassium levels remain elevated, according to the investigators.

“If prospectively confirmed, our findings will have implications for ED operations as to more rapidly identifying hyperkalemic patients (e.g., the more standard use of rapid point of care testing as a mortality reduction intervention), as well as suggesting the necessity of the immediate implementation of [potassium] lowering therapy,” the authors wrote.

Newer potassium binding agents were not evaluated in this study, which is a limitation. Additional evidence and guidelines on which, or how many, therapies are safe and effective are needed, the investigators stated. ■

Robert M. McLean, MD, stated in a news release. “The evidence does not support prescribing testosterone for men with concerns about energy, vitality, physical function, or cognition.”

ACP suggests that clinicians consider intramuscular rather than transdermal formulations when starting TRT, as costs are considerably lower for the former and the clinical effectiveness and harms are similar. Based on paid pharmaceutical claims provided in the 2016 Medicare Part D Drug Claims data, ACP noted that the annual cost in 2016 per beneficiary of TRT was $2135.32 for transdermal formulations compared with $156.24 for intramuscular formulations.

“Most men are able to inject the intramuscular formulation at home and do not require a separate clinic or office visit for administration,” Dr McLean stated.

“These guidelines agree fairly closely with guidelines recently proposed by the Endocrine Society and the American

Urological Association,” E. Victor Adlin, MD, of Lewis Katz School of Medicine at Temple University in Philadelphia, commented in an accompanying editorial.

“Those organizations agree that treatment should be offered to older men with diminished sexual function and welldocumented low testosterone levels but should not be used for the less specific symptoms of fatigue and loss of vitality.”

With respect to serious adverse events from treatment, no trials were adequately powered to assess cardiovascular events, thromboembolic disease, prostate cancer, or death.

In a section on talking points with patients, ACP noted that clinicians should mention that TRT may improve sexual function in some men, but the amount of improvement varies. They also should point out that TRT is used to treat sexual symptoms, and therapy should be discontinued if these symptoms do not improve. ■

Anemia, Hyperuricemia Linked in Chronic Kidney Disease PATIENTS WITH chronic kidney disease

“These results demonstrate that the

(CKD) are at higher risk for hyperurice-

two conditions may have a direct rela-

mia if they have anemia, according to

tionship, and are not merely coexisting

findings of a Korean study published in

conditions,” the authors concluded.

Scientific Reports.

Jaejoon Lee, MD, of Samsung Medical

Among patients with CKD, anemia was significantly associated with

Center in Seoul, and collaborators ana-

hyperuricemia in patients with an eGFR

lyzed the relationship between anemia

of 30 to 60 mL/min/1.73 m2, but not in

and hyperuricemia in 10,794 adults from

those with an eGFR less than 30 mL/

the Korean National Health and Nutrition Examination Survey, 2016–2017, of

min/1.73 m2, Dr Lee’s team reported.

Anemia was more strongly associ-

whom 1302 (12.1%) had hyperuricemia

ated with hyperuricemia in patients

and 9494 (87.9%) did not (mean serum

aged 65 years or older and those with

uric acid levels 7.5 vs 4.8 mg/dL). In

hypertension or diabetes, regardless of

the CKD group, the prevalence of ane-

CKD status.

mia was higher in the patients with than without hyperuricemia (43.2% vs 28.6%).

Among individuals with CKD, the

In the non-CKD group, anemia was significantly associated with 32% decreased odds of hyperuricemia after

presence of anemia, compared with

adjusting for age, sex, BMI, alcohol

its absence, was significantly associ-

consumption, and other potential

ated with a 2.3-fold increased odds of

confounders.

hyperuricemia after adjusting for esti-

“The results of this study showed that

mated glomerular filtration rate (eGFR),

anemia and hyperuricemia are inversely

diabetes, hypertension, demographics,

correlated in non-CKD subjects,

body mass index, smoking, alcohol,

contrary to that in CKD subjects,” the

and physical activity.

authors wrote. ■

www.renalandurologynews.com JANUARY/FEBRUARY 2020

■ SUO 2019, Washington, DC

Renal & Urology News 21

Society of Urologic Oncology 2019 annual meeting, Washington, DC

Risk Factors for Post-RC Reoperation ID’d Higher BMI, COPD history, and black race predict a greater likelihood of reoperation within 30 days INVESTIGATORS HAVE identified factors that increase patients’ risk of reoperation following radical cystectomy (RC).

The results could help physicians identify patients at higher risk of adverse events prior to RC and allow them to adopt more aggressive approaches to minimize postoperative surgical complications, a team led by Zachary Klaassen MD, of the Medical College of Georgia in Augusta, and colleagues concluded in a poster presentation.

Using the American College of Sur­geons National Surgical Quality Improve­ment Program (NSQIP) database, Dr Klaassen and his colleagues identified 2608 patients (median age 69 years) who underwent RC for non-­ metastatic muscle-invasive bladder cancer (MIBC). Of these, 152 (5.8%) had a reoperation within 30 days of their RC. The median body mass index (BMI) of patients who had a reoperation within 30 days of RC was significantly higher than for those who did not (29.1 vs

Post-RC Reoperation Risk by Race Black race is among the risk factors for reoperation within 30 days of radical cystectomy, a study found. Shown here are the proportions of patients who underwent reoperation by race.

12

10.9%

n Black

10

n White n Other

8 6

5.1%

4

4.0%

2 0

Source: Sayyid R, Magee D, Hird A, et al. Reoperation within 30 days of radical cystectomy: Identifying high-risk patients using the American College of Surgeons National Surgical Quality Improvement Program Database. Presented at the Society of Urologic Oncology 20th Annual Meeting in Washington, DC. Poster 11.

27.8 kg/m2). The proportion of patients who had a reoperation in this timeframe was significantly higher for those with a history of COPD than for those no COPD history (12.3% vs 5.3%). In addition, black patients had a significantly higher rate of reoperation within 30 days compared with white patients and those of other races (10.9% vs 5.1% and 4.0%, respectively).

On multivariate analysis, each 1 kg/m2 increment in body mass index was significantly associated with 4% increased odds of reoperation within 30 days. A history of COPD was significantly associated with 2.2fold increased odds of reoperation compared with no history of COPD. In addition, compared with white race, black race was significantly associated

CN May Offer Survival Edge in mRCC CYTOREDUCTIVE nephrectomy (CN) may improve survival in patients with metastatic renal cell carcinoma (mRCC) receiving modern immunotherapy.

Nirmish Singla, MD, MSCS, of the University of Texas Southwestern Medical Center in Dallas, and colleagues studied 391 patients diagnosed with mRCC between 2015 and 2016 who were identified using the National Cancer Data Base (NCDB). Of these, 221 (56.5%) received both CN and immunotherapy and 170 (43.5%) received immunotherapy only. Of the

221 patients who received both treatments, 197 had upfront CN prior to immunotherapy and 24 received immunotherapy prior to CN. The median follow-up was 14.7 months among 183 patients with available survival data.

Patients who underwent CN plus immunotherapy had a significant 77% decreased risk of death compared with the immunotherapy-only group.

Immunotherapy prior to CN resulted in lower pT stage, Fuhrman grade, tumor size, and frequency of lymphovascular invasion compared with upfront CN.

The investigators observed no positive surgical margins, 30-day readmissions, or prolonged inpatient lengthof-stay among patients undergoing delayed CN after immunotherapy.

“This retrospective analysis must be interpreted within the context of limitations and biases inherent to the NCDB,” Dr Singla said. “However, our findings support an oncologic role for CN in the modern IO [immunotherapy] era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.” ■

with nearly 2.3-fold increased odds of reoperation.

Further, patients who had a reoperation within 30 days of RC were more likely to die and experience cardiac, pulmonary, neurologic, and venous thromboembolic events than those not reoperated on within 30 days of RC. They also had a longer hospital length of stay and infectious complications.

Results of the new study are in line with those of a study published online recently in Urologic Oncology, which found that COPD and obesity (BMI of 30 kg/m2 or higher) were significantly associated with 1.34- and 1.74-fold increased odds of reoperation within 30 days, respectively.

Longer operative times and smoking also increased 30-day reoperation risk.

The study, by Stephen W. Reese, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues, included 10,848 RC patients identified using the NSQIP database (2012-2017). Of these, 633 (5.8%) underwent unplanned reoperations. ■

PCa Death Risk Lower With RP RADICAL PROSTATECTOMY (RP) for non-metastatic prostate cancer is associated with better overall and cancer-specific survival than radiation therapy (RT).

Using a provincial population-based linked dataset from an equal-access universal healthcare system, Justin Oake, MD, and colleagues at the University of Manitoba in Winnipeg,

Long-Term RP Outcomes Good Despite High PSA MEN WITH prostate cancer (PCa) who have high PSA levels have good long-term cancer-specific survival following radical prostatectomy (RP), investigators reported.

Jack R. Andrews, MD, and colleagues at Mayo Clinic in Rochester, Minnesota, examined long-term outcomes among

1307 men who underwent RP at their institution and had a preoperative serum PSA level of 20 ng/mL or higher.

The investigators divided patients into 2 groups: high PSA (20-49 ng/mL, 1051 men) and extremely high PSA (50 ng/ mL or higher, 256 men). At 20 years, men with high and extremely high PSA

levels had rates of biochemical recurrence of 59.6% and 63.2%, respectively.

Rates of systemic progression at 20 years were 19.8% and 28.5%, respectively. The 20-year cancer-specific mortality rates were 12.8% and 20.5%, respectively.

None of the between-group differences were statistically significant. ■

Canada, compared 2540 men treated with RP and 1895 who underwent RT from 2004 to 2016 in Manitoba. The unadjusted 5-year overall survival rate was significantly higher in the RP than RT group (95.4% vs 84.5%). RT was significantly associated with a nearly 2-fold increased risk death from any cause and 4-fold increased risk of death from prostate cancer. ■

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Kegel Exercises May Not Be Best Option for SUI After RP

Cannabis Use Increases ED Risk in Men

Pelvic physical therapy appears more beneficial in a subset of men

MEN WHO SMOKE cannabis have nearly quadruple the risk of erectile dysfunction (ED) compared with men who do not use the substance, according to a new systematic and meta-analysis published in the American Journal of Men’s Health.

In 5 case-control studies of “good” quality—3 conducted in the Middle East and 2 in Europe — involving 3395 healthy men with a mean age of 20.1 years, 1035 disclosed cannabis smoking. In this group, 69.1% of cannabis smokers versus 34.7% of nonusers reported ED on the International Index of Erectile Function-5 questionnaire. In a meta-analysis, cannabis smokers had 3.8-fold increased odds of ED compared with nonusers, lead researcher Damiano Pizzol, MD, PhD,

BY JOHN SCHIESZER INDIVIDUALIZED PELVIC physical therapy may be a better option than standardized Kegel exercises for a subset of men who experience stress urinary incontinence (SUI) and pelvic pain following radical prostatectomy, according to study findings published in International Urology and Nephrology.

“This study is the first to demonstrate that pelvic physical therapy may be a beneficial treatment modality for men who have pelvic pain after prostatectomy, because the pain for some men may be attributable to pelvic floor myofascial pain associated with the pelvic floor overactivity issue,” first author Kelly M. Scott, MD, told Renal & Urology News.

The traditional line of reasoning is that men who have SUI after RP need to do Kegel exercises because their pelvic floor muscles are too weak, Dr Scott said. However, now it appears that men who have surgery often develop pelvic floor overactivity or muscle tightness postoperatively, and any type of pelvic floor dysfunction can lead to stress incontinence.

Individualized care may be needed “We may want to move toward a more individualized approach aimed at normalizing the pelvic floor function for each man,” said Dr Scott, Associate Professor, Department of Physical Medicine and Rehabilitation, University of Texas Southwestern Medical Center in Dallas.

She and her colleagues conducted a retrospective study with 136 patients with post-RP SUI and treated with pelvic physical therapy. Of these, 25 had underactive pelvic floor muscles, 13 had overactive pelvic floor muscles, and 98 had evidence of both. The mean time between surgery and start of physical therapy was 6.8 months.

Pelvic muscle relaxing, strengthening All men received therapy to either relax or strengthen their pelvic muscles. The total number of pelvic physical therapy sessions depended on a patient’s progress. Incontinence improved in 87% of them, with 58% achieving what is considered the optimal improvement

of needing 2 or fewer protective pads per day, according to the investigators.

In addition, pain was a problem for 27% of the men, but that proportion dropped to 14% by the end of therapy, which averaged slightly more than 4 sessions. In those men still experiencing pain at the end of therapy, the pain was significantly decreased (mean initial pain score 3.62 vs final mean pain rating of 1.08).

Healthcare providers who specialize in pelvic floor problems have come to understand that Kegel exercises can worsen pelvic floor overactivity and are not the best treatment for every patient, he said.

“We were expecting this study to show that a significant minority of men had overactivity in their pelvic floor muscles that could be contributing to their urinary incontinence, but the study actually showed that a majority of men have overactive pelvic floor dysfunction in this population. Most of the men also had some degree of muscle weakness, but not all of them,” Dr Scott said.

Compliance a problem Study limitations include problems with compliance, as 21% of the men did not fully adhere to treatment recommendations, Dr Scott and her collaborators reported. Some men attended fewer physical therapy sessions than

Most men with SUI following RP have overactive pelvic floor dysfunction. recommended or did not perform their ­prescribed home exercises. Another limitation was absence of long-term follow-up to determine whether improvement in incontinence was sustained beyond the end of treatment.

Aria F. Olumi, MD, Chief of Urologic Surgery at Beth Israel Deaconess Medical Center and Professor of Surgery/Urology at Harvard Medical School, Boston, pointed out that physical therapy was started close to the time

of surgery, so it is likely that many men would have experienced improvement in their urinary and pain related issues with time.

“Given the retrospective nature of the study and lack of a control group, the study is not designed to conclude whether pelvic floor training exercises would be beneficial for patients who have undergone radical prostatectomy,” Dr Olumi said. “However, pelvic floor training engages the patients in their rehabilitation process, and when available it’s a good resource to utilize postoperatively.”

Findings ‘hypothesis generating’ Shubham Gupta, MD, Chief of the Division of Reconstructive Urology at University Hospitals Urology Institute in Cleveland, Ohio, said the findings from this current study should be considered hypothesis generating rather than paradigm shifting. The study has important methodological limitations, Dr Gupta said, including its retrospective design, selection bias, and lack of a control group. “As such, the results are not generalizable,” Dr Gupta said.

Nevertheless, he noted that the study underscores that personalized treatment of post-RP incontinence may be warranted.

“Overall, this is excellent preliminary demonstration of the complex role of pelvic floor dysfunction in a setting of prior prostatectomy,” said Irene Crescenze, MD, a urologist at The Ohio State University Wexner Medical Center in Columbus. The role of pelvic floor physical therapy is well established in the management of female pelvic floor dysfunction and urinary incontinence, and it has been accepted by various national organizations, she said.

“As a field, we have been slow to adapt the role of pelvic floor in male voiding function, and male patients have been relatively resistant to accept pelvic floor physical therapy as a treatment option,” Dr Crescenze said. This new study, however, may convince both providers and patients of a need to seriously consider pelvic floor physical therapy as a treatment option for male patients with incontinence and pain. ■

Slightly more than 69% of men who smoke cannabis have erectile dysfunction. of the Italian Agency for Development Cooperation in Jerusalem, Israel, and colleagues stated.

“Understanding emerging risk factors for ED, particularly in relation to the increasing legalization of cannabis, is highly important. Approximately 147 million people—2.5% of the world’s population—consume cannabis annually. Although no medical specialty is dedicated to monitoring cannabis use and abuse, we believe urologists should make all male patients aware of the associated risk of ED,” Dr Pizzol told Renal & Urology News.

Among the possible mechanisms, cannabis smoking may bind receptors in the paraventricular nucleus of the hypothalamus, which regulates erectile function, Dr Pizzol’s team explained.

This mechanism could also explain why cannabis can improve sexual function in some patients affected by depression, anxiety, or pain, the authors noted. Other research suggests a peripheral effect of cannabis smoking on the cannabinoid receptors of the corpus cavernosum.

Most of the studies did not report the type, potency, and frequency of cannabis smoked, which is a limitation. ■

www.renalandurologynews.com JANUARY/FEBRUARY 2020

Renal & Urology News 23

Ethical Issues in Medicine Managing conflict of interest allows physicians to have industry relationships without biasing patient care BY DAVID J. ALFANDRE, MD, MSPH consequences are not significant. A recent study demonstrated that an author’s disclosure of a COI in academic publications did not affect peer reviewers’ assessment of the manuscript as high quality or appropriate for publication.4

Balancing risks and benefits Ethical principles both underlie and guide the COI process by helping to evaluate and balance the risks and benefits of relationships between physicians and industry. Partnerships between physicians and industry are common and may occur in a variety of settings, such as when pharmaceutical companies collaborate with physicians to participate in community-based research or when physicians are solicited to serve on speaker bureaus. Some of these relationships may present valuable opportunities to advance medical knowledge and even the quality of patient care. In other cases, however, these relationships may establish a secondary financial interest that introduces conscious or unconscious bias into clinical decision making and thus potentially adversely affect patient care. Balancing the potential risks and expected benefits of relationships with industry is critical to

Managing COI is necessary when disclosure alone is insufficient to protect patient interests but eliminating or avoiding COI is not possible or reasonable. their interests first, then patients are likely to mistrust them.2

Unintended consequences Despite the laudable goal of avoiding COI in medicine, debate remains about potential negative unintended consequences of COI disclosure. For example, critics of broad COI disclosure policies argue that such practices disrespect physicians by encouraging the public to assume that industry ties are always problematic.3 At the same time, empirical data suggest that other unintended

managing this problem and maintaining public trust. Avoiding, disclosing, ­ anaging COI then enables the and/or m medical profession to safeguard patient interests while allowing for reasonable financial relationships with industry.

Depending on a physician’s professional setting, there may be a policy or multiple policies that circumscribe acceptable practices regarding COI. These could include COI policies from physicians’ local medical institutions or professional societies, medical journals, state or federal employers, or

© SUEDHANG / GETTY IMAGES

D

iscussions about the role of conflicts of interest (COI) in medicine persist and are characterized by confusion, frustration, and debate over appropriate COI management. In my last column, I introduced the topic of COI by focusing on the importance of disclosure in the process. Although the column focused on COI in clinical care, the process is conceptually similar to the process for COI disclosure in research and continuing medical education. In this column, I discuss why, when, and how to manage COI. A COI in clinical care refers to instances in which physician judgment regarding a patient’s well-being is at risk of being biased by a secondary interest (like financial compensation) that can harm patients.1 A COI does not require that a patient be harmed or that it be proved a physician’s professional judgment is or was biased. COI only requires that the judgment regarding a patient’s well-being is at risk of being biased by a secondary interest. Disclosure of and managing COI is vital to establishing and maintaining the integrity of the medical profession and public trust.

If patients are not confident that their healthcare ­professionals are putting

Partnerships between physicians and industry may occur in a variety of settings.

grant funders. Broadly speaking, COI policies guide acceptable practices for how COI should be disclosed, which relationships should be prohibited or avoided, and, if not avoidable, how they can be managed appropriately.

Restricting involvement Managing COI is necessary when disclosure alone is insufficient to protect patient interests but eliminating or avoiding COI is not possible or reasonable. A physician who has a COI because of financial compensation from a device manufacturer should forgo membership on his hospital’s surgical device committee because that committee approves contracts between the hospital and device manufacturers.

Physicians have a COI because they sit on the board of a start-up medical services company competing for business at the hospital where they work. If eliminating the relationship entirely is impossible or impractical, restricting physicians’ involvement may help to manage the conflict. This might mean having the physicians serve only in a non-voting role on the company board, or recusing themselves from hospital deliberations that relate to the conflict.

COI will continue to be debated.

Promoting patients’ interests and

advancing productive collaboration with industry are both important goals.

For the debate to be productive, physicians should recognize the real ethical concerns raised and how they can affect patient care and professional integrity. At the same time, demanding good empirical data will help inform the debate by ensuring that arguments are not simply opinion, but grounded in science. ■ 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. McCoy M, Emanuel E. Why there are no “potential” conflicts of interest. JAMA. 2017;317:1721-1722.

2. Institute of Medicine. Conflict of interest in medical research, education, and practice. Washington, DC: National Academies Press, 2009.

3. Stossel TP 2008. Has the hunt for conflicts of interest gone too far? Yes. BMJ. 2008;336(7642):476.

4. John LK, Loewenstein G, Marder A, Callaham ML. Effect of revealing authors’ conflicts of interests in peer review: randomized controlled trial. BMJ. 2019;367:15896.

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Practice Management I

n medical school, students spend a lot of time thinking about how to communicate with patients and incorporate shared decision-making into their treatment. The American Medical Associ­a­ tion (AMA) believes it is time finance becomes part of that crucial conversation.

The AMA recently adopted a policy calling on medical schools and residency programs to include content related to healthcare economics. The AMA recommends training on topics like modes of practice, cost-effective treatments and testing, practice management, and the economics of practices in various financing systems.

Wise use of limited resources Susan Skochelak, MD, the AMA’s Group Vice President for Medical Education, said physicians can no longer separate clinical care and economics. She said she remembers being a broke college student years ago and needing antibiotics. Her doctor wrote her a prescription for a $40 medication when a much cheaper option, amoxicillin, would have been just as effective.

“Doctors may not be paying attention to things that could make a huge difference to patients,” Dr Skochelak said.

“They need to be trained to understand

Creating a curriculum To begin the process of familiarizing physicians with the financial and economic issues of patient care, AMA gave grants to 11 medical schools 5 years ago to develop curricula that incorporate instruction on these topics. Two years later, the AMA offered another round of grants and now supports 37 of the 150 medical schools nationwide in developing health sciences curricula.

With health economics training, AMA hopes to equip new doctors to provide cost-effective care and understand how the system works and impacts patients. Another objective is to help physicians understand that they have a leadership role in working with patients to select high-value care.

“They shouldn’t just order a hundred things and think more is better,” Dr Skochelak said. “And don’t just order something without knowing the patient’s copay.”

No one expects medical students to have an education in finance, but it is important they understand cost in a clinical context, she said.

“If they have an understanding around value-based care and looking at payments and payment approaches, they will have the confidence they need

AMA initiative is aimed at helping physicians understand that they have a leadership role in working with patients to select high-value care. they have a role in making sure they are using resources wisely and bringing value to their patients.”

Physicians need to place patient care into context by taking into account insurance coverage, copays, and eligibility for care such as mental health or long-term services. “A graduating student who doesn’t know the difference between Medicare and Medicaid is not good,” she said. “They are definitely smart enough to know that, we are just not putting it in front of them.”

when trying to negotiate contracts with insurers,” she said.

At the University of Michigan Medical School in Ann Arbor, students take an online course during the first year to learn about the university’s healthcare system and policies as well as various insurance options. Much of this information will help as the system moves toward value-based care, said Rosalyn Maben-Feaster, MD, assistant professor and director of the health systems science curriculum at the university.

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Integrating economics into medical training can help physicians deliver cost-effective clinical care BY TAMMY WORTH

Avoiding unnecessary tests is among the ways to deliver more cost-effective care.

In their fourth year, students learn about cost-conscious care, a response to the American Board of Internal Medicine’s (ABIM) Choosing Wisely campaign. As part of this initiative, some 70 medical societies have created more than 400 recommendations of tests and treatments that are overused.

ABIM survey findings In a physician survey about unnecessary testing in healthcare, ABIM found: • 73% said the frequency of unnecessary tests is a problem.

• 58% think providers are in the best position to deal with the problem.

• 53% said they will order an unnecessary test if a patient insists.

• 70% said if they tell the patient there is no need for the test, the patient typically avoids it.

The University of Michigan health system has tried to combat unnecessary testing and other services among providers in the field. For instance, Dr Maben-Feaster said if a provider tries to order a vitamin D test, a computer alert pops up with different indications that are not appropriate for testing. It suggests that the provider prescribe vitamin D supplements

instead of testing when a test will not change the outcome.

Dr Maben-Feaster said it was not until after medical school that she realized a patient’s insurance coverage or ability to pay for medications may impact a treatment plan. In today’s complex healthcare system, a patient’s drug formulary may differ each year. Something a patient was using one month may suddenly not be affordable the next.

“Doctors need to address that,” she said. “That may include talking to an insurance company or finding an alternative. But if they are not asking patients about these things, they don’t have the opportunity to help.”

Doctors can learn more about health economics by working with their billing department or their community’s social services agencies to understand external patient resources, Dr Maben-Feaster said.

In addition, the AMA has modules on health systems sciences on their website.

“The modules are well done and the people who did them are experts in those fields,” she said. “Those are a great way for people to get a quick overview and get some CME credit as well.” ■ Tammy Worth is a freelance medical journalist based in Blue Springs, MO.