Renal & Urology News - March-April Issue by Haymarket Media

M A R C H /A P R I L 2 0 2 0

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VOL UME 19, IS SUE NUMBE R 2

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Real-World mCRPC Treatment Revealed Recent studies shed light on how newer therapies work and are being used in routine clinical practice SIPULEUCEL-T

ORAL AGENTS

An analysis of Medicare claims data showed that men with metastatic castration-resistant prostate cancer who received sipuleucel-T as either first-line or any line of therapy had a longer median overall survival (OS)—shown below in months—than those treated with either abiraterone or enzalutamide. Sipuleucel-T 40

35.0%

35.2%

Oral agent (abiraterone or enzalutamide)

21.0%

20.7%

■ First line ■ Any line

Source: McKay RR, Flanders SC, Ferro C, et al. Overall survival (OS) among Medicare beneficiaries receiving sipuleucel-T (Sip-T) vs oral treatment for metastatic castration resistant prostate cancer (mCRPC). Data presented at the 2020 Genitourinary Cancers Symposium in San Francisco. Abstract 42.

RCC Linked to BMI in Early Life BY JODY A. CHARNOW EARLY BODY size, including birth weight and overweight, may predict a person’s risk of renal cell carcinoma (RCC) as adults, according to investigators. “Our findings indicate that RCC may originate earlier in life than previously thought and suggest that new explorations into the mechanisms underlying these associations should be undertaken,” a team led by Jennifer Lyn Baker, PhD, of the Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, reported in the European Journal of Epidemiology. For their observational cohort study, Dr Baker and her colleagues obtained information on measured heights and

weights of 301,418 children from the Copenhagen School Health Records Register born 1930 to 1985 and information on birth weight by parental report. The investigators identified RCC cases using the Danish Cancer Registry. RCC was diagnosed in 1010 individuals (680 boys, 330 girls) during 8.9 million person-years of followup. The median age at diagnosis was 62 years for both men and women. Results showed that each 500-gram increase in birth weight was significantly associated with a 12% increased risk of RCC in adulthood. Children who were overweight at age 13 had a significant 40% increased risk of RCC compared with those who had a continued on page 9

BY JODY A. CHARNOW SAN FRANCISCO—Physicians have seen their pharmaceutical options for treating advanced prostate cancer expand substantially in the past decade. In the years since these new medications received FDA approval and entered the marketplace, researchers have been evaluating the safety and efficacy and the prescribing of these drugs in the more varied population of patients seen in clinical practice than in the clinical trials that led to approval of the drugs. Such real-world studies presented at the 2020 Genitourinary Cancers Symposium have found that the performance of these newer treatments generally are in line with clinical trial findings but also have revealed

Intermittent Enzalutamide Dosing Safe SAN FRANCISCO—Evidence from a small single-center study suggests intermittent dosing of enzalutamide for metastatic castration-resistant prostate cancer (mCRPC) does not adversely impact overall survival (OS), increasing the time patients remain on treatment, investigators reported at the 2020 Genitourinary Cancers Symposium. Men who had intermittent dosing of enzalutamide also had prolonged time to PSA failure (TTF). A team led by Alastair Thomson, BM, MRCP, FRCR, of Royal Cornwall Hospital in Truro, United Kingdom, and colleagues retrospectively compared 110 men who were responding on continuous dosing to 29 who had at least a 1-month treatment break (intermittent group). All intermittently treated patients had a PSA response prior to their first treatment break, which was most commonly for fatigue (72%), Dr Thomson and his collaborators reported. The median continued on page 9

new information about treatment efficacy and provide a snapshot of how doctors are using the therapies in routine clinical practice. “These studies really help reinforce the translation of randomized clinical trial data to clinical care,” said symposium attendee Tanya B. Dorff, MD, a medical oncologist who is head of genitourinary cancers at City of Hope, a comprehensive cancer center in Duarte, California. “The clinical trials can tell us success rates in a select population, but they cannot tell us how those are translating into clinical practice. Almost always it seems like people are practicing differently than what data might suggest is recommended, and continued on page 9

IN THIS ISSUE 5

Researchers recommend a new standard of care for UTUC

Outpatient HoLEP can be safe regardless of prostate size

Aquablation and TURP offer similar long-term outcomes

Cooked or canned tomatoes may protect against prostate cancer

Cabazitaxel shows superiority for pain control in mCRPC

Metastasectomy beneficial in selected mRCC cases

Water irrigation found safe for uncomplicated URS Bone imaging for metastases should not be omitted in the staging of advanced PCa. PAGE 16

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SRT a Viable Option for Recurrent Prostate Cancer BY JOHN SCHIESZER NO CLEAR CONSENSUS guidelines exist for managing biochemically recurrent prostate cancer (PCa) after radical prostatectomy (RP), but evidence suggests salvage radiotherapy (SRT) is a viable option, according to the authors of an article in Nature Reviews Urology.

In addition, improved imaging and biomarkers are needed to help guide the management of patients with prostate cancer (PCa) who experience disease recurrence, according to Nicholas G. Zaorsky, MD, and Amar U. Kishan. “The results of the JCOG0401 trial suggest that standard hormonal

therapy alone is not an appropriate management strategy for recurrence when compared with salvage radiation therapy,” said Dr Kishan, Assistant Professor and Chief of Genitourinary Oncology Service at the University of California, Los Angeles. “Given the variable natural history of prostate

cancer after recurrence, not all recurrences need treatment.” The JCOG0401 trial showed that salvage ADT (SADT) was less effective than SRT. Dr Kishan and Dr Zaorsky wrote that these findings combined with subset results from the TOAD trial call into question the routine use

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of SADT alone in managing this patient population. The TOAD Trial examined immediate ADT versus ADT delayed by 2 years or more in men with PSA failure after initial definitive therapy or with noncurable disease. It was a randomized, multicenter, phase 3, nonblinded trial conducted at 29 oncology centers in Australia, New Zealand, and Canada. In general, patients with a recurrence after surgery stand to benefit more

from a local therapy (ie, salvage radiation) than simply a systemic therapy (ie, standard salvage hormonal therapy), Dr Kishan told Renal & Urology News. “However there are important emerging data about combining hormonal therapy with radiation, and there are also new imaging studies to help guide treatment decisions that will help identify who may benefit more from systemic versus local therapy,” he said.

Current guidelines from the National Comprehensive Cancer Network, American Urological Association, and European Association of Urology recommend considering SRT with or without SADT, or observation. None of these organizations recommend specific types of imaging in the salvage setting, however. JCOG0401 was a multicenter, randomized, open-label phase 3 trial that investigated whether SRT (64.8 Gy)

Renal & Urology News 3

followed by SADT (80 mg bicalutamide daily) in cases of SRT failure was superior to SADT alone in men with likely prostate-bed-predominant failures. In the study, which was the first to compare these strategies, time to treatment failure with bicalutamide was significantly longer among recipients of SRT with or without SADT than in the SADT-only arm (8.6 vs 5.6 years), with the SRT arm experiencing

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SRT a Viable Option

continued from page 3

a 44% decreased risk of treatment failure. However, the researchers found no differences in clinical relapse-free survival and overall survival. “I agree these data do not support use of SADT alone in patients with biochemical recurrence post-RP, and not all patients necessarily need to

be treated in this setting,” said Neha Vapiwala, MD, Associate Professor of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. “We do not presently have validated biomarkers ready for the clinic to help identify these different subsets, but ongoing improvements in imaging technologies and genomic capabilities can help to get us there.”

Howard Sandler, MD, Professor and Chair of Radiation Oncology at CedarsSinai Medical Center in Los Angeles, said men with recurrence after RP have an important opportunity for curative salvage therapy with radiotherapy as shown by older studies and the JCOG0401 trial. Although evidencebased guidelines support the recommendation for SRT, it is relatively underused in the United States. “The role

of hormonal therapy along with salvage RT is still being explored, but there are clearly subsets of patients who benefit from the combination of hormonal treatment and radiotherapy for recurrence after prostate surgery,” he said. “We hope that we can use tumor genomics and better imaging to better personalize recommendations for salvage treatment for the 30% or so of men who develop recurrence after prostate surgery.” ■

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Renal & Urology News 5

New UTUC Standard of Care Recommended ADJUVANT platinum-based chemotherapy within 90 days of nephroureterectomy reduces disease recurrence among patients with locally advanced upper tract urothelial carcinoma (UTUC), according to long-awaited results from the POUT (Peri-Operative chemotherapy versus sUrveillance in

upper Tract urothelial cancer) trial. In the phase 3 trial, 132 patients (pT2– T4, pN0–N3, M0 or pTany N1–3 M0) were assigned to chemotherapy and 129 patients to surveillance (standard care) after surgery. Adjuvant chemotherapy significantly improved disease-free survival by 55% at a median follow-up

of 30.3 months, with a 3-year diseasefree estimate of 71% compared with 46% for surveillance. In addition, adjuvant chemotherapy improved metastasis-free survival by 52% compared with surveillance, with a 3-year metastasis-free rate of 71% vs 53%, respectively, Alison Birtle, MD,

of the Royal Preston Hospital in the United Kingdom, and colleagues reported in The Lancet. With respect to safety, 44% of the chemotherapy group vs 4% of the surveillance group experienced acute grade 3 or worse treatment-emergent adverse events. “Our data, therefore, suggest that adjuvant platinum-based chemotherapy should be recommended as a new standard of care after nephroureterectomy for all patients with locally advanced UTUC in whom there are no definitive contraindications to chemotherapy,” Dr Birtle’s team wrote. “This regimen should be routinely considered for all patients in this population, and future studies should focus on combinations with novel agents in the adjuvant setting, which might further improve the prognosis for locally advanced UTUC.” The adjuvant chemotherapy regimen involved four 21-day cycles of intravenous (IV) cisplatin (70 mg/m2) or carboplatin (when glomerular filtration rate [GFR] was 30 to 50 mL/min/1.73 m2) on day 1 and (IV) gemcitabine (1000 mg/m2) on days 1 and 8. “Although the POUT trial has shown superiority of adjuvant chemotherapy over surgery alone, it is not clear that patients previously planned for neoadjuvant chemotherapy should now defer treatment until surgery is complete,” Dr Birtle and her collaborators wrote. “However, until further robust evidence becomes available, we propose that adjuvant treatment should be considered the preferred setting for future trials of perioperative chemotherapy in UTUC.” “Uro-oncologists now need to decide whether disease-free survival benefit represents an appropriate bar for practice change,” Simon J Crabb, MBBS, PhD, Associate Professor in Medical Oncology within Medicine at the University of Southampton in the UK, commented in an accompanying editorial. “Validation of disease-free survival as a surrogate for overall survival benefit is not yet formally established. Overall survival was a secondary endpoint but is not yet mature and will be the key question for planned future updates from POUT.” POUT investigators safely administered cisplatin at GFRs down to 50 mL/ min/1.73 m2, which possibly supports re-evaluation of the cutoff of 60 mL/ min/1.73 m2 used in most urothelial carcinoma trials, Dr Crabb wrote. ■

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FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Cancers, Viruses, and the Evolution of Fear

n The Emperor of All Maladies: A Biography of Cancer, the oncologist Siddhartha Mukherjee, MD, intuits, “Down to their innate molecular core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves.”1 Replace “cancer cells” with “viruses” and the quote holds equally true. Viruses and cancer cells share many traits. They are both enormously diverse, selfish, successful, Darwinian perpetrators of genomic dysregulation. Many viruses have integrated foundationally into the human genome. Indeed, nearly 8% of our genome is believed to consist of inactive viral sequences, an ancient graveyard of disabled invaders that attacked our ancestors eons ago now lying as “remnants of past infections.”2 Over billions of years of evolution, the complex genomic battle between virus and cellular host has varied from symbiosis, to detente, to revolution. In its most rapid, extreme, and antagonistic form, infection results in exuberant viral replication, uncontrolled inflammatory responses, communicable dissemination, and swift death of individuals or species by pandemic. In a slower but invariably malignant process, viral mediated cellular transformation leads to uncontrolled host cell proliferation and cancer death. For his discovery of hepatitis B virus and connecting the concepts of viral genomic integration and certain cancer risks along with the development of a vaccine and prevention of liver cancer by this mechanism, Barry Blumberg, MD, of Fox Chase Cancer Center in Philadelphia, won the Nobel Prize in Medicine some 40 years ago. Viral infections and cancers share more than just their desire for nucleic control. While the spectrum of these disease states are equally broad, ranging from indolent to virulent, perhaps the greatest and most universal human emotion stoked by both invasive ailments is fear. This is partly because of their universality, our personal histories, and their cryptic inevitability. It has been said that what the mind does not understand, it fears. As the world negotiates its first global pandemic in over a century, the lessons learned from our human responses to COVID-19 can teach us a great deal about our visceral response to cancer. As Neil Shubin put it in a Wall Street Journal article, both literally and figuratively, “Each of us is part virus (and part cancer), in ways that affect who we are and what we do.”2 Robert G. Uzzo, MD, MBA, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman, Department of Surgery Fox Chase Cancer Center, Temple University 1. Mukherjee S. The Emperor of All Maladies: A Biography of Cancer. Detroit: Gale, Cengage Learning. 2012. 2. Shubin N. The viruses that shaped our DNA. Wall Street Journal. Published online March 14, 2020.

Medical Director, Urology

Medical Director, Nephrology

Robert G. Uzzo, MD, MBA, 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 Kim Daigneau

Group creative director, medical communications Jennifer Dvoretz

Production manager Brian Wask

Vice president, sales operations and production Louise Morrin Boyle

Director of audience insights Paul Silver National accounts manager William Canning Editorial director, Haymarket Oncology Lauren Burke

Vice president, content, medical communications Kathleen Walsh Tulley

General manager, medical communications James Burke, RPh President, medical communications Michael Graziani Chairman & CEO, Haymarket Media Inc. Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 19, Number 2. 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). For reprints/ licensing, email Lauren Lau, The YGS Group, haymarketmedia@theygsgroup.com, (800) 290-5460. 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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Contents

MARCH/APRIL 2020

■

VOLUME 19, ISSUE NUMBER 2

Urology

ONLINE

this month at renalandurologynews.com

Study: Statins Protective in High-Risk PCa Men who used statins after their cancer diagnosis experienced decreased risks of allcause and cancer-specific mortality.

Anemia Linked to Prostate Cancer ADT Androgen deprivation therapy alone increased anemia risk by 63% compared with radical prostatectomy, a study found.

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

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

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

Kidney Disease Linked to Air Pollution The risk of chronic kidney disease stage 3 or higher increases along with concentrations of airborne fine particulate matter.

Frailty Ups Stone Risk in Diabetics Patients who reported 2 or more items on the FRAIL scale had a higher risk for urinary tract stones compared with non-frail patients.

Increasing Parathyroid Hormone Found to Worsen Symptoms Investigators document increased tiredness, bone aches and stiffness, muscle soreness, joint aches, overall pain, and itchy skin as PTH levels rise over time.

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

Some Approaches for Lower Pole Stones Better Than Others PCNL or retrograde intrarenal surgery are the most appropriate approaches for treating 1 to 2 cm lower pole kidney stones, a new systematic review and meta-analysis.

Editor’s note: With the cancellation of medical conferences thus far in 2020 in response to the COVID-19 pandemic and the status of other meetings unclear, we are providing listings of medical conferences scheduled for 2021. Genitourinary Cancer Symposium San Francisco January 21 to 23, 2021 American Urological Association Annual Meeting Las Vegas May 13–14, 2021 ERA-EDTA Annual Congress Berlin, Germany June 5–8, 2021 Canadian Urological Association Annual Meeting Niagara Falls, Ontario, Canada June 26–29, 2021 International Continence Society Annual Meeting Melbourne, Australia October 12–15, 2021

Nephrology

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

Metastasectomy May Benefit Selected Patients with mRCC Investigators observed improved survival among patients with intermediate- and highrisk disease who underwent the procedure.

CALENDAR

Elevated CKD Risk Observed in IBD Patients In a recent study, chronic kidney disease stage 3 or higher developed in 5.1% of patients with inflammatory bowel disease vs 3.5% of control patients.

The current study underlines the need to perform diagnostic imaging in men diagnosed with advanced prostate cancer in order to obtain correct diagnostic stage.

See our story on page 16

Departments 6

From the Medical Director Viruses, cancers, and the human response to COVID-19

News in Brief Poor compliance with trial reporting requirements documented

Ethical Issues in Medicine Physicians must manage their implicit biases

Practice Management Patient lawsuits for HIPAA breaches bring big settlements and awards

www.renalandurologynews.com MARCH/APRIL 2020

Real-world mCRPC tx continued from page 1

patients aren’t getting as many lines of therapy as we might hope they would.”

Sipuleucel-T Clinical trials leading to approvals of the newer therapies for advanced genitourinary cancers compared the treatments with placebo. Real-world studies, however, have enabled researchers to evaluate the performance of different agents in clinical practice, Dr Dorff said. She cited as an example a study by Rana R. McKay, MD, of Moores Cancer Center at the University of California, San Diego, and colleagues, who used Medicare claims data to examine the effect of sipuleucel-T on survival among 6125 men with metastatic castration-resistant prostate cancer (mCRPC). (See chart on cover.) Dr McKay’s team found that men who received sipuleucel-T—an autologous cellular immunotherapy approved in 2010 for treating asymptomatic or minimally symptomatic mCRPC—at any point in their therapeutic continuum experienced a significant 45% decreased risk of death and lived a median of 14.5 months longer than men who received only abiraterone or enzalutamide, Dr McKay’s team reported in a poster presentation at the symposium. In the setting of first-line

Enzalutamide dosing continued from page 1

number of treatment breaks was 1 (range 1-7), time to first break was 5 months, and time on treatment was 70%. The intermittent group had significantly improved OS compared with the continuous dosing group. The median survival time was not reached in the intermittent group and was 19 months for the continuous responders. The intermittent group had a significant 2.4fold reduced risk of death compared with the continuous dosing group. In addition, compared with the continuous dosing group, the intermittent group had significantly prolonged TTF (median 13 vs 6 months).

RCC linked to BMI continued from page 1

ormal body mass index (BMI) at that n age, according to the investigators. In addition, compared with children who had a normal BMI at ages 7 and 13 years, those who were overweight only at age 13 years had a significant 67% increased risk of RCC, a ccording to the

treatment, recipients of sipuleucel-T had a 43% lower risk of death than patients treated only with abiraterone or enzalutamide. Median survival was 14 months longer for the sipuleucel-T group than the recipients of only abiraterone or enzalutamide. Analyses did not adjust for potential confounding variables. “We believe these findings have revealed the importance of using treatments with complementary [mechanisms of action] to maximize patient survival outcomes,” Dr McKay said.

Medication sequencing Some studies presented at the symposium characterize how physicians today use the newer agents in sequence. A separate retrospective institutional study by Dr McKay and colleagues demonstrated wide variation in the use of radium-223, a bone-seeking radioactive isotope that emits alpha particle radiation that was approved in 2013 for use in men who have mCRPC with bone metastases. Of 220 men treated with radium-223 at Dana-Farber Cancer Institute in Boston, 64 received the drug prior to chemotherapy, 83 received it after chemotherapy, and 73 received no chemotherapy. And in a study of patients receiving care for advanced prostate cancer at Veterans Affairs medical centers, a

team led by Stephen J. Freedland, MD, of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai Medical Center in Los Angeles, found that sequential use of one androgenreceptor (AR) targeted agent (abiraterone or enzalutamide) after another was common despite new evidence that such back-to-back use of AR-targeted agents is associated with relatively low efficacy in certain scenarios. Among 32 men who received abiraterone for metastatic castration-sensitive prostate cancer, 25 (78%) received enzalutamide as their first-line treatment after progressing to mCRPC. Among 208 men whose disease progressed to mCRPC after receiving docetaxel, 196 (94%) received an AR-targeted agent as first-line therapy. Of the 113 who went on to receive a second line mCRPC drug, 70 (62%) received an AR-targeted agent again. In a separate study of 931 chemotherapynaïve men with mCRPC treated at private urology practices in the United States, Dr Freedland and colleagues found that the median baseline PSA at enzalutamide initiation was much lower in their cohort than in the patients in the randomized phase 3 PREVAIL trial (9 vs 54.1 ng/mL). The lower PSA at enzalutamide initiation could explain the longer time to PSA progression found in their study compared with the PREVAIL trial

Renal & Urology News 9

(median 18.5 vs 11.2 months). It might be that doctors are prescribing the drug earlier in the disease course than in the clinical trial, Dr Freedland said. In addition, unlike the PREVAIL trial, the study found that a lower proportion of patients had PSA reductions of 50% or more and 90% or more, “which may be attributed to more frequent PSA monitoring within a clinical trial setting and, thus, more opportunity to capture the true best PSA response,” Dr Freedland’s group reported in a poster presentation.

Investigators found wide variation in the use of radium-223 in men with mCRPC. As for why the use of medications might differ in real-world practice, Dr Dorff speculated that patient preferences might be a factor. For example, even when patients with mCRPC are informed that back-to-back use of AR-targeted agents would likely be less effective than moving on to chemotherapy, they may opt for the sequential AR-targeted therapy because they are concerned about the potential impact of chemotherapy on their quality of life, Dr Dorff said. ■

Men with metastatic prostate cancer are frequently on treatment for extended periods, so prevention and management of toxicity is key to maintaining quality of life, the authors wrote. “Our study suggests that the use of intermittent dosing of enzalutamide may be a safe and effective way of managing toxicities in patients who have already demonstrated a response to the drug,” the investigators concluded in their poster presentation. Although the intermittent group had improved overall survival, the authors acknowledged that the study population was small, so they interpret their survival data with caution. Dr Thomson’s group pointed out that, numerically, the intermittent group took longer to become castration

resistant than the continuous dosing group (median 37.8 vs 29 months). “It is possible that the intermittent group may be a subset of men particularly

sensitive to enzalutamide and would have had a long-lasting response if the drug had been given continuously. “Overall, I think it’s a good retrospective study,” said Yung Lyou, MD, PhD, a medical oncologist at City of Hope, a

comprehensive cancer center in Duarte, California, who was not involved in the research. Prospective studies are needed to establish whether intermittent dosing of enzalutamide and perhaps other antiandrogens is a safe strategy, but “at least the investigators showed that doing the intermittent dosing of enzalutamide didn’t have any detrimental effects.” If intermittent dosing is shown to be a safe and effective strategy, the approach could be used to improve patients’ quality of life and perhaps help patients save money, he said. Dr Lyou related that some of his patients decide on their own to stop taking enzalutamide periodically or take less than the prescribed dosage as a result of fatigue induced by the medication. ■

researchers. Individuals who were overweight at age 7 years only and at ages 7 and 13 years did not have an increased risk of RCC. The investigators defined overweight according to cut points suggested by the International Obesity Task Force. For girls, overweight at ages 7 and 13 years was a BMI of 17.69 kg/m 2 or higher and 22.49 kg/m2 or higher,

respectively. For boys, overweight at ages 7 and 13 was a BMI of 17.88 kg/m2 or higher and 21.89 kg/m2 or higher, respectively. Children who were persistently taller than average at ages 7 and 13 had a higher risk of RCC in adulthood than boys and girls with average height at ages 7 and 13 years. “Our results show that a high BMI in childhood relates to the risk of

RCC, and this extends the associations to younger ages than shown in previous studies,” Dr Baker and her collaborators wrote. “Adjustment for birth weight had little influence on the results, thus suggesting that the observed associations were not due to an effect of children with a high BMI also having a high birth weight.” ■

Men with intermittent dosing experienced significantly improved overall survival.

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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 FDA Agrees to Review NDA for Roxadustat

University School of Medicine in Suwon,

The FDA has accepted for review the

PNI using a combination of serum

New Drug Application (NDA) for roxa-

albumin level and lymphocyte count

dustat (FibroGen) for the treatment

in peripheral blood. On multivariate

of anemia of chronic kidney disease

analysis, PNI was an independent

(CKD) in both nondialysis-dependent

prognostic factor for recurrence-free

and dialysis-dependent patients.

and cancer-specific survival.

Korea, and colleagues calculated the

Roxadustat, an oral hypoxia-inducible promotes erythropoiesis by increasing

Study: Adverse Pregnancy Outcomes Up ESKD Risk

endogenous erythropoietin production.

Pregnant women who experience

Phase 3 trial data demonstrated that

adverse pregnancy outcomes such

roxadustat increases hemoglobin levels

as preeclampsia are at increased risk

and decreases the need for intravenous

for kidney disease later on, according

iron to a greater extent than epoetin

to new research findings published in

alfa in dialysis patients with anemia,

JAMA Network Open.

factor prolyl hydroxylase inhibitor,

with superior cardiovascular safety.

In a systematic review and meta-analysis of 23 studies involv-

PNI Found to Predict RCC Surgery Outcomes

ing 5,769,891 pregnant women,

The preoperative prognostic nutri

sociated with 2.1-, 4.9-, and 2.6-fold

tional index (PNI) independently

increased risks of chronic kidney

predicts survival outcomes among

disease, end-stage kidney disease

patients with nonmetastatic renal cell

(ESKD), and kidney-related hospitaliza-

carcinoma (RCC) who undergo partial

tion, respectively, Peter M. Barrett,

or radical nephrectomy, investigators

MB, MSc, of University College Cork

reported in the American Journal of

in Ireland, and colleagues reported.

Clinical Oncology.

Preterm preeclampsia was sig-

In their study of 459 patients, Se Joong Kim, MD, PhD, of Ajou

preeclampsia was significantly as-

nificantly associated with a 5.7-fold increased risk of ESKD.

Obesity Prevalence in the US Data from the National Health and Nutrition Examination Survey show that the age-adjusted prevalence of obesity (body mass index of 30 kg/m2 or higher) among US adults was 42.4% during 2017-2018. Here is the breakdown by age group. There were no significant differences in prevalence by sex or age group. 50 40

40.0%

44.8%

42.8%

40-59

60 and older

30 20 10 0

20-39

Age Group (in years) Source: Centers for Disease Control and Prevention; National Center for Health Statistics.

Gout Drug Safe, Effective for Patients on Dialysis F

ebuxostat is safe and effective for treating gout in patients on dialysis, according to a new study. A retrospective review of clinical and laboratory data from 62 dialysis patients (45 on hemodialysis and 17 on peritoneal dialysis) with gout treated with febuxostat showed that the mean serum uric acid level decreased significantly from 9.36 mg/dL prior to treatment to 3.71 mg/dL after 3 months of treatment, See Yoon Choi, MD, of Ulsan University Hospital in Ulsan, Korea, and colleagues reported in the Internal Medicine Journal. The serum uric acid level was significantly reduced at 3 months in both HD and PD patients, and subsequently remained at a significantly reduced level for 12 months. Of the 62 patients, only 2 discontinued febuxostat because of its adverse effects. An initial dose of 80 mg per day was associated with 8.2-fold increased odds of adverse events compared with a dose of 20 to 40 mg per day.

Reporting of Clinical Trial Results Poor, Study Finds C

ompliance with the federal requirements for reporting clinical trial results is poor and not improving, investigators concluded in a paper published in The Lancet. The Final Rule of the Food and Drug Administration Amendments Act (FDAAA) of 2007 requires sponsors of applicable trials to report their results directly onto the ClinicalTrials.gov website within 1 year of completion. The first trials were due to report results in January 2018. Of 4209 trials due to report results, only 1722 (40.9%) did so within the 1-year deadline, whereas 2686 (63.8%) had submitted results at any time, the investigators reported. “Our findings raise important questions around lack of enforcement and the need for public accountability,” Nicholas J. DeVito, MPH, and colleagues at the University of Oxford in the United Kingdom wrote. “This law was widely celebrated as a solution to the problems of publication bias and clinical trial reporting.

Oncologic Outcomes in UTUC Better With IVBC, Data Show I

ntravesical incision of the bladder cuff (IVBC) may provide better oncologic outcomes than non-intravesical techniques for patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). In a systematic review and meta-analysis of 9 international studies involving 4683 patients with primary UTUC, investigators found no significant differences among IVBC, extravesical incision of the bladder cuff (EVBC), and transurethral incision of the bladder cuff (TUBC) techniques. Compared with IVBC, however, non-IVBC methods were significantly associated with 37% and 45% increased risks of overall recurrence and intravesical recurrence, respectively, Shicong Lai, MD, and colleagues from the Chinese Academy of Medical Sciences in Beijing reported in the International Journal of Surgery. No significant differences were found between the EVBC and TUBC groups. “The findings suggest that IVBC is associated with improved oncologic outcomes and that it may be recommended for distal ureter management,” Dr Lai’s team wrote.

12 Renal & Urology News

MARCH/APRIL 2020 www.renalandurologynews.com

Kidney Disease Linked to Air Pollution As concentrations of fine particulate matter rise, so does the risk of CKD stage 3 or higher EXPOSURE TO HIGH LEVELS of air pollution containing fine particulate matter may increase an individual’s risks for albuminuria and chronic kidney disease (CKD), new study findings suggest. A growing body of evidence has linked particulate matter less than 2.5 µm in diameter (PM2.5) with a variety of health problems, including cardiovascular and respiratory diseases, diabetes mellitus, and early death. Recent studies have also linked PM2.5 with CKD death and increased hospitalization of hemodialysis patients. In the current study, published in the Clinical Journal of the American Society of Nephrology, Matthew F. Blum, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues estimated monthly mean PM2.5 concentrations (µ/m3) for 10,997 participants in the Atherosclerosis Risk in Communities (ARIC) cohort who resided in 4 US localities: Forsyth County, North Carolina; Jackson, Mississippi; suburbs of Minneapolis, Minnesota; and Washington County, Maryland. ARIC participants (mean age 63 years) were initially free of CKD (mean estimated glomerular filtration rate [eGFR] 86 mL/min/1.73 m2) and were followed from 1996–1998 through 2016.

Industrial processes are among the sources of fine airborne particulates.

Each 1-µ/m 3 increment in mean annual PM2.5 concentration was significantly associated with a 6.6% increase in urinary albumin to creatinine ratio (UACR) and a 5% increase in the risk for stage 3 or higher CKD (or 17.8 excess events per 1000 person-years), Dr Blum’s team reported. The investigators found no relationship between PM2.5 and baseline eGFR or conditions (such as cellulitis) serving as controls. The current findings generally agree with some previous studies on the topic conducted in various countries. “It is estimated that 17%–20% of the global toll of CKD burden may be attrib-

utable to PM2.5 pollution, and that the burden is unevenly distributed geographically and is more heavily tilted toward low and low-middle income countries, which might be least equipped to deal with the adverse health consequences of air pollution,” Ziyad Al-Aly, MD, and Benjamin Bowe, MPH, of Veterans Affairs St. Louis Health Care System, stated in an accompanying editorial. PM 2.5 are small enough to reach distal airways and alveoli. The timing, duration, and specific components of exposure are likely important. “The classic view that air pollution is a risk factor for upper and lower

respiratory airways is now challenged by evidence that air pollution may also impact other organs such as heart, vessels and kidneys,” Baris Afsar, MD, of Suleyman Demirel University School of Medicine, Isparta, Turkey, and colleagues stated in a 2018 review on air pollution and kidney disease published in the Clinical Kidney Journal. “The inflammatory mediators induced by PM and other pollutants in the lungs could spill over into the circulation, resulting in systemic inflammation, oxidative stress and damage to distant organs including kidneys. However, there is also evidence of direct harm to the kidneys. The pathogenesis is still not fully understood.” Fine particulate matter arises from many sources, including fossil fuel combustion, industrial processes, and natural sources such as wildfires or volcanic eruptions. Indoor sources of fine particles include smoke and fumes from tobacco, cooking, lit candles or oil lamps, fireplaces, and fuel-burning space heaters. According to Dr Blum’s team, “These findings support the role of PM2.5 exposure as a potential risk factor for CKD and suggest PM 2.5 mitigation efforts as a potential avenue for reducing CKD burden.” ■

HOLMIUM LASER enucleation of the prostate (HoLEP) can be performed safely as a same day surgical procedure for selected patients regardless of prostate size, according to investigators. In a retrospective study of 377 patients who underwent HoLEP from November 2013 through December 2018, investigators found that patients who underwent same day surgery (SDS) had postoperative complication rates and 30-day readmission rates that were not statistically different from those of patients admitted to a hospital overnight (non-SDS patients), a team led by Joel T. Funk, MD, of the University of Arizona in Tucson, reported in Urology. In addition, at 1 year follow-up, the 2 groups did not differ significantly with respect to maximum flow rate, postvoid residual, or International Prostate Symptom Score.

Dr Funk and his collaborators defined SDS patients as those discharged directly from a post-anesthesia care unit (PACU). To be considered for SDS, they had to live within the local metropolitan area (defined as living within city limits), have

Postop complication rate for outpatients was similar to that of hospitalized patients. immediate access to an emergency room, and have an ECOG 0-2 performance status. SDS exclusion criteria included any of the following: ECOG performance status 3-5, residence outside the local metropolitan area, unwillingness to be sent home with an indwelling catheter.

“The rationale of excluding patients for SDS was so that they would not have to make a long commute to clinic for their Foley catheter removal or in situations where patients may not have access to an emergency room if discharged.” Of the 377 patients, 199 met the criteria for SDS and 178 were categorized as non-SDS patients. Patients had a mean prostate volume of 89 cm3. The nonSDS group had a significantly higher proportion of patients with a history of urinary retention (54.5% vs 43.2%), lower mean preoperative maximum flow rate (5 vs 6 mL/s), and larger mean prostate volume (96 vs 83 cm3). The non-SDS group had a significantly longer mean operative time (132 vs 110 minutes) and longer mean length of stay (30.5 vs 3.9 hours average) than the SDS group. “Same day outpatient surgery for HoLEP is both safe and feasible and

should be considered regardless of prostate size, comorbidities, age, or anticoagulation status to decrease hospital stay and medical care costs,” the authors concluded. “HoLEP patients can be offered SDS if they live in relative close proximity, and have good functional status with ECOG 0-2. Other strict inclusion criteria or discharge criteria may not be necessary.” The authors acknowledged that their study had a potential for selection bias because it was retrospective and conducted at a single institution. In addition, the attending urologist’s assessment in the PACU of whether to discharge a patient was a subjective judgment based on preoperative ECOG status, hematuria, and recovery from anesthesia. “It is also possible that not all complications were captured due to patients reporting to other hospitals postoperatively.” ■

Same Day HoLEP Safe Regardless of Prostate Size

16 Renal & Urology News

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Report: Bone Imaging Needed When Staging Advanced PCa

Frailty Ups Stone Risk in Diabetics

Clinical factors do not reliably predict bone metastases, study finds

PHYSICAL FRAILTY increases the risk for urinary tract stones in patients with diabetes mellitus (DM), a population already shown to be at elevated risk for urolithiasis, according to a new report. “Our findings thus imply that frailty, as a degenerative trait that occurs prematurely in patients with diabetes, plays an under-recognized role in modulating their likelihood of developing urolithiasis in the future,” Chia-Ter Chao, MD, of National Taiwan University Hospital Beihu Branch, Taipei, and colleagues reported in BMJ Open Diabetes Research & Care. Using data from Taiwan’s Longitudi nal Cohort of Diabetes Patients from 2004 to 2010, the investigators studied 525,368 patients with DM: 338,121 (64.4%) without frailty and 187,247 with frailty as defined using the FRAIL scale. The scale includes 5 self-reported items: fatigue, resistance, ambulation,

2006 to 2016. Of these, 30,426 had undergone imaging at diagnosis. Of the 70,313 men who did not undergo imaging, 45,965 (66%) had favorable-risk PCa (T1-2, PSA less than 20 ng/mL, and GGG 1-2). These patients were considered to have nonmetastatic PCa and imaging had not been performed in accordance with Swedish guidelines.

BY JOHN SCHIESZER BONE IMAGING for metastases cannot safely be excluded when staging advanced prostate cancer (PCa), investigators concluded. In a nationwide, population-based cohort study, Frederik B. Thomsen, MD, of the Copenhagen Prostate Cancer Center at the Rigshospitalet,

Bone imaging is necessary when staging advanced prostate cancer because clinical factors such as PSA, T stage, and Gleason Grade Group cannot safely rule in bone metastases.

University of Copenhagen, and colleagues found that bone metastases could not be safely ruled in with sufficient accuracy using any combination of T stage, Gleason Grade Group (GGG), and PSA level. No PSA threshold could precisely identify the majority of men with metastatic PCa while also correctly classifying most men without metastasis. “We were surprised in that we could not identify a group of men with advanced tumor characteristics where we could rule in presence of bone metastases,” Dr Thomsen told Renal & Urology News. “There has previously been a perception that if the diagnostic PSA is 100 ng/mL or higher all men will have metastatic prostate cancer. This perception is based on older studies conducted before the introduction of PSA testing. This likely has resulted in omitting imaging in some men with advanced tumor characteristics because identifying metastases would not change the choice of treatment.” The study included 102,076 men diagnosed with PCa in Sweden from

Dr Thomsen’s group assessed metastasis risk by stratifying PSA levels based on T stage and 5-tier GGG. Among men who had not undergone bone imaging, advanced T stage, high GGG, and high PSA were related to bone metastases. Results showed that 0.2% of men with T1-2 and GGG 1 disease had PSA levels above 500 ng/mL, and 44% of these men had bone metastases, whereas 16% of men with T3-4 and GGG 5 disease had PSA levels above 500 ng/mL, and 94% of them had bone metastases. “The current study underlines the need to perform diagnostic imaging in men diagnosed with advanced prostate cancer in order to obtain correct diagnostic stage,” Dr Thomsen said. “We consider the study large enough to justify including imaging as a mandatory part of the diagnostic examination in these men.” He and his colleagues noted that PSA levels above 100 ng/mL have been used as a proxy for metastatic PCa based on results from small, single-center studies published in the 1990s. They

c ontend, however, that identification and quantification of metastases may be more important today in determining whether radical treatment is warranted. Extent of tumor on bone imaging is an indication for using treatments in addition to androgen deprivation therapy in men with metastatic PCa. Medical oncologist Rana McKay, MD, of Moores Cancer Center at the University of California, San Diego, said while PSA, Gleason score, and T stage are important clinical factors used for risk stratification, they have limitations when used to predict the presence of metastases at PCa diagnosis. “Imaging with computed topography and technetium 99m bone scans can be used for metastasis detection,” Dr McKay said. “Given that prostate cancer is the most common cancer in men, and the majority of patients present with lower risk disease, the routine use of imaging for all patients with prostate cancer independent of risk stratification requires caution.” In addition, she pointed out that positron emission tomography (PET), which has emerged as a diagnostic imaging platform for PCa detection, can complicate staging evaluation for patients with newly diagnosed disease. “My take is that this study doesn’t impact the current standard at all and only adds modest data to support current standard of care,” said Young E. Whang, MD, PhD, Associate Professor of Medicine in the Division of Hematology/Oncology at the University of North Carolina (UNC) School of Medicine in Chapel Hill, and member of the UNC Lineberger Comprehensive Cancer Center. Julio Pow-Sang, MD, Chairman of the Genitourinary Oncology Department at the Moffitt Cancer Center in Tampa, Florida, said the new findings are not surprising. Generally, the higher the Gleason score, PSA, and T stage, the higher the risk of finding metastasis in newly diagnosed men with PCa, especially those with the highest-risk disease. The probability of finding bone metastases on radiographic scans is extremely unlikely among men with low- and intermediate-risk newly diagnosed PCa, Dr Pow-Sang said. ■

Interventions directed at frailty may offer a way to ameliorate the risk of urolithiasis. illness, and loss of weight. Of the frail patients, 149,748 (79.9%), 34,463 (18.4%), and 3036 (1.6%) had 1, 2, and 3 or more FRAIL items at baseline. At least 1 episode of incident urolithiasis — most commonly renal stones — developed in 18,034 patients (3.4%) after 4.2 years of follow-up. Compared with non-frail patients, those who reported 2 items and 3 or more items on the FRAIL scale had significant 23% and 46% increased risks for urinary tract stones, respectively, in adjusted analyses. Patients who reported only 1 FRAIL item had a nonsignificant 4% increased risk of urolithiasis. “We discovered that having frailty was a significant predictor of developing urolithiasis in the future, with the probability of stone formation increasing stepwise with the severity of frailty,” the investigators reported. “Based on our findings, treatment against frailty may be a potential approach for reducing the risk of developing first-time and recurrent urolithiasis in patients with DM. ■

www.renalandurologynews.com MARCH/APRIL 2020

Renal & Urology News 17

Canned Tomatoes May Lower PCa Risk No protective effect found with raw tomatoes, tomato sauce, and tomato-based vegetable juice CONSUMPTION OF CANNED and cooked tomatoes may be associated with a decreased risk of prostate cancer (PCa), according to investigators. A prospective study of 27,934 Adventist men free of cancer at enrollment found that consumption of canned and cooked tomatoes 5 to 6 times a week was significantly associated with a 28% decreased risk of PCa compared with never consuming this food after adjusting for multiple potential confounders, Gary E. Fraser, MBChB, PhD, of Loma Linda University in Loma Linda, California, and colleagues reported in Cancer Causes & Control. The study found no significant association between PCa and consumption of raw tomatoes, tomato soup, tomato sauce, and tomatobased vegetable juice. “If our findings are explained by the lycopene contents of the tomato products, it is noted that lycopene is absorbed to a different degree by consumption of

different tomato-based products,” the investigators wrote. “Bioavailability is better if the tomatoes have been heated, as this facilitates the separation of the lycopene from the carrier proteins.” Dr Fraser’s team studied patients men enrolled in the Adventist Health Study2. At baseline, study participants filled out self-administered food frequency questionnaires in which they reported their average frequency of intake of various foods and beverages and serving sizes during the past year. During a mean follow-up of 7.9 years, the investigators identified 1226 new PCa cases, 355 of them aggressive. In a discussion of study strengths, the investigators noted that their data are based on extensive information on dietary habits, “which makes it possible to estimate the intake of lycopene and we have, at least to some extent, been able to correct for the considerable misclassification that complicates most

Aquablation, TURP Offer Similar Long-Term Outcomes AQUABLATION therapy is associated with

lower urinary tract symptoms (LUTS)

3-year outcomes similar to that of trans-

as indicated by an IPSS of 12 or higher,

urethral resection of the prostate (TURP)

and a Qmax less than 15 mL/sec.

for the treatment of lower urinary tract symptoms related to benign prostatic

years was 14.4 in the Aquablation

hyperplasia (BPH), new data suggest.

group and 13.9 in the TURP arm,

At 3 years, men who underwent

Peter Gilling, MD, of Tauranga Urology

Aquablation—which involves the use of

Research in Tauranga, New Zealand,

a high-velocity waterjet to resect pros-

and colleagues reported in the

tate tissue—and TURP showed similar

Canadian Journal of Urology. The mean

improvements in International Prostate

percent reduction in IPSS score was

Symptom Score (IPSS), maximal

64% and 61%, respectively. The 3-year

urinary flow rate (Qmax), and post-void

improvements in Qmax were 11.6 and

residual (PVR).

8.2 mL/sec, respectively. The mean

Investigators compared the treatment

3-year reduction in PVR was 52 and

approaches in a prospective study of

53 mL, respectively. The differences

181 men, of whom 116 and 65 were ran-

between the treatment arms were not

domly assigned to undergo Aquablation

statistically significant.

and TURP, respectively. Three-year

The mean reduction in IPSS at 3

“Combined with results of other

follow-up data were available for 97

prospective trials, 3-year results from

Aquablation and 55 TURP patients.

the current study provide compelling

The study included men aged 45 to

long term evidence for the safety and

80 years with a prostate size of 30 to

effectiveness of Aquablation therapy

80 mL (as measured by transrectal

in men with LUTS due to BPH,” the

ultrasonography), moderate to severe

authors wrote. ■

Canned or cooked tomatoes may protect against prostate cancer, a study found.

studies in nutritional epidemiology.” With regard to limitations, the authors acknowledged that they collected data on dietary habits only at baseline. Some previous studies have found associations between high intake of

Study: Statins Protective in High-Risk PCa STATIN USE ALONE or combined with metformin is associated with reduced all-cause and cancer-specific mortality among men with high-risk prostate cancer (PCa), according to a new study published in Cancer Medicine. In a population-based retrospective cohort study of 12,700 men with high-risk PCa identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, a team led by Grace Lu-Yao, PhD, MPH, of the Sidney Kimmel Cancer Center at Jefferson in Philadelphia, found that statin use alone or combined with metformin was significantly associated with an 11% decreased risk of allcause mortality and 20% decreased risk of PCa-related mortality compared with men who did not use either medication. The risk reductions were more pronounced among men who used statins after their cancer diagnosis. In these men, statin use alone was significantly associated with 27% and 42% decreased risks of all-cause and PCa-specific

lycopene, a carotenoid with antioxidant properties, and a reduced risk of PCa. For example, among 47,365 men in the Health Professionals Follow-Up Study, the highest vs lowest quintile of lycopene intake was significantly associated with a 16% reduced risk of PCa, according to findings published in 2002 in the Journal of the National Cancer Institute. Compared with consumption of less than 1 serving of tomato sauce per month, consumption of 2 or more servings per week was significantly associated with a 28%, 35%, and 36% reduced risk of organ-confined, advanced, and metastatic PCa, respectively. A systematic review and meta-analysis of 24 published studies found that the highest category of tomato intake, compared with the lowest category, was significantly associated with a 16% reduced risk of PCa, according to findings published in Scientific Reports in 2016. ■

ortality, respectively, compared with m men who did not use statins or metformin. Combined use of statins and metformin was significantly associated with a 32% and 54% reduction in the risk of all-cause and PCa-specific mortality, respectively. The study found no significant association between use of metformin alone and either all-cause or PCa-specific mortality. “The data presented in this paper provide crucial insight for the design of future randomized clinical trials of statin for high-risk PCa patients,” the authors wrote. The authors stated that their study, to the best of their knowledge, is the first to distinguish the individual and joint effects of statins and metformin on all-cause and PCa-specific mortality in patients with high-risk PCa. The study included men with highrisk prostate cancer who survived for at least 6 months. The men received their diagnosis of high-risk PCa from 2008 to 2011. The median age at diagnosis was 74 years. During a median follow-up of 42 months, 2182 patients (17.2%) died from any cause and 1078 (8.5%) died from PCa. Median survival with statins, metformin, and the combination of the drugs was 3.6, 3.1, and 3.9 years, respectively, and was 3.1 years for men who did not use either medication. ■

www.renalandurologynews.com MARCH/APRIL 2020

Renal & Urology News 23

Anemia Linked to Prostate Cancer ADT

Androgen deprivation therapy alone increased anemia risk by 63% compared with radical prostatectomy BY NATASHA PERSAUD ANDROGEN DEPRIVATION therapy (ADT) for prostate cancer (PCa) may increase the risk for anemia other hematologic disorders, new research suggests. Among 13,318 patients diagnosed with PCa in Taiwan’s National Health Insurance Research Database (NHIRD) from 1997 to 2013, a total of 8122, 1797, and 3399 patients received ADT only, radiation therapy (RT) only, and radical prostatectomy (RP) only, respectively. By design, no one could have received chemotherapy. Investigators matched the 3 treatment groups of 1797 patients by propensity score. Among the propensity-score matched groups, hematologic disorders developed in 787 patients during a median follow-up of more than 4.32 years. Compared with the RP group, men treated with ADT had a significant 1.63-fold increased risk for anemia and

1.60-fold increased risk for hematologic disorders overall in adjusted analyses, Jui-Ming Liu, MD, of Taoyuan General Hospital, and colleagues reported in PLOS One. The study found no significant increase in the risk of hematologic malignancies associated with ADT use. RT patients had significant 1.92- and 2.48-fold increased risks for anemia or hematologic malignancy, respectively. Patients with bone metastases who received only ADT had a 2.87-fold greater risk for hematologic disorders overall. Longer duration of ADT use was associated with higher risks. ADT for 12 months or more was associated with a 1.85-fold increased risk for hematologic disorders overall, whereas ADT use for less than 12 months was associated with a 1.56-fold increased risk, according to the investigators. Regarding the increased risk of hematologic malignancy associated with RT,

Elevated CKD Risk Observed in IBD Patients

impaired renal function. In this study, neither 5-aminosalicylate nor methotrexate was associated with reduced eGFR. Azathioprine was associated with a slightly higher eGFR (0.32 mL/ min/1.73 m2). Biologic medications are not usually prescribed by general practitioners in the UK, but these medications have not been associated with CKD among IBD patients in prior studies, according to the authors. “These findings have important implications for clinical practice, because gastroenterologists often monitor the renal function of patients receiving mesalamine to avoid nephrotoxicity, Dr Vajravelu’s team wrote. “Because this study indicates that all patients with IBD are at increased risk for CKD and that the risk is not conferred by mesalamine use, it may be reasonable to periodically monitor renal function in all patients with IBD, not just those taking mesalamine.” In a 2018 paper published in the World Journal of Gastroenterology, investigators in South Korea reported on a retrospective study that demonstrated a link between Crohn’s disease and an increased risk of end-stage kidney disease (ESKD). In adjusted analyses, patients with Crohn’s disease had a significant 6.3-fold greater risk of ESKD than age- and sex-matched controls without IBD. The study found no significant increase in ESKD risk among patients with ulcerative colitis. ■

INFLAMMATORY bowel disease (IBD), such as ulcerative colitis and Crohn’s disease, or their treatments may increase the risk for chronic kidney disease (CKD), according to new research findings published in Clinical Gastroenterology and Hepatology. Ravy K. Vajravelu, MD, of the University of Pennsylvania in Philadelphia, and colleagues conducted a retrospective study comparing 17,807 IBD patients from the United Kingdom with 63,466 matched control patients. Stage 3 or higher CKD, assessed by repeat measurements of estimated glomerular filtration rate (eGFR) or diagnosis code, developed in 5.1% of IBD vs 3.5% of control patients, with age-standardized incidence rates of 130.3 vs 91.3 per 100,000 personyears. The risk of CKD in patients with IBD diminished with age, from a 7.9-fold increased risk of CKD by age 16 years to a 1.13-fold increased risk at age 77 years. The risk was slightly lower with ulcerative colitis than Crohn’s disease. Active flare did not appear to influence eGFR. Previous studies have linked common nonbiologic IBD therapies with

the authors noted that exposure to ionizing radiation is known to increase the risk of cancer. Previous studies have linked RT to an increased risk of leukemia and lymphoma and found that bone

Risk of anemia and other hematologic disorders is highest with GnRH use. metastases involving bone marrow infiltration reduce hematopoiesis, resulting in anemia and leukopenia, they pointed out. ADT included gonadotropin-releasing hormone (GnRH) agonists (leuprolide, goserelin, buserelin, and triptorelin), oral antiandrogens (cyproterone acetate, bicalutimide, flutamide, and nilutamide), and estrogens (diethylstilbestrol and

estramustine). GnRH use was associated with significant 2.82- and 2.75-fold increased risks for anemia and hematologic disorders overall, whereas the oral antiandrogens alone were associated with significant 1.80- and 1.79-fold increased risks, respectively. Estrogen use was not associated with increased risks of any hematologic disorders. Regarding study limitations, the authors noted that PCa characteristics, including PSA level, clinical stage, and Gleason scores, were not captured in the database, precluding assessments by disease severity. Hemoglobin levels and other laboratory data also were not available, so they defined anemia according to the use of relevant ICD-9-CM codes and receipt of further treatments. In addition, despite their study’s long follow-up, “a longer lag time period may be required for the complete assessment of the incidence of subsequent hematologic malignancies.” ■

Increasing Parathyroid Hormone Found to Worsen Symptoms PATIENTS WITH secondary hyperpara-

of tiredness, bone aches and stiffness,

thyroidism (SHPT) experience worsen-

muscle soreness, joint aches, overall

ing of certain symptoms as parathyroid

pain, and itchy skin, Adrian Levy, PhD,

hormone (PTH) levels increase, new

of Dalhousie University in Halifax, Nova

data suggest.

Scotia, and collaborators reported

Investigators asked 165 patients with

in the American Journal of Kidney

SHPT (mean PTH greater than 600 pg/

Diseases. The remaining symptoms

mL or use of a calcimimetic and/or

might reflect some combination of

intravenous vitamin D) and who were

SHPT worsening, kidney failure, and/or

receiving hemodialysis to complete a

dialysis, they said. Greater use of SHPT

symptom assessment survey during

medications might explain the worse

4 successive visits within 6 months.

nausea. Overall, symptoms were most

Investigators developed the special-

severe when PTH levels increased by

ized survey using input from various

1000 pg/mL or more.

health care providers and focused on

“If proven valid and reliable, future

19 symptoms thought to worsen with

treatment of secondary hyperparathy-

SHPT: tiredness, overall weakness,

roidism could be based on symptoms

shortness of breath, diarrhea, vomiting,

such as aches/soreness/pain, itchy

nausea, loss of appetite, joint aches,

skin, and/or tiredness in addition to

joint stiffness, bone aches, bone stiff-

levels of PTH and other laboratory

ness, muscle soreness, muscle pain,

markers of disordered mineral metabo-

headaches, back pain, overall pain,

lism,” Dr Levy’s team wrote.

itchy skin, skin problems, and difficulty

They also observed: “Tailoring treat-

sleeping. Patients reported the severity

ment for the individual involves isolating

of each symptom using a Likert scale.

the relative contribution of the different

Increases in PTH levels over time were significantly associated with worsening

domains of difficulty and adjusting patient management accordingly.” ■

24 Renal & Urology News

■ GUCS 2020, San Francisco

MARCH/APRIL 2020 www.renalandurologynews.com

2020 Genitourinary Cancers Symposium, San Francisco

Metastasectomy In Selected mRCC Cases Found to Improve Survival Study reveals benefit in patients with intermediate- and high-risk disease BY NATASHA PERSAUD METASTASECTOMY IS associated with increased survival in patients with intermediate- and high-risk metastatic renal cell carcinoma (mRCC), new data suggest. In patients with intermediate-risk mRCC, the procedure also is associated with improved progression-free survival. “Metastasectomy should be part of multimodal treatment including systemic therapies for mRCC, especially in the intermediate-risk group,” researcher Margaret Frances Meagher, a medical student at the University of California San Diego, told Renal & Urology News. “Patient selection is critical and should take into account other important risk factors such as performance status, baseline hemoglobin and LDH levels, as well as surgical risks due to the location of metastasis. Further investigation is requisite to refine criteria.” Among 438 patients in the REgistry of MetAstatic RCC (REMARCC) database, 39% (18 of 46) of low-risk, 24% (63 of 262) of intermediate-risk, and 23% (32 of 140) of high-risk patients according to Motzer criteria underwent metastasectomy. A total of 180 patients

(41%) had oligometastatic disease. Metastasectomy was associated with significantly longer median overall (OS) in intermediate-risk patients (56.9 vs 29.3 months) and high-risk patients (18.2 vs. 10.5 months) patients, but not in low-risk patients, Meagher reported. Metastasectomy also was associated with significantly longer median progression-free survival (PFS) in interme-

Intermediate-risk patients experienced significantly longer median PFS. diate-risk patients (24.0 vs 6.7 months) but not in high- or low-risk patients. The sample size may have been too small to show a benefit in low-risk patients, Meagher said. The team is conducting a follow-up analysis to verify or refute these initial findings. Multivariate analyses revealed that older age, higher body mass index, and higher risk category significantly and independently predicted worse OS.

Compared with patients with low-risk disease, those with intermediate- and high-risk disease had 7.4- and 3.4-fold greater odds of disease progression, respectively, and 2.8- and 2.3-fold greater odds of death, the investigators reported. As expected, low-, intermediate-, and high-risk patients differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, hemoglobin levels, lactic acid dehydrogenase (LDH), and metastases at diagnosis (as risk category increased from low to intermediate to high, the odds of metastases increased by 1.7-, 3.5, and 6.5-fold, respectively). “The role of metastasectomy has been in flux as treatment paradigms for management of metastatic renal cell carcinoma have shifted,” Meagher said. “These study findings challenge prevailing assumptions about the utility of metastasectomy.” In the study, 29.2% of patients experienced a complication within the first 30 days of surgery, which compares well with published reports of complications for radical and partial nephrectomy in the setting of localized disease, according to Meagher. ■

PCa Deaths Not Linked to 5-ARIs USE OF 5-alpha-reductase inhibitors (5-ARIs) is not associated with an increased risk of death from prostate cancer (PCa), investigators reported. Lorelei Mucci, ScD, MPH, of the Harvard T.H. Chan School of Public Health in Boston, and colleagues performed 2 parallel analyses of data from the Health Professionals Follow-up Study. In that study, male health professionals reported 5-ARI use or nonuse on biennial questionnaires starting in 1996. Dr Mucci’s team examined 38,047 men for PCa incidence and mortality through 2016 and conducted a case-only study of 4225 men with localized/locally advanced PCa followed over a similar period. A total of 4101 men (10.7%) reported having ever used 5-ARIs, according to the investigators. These men were more likely to have had regular PSA screening (74% vs 57% for nonusers) and were more likely to have had a negative prostate biopsy prior to diagnosis (21% vs 9%). The investigators found no association between 5-ARI use overall or for longer use and risk of PCa death.

Cabazitaxel Possibly Better for Pain in mCRPC MEN WITH METASTATIC castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and an androgen-signaling-targeted agent (ARTA)—either abiraterone or enzalutamide—experience greater reductions in pain when treated with cabazitaxel rather than switching to the other ARTA. The new findings emerged from an evaluation of changes in pain and healthrelated quality of life (HRQoL) in the CARD trial, in which investigators randomly assigned 255 men with mCRPC who previously had received docetaxel and either abiraterone or enzalutamide to receive cabazitaxel or the alternative ARTA. Of the 255 men, 172 (67.5%) had moderate to severe pain at randomization. Pain response and HRQoL were evaluable for 111 men (86%) and 108 (83.7%) for cabazitaxel and 114

(90.5%) for ARTA recipients. A team led by Karim Fizazi, MD, PhD, of Institut Gustave Roussy, University of Paris Sud, Villejuif, France, defined pain response as a greater than 30% decrease from baseline in Brief Pain Inventory-Short Form (BPI-SF) pain intensity score with no analgesic use. Dr Fizazi and his colleagues assessed HRQoL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Pain response rates were significantly higher for cabazitaxel than ARTA (45.9% vs 19.3%). The probability of not having pain progression after 12 months also was significantly greater for the cabazitaxel recipients (66.2% vs 45.3%). Cabazitaxel-treated patients had a significant 45% decreased risk of pain progression after 12 months compared with ARTA recipients.

Cabazitaxel and ARTA patients experienced similar trends in HRQoL, Dr Fizazi’s team reported. An improvement in total FACT-P score from baseline was reported by 25% and 22.8% of the cabazitaxel and ARTA groups, respectively. FACT-P score was maintained or improved for 75% of the cabazitaxel arm and 75.4% of the ARTA recipients. “I think it’s a good study and a very important one, and I wish it had been done a lot earlier,” said Cy A. Stein, MD, PhD, a medical oncologist at City of Hope, a comprehensive cancer center in Duarte, California, who was not involved in the research. “It makes no sense to go from oral to oral [medication] when you have a drug like cabazitaxel, which can provide responses. This trial has really borne out that kind of thinking.” ■

As expected, median PSA levels at diagnosis were lower among men using 5-ARIs (10 vs 16 ng/mL for nonusers). Among nonmetastatic cases, 278 men died from PCa, but Dr Mucci’s team observed no association between 5-ARIs and PCa survival. The findings are in line with a study of participants in the Prostate Cancer Prevention Trial, which demonstrated no excess PCa mortality risk among 5-ARI recipients. The new study, however, contrasts with the findings of a study of veterans showing that prediagnostic use of 5-ARIs was associated with delayed PCa diagnosis and worse cancer-specific and overall survival in men with PCa. Dr Mucci and her colleagues noted that their data show the importance of using real-world data to examine the benefits and risks of 5-ARIs. ■

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MARCH/APRIL 2020 www.renalandurologynews.com

Water Irrigation Found Safe in Ureteroscopy Study reveals improved visualization compared with saline irrigation in uncomplicated cases WATER RATHER than saline irrigation for uncomplicated ureteroscopy (URS) does not increase the likelihood of hyponatremia and provides clearer endoscopic visualization, according to a new study. “The improved visualization with water irrigant offers an incentive to use water in URS and may improve efficacy and safety of URS, although this was not studied,” investigators reported in European Urology Focus. “Other incentives include higher availability of water and its low cost, relevant in resourcepoor countries.” In a prospective, double-blinded study, Kenneth Ogan, MD, of Emory University School of Medicine in Atlanta, and colleagues randomly assigned 121 undergoing URS to water irrigation (61 patients) or saline irrigation (60 patients). Patients’ median age was 56 years. Among the 101 patients who had nephrolithiasis, the mean number of

ED Is Linked to Prostate Zonal Volume GREATER PROSTATE zonal volume in patients with benign prostatic hyperplasia is associated with an increased likelihood of erectile dysfunction (ED), a new study found. Investigators at Suez Canal University in Ismailia, Egypt, found significant correlations between increased transitional

Erectile dysfunction is associated with increased transitional zone volume. zone volume (TZV), transitional zone index (TZI), and both the International Index of Erectile Function (IIEF) and penile peak systolic velocity (PSV). The study included 70 men, of whom 60 were assigned to 1 of 3 study groups (20 each). Group A included men who had lower urinary tract symptoms (LUTS)

stones was 1.96 and the mean stone burden was 12.68 mm. Overall, mean operative time was 35 minutes and mean irrigation volume was 839 mL. The water and saline groups did not differ significantly in rates of hyponatremia (2 vs 5 patients, none requiring treatment), hypo-osmolality (0 vs 0 patients), or hypothermia (3 vs 2 patients). The investigators observed no differences between the groups in hemolysis or fluid overload, although they did not objectively evaluate these conditions. With respect to adverse events, no between-group differences were observed in mortality, grade III Clavien-Dindo complications, emergency department visits, hospital admissions, or surgical reinterventions. Water provided better visualization than saline in URS. Mean postoperative turbidity was significantly lower with water: 64 vs 144 nephelometric turbidity units. Median surgeon visualization score, based on a Likert rating scale

and ED; group B included men who had LUTS with no ED; and group C included men who had ED but no LUTS. The other 10 men made up a control group (group D) of age-matched patients with no ED or LUTS. The investigators assessed ED using the International Prostate Symptom Score (IPSS) and IIEF questionnaires. They used Doppler ultrasonography to assess zonal anatomy and vascular patterns of erection. Groups A and C had a significantly lower PSV than groups B and D, a team led by Ahmed I. El-Sakka, MD, reported in Sexual Medicine. They found a significant positive correlation between TZI and IPSS and a significant negative correlation between TZI and both IIEF and PSV. The median total prostate volume was 41.5, 37.6, 23.5, and 20.5 mL in groups A, B, C, and D, respectively, the investigators reported. The median peripheral zonal volume (PZV) was 8, 10, 14, and 16 mL, respectively. The median TZV was 20.2, 16.7, 8, and 5 mL. The median TZI was 48.6%, 44.4%, 34%, and 25%. The median IPSS was 26, 19, 0, and 0. The mean IIEF was 10, 26, 15, and 28. Groups C and D had a significantly lower TZI and central zonal volume than groups A and B. ■

from 1 to 5, with 1 being poor visualization and 5 being excellent visualization, also was significantly higher with water: 4 (above average) vs 3 (average). “These appropriately powered findings suggest that water irrigant may be safe for use in uncomplicated URS procedures

Water vs saline irrigation did not increase the rate of hyponatremia. for the benefit of improved visualization,” Dr Ogan’s team wrote. “However, it would be prudent to have these results verified in larger studies to affirm the safety of water irrigant in URS and further characterize in which cases water may be used prior to changing practice.” According to the investigators, saline irrigation might be preferable for lengthy

or complex URS cases with ureteral perforation, children, and patients with renal failure or cardiorespiratory complications because these groups are at greater risk for fluid absorption and possibly electrolyte imbalances. The American Urological Association (AUA) guidelines on surgical stone management recommend saline irrigant in URS because risks associated with water irrigant have been reported in other endoscopic procedures, particularly in transurethral resection of the prostate (TURP) and, sometimes, in percutaneous nephrolithotomy (PCNL), the authors noted. Dr Ogan’s team pointed out that their findings differ from literature demonstrating the danger of using water irrigant in other endoscopic procedures, especially TURP and, when absorption is severe, PCNL. “We attribute this difference to the inherently increased invasiveness of PCNL and TURP.” ■

Some Approaches for Lower Pole Stones Better Than Others PERCUTANEOUS nephrolithotomy (PCNL)

“The decision between the two

or retrograde intrarenal surgery (RIRS)

approaches (PCNL or RIRS) should be

are the most appropriate approaches

individual, based on the anatomical

for treating lower pole kidney stones

parameters, the comorbidity and the

1 to 2 cm in size, according to a new

preferences of each patient,” Panagiotis

systematic review and meta-analysis

Kallidonis, MD, PhD, of the University of

published in the Journal of Urology.

Patras in Greece, and colleagues wrote.

For lower pole stones smaller than

Other important factors, such as stone

1 cm, RIRS outperforms shock wave

volume and hardness, could not be

lithotripsy (SWL).

assessed, which was a study limitation,

The study of data from 15 randomized controlled trials (published after

the authors noted. RIRS was 1.7-fold more effective at

2000) of moderate to high quality, PCNL

removing stones up to 1 cm in the

and RIRS resulted in 5.9- and 3.0-fold

lower pole than SWL. (PCNL was never

higher stone-free rates, respectively,

employed for these small stones.)

compared with SWL in patients with 1

RIRS took about 11 minutes longer to

to 2 cm stones. SWL was associated

perform than SWL, but complication

with shorter operative times and fewer

rates were similar and SWL required

complications than PCNL (for example,

more retreatment.

more blood transfusions were needed

“This observation underlines the higher

after PCNL), but required more retreat-

difficulty of SWL to treat the [lower

ment sessions (using any procedure).

pole stones] in comparison to stones

Hospital length of stay was longer for

located in other sites of the pelvicalyceal

PCNL compared with RIRS and SWL.

system,” Dr Kallidonis’ team stated. ■

www.renalandurologynews.com MARCH/APRIL 2020

Renal & Urology News 27

Ethical Issues in Medicine S

ignificant gaps in health outcomes by race, gender, and ethnicity persist. These health disparities are troubling to confront because they suggest some form of inequality in healthcare. For example, in the United States, compared with whites, black women have significantly higher rates of maternal mortality and black men have higher rates of prostate cancer mortality. Examining the problem at the level of an individual patient illustrates how the various influences may interfere with high-quality care. For example, one patient may not receive preventive colon cancer screening because of his or her autonomous choice to decline the recommended procedure as part of an informed consent discussion. Another patient, however, might not receive this cancer screening because his healthcare provider was less likely to recommend it to some of his patients. Finally, larger social determinants of health, like poverty and low literacy, may interfere with another patient obtaining such appropriate care. In reality, these factors probably combine with one another in many patients. From an ethics perspective,

unconscious bias. Implicit bias (IB) in healthcare is unconscious, unacknowledged thoughts and feelings that may interfere with fair, objective evaluations of different groups of people.1 This type of thinking is automatic, often culturally conditioned, and separate from rational thought processes. IB is distinguished from explicit bias or explicit prejudice in that IB is often contrary to one’s personal stated beliefs. For example, explicit bias is believing and taking a position that women are less competent than men in leadership positions. IB is an unconscious and unacknowledged attitude about women’s diminished competence in leadership positions but which is at odds with one’s explicit beliefs in gender equality. To the object of the bias, the explicit/implicit distinction is less important — bias or prejudice is always disrespectful regardless of whether the person is conscious of it or not. However, IB may be more amenable to change than explicit bias. There is strong evidence for the presence of IB among healthcare professionals. Using the Implicit Association Test, which measures unconscious implicit preferences, physicians demonstrate IB in their thinking in n umerous

Unconscious, unacknowledged thoughts and feelings may interfere with fair and objective evaluations of different groups of people. physicians have obligations to promote high-quality care, reduce healthcare disparities, and ensure they provide equal treatment to all of their patients. The AMA Code of Ethics specifies this responsibility in 1 of its 9 principles of medical ethics: A physician shall recognize a responsibility to participate in activities contributing to the improvement of the community and the betterment of public health. One way that physicians may be contributing to the perpetuation of healthcare disparities is through implicit or

contexts. In these studies, primarily using hypothetical scenarios, white physicians demonstrate a pro-white bias in providing more guideline-concurrent care to white patients over other racial minorities.2,3 Similar implicit biases have been demonstrated toward obese patients compared to those with normal weight and toward women compared with men.4,5 How exactly IB leads to health disparities is less clearly established and is an active area of research. Researchers believe that if IB leads to biased physician recommendations or

Physicians have an obligation to manage their implicit biases to address healthcare disparities BY DAVID J. ALFANDRE, MD, MSPH

Physicians should accept that implicit bias is an occupational hazard, not a moral failing.

to less positive, trustful clinical interactions with patients (which could reduce patient adherence), these could both lead to worse health outcomes for the biased populations.6 Because all physicians are susceptible to unconscious associations (in some cases, even physicians who are members of the biased group7), the first and most critical step is to recognize that IB can interfere with good clinical judgment. Indeed, “simply knowing about a stereotype distorts processing of information about individuals.”1 Physicians should accept that IB is an occupational hazard and not a moral failing or simply a way of assigning blame for health disparities. Second, slowing down the clinical reasoning process can allow for better appreciation of a patient’s perspective and individualizing of patient care.8 Despite the challenges, righting health disparities is the responsibility of all healthcare professionals. Even when the reasons for such disparities are multifactorial, healthcare professionals should minimize their contribution, whatever they might be. Seeking healthcare should not make some patients more vulnerable. That is something we should all get behind. ■

David J. Alfandre MD, MSPH, is a healthcare 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. Chapman EN, Kaatz A, Carnes M. Physicians and implicit bias: how doctors may unwittingly perpetuate health care disparities. J Gen Intern Med. 2013;28:1504-1510. 2. Green AR, Carney DR, Pallin DJ, et al. Implicit bias among physicians and its prediction of thrombolysis decisions for black and white patients. J Gen Intern Med. 2007;22:1231-1238. 3. Weitzman S, Cooper L, Chambless L, et al. Gender, racial, and geographic differences in the performance of cardiac diagnostic and therapeutic procedures for hospitalized acute myocardial infarction in four states. Am J Cardiol. 1997;79:722-726. 4. Borkhoff C, Hawker GA, Kreder HJ, et al. The effect of patients’ sex on physicians’ recommendations for total knee arthroplasty. CMAJ. 2008;178:681-687. 5. Schwartz MB, Chambliss HO, Brownell KD, et al. Weight bias among health professionals specializing in obesity. Obes Res. 2003;11:1033-1039. 6. Zestcott CA, Blair IV, Stone J. Examining the presence, consequences, and reduction of implicit bias in health care: a narrative review. Group Process Intergroup Relat. 2016;19:528-542. 7. Sabin J, Nosek BA, Greenwald A, Rivara FP. Physicians’ implicit and explicit attitudes about race by MD race, ethnicity, and gender. J Health Care Poor Underserved. 2009;20:896-913. 8. Burgess DJ, Fu SS, van Ryn M. Why do providers contribute to disparities and what can be done about it? J Gen Intern Med. 2004;19:1154-1159.

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Practice Management Patient lawsuits for breaches of protected health information result in big jury awards and settlements BY TAMMY WORTH

Actions taken Courts recognize a few different actions against providers who have a breach. Wolff said the suits are typically filed under breach of fiduciary duty, breach of contract, or negligence. State attorneys general can bring a class action civil suit on behalf of people harmed by a HIPAA violation. State laws regulating HIPAA suits vary widely. In some

how many people might have seen it, and strength of the evidence to prove the case. What potential plaintiffs want also matters, Wolff said. He typically will not take a case if they are just seeking money, but he listens when patients say breaches destroyed their lives and they want to ensure it does not happen to anyone else.

Major awards, settlements HIPAA compliance officers can only force providers to make changes within an organization to avoid future breaches, but the only recourse for patients who have been harmed by breaches is to sue for damages. This can be an effective deterrent. “Conduct rewarded is conduct repeated,” he said. “If they [providers] are hit in the pocketbook, they will retrain staff and make sure there is no second time.” Settlements and jury awards in these cases vary widely and can be well into 6 figures, depending on the facts and whether disclosure was accidental or intentional. “It’s like the difference between a car crash from someone skidding on ice versus one caused by someone who drives drunk and totals a car,” he said. A woman in St. Louis, Missouri, whose mental health records were released to her ex-husband during a c ustody

Providers often settle to avoid publicity and because they know the damages from a HIPAA breach will resonate with juries. an employer can be found liable for a snooping employee; in others, that’s not the case. Wolff said he signs up about 1 in every 10 patients who consult with him about suing a provider for an information breach. Many have legitimate cases, but these cases either cannot be proven or are weak. Factors affecting his decision to take a case include the sensitivity of the information, how it was transmitted,

suit settled a case for $385,000. In that case, the ex’s attorney subpoenaed the records and, without notifying the patient, the hospital mailed the records to the attorney. In a case in Alabama, a jury awarded $300,000 after a doctor accessed a woman’s drug history from the state’s prescription monitoring program. The woman was in a custody battle with her ex-husband, and his current wife asked

IPAA-related lawsuits came to the attention of Alexander Wolff when a fellow attorney called him with a case a few years ago. The plaintiff was a woman and friend of a man who was dating a nurse. The nurse, who worked at a hospital where the plaintiff received healthcare, was suspicious that the plaintiff and man were having an affair, so she accessed the woman’s chart. The nurse sent the man screen shots of the woman’s records. When he received the screen shots, he told the plaintiff. Wolff, a partner at Wolff & Wolff Trial Lawyers in St. Louis, Missouri, took the case and went to the hospital with the information and photos. The organization quickly settled the case, paying more money than he had anticipated. “They clearly wanted to make it go away,” he said. This initial case put HIPAA breach law on his radar.

HIPAA suits typically center on breach of fiduciary duty, breach of contract, or negligence.

the doctor to retrieve the records. The plaintiff sued the hospital for failing to discipline the doctor after notification of the breach. Some organizations are more likely to take cases to court than settle, such as when evidence is weak, Wolff said. Providers often settle to avoid publicity and because they know the damages from a HIPAA breach will resonate with juries, Wolff said. He added that he prefers to settle cases “if the value is there, but I am ready and willing to file suit if the provider does not take the complaint seriously or makes a low offer that does not satisfy my client.” He said he also prefers to settle with providers if this would make them less prone to future mistakes. “If you choose to operate a healthcare facility, you have to take it upon yourself to make sure employees are trained not to snoop on patients,” he said.

Proving damages Personal injury attorneys typically want objective evidence of injuries, such as X-rays or computed tomography scans. After Wolff took his first case and did some research, he realized he had happened upon a new kind of injury that would be hard to define.

For Wolff to take a case, he must be able to prove damages. His first client was humiliated and suffered sleepless nights for weeks. She was embarrassed her friend found out her personal information, but her real concern was who else might know. “She had no idea who else this nurse had told and there is no way to put that toothpaste back in the tube,” Wolff said. The plaintiff did not feel comfortable going back to the hospital where the breach occurred. Afterward, she found it difficult to reengage with the medical community in general.

Prevention An important way to prevent lawsuits is to perform consistent IT audits. Providers must understand who has access to different parts of an electronic medical records system and, when possible, allow staff to access only those parts of the system that enables them to do their jobs. “They have to have the flexibility to be able to do jobs,” Wolff said. “But there should be firewalls built into the system to keep people from doing things to expose you to trouble.” ■ Tammy Worth is a freelance medical journalist based in Blue Springs, MO.