Renal & Urology News - Nov/Dec 2018 by Haymarket Media

NOV EMBER /DECEMBER 2018

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VOL UME 17, IS SUE NUMBER 6

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Prostate Cancer AS: ‘Real-World’ Data Findings from community-based urology practices show disease factors guide PCa management WHY MEN GO OFF ACTIVE SURVEILLANCE Data from a community-based cohort of men on active surveillance (AS) for prostate cancer show that an increase in Gleason score on repeat prostate biopsy is the most common reason for abandoning AS.

55%

Gleason score increase

15%

Rising PSA Increase in disease volume on repeat biopsy Concerning findings on genetic testing

14% 0.6% 14%

No documented reason

Note: Percentages do not add up to 100% because of rounding.

Source: Shelton J. Data presented at the 2018 annual meeting of the Large Urology Group Practice Association, Chicago, Nov. 1-3.

PCa, Fatty Acid Intake Linked GREATER INTAKE of some fatty acids is associated with a higher risk of prostate cancer (PCa), with the risk increasing along with consumption, according to a new study. The finding is based on data obtained from 1903 men enrolled in a prospective cohort from 2000 to 2010 as part of the SABOR (San Antonio Biomarkers

of Risk) study and who had completed food frequency questionnaires. PCa was subsequently diagnosed in 229 of these men. The nutrient with the strongest association with PCa was stearic acid. As baseline intake of stearic acid increased from one quintile to the next, the risk of continued on page 14

ANSWERING A CALL FOR HELP IN PUBLIC PLACES

What is a doctor’s ethical obligation to assist a stranger? PAGE 23

BY JODY A. CHARNOW CHICAGO—Real-world evidence from a large contemporary cohort of men on active surveillance (AS) for prostate cancer (PCa) provides reassurance that disease characteristics rather than socioeconomic factors are driving how PCa patients are managed, Jeremy Shelton, MD, MSHS, Assistant Professor of Urology at the University of California, Los Angeles, told attendees at the 2018 annual meeting of the Large Urology Group Practice Association. The fi ndings are from an analysis of data from a retrospective review of charts from 557 patients placed on AS for localized PCa during 2013 and early 2014 at 9 large urology practices around the United States. The cohort

Upfront Combo for Advanced RCC Superior AVELUMAB PLUS AXITINIB combination therapy is associated with better outcomes compared with sunitinib alone as first-line treatment of advanced renal cell carcinoma (RCC), according to study findings presented at the European Society for Medical Oncology 2018 Congress in Munich, Germany. Avelumab is a PD-L1 inhibitor and axitinib is a tyrosine kinase inhibitor (TKI). In the randomized JAVELIN phase 3 trial that included patients with advanced RCC who received no prior systematic therapy, the median progression-free survival (PFS) irrespective of PD-L1 status was 13.8 months among recipients of the dual regimen compared with 8.4 months in the sunitinib arm, Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues reported. Among patients with PD-L1 positive tumors, median continued on page 14

is notable for its size, which is comparable to that of AS cohorts at major academic centers (“a little bit smaller, but in the same ballpark”) and because of how contemporary it is, Dr Shelton told Renal & Urology News. After a 3-year follow-up, 89% of the initial cohort was still receiving care at the diagnosing practice. Only 11% of patients were lost to follow-up, a proportion that Dr Shelton said he thought was low given that it is not uncommon for patients’ insurance plans to change and for people to move to different communities, among other reasons for changing providers At 31⁄3 years, 68% of the 591 patients remained on AS and 32% went off, continued on page 14

IN THIS ISSUE 2

Focal ablation for prostate cancer can be a reasonable option

Drinking more water may prevent recurrent cystitis

Neutrophil-to-lymphocyte ratio predicts response to abiraterone

Excellent outcomes reported for LDR brachytherapy

Androgen deprivation therapy increases fracture risk

Risk factors for RCC bone metastases identified

Ask the Experts: The role of race in PCa management

Smoking pot may hasten renal function decline in CKD patients. PAGE 12

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PCa Focal Ablation Can Be a Reasonable Option CHICAGO—Current imaging and biopsy capabilities make it possible for urologists to identify men for whom focal therapy for prostate cancer (PCa) is a reasonable option, according to Herbert Lepor, MD, Martin Spatz Chairman of the Department of Urology at New York University School of Medicine.

Although many important aspects of this approach are unknown, focal therapy is a minimally invasive procedure done on an outpatient basis and is associated with minimal treatment-related complications and expedited recovery, he said. “I’m very confident there’s no impact on

continence and minimal impact on potency,” Dr Lepor told attendees at the 2018 annual meeting of the Large Urology Group Practice Association. “I’m uncertain, of course, whether clinically significant recurrences or new tumors will develop during the patient’s life expectancy. I’m confident

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we don’t burn bridges for future curative intervention.” Some of the unknowns related to focal ablation include the optimal energy that should be used to ablate tissue, the extent of ablation necessary to achieve oncologic control, and the optimal way to assess oncologic control

www.renalandurologynews.com NOVEMBER/DECEMBER 2018

(such as the timing of PSA testing, magnetic resonance imaging [MRI], and biopsies). Moreover, no intermediateor long-term outcome data are available. Careful patient selection is paramount. For a patient to be a good candidate for focal therapy, he should meet certain criteria, which include high-quality pretreatment multiparametric MRI scans showing unilateral lesions; risk stratification into a Gleason grade group less

than 4; no Gleason pattern 4 found on systematic biopsy in the contralateral part the prostate; and no gross extracapsular extension. Other factors that may influence the decision to undergo focal therapy include life expectancy, site, extent, and aggressiveness of the cancer, and outcome priority of the patient. “A radical prostatectomy can be a very reasonable option, but if someone’s going to be devastated by poten-

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tial complications of sexual dysfunction, then [it] may not be such an excellent option,” he said. Patients need to be fully informed about the risks and benefits of focal therapy as well as the unknowns. “In counseling patients, it’s so critical to give valid outcomes expectations,” Dr Lepor stated. In addition, patients have to be willing to undergo postablation imaging

Renal & Urology News 3

and biopsy. “If you offer this [focal ablation], there must be a commitment on your part and the patient’s part for careful follow-up,” he said. Dr Lepor discussed the findings of a study in which he and his colleagues enrolled 59 men who met criteria for focal ablation but who underwent radical prostatectomy (RP). They examined the RP specimen for the presence of continued on page 4

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PCa focal ablation continued from page 3

Gleason pattern 4 disease outside of the focal ablation area. Prostate specimens from 15 of the 59 patients (25.4%) had at least 1 Gleason pattern 4 lesion outside of the focal ablation area. Of a total of 20 Gleason pattern 4 lesions, 7 (35%) were ipsilateral and 13 (65%) were contralateral to the MRI-detected lesion.

If hemiablation had been performed, some Gleason pattern 4 disease would have been left behind in 18.6% of cases. In virtually all cases, however, that lesion would have been less than 1 mm in diameter, Dr Lepor and colleagues reported in Urology (2018;112:121-125). He noted that about half of men placed on active surveillance for Gleason grade group 1 disease are found to have Gleason pattern 4 disease

after RP. Thus, the patients he selects for focal therapy actually have lower-risk disease remaining after ablation than patients placed on AS, he pointed out. Of the 200-300 cases of focal ablations for PCa performed at his institution, he related, he has yet to see a patient experience any level of incontinence, even immediately after catheter removal. Erectile function can be affected, however. The greater the

extent of the ablation, especially in cases in which a lesion is encroaching on the prostate capsule, the more likely it is that patients will experience transient erectile dysfunction. At his institution, surgeons usually remove patients’ catheters 2 to 4 days after the procedure, depending on the extent of ablation. Patients get PSA tests at 3 months and then every 6 months thereafter. “At the moment, our protocol is every patient at 6 months gets an MRI and a targeted biopsy of the ablation zone.” If patients have a negative MRI at 6 months and a stable lowering of PSA, the likelihood of finding significant disease in the ablation zone is very low, he said. Consequently, his institution is reassessing its existing follow-up protocol. ■

PPIs May Up Hip Fracture Risk in HD PROTON PUMP inhibitor (PPI) use may raise hip fracture risk among patients on hemodialysis (HD), researchers reported in the Clinical Journal of the American Society of Nephrology. “This investigation confirms needed vigilance for unnecessary long-term PPI use,” concluded a team led by Chandan Vangala, MD, of the Baylor College of Medicine in Houston. Using the US Renal Data System, Dr Vangala and colleagues identified 4551 patients on HD who had experienced hip fractures from 2009 to 2014. They compared these patients with 45,510 controls matched by index date (date of hip fracture). PPI use in the 3 years preceding a hip fracture was associated with significant 19% increased odds of hip fracture, in adjusted analyses. The study found no significant association between hip fracture and use of histamine-2 receptor antagonists. “The lack of an association with prior histamine-2 receptor antagonist use and the study patients’ hemodialysis-dependent status may suggest a more direct influence of PPIs on bone quality, as opposed to an effect on cation and nutrient stores,” Dr Vangala’s team concluded. ■

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Renal & Urology News 5

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD Medical Director, Urology

Medical Director, Nephrology

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

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

Urologists

Nephrologists

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

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

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

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

Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD, FACS Chief Executive Officer Inova Health System Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology CCLCM (ret.) Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California Irvine James M. McKiernan, MD John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology Columbia University College of Physicians and Surgeons, New York City Kenneth Pace, MD, MSc, FRCSC Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center, Memphis Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc. Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center Detroit Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J.

Renal & Urology News Staff Editor Web editor Production editor

Jody A. Charnow Natasha Persaud Kim Daigneau

Group art director, Haymarket Medical

Jennifer Dvoretz

Senior production manager

Krassi Varbanov

Director of production Assistant manager, audience development Director of audience insights National accounts manager Vice president, content, medical communications General manager, medical communications President, medical communications CEO, Haymarket Media Inc.

Louise Morrin Boyle Ashley Noelle Paul Silver William Canning Kathleen Walsh Tulley Jim Burke, RPh Michael Graziani

The Rapidly Evolving Landscape for mRCC

ess than 20 years ago, an individual with stage IV kidney cancer had few options: interferon or IL-2 immunotherapy with or without upfront cytoreductive nephrectomy (CRN). Outcomes with either treatment were poor, with a median overall survival of 8 months for immunotherapy alone and 14 months when combined with surgery. 1 Around 2006, the field underwent its first major breakthrough with the introduction of multitargeted tyrosine kinase inhibitors (TKIs). Suddenly, the median overall survival rates doubled to between 24 and 30 months depending on other risk factors. On October 1, 2018, the Nobel Prize in Physiology or Medicine was jointly awarded to Drs James Allison (USA) and Tasuku Honjo (Japan) for their discoveries of immune checkpoint inhibitors. Sentinel work performed by Dr Allison on the T-cell protein CTLA-4 and separately by Dr Honjo on PD-1 expressed on the surface of T cells led to their discovery of effective cancer therapies by inhibition of negative immune regulation: in other words, reinvigorating an antitumor immune response. Just 6 months earlier, the results of the Checkmate 214 trial were published. The study showed that in a population of primarily intermediate- to poor-risk metastatic renal cell carcinoma (RCC), treatment with the combination of ipilimumab (a CTLA-4 inhibitor) and nivolumab (a PD-1 inhibitor) was associated with a nearly 10% complete response rate and a median overall survival that had not been reached at the time of publication! In just over a decade, overall survival for metastatic RCC has increased 3- to 4-fold, forcing physicians to reassess the role of extirpative surgery for stage IV disease. Importantly, the recently published CARMENA trial noted that upfront systemic therapy with an oral TKI was noninferior to CRN followed by systemic therapy in selected intermediate- to poor-risk patients.2 While caveats exist, the trial demonstrates that refinements in surgical thinking must occur in parallel with improvements in systemic therapies. The speed of the evolving science and therapeutics in RCC is staggering. Most physicians do not see such incremental benefits and new treatment paradigms in their entire career, but in kidney cancer, we are seeing incredible progress in only a fraction of our own careers, and this progress is expected to keep accelerating. Robert G. Uzzo, MD, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman, Department of Surgery Fox Chase Cancer Center Temple University School of Medicine, Philadelphia

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 17, Number 6. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2018.

1. Flanigan RC, Mickisch G, Sylvester R, et al. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004;171:1071-1076. 2. Méjean A, Ravaud A, Thezenas S, et al. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med. 2018;379:417-27.

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Contents

NOVEMBER/DECEMBER 2018 ■ VOLUME 17, ISSUE NUMBER 6

Urology 16

ONLINE

this month at renalandurologynews.com 20

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.

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

RCC Bone Mets Risk Factors ID’d Older age and higher T stage at the initial diagnosis of renal cell carcinoma are among the risk factors for bone metastases. ADT Ups Fracture Risk, Study Confirms New findings strengthen the assumption that the link between androgen deprivation therapy and fracture is primarily bone related, according to researchers. The Role of Race in Prostate Cancer Management Michael S. Leapman, MD, and Adam C. Reese, MD, address questions related to whether a man’s race should enter into decision making.

CALENDAR 2019 Canadian Uro-Oncology Summit Toronto January 10–12 Genitourinary Cancers Symposium San Francisco February 14–16 European Association of Urology 34th Congress Barcelona, Spain March 15–19 American Urological Association Annual Meeting Chicago May 3–6 National Kidney Foundation Spring Clinical Meetings Boston May 7–11 ERA-EDTA 56th Congress Budapest, Hungary June 13–16

Nephrology

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

LDR Brachytherapy for PCa Yields Excellent Outcomes A study of 974 men with low- and intermediaterisk disease found an overall 10-year rate of freedom from biochemical failure of 88%.

Metabolic Syndrome Raises MI Risk Following PCNL Patients with 3–4 MetS conditions vs none have 2.2-fold greater odds of postoperative myocardial infarction. ESRD Tied to Oxalate Excretion Highest vs lowest quintile of 24-hour urinary oxalate excretion is associated with a 41% higher adjusted risk of end-stage renal disease. Dementia More Likely After AKI Among hospitalized patients, patients with AKI followed by complete renal recovery had a 3.4-fold increased risk of dementia compared with those who did not have AKI. CV Risk in Dialysis Patients Higher Among Women In a study of 96,729 patients who initiated dialysis, 41.8% of women had acute hospitalizations for major adverse cardiovascular events compared with 38% of men.

Departments 5

From the Medical Director The science and therapeutics in RCC are evolving rapidly.

News in Brief Regional disease at RCC diagnosis is more likely in blacks.

Ethical Issues in Medicine Are doctors obligated to render emergency medical aid?

Practice Management Behavioral economics can be used to improve patient care.

For low-risk and favorable intermediate-risk prostate

cancer, prostate brachytherapy represents an elegant and highly effective treatment in expert hands.

See our story on page 16

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Renal & Urology News 7

News in Brief

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

Short Takes Regional Disease at RCC Dx Less Likely in Blacks

colleagues identified 9 (6.5%) who had

Blacks are less likely than whites to

by magnetic resonance imaging. The

have regional or distant disease when

abnormalities included subacute hem-

diagnosed with renal cell carcinoma

orrhage in 3 patients and ischemia in

(RCC), regardless of cancer histology,

6 patients. All 9 patients complained

according to a new study.

of a few episodes of mild hematosper-

seminal vesicle abnormalities detected

An analysis of data from the Surveil-

mia during the 1 to 4 weeks following

lance, Epidemiology, and End Results

PAE. Hematospermia resolved sponta-

database found that, compared with

neously without treatment.

whites, blacks had significant 33% 18% lower odds of distant disease at

No Increased Diabetes Risk Found With SWL

RCC diagnosis after adjusting for age,

Patients who undergo extracorporeal

sex, tumor grade, and year of diagno-

shockwave lithotripsy (SWL) do not

sis, Jie Lin, PhD, MPH, and colleagues

have an increased risk of diabetes

from the Uniformed Services Univer-

mellitus compared those treated with

sity of the Health Science in Bethesda,

ureteroscopy, according the result of

Maryland, reported in the European

a retrospective study published in BJU

Journal of Cancer Prevention.

International.

lower odds of regional disease and

Michael Ordon, MD, of the University

Seminal Vesicle Problems May Be a PAE Complication

of Toronto, and colleagues identified

Seminal vesicle abnormalities may be

or ureteroscopy from January 1994 to

among the complications of prostatic

March 2014. Patients had a median

artery embolization (PAE), according to

follow-up of 6.6 years: 8.5 years in

a new report published in BMC Urology.

the SWL group and 5.6 years in the

In a review of 139 patients who

106,963 patients who underwent SWL

ureteroscopy group. On multivariable

underwent PAE for benign prostate

analysis, the investigators found no

hyperplasia, Jin Long Zhang, MD, of

elevated risk of diabetes mellitus in

Nan Kai University in Tianjin, China, and

the SWL patients.

Hypertension in United States Hypertension prevalence increases with age. According to federal statistics, here are the proportions of individuals aged 20 years or older in the United States who had hypertension in 2015–2016 by sex and age group. 80

71.7% 59.8%

43.4% 40 20

13.3%

38%

8.7%

20–44 years

45–64 years

65 and older

Age Groups Source: National Center for Health Statistics, Centers for Disease Control and Prevention. Health, United States, 2017.

■ Men ■ Women

Drinking More Water May Prevent Recurrent Cystitis D

rinking more water may prevent recurrent cystitis in premenopausal women who drink low volumes of fluid daily, researchers reported. Thomas M. Hooton, MD, of the University of Miami School of Medicine, and colleagues studied 140 healthy women (mean age 35.7 years) with recurrent cystitis (3 or more episodes in the past year) who reported drinking less than 1.5 L of fluid daily. They randomly assigned participants to drink 1.5 L of water daily in addition to their usual fluid intake (water group) or no additional fluids (control group) for 12 months. Each group had 70 participants. During the 12-month study period, the mean number of cystitis episodes was 1.7 in the water group compared with 3.2 in the control group, the investigators reported in JAMA Internal Medicine.

Metabolic Syndrome Raises MI Risk Following PCNL P

atients with metabolic syndrome (MetS) are at higher risk of myocardial infarction after undergoing percutaneous nephrolithotomy (PCNL), according to study findings published in the Journal of Endourology. “Routine preoperative cardiac testing may benefit this population before PCNL,” investigators concluded. MetS is a constellation of conditions that includes hypertension, diabetes mellitus, dyslipidemia, and obesity. Using the Healthcare Cost and Utilization Project State Inpatient Database for Florida and California, Carrie E. Johans, MD, of Loyola University Medical Center in Maywood, Illinois, and colleagues identified 39,868 patients who underwent PCNL for upper urinary tract stones. Of these, 19,268 (48.3%) and 2668 (6.7%) had 1–2 and 3–4 MetS conditions, respectively. The remaining 17,932 (45%) had no MetS conditions. On multivariate analysis, patients with 3–4 MetS conditions had significant 2.2fold increased odds of postoperative MI compared with those who had no MetS conditions. The odds of MI were not significantly increased among patients with 1–2 MetS conditions.

CKD Linked to Greater Interarm BP Difference I

ncreased difference in systolic blood pressure (SBP) between arms is an independent predictor of chronic kidney disease (CKD) in the general population, according to a retrospective study of 8780 adult patients. Investigators defined increased interarm SBP difference (IASBPD) as an SBP difference of at least 15 mm Hg and defined CKD as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. During a mean follow-up period of 8.5 years, CKD developed in 96 (16.5%) of 581 patients with IASBPD and 1037 (12.6%) of 8199 without IASBPD, Gwang-Sil Kim, MD, and colleagues at Inje University College of Medicine in Seoul, reported in the Journal of Hypertension. IASBPD was associated with a significant 27% increased risk of CKD compared with the absence of IASBPD, after adjusting for potential confounders, including age, diabetes, hypertension, and obesity.

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■ ASN 2018, San Diego

NOVEMBER/DECEMBER 2018 www.renalandurologynews.com

American Society of Nephrology Kidney Week 2018

ESRD Tied to Oxalate Excretion

Marijuana Use Found to Speed Renal Function Decline in Patients With CKD Study finds a more rapid annual drop in estimated glomerular filtration rate

HIGHER BASELINE 24-hour urinary oxalate excretion among patients with chronic kidney disease (CKD) is associated with an elevated risk of endstage renal disease (ESRD) and CKD progression, researchers reported. In a study of 3123 participants in the Chronic Renal Insufficiency Cohort (CRIC) study with median baseline eGFR of 43 mL/min/1.73m2, patients in the highest quintile of oxalate excretion (27.5–102.1 mg/24h) had a 41% higher adjusted risk of ESRD and 28% higher adjusted risk of CKD progression compared with those in the lowest quintile (1.4–11.5 mg/24h), according to a team led by Sushrut S. Waikar, MD, of Harvard Medical School in Boston. The investigators adjusted findings for age, sex, race/ ethnicity, baseline estimated glomerular filtration rate (eGFR), diabetes, body mass index, systolic blood pressure, hemoglobin level, serum albumin level, and medications. The study population had a median baseline eGFR of 43 mL/min/1.73 m2 and a median 24-hour oxalate excretion of 18.6 mg. The findings, if confirmed in other

BY JODY A. CHARNOW PATIENTS WITH chronic kidney disease (CKD) who use marijuana use may experience a more rapid decline in renal function than nonusers, a study found. The finding is from a post-hoc analysis of data from the ASSESSAKI (Assessment Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury) matched cohort study. Investigators defined CKD as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. Of the 1599 participants in the study, 113 (7%) used marijuana. Marijuana users were significantly younger than nonusers (mean 54 vs 65 years). Among patients with CKD at baseline, the mean annual rate of decline in eGFR was 3.22 mL/min/1.73 m2 among marijuana users compared with 1.42 mL/min/1.73 m2 among nonusers, a significant difference between the groups, a team led by Joshua L. Rein, DO, of the Icahn School of Medicine at Mount Sinai in New York, reported. Among individuals without CKD at baseline, the mean annual rate of decline in eGFR was 1.74 and 1.63 mL/min/1.73 m2 for marijuana users and nonusers, respectively, a nonsignificant difference.

CKD patients may need to avoid smoking pot.

In this group, marijuana use was not associated with development of CKD. Marijuana use was not associated with changes in albuminuria over time in patients with or without CKD. The investigators observed a strong but nonsignificant trend toward CKD progression—defined as a greater than 50% decrease in eGFR from baseline—among marijuana users with CKD at baseline. “Marijuana is the most commonly used recreational drug, and legal recreational and medicinal use is increasing worldwide,” Dr Rein told Renal &

Urology News. “With increasing use and availability of marijuana, we felt it was important to understand the impact of marijuana use on the risk of CKD.” Patients with advanced CKD and endstage renal disease experience substantial symptom burden that is frequently undertreated due to adverse medication side effects, he stated. “Medical marijuana may be effective at treating chronic pain and nausea, among other symptoms common to this patient population,” Dr Rein said. “However, the effects of smoked marijuana in those with significant kidney disease are unknown.” Marijuana use is increasing among adults, most rapidly among middle aged and elderly individuals, populations with a substantial CKD burden. “Recreationally, marijuana is most often smoked, and just like for tobacco, patients with CKD should not smoke marijuana,” Dr Rein said. “Medical marijuana is more commonly vaporized or consumed as a capsule or in food, which remove the cardiopulmonary side effects, but the renal effects remain unknown. Renal function in marijuana users with CKD should be closely monitored.” ■

studies, could lead to more wideoxaluria in patients diagnosed with CKD. The findings may also stimulate studies looking at whether lowering oxalate excretion could be a therapeutic strategy to preserve kidney function in CKD, Dr Waikar said. In an interview with Renal & Urology News, Dr Waikar said he became interested in oxalate excretion in CKD after diagnosing oxalate nephropathy in a long-term patient who had a typical case of CKD that he thought was due to hypertension. “She developed progressive kidney failure requiring dialysis, and we biopsied her due to the remote possibility of a druginduced interstitial nephritis from a new cancer chemotherapy drug,” Dr Waikar related. ■

Home Hemodialysis May Offer Better Survival MORE FREQUENT home hemodialysis (HHD) is associated with better first-year survival odds than in-center hemodialysis (IHD) among patients new to dialysis, a new study suggests. After 1 year of follow-up, the survival rate was significantly higher among patients on HHD compared with those on IHD (91.7% vs 81.4%), Eric D. Weinhandl, PhD, MS, and colleagues at NxStage Medical, Inc., of Lawrence, Massachusetts, reported. In adjusted analyses, HHD was associated with a significant 23% decreased risk of death compared with IHD. The survival advantage conferred by HHD was stronger among younger patients and decreases with age. Among patients aged 20–44 years,

45–64 years, and 65 years or older, HHD was associated with a 44%, 26%, and 11% decreased risk of death compared with IHD. Compared with IHD, HHD was associated with a significant 32% and 20% decreased risk of death among patients with an estimated glomerular filtration rate (in mL/min/1.73 m2) less than 10 and 10 or higher, respectively. “There are 3 key factors that distinguish the HHD population in this study: greater likelihood of pre-ESRD nephrology care, dialysis treatment in the home setting, and more frequent hemodialysis—4 to 6 treatments per week,” Dr Weinhandl told Renal & Urology News. “More frequent hemodialysis, in particular, has been shown

to improve multiple parameters of cardiovascular health.” The study included 1773 HHD and 555,366 IHD patients. HHD patients were younger than IHD patients (mean age 55.3 vs 60.3 years) and had higher proportions of white patients (81.3% vs 62.7%) and male patients (71.1% vs 57.0%), Dr Weinhandl’s team reported. HHD patients were less likely to be on Medicaid (9.5% vs 28.3%) and less likely to have heart failure (15.8% vs 31.3%). Investigators followed up HHD patients from the day of the first athome treatment and IHD patients from the 45th day after dialysis initiation. They followed patients until death, but for a maximum of 1 year. ■

spread screening for occult hyper-

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Renal & Urology News 13

High FGF23 Levels Increase Fall Risk in CKD HIGH LEVELS OF fibroblast growth factor 23 (FGF23) are associated with an increased risk of falls in patients with chronic kidney disease (CKD). The study, by Anna J. Jovanovich, MD, Assistant Professor of Medicine at the University of Colorado in Aurora, and colleagues, included 2488 participants in SPRINT (Systolic Blood Pressure Interventional Trial) with an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2. At baseline, the study population had a mean age of 73 years and mean eGFR of 49 mL/min/1.73 m2. After full adjustment, patients in the highest quartile of baseline intact FGF23 (iFGF23) had a significant 2-fold increased risk of a first fall compared with those in the lowest quartile. A doubling of iFGF23 was associated with a significant 2.3-fold increased risk of a first fall.

Dementia More Likely After AKI Acute kidney injury (AKI), even with complete renal recovery, is associated with a significantly increased risk of dementia. A team led by Jessica B. Kendrick, MD, of the University of Colorado School of Medicine in Aurora, performed a retrospective propensity score-matched analysis of 2082 hospitalized patients with no previous history of dementia. The investigators propensity score-matched 1041 patients with AKI followed by complete recovery (defined as discharge serum creatinine level less than 1.10 times the pre-admission baseline) with 1041 patients with AKI during the index admission. Dementia developed in 97 patients during a median follow-up time of 5.8 years. Dementia developed in a significantly greater proportion of patients in the AKI group than those in no-AKI group (7.0% vs 2.3%). Dementia was 3.4-fold more likely to develop among those in the AKI group compared with those in the no-AKI group. ■

“Frailty and falls are associated among older adults and individuals with end-stage renal disease,” Dr Jovanovich told Renal & Urology News. “Although we did not test for

frailty in our analysis, FGF23 could be a marker for frailty and falls in the CKD population.” Dr Jovanovich’s team obtained data on incident falls via a struc-

tured interview that occurred every 3 months. They recorded injurious falls as an adverse event if they were evaluated in the emergency department or required hospitalization. ■

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Abiraterone Outcomes Tied to NLR NEUTROPHIL-to-lymphocyte ratio (NLR) may predict response to firstline abiraterone treatment in men with metastatic castration-resistant prostate cancer (mCRPC), according to study findings presented at the European Society for Medical Oncology 2018 congress in Munich, Germany. In a retrospective analysis of the COU302 trial, which compared abiraterone-prednisone therapy with prednisone-placebo therapy in men with minimally symptomatic mCRPC, investigators found that patients with a baseline NLR less than 2.5, but not 2.5 or higher, derived significant benefit in terms of overall survival

Superior combo for RCC continued from page 1

PFS was 13.1 years in the dual-therapy arm compared with 7.2 months among sunitinib recipients. Compared with sunitinib therapy, the combination regimen was associated with a significant 39% decreased risk of disease progression in the overall cohort and 31% decreased risk among patients with PD-L1 positive tumors. The objective response (OR) rate was significantly higher for recipients of the avelumab-axitinib regardless of PD-L1 status (51.4% vs 25.7%) and among patients with PD-L1 positive tumors (55.2% vs 25.5%), according to the investigators. Dr Motzer’s team said they observed the PFS and OR benefit across all prognostic risk groups. As of June 20, investigators had randomly assigned 886 patients: 442 to the avelumab-axitinib group and 444 to the sunitinib group. Based on IMDC (International Metastatic Renal Cell

Carcinoma Data Consortium) c riteria, 21%, 62%, and 16% had favorable-, intermediate-, and poor-risk disease, respectively. For fewer than 1% of patients, no IMDC risk group was reported. Safety profiles were consistent with those of previous studies of each drug. Grade 3 or higher treatment-emergent

adverse events (AEs) occurred in 71.2% and 71.5% of patients in the combination and sunitinib arms, respectively. These AEs led to discontinuation of treatment by 22.8% and 13.4% of patients in the combination and sunitinib arms, respectively. The authors concluded that their findings support avelumab plus axitinib as a potential new first-line

standard of care for patients with advanced RCC. The study joins other recent trials showing inferior outcomes with sunitinib compared with other medications used as first-line therapies for advanced RCC. At the 2018 Genitourinary Cancers Symposium in February, Dr Motzer and colleagues reported on a phase 3 study showing that a first-line dual regimen of atezolizumab, a PD-L1 inhibitor, and bevacizumab, a vascular endothelial growth factor inhibitor, significantly decreased the risk of disease progression compared with first-line sunitinib in patients with previously untreated PD-L1 positive metastatic RCC. In the phase 2 CABOSUN trial, published in the European Journal of Cancer in May, Toni K. Choueiri, MD, of Dana Farber Cancer Institute in Boston, and colleagues demonstrated that cabozantinib, a TKI, significantly prolonged PFS compared with sunitinib as initial systemic therapy in patients with pooror intermediate-risk advanced RCC. ■

c olleagues said their analysis is the first to demonstrate a dose-dependent predictive value of fatty acid intake on future PCa risk. “These findings add further evidence that the intake of dietary fat is an important predictor of prostate cancer risk, and dietary modification of fatty acid intake may reduce this risk,” Dr Liss and his team concluded. “With a renewed interest in prostate cancer screening particularly for patients at high risk, dietary modification could be considered as a prevention strategy.” The PCa group was significantly older than men not diagnosed with PCa (mean age at baseline 61.7 vs 58.7 years) and they had a significantly

higher mean baseline PSA level (2.37 vs 1.29 ng/mL) and a significantly lower body mass index (27.15 vs 28.26 kg/m 2). The PCa group also had a higher proportion of men with a family history of PCa (39.7% vs 21.4%). The SABOR study is a National Cancer Institute Early Detection Research Network-sponsored Clinical and Epidemiologic Validation Center. It includes a multi-ethnic cohort of 3880 men from San Antonio and other south Texas areas. Although the study has limitations, it is strengthened by the large sample, prospective ascertainment of PCa cases, high PCa event rate, the ability to control for confounding variables, and regular protocol-specified follow-up. ■

on genetic testing (0.6%). No documented reason was available for 14%. “This work suggests that basic clinical factors predict adherence to active surveillance and we demonstrate that in the real world, it appears that patients are being managed by disease characteristics as opposed to socioeconomic characteristics,” he stated. Although only a small percentage of the cohort had intermediate-risk disease, he said AS may be an option for these patients if they have favorable characteristics, such as Gleason 3+4 disease. Dr Shelton said advances in magnetic resonance imaging (MRI) and genetic testing “will make AS even more safe

and effective because of improved risk stratification.”

Avelumab + axitinib found to improve PFS irrespective of PD-L1 status vs sunitinib.

(OS) from abiraterone-prednisone compared with prednisone-placebo. Among men with a baseline NLR below 2.5, patients who received abiraterone had a significant 28% decreased risk of death in adjusted analyses compared with those in the placebo arm, Thomas Loubersac, MD, of CHU de Nantes, Nantes, France, and colleagues reported. With respect to radiographic progression-free survival, men in both NLR groups experienced benefit from abiraterone, with the magnitude of benefit greater among those with an NLR below 2.5, according to the investigators. Among patients receiving abiraterone, those with a baseline NLR

PCa, fatty acid link continued from page 1

PCa increased by 23%, Michael A. Liss, MD, of the University of Texas Health San Antonio, and colleagues reported in Prostate Cancer and Prostatic Disease. Each successive quintile of baseline intake of total transfatty acids, total saturated fatty acids, gamma-tocopherol, and total fat was associated with a significant 21%, 19%, 15%, and 11% increased risk of PCa, respectively. Omega-3 fatty acids and polyunsaturated fatty acids (PUFAs) or any individual PUFAs were not associated with PCa risk. Previous studies have linked dietary fat to PCa risk, but Dr Liss and his

below 2.5 had significantly better PSA progression-free survival compared with patients who had a baseline NLR of 2.5 or higher. The investigators observed no significant differences in the placebo arm. The study by Dr Loubersac’s team included 1088 patients who were randomly assigned to receive either 1000 mg of abiraterone once daily plus 5 mg of prednisone twice daily or placebo plus 5 mg of prednisone twice daily. Mean NLR values increased significantly after treatment initiation and the end of the study compared with baseline. ■

PCa AS: ‘Real world’ data continued from page 1

57% had a repeat biopsy, and 21% had some kind of genetic testing to help stratify their risk of progression. Among men who discontinued AS, similar numbers of patients underwent surgery and radiation (48% vs 52% respectively). “People received treatment as one would expect by their disease and staging characteristics,” Dr Shelton said. The most common reason for men to go off AS was a rise in Gleason score on repeat biopsy (55% of cases), a rising PSA (15%), increase in disease volume (14%), and concerning findings

Younger patients Although AS may be seen as more risky for younger men because of their longer life expectancy, Dr. Shelton said “the evidence from other studies suggest that they do fine.” “Personally, I favor following younger patients more closely, potentially with regular repeat biopsies in addition to routine PSA and DRE, as well as utilizing genetic profiling and possibly MRI imaging, but the precise role and timing of these tools remains to be fully elucidated.” ■

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■ ASN 2018, San Diego

Renal & Urology News 15

American Society of Nephrology Kidney Week 2018

CV Risk in Dialysis Patients Higher Among Women WOMEN ARE more likely than men in the first year after starting dialysis to be hospitalized for major adverse cardiovascular events (MACE), investigators reported. In a study of 96,729 patients who initiated dialysis from January 1, 2007 to December 31, 2008, Silvi Shah, MD, and colleagues at the University of Cincinnati in Ohio found that, compared with men, women had a significantly higher frequency of acute hospitalizations for MACE (41.8% vs 38.3), congestive heart failure (CHF, 36.7% vs 33.1%), and stroke (5.8% vs 4.5%). Men and women had similar rates of unstable angina and acute myocardial infarction. In adjusted analyses, women had significant 16%, 17%, and 28% increased adjusted odds of acute hospitalization with MACE, CHF, and stroke, respectively, compared with

Gout Burden High in SOT Recipients GOUT IS MUCH MORE common among solid organ transplant (SOT) recipients than in the general US population, study findings suggest. Using Medicare and commercial claims databases, Mark D. Brigham, PhD, of Trinity Partners LLC in Waltham, Massachusetts, and colleagues found that the prevalence of active gout was 11.3% among SOT recipients (40,400 of 356,000 recipients) compared with 1.1% of the general US population (3,420,000 of 323,100,000 individuals), based on 2016 claims data. The prevalence was highest among kidney and heart transplant recipients (13.1% and 12.7%, respectively). Liver and lung transplant recipients had a prevalence of 6.7% and 5.6%, respectively, the investigators reported in a poster presentation. Of the SOT recipients with active gout, 73% received gout treatment and 27% did not. The investigators defined active gout as at least 1 claim with any gout diagnosis code in 2016. ■

men in the first year after starting dialysis, according to the investigators. Dr Shah’s team analyzed data from the US Renal Data System and linked Medicare claims data. Women made up

45.2% of the study population, which had a mean age of 70 years. The allcause 1-year mortality rate was 43.3%. “Cardiovascular disease remains the ortality leading cause of morbidity and m

in patients with end-stage renal disease,” Dr Shah told Renal & Urology News. “Our study finding indicates significant sex disparities in cardiovascular health among patients on dialysis.” ■

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LDR Brachytherapy for PCa Yields Excellent Outcomes

Dementia Not Linked to ADT, Study Finds

Long-term data show a local disease recurrence rate of 2.1% at 10 years

NEW RESEARCH may ease concerns that androgen deprivation therapy (ADT) contributes to dementia in patients with prostate cancer (PCa). Among 45,218 veterans who received definitive radiotherapy, with or without ADT, for nonmetastatic PCa, vascular dementia developed in 335 patients, Alzheimer disease in 404, and any other dementia in 758 over a median of 6.8 years, investigators reported. A regression model showed no statistically significant associations between ADT use and any form of dementia. Length of ADT use, whether 1 year or longer, did not alter the results. Investigators adjusted the model for demographics, Charlson Comorbidity Index score, and use of statins, antiplatelets, antihypertensives, alcohol, tobacco, and other substances. “These results may mitigate concerns regarding the long-term risks of ADT on cognitive health in the treatment of PC,” Rishi Deka, PhD, of Veterans Affairs San Diego Health Care System, and colleagues concluded in JAMA Oncology. They cautioned that the findings cannot be generalized to PCa patients having other treatments. With regard to study limitations, the authors noted that they only looked at patients who received radiotherapy, so results may not be generalizable to patients with PCa treated with another modalities. In addition, their study population included only veterans, so some differences in sociodemographic factors may exist that limit generalizability of results to the larger population of men with PCa. For the study, the investigators excluded patients who initiated ADT more than 1 year after their PCa diagnosis to avoid including men with metastatic disease. They also excluded patients who received chemotherapy because it may be related to development of dementia. Previous studies have found a statistically significant association between ADT use and dementia and Alzheimer’s disease risk in men with PCa, but these studies looked at heterogenous cohorts, including patients with localized and metastatic disease, treated with curative and palliative intent, and ADT use in the upfront or recurrent setting, Dr Deka’s team pointed out. ■

high-quality investigation with a carefully followed patient population. “This paper reaffirms what most radiation oncologists specializing in prostate brachytherapy already know,” Dr Folkert told Renal & Urology News. “For low-risk and favorable intermediaterisk prostate cancer, prostate brachytherapy represents an elegant and highly

BY JOHN SCHIESZER LOW-DOSE-RATE (LDR) brachytherapy appears to provide excellent outcomes in men treated for localized organ-confined prostate cancer (PCa), according to researchers at Mayo Clinic in Rochester, Minnesota. In a study of 974 men who received I-125 LDR brachytherapy for low- and

Study finds an 88% 10-year rate of freedom from biochemical failure with LDR brachytherapy.

intermediate-risk PCa, a team led by radiation oncologist Brian Davis, MD, found that the 10-year rate of freedom from biochemical failure was 88% overall, but was significantly worse for men with intermediate- than low-risk disease (76% vs 92%). The local recurrence rate was 2.1% at 10 years. The men had a mean follow-up period of 72 months. The investigators defined biochemical failure by Phoenix criteria (PSA nadir + 2 ng/mL). On multivariable analysis, primary Gleason 4+3 disease, higher pretreatment PSA, and absence of androgen deprivation therapy (ADT) were the only factors associated with biochemical failure. Gleason 4+3 disease increased the likelihood of distant metastasis and PCa-specific death, Dr Davis’ team reported online ahead of print in Brachytherapy. Michael R. Folkert, MD, PhD, Assistant Professor of Radiation Oncology at the University of Texas Southwestern Medical Center in Dallas, who was not involved in the new study, called the work by Dr Davis and his colleagues a

effective treatment in expert hands. Prostate brachytherapy is a convenient and proven approach for managing prostate cancer with a single visit to the operating room for seed placement.” For patients with more aggressive disease, such as those with Gleason 4+3 disease, a PSA level greater than 10 ng/mL, or disease involving half or more of the prostate, brachytherapy alone may be insufficient, as cancer control rates were only 74% at 5 years in the current study. “This still compares favorably with surgery, where 5-year control in the unfavorable intermediate-risk population would be expected to be between 32% and 68%,” Dr Folkert said. Judd W. Moul, MD, Professor of Surgery and the Director of the Duke Prostate Center at Duke University Medical Center in Durham, North Carolina, said these study findings are highly relevant because the researchers looked at a very large series with a relatively long-term follow-up. “The authors use the Phoenix criteria, which is a full 2-point rise in the posttreatment PSA level from the posttreatment nadir PSA,”

Dr Moul said. “While this is proper and meets guideline criteria for biochemical recurrence after radiation, it is also somewhat controversial as compared to the recurrence definition of 0.2 or higher for surgically treated men. In other words, some experts, particularly experts who favor surgery, feel the Phoenix definition of recurrence of allowing the PSA as high as 2.0 ng/mL or even greater (if the nadir was detectable) artificially makes radiation ‘look better’ than surgery with regard to biochemical control.” However, he said he generally tells his patients that all treatments for low- and intermediate-risk disease offer similar outcomes at 7 to 10 years, and this study confirms that. Despite the findings from Dr Davis’ team, Dr Moul said he believes surgery is generally preferable for disease control for men who have a greater than 20-year life expectancy. “However, I really would love to see these data reexamined after a median of 15 years of follow-up to help answer the age-old question of what is better for young men with very long life expectancy,” he said. Urologic oncologist Soroush RaisBahrami, MD, Associate Professor of Urology and Radiology at the University of Alabama at Birmingham,

Primary Gleason 4+3 disease increased the likelihood of death from prostate cancer. said the oncologic outcomes with LDR prostate brachytherapy as measured in this current study are less optimal in patients with Grade Group 3 or greater tumors. These men may be better candidates for other forms of treatment, including radical prostatectomy or external beam radiation therapy with concurrent ADT. Also, “as the use of active surveillance increases for men diagnosed with low-grade and selected favorable intermediate-risk Grade Group 2 cancers, the oncologic efficacy of LDR brachytherapy as a singlemodality treatment should be balanced with its risks and side effect profile,” Dr Rais-Bahrami said. ■

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ADT Ups Fracture Risk, Study Confirms New findings strengthen the assumption that the link between ADT and fracture is primarily bone-related

RCC Bone Mets Risk Factors ID’d OLDER AGE, male sex, lymph node involvement, and higher T stage are among the risk factors for bone metastases at the initial diagnosis of renal cell carcinoma (RCC), according to investigators. In a study of 45,824 patients newly diagnosed with RCC, 1509 (3.29%) had bone metastases at initial diagnosis, Qi Guo, MD, of the First Affiliated Hospital, Army Medical University, Chongqing, China, and colleagues reported recently in Cancer Management and Research. The incidence of bone metastases was 3.87%, 1.52%, 0.80%, and 18.1% among patients with clearcell, papillary, chromophobe, and collecting duct RCC, respectively. On multivariable analysis, older age, male sex, higher T stage, lymph node involvement, poor tumor grade, and the presence of lung, liver, or brain metastases were associated with significantly greater odds of bone metastases at diagnosis. Compared with patients aged 40 years or younger, those aged 41–69 and 70 years or older had 1.9- and 1.6-fold

ADT increased hip fracture risk by 38%.

13,128 men with PCa who did not receive ADT. The investigators identified 10,916 incident fracture—including 4860 hip fractures—during a followup of about 270,300 patient-years.

increased odds of bone metastases at diagnosis, respectively. The odds of bone metastases at diagnosis were 25% higher among men than women, and 2.2-fold greater among patients who had lymph node involvement compared with those who did not. Compared with patients who had T1 disease, those with T2, T3, and T4 disease had 3.8-, 3.0-, and 2.8-fold increased odds of bone metastases, respectively. The median survival time for RCC patients with bone metastases was 12 months, but this varied by RCC subtype. The median survival times for those with collecting duct, clear-cell, papillary, and chromophobe subtypes were 3, 13, 8, and 11 months, respectively. On multivariable analysis, patients with papillary and collecting duct RCC had a 1.8- and 2.1-fold increased risk of death, respectively, compared with patients who had clear-cell RCC. Dr Guo’s team identified their study population using the database of the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The investigators acknowledged that their study had limitations. For example, they lacked information on asymptomatic patients, so the actual incidence rate of bone metastases among patients with RCC may be underestimated, they pointed out. ■

Compared with men who did not have PCa, those who had PCa with ADT had a significant 40% higher risk of any fracture, 38% higher risk of hip fracture, and 44% higher risk of major osteoporotic fracture (MOF), after adjusting for multiple potential confounding variables. Compared with men with PCa but not ADT, ADT recipients had a significant 34%, 38%, and 34% increased risk of any fracture, hip fracture, and MOF, respectively. The investigators found no increased risk of any fracture, hip fracture, or MOF among men with PCa who did not receive ADT. Men with PCa receiving ADT did not have an increased risk of nonskeletal fall injury. Dr Lorentzon’s team identified the study cohort using a Swedish national registry to which various national directories were linked. Among men who received ADT, the median treatment

duration with a GnRH-agonist was 3.7 years. More than 90% of ADT recipients had been prescribed their final dose within the previous 3 months. A strength of the study was the availability of body mass index data and self-reported information on prior falls, “which are unique features of such a large database and of great importance in studies of fracture risk,” according to the investigators. With regard to study limitations, Dr Lorentzon and colleagues noted that they did not have access to measurements of bone mineral density, smoking, or alcohol use. Vertebral fractures that frequently are bypassed and not diagnosed in registries could not be studied reliably in their cohort, they noted. In addition, the investigators acknowledged that they lacked detailed clinical information on patients’ PCa, such as Gleason score. ■

RN, PN for cT1 RCC Offer Similar Survival Outcomes RADICAL AND partial nephrectomy for

disease compared with PN, but a sig-

small renal cell carcinoma (RCC) tumors

nificant 2-fold increased risk of a 10%

are associated with similar cancer-

decrease in estimated glomerular filtra-

specific and all-cause mortality.

tion rate (eGFR) and 2.7-fold increased

Radical nephrectomy (RN), however, is

risk of a decrease in eGFR to below 45

associated with a higher risk of chronic

mL/min/1.73 m2, Dr Gershman’s team

kidney disease (CKD) compared with

reported in European Urology.

partial nephrectomy (PN). In their propensity score (PS)-based

The 1609 patients with cT1 RCC in the PS analytic cohort were a subset of

analysis of 1609 patients with cT1

an overall cohort of 2459 patients with

RCC (of whom 919 and 690 under-

a cT1 solid renal mass treated with RN

went PN and RN, respectively), Boris

(39%) or PN (61%). In the overall cohort,

Gershman, MD, of the Warren Alpert

the RN group was older than the PN

Medical School of Brown University

group (mean 66 vs 61 years) and had

in Providence, Rhode Island, and col-

more advanced tumors and more

leagues at Mayo Clinic in Rochester,

adverse tumor features. The RN group

Minnesota found no statistically signifi-

also had a greater comorbidity burden.

cant associations between nephrec-

“Our findings reinforce prior observa-

tomy type and distant metastases,

tions that patients who undergo RN

cancer-specific, or all-cause mortality,

have more aggressive tumor character-

after adjusting for preoperative and

istics and more advanced disease,” the

pathologic features.

authors wrote. “The inability to properly

In a subset of 363 matched pairs of

adjust for these confounding variables

RN and PN patients, RN was associ-

may result in the paradoxical associa-

ated with a significant 73% decreased

tion of inferior oncologic outcomes with

risk of local ipsilateral recurrence of

more radical surgery.” ■

MEN WHO RECEIVE androgen deprivation therapy (ADT) for prostate cancer are at elevated risk of osteoporotic fractures, a new study confirms. The study found no clinically relevant relationships between ADT and nonskeletal fall injury, “which further strengthens the assumption that the relationship between ADT and fracture is primarily bone-related,” a team led by Mattias Lorentzon, MD, PhD, of the University of Gothenburg in Gothenburg, Sweden, and Sahlrenska University Hospital in Mölndal, Sweden, reported in Osteoporosis International. The researchers concluded that use of osteoporosis medications should be considered routine for all men with PCa at ADT initiation. The study included 179,744 men with a mean age of 79.1 years. The cohort included 159,662 without PCa, 6954 with PCa and current ADT, and

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Renal & Urology News 21

n ASK THE EXPERTS

The Role of Race in Prostate Cancer Management How differences in PCa between blacks and whites should affect clinical decisions is unclear

umerous studies have revealed important racial differences in prostate cancer (PCa) pathology, epidemiology, and clinical outcomes. To explore whether race should be taken into account when managing men with PCa, Renal & Urology News spoke with Michael S. Leapman, MD, Associate Professor of Urology at Yale School of Medicine in New Haven, Connecticut, and Adam C. Reese, MD, Associate Professor of Urology and Chief of Urologic Oncology at the Lewis Katz School of Medicine at Temple University in Philadelphia.

Should race enter into treatment decisions?

Dr Leapman: How race should influence management decisions for prostate cancer is an important and complex issue. To begin with, we know that there are significant differences in cancer incidence and outcome for patients who identify as Black or African American. African Americans continue to have the highest death rate and poorest survival of any racial group in the United States for most cancers, including prostate. African-American men are significantly more likely to be diagnosed with prostate cancer (1 in 6 versus 1 in 8 nonHispanic Whites), and almost twice as likely to die of the disease (1 in 23 patients diagnosed compared with 1 in 42 non-Hispanic White patients diagnosed). Although it is encouraging that some gaps in outcome appear to be narrowing, there are persistent disparities in rates of definitive treatment for prostate cancer, including for men with intermediate and high-risk cancers. From this perspective, most clinical guidelines, including the National Comprehensive Cancer Network, the American Urological Association, and

the American Cancer Society, regard African Americans as a high-risk group in which PSA screening should begin earlier. Yet, there is limited evidence to suggest that a patient’s race alone should lead them to be treated differently if prostate cancer is detected. Therefore, it seems that race should be regarded as one of many important variables to consider about an individual’s cancer. Dr Reese: This is an excellent question that I am not sure we are able answer with 100% accuracy from the current literature. It is my opinion that no patient should be precluded from undergoing a particular treatment, nor should a specific treatment be encouraged, based on race alone. However, patients should be informed that the outcomes of certain treatment strategies may differ somewhat among racial groups. For example, there are data to suggest that African-American men managed with active surveillance may have higher rates of disease reclassification and need for definitive treatment during follow up, relative to Caucasians. Patients should be educated about these potential differences to allow them to

make an informed decision when choosing a treatment strategy.

For you, what stands out as notable differences between whites and blacks with respect to cancer-related clinicopathologic factors?

Dr Leapman: Although in aggregate African-American men face greater risks of being diagnosed or dying from prostate cancer, national cancer registry data indicate that the proportion of men diagnosed with localized versus distant disease are actually quite similar. Numerous forces contribute to a patient’s outcome for prostate cancer, including biological factors, the time that their cancer is detected, their diet/lifestyle/exposures, and the treatment they receive. As a result, it has been difficult to determine whether differences in outcome extend from biological differences associated with a patient’s race/ethnicity, or other factors such as lifestyle, socioeconomic status, and treatment preferences. Yet, complex statistical modeling studies incorporating PSA screening patterns do

appear to suggest that African-American men do face higher risks of progression to metastatic disease from preclinical prostate cancer. If African-American men do face greater risks of metastatic progression, improving early detection through more thoughtful, tailored screening might be an effective tool to identify and selectively treat high-risk cancers. Dr Reese: Unfortunately, it is generally accepted that African-American men have a higher incidence of prostate cancer, are more likely to be diagnosed with advanced stage or aggressive disease, and are often diagnosed at a younger age compared to Caucasian men. In addition, the risk of death from prostate cancer is significantly higher in AfricanAmerican men than Caucasians. There are likely to be a number of factors that explain this phenomenon. First, there is clearly a genetic component contributing to the increased cancer risk in African-American men. Second, African-American men may be less likely to undergo screening due to lack of access to care or mistrust of the medical profession. Finally, dietary factors, environmental exposures, and socioeconomic disparities have also been hypothesized to play a role, although the data supporting these associations are less robust.

In your experience, do certain treatments work better in whites vs blacks?

Michael S. Leapman, MD

Adam C. Reese, MD

Dr Leapman: I do not think that any particular treatment approach is better suited for a patient based on their race. Numerous factors contribute to every patient’s decision to be treated for prostate cancer, including their age, urinary and sexual function, support system, and personal preferences. continued on page 22

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Prognostic Factors in nmCRPC ID’d A combination of age, comorbidity, and PSA doubling time can risk stratify cause of death

AGE, COMORBIDITY, and PSA doubling time (PSADT) influence the longterm risk and cause of death among men with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to a new study. “Integrating simple clinical variables such as these into decision making represents a key component of precision medicine that is too often ignored,” a team led by Timothy J. Daskivich, MD, of Cedars-Sinai Medical Center in Los Angeles, concluded in Prostate Cancer and Prostatic Diseases. “We strongly believe that these factors should be taken into account when counseling patients

about prognosis, and they may be important in selecting subgroups for future clinical trials in men with nmCRPC.” The study included 1238 men diagnosed with nmCPRC from 2000 to 2015. The median follow-up after onset of CRPC was 33.5 months. During followup, 569 patients (46%) died from prostate cancer (PCa) and 320 (26%) died from other causes (other-cause mortality, OCM). A Charlson comorbidity index (CCI) of 3 or higher compared with a CCI of 0, was associated with a 2.7-, 2.0-, and 2.5-fold increased risk of non-PCa death among men aged less 70, 70 to 79, and 80 years or older, respectively. Among

men in these age groups, a PSADT of 9 months or longer, compared with less than 9 months, was associated with an approximately 50%, 40%, and 40% decreased risk of PCa-specific mortality (PCSM), respectively. According to Dr Daskivich and his collaborators, PCSM and OCM were relatively equal competitors for death among patients with a PSADT of 9 months or longer, except among men aged 80 years or more with a CCI of 3 or greater. In these men, OCM was the predominant cause of death. Among patients with a PSADT of less than 9 months, PCSM was the

redominant cause of death across all p age and comorbidity groups. “We found that a combination of age, comorbidity, and PSADT could strongly risk stratify cause of death among these men,” the authors wrote. In acknowledging study limitations, Dr Daskivich and his colleagues pointed out that, because of the retrospective nature of their investigation, important predictors of prognosis such as functional status and fraility were not available. In addition, their study population only included patients from Veterans Affairs medical centers, which may affect external generalizability to other patient populations. ■

Role of race in PCa

making it difficult to directly compare outcomes over time for patients who choose this approach. In the absence of direct study, the suitability of active surveillance has been estimated using other surrogate endpoints, such as the likelihood of pathologic upgrading or upstaging. In a cohort of men with very-low risk prostate cancer (defined by Gleason 3+3, PSA density 0.15 ng/mL/cm3 or less, clinical stage T1c or less, 2 or fewer biopsy cores involved, and 50% or less cancer in a given core), who were instead treated with radical prostatectomy, African-American men were significantly more likely to experience pathologic upgrading and positive surgical margins. Moreover, African-American patients who were upgraded at the time of radical prostatectomy were more likely to have dominant, high-grade cancers in the anterior gland that may be missed on standard template biopsy. Other studies that have examined this question in other databases with a greater representation of African-American patients appear to show no significant associations. Studies addressing the risk of biopsy reclassification over time by race have been performed and appear to indicate greater risks of pathologic progression over time. For example, in a study of the Johns Hopkins active surveillance cohort consisting of 39 African-American men compared with 615 Caucasian men, African-American race was associated with a significantly higher risk of upgrade over time.

African-American men should be informed that they may have a higher risk of disease reclassification while under surveillance, and therefore may be more likely to require delayed intervention. As such, vigilant follow up of African-American men is crucial, as is the case with all men on surveillance. I am not aware of any data showing that cancer control in AA men initially managed with surveillance is inferior to that of Caucasians. Therefore, I do not see a convincing reason to use stricter selection criteria for African-American men, which would likely limit the number of men for whom surveillance is offered as a management strategy.

stage T1c or less, 2 or fewer biopsy cores involved, and 50% or less cancer in a given core), who were instead treated with radical prostatectomy, African-American men were significantly more likely to experience pathologic upgrading and positive surgical margins. Moreover, AfricanAmerican patients who were upgraded at the time of radical prostatectomy were more likely to have dominant, high-grade cancers in the anterior gland that may be missed on standard template biopsy. Other studies that have examined this question in other databases with a greater representation of African-American patients appear to show no significant associations. Studies addressing the risk of biopsy reclassification over time by race have been performed and appear to indicate greater risks of pathologic progression over time. For example, in a study of the Johns Hopkins active surveillance cohort consisting of 39 African-American men compared with 615 Caucasian men, African-American race was associated with a significantly higher risk of upgrade over time.

continued from page 21

Dr Reese: This is another area where there is no consensus, but there are data to suggest that treatment outcomes may differ by race. For patients managed with active surveillance, some studies have reported that cancer risk is more often underestimated in African-American men. This means that some African-American men placed on surveillance may have more aggressive tumors that potentially would have been better managed with definitive treatment. In addition, research from my institution and others has suggested that African-American men on active surveillance may have higher rates of disease reclassification and delayed treatment compared to Caucasians. The data regarding racial differences in radical prostatectomy outcomes are conflicting. Some studies have suggested that African-American men undergoing radical prostatectomy are more likely to have adverse pathology and cancer recurrence, whereas other studies have not found this association.

Should stricter selection criteria for active surveillance (AS) be applied to black patients?

Dr Reese: In my opinion, the same AS selection criteria can be used in AfricanAmerican and Caucasian men. However,

Should black men on AS be subject to more frequent follow-up studies (MRIs, biopsies)?

Dr Leapman: Whether African-American patients with low-risk prostate cancer are appropriate candidates for active surveillance is a question that is still debated. African-American patients are underrepresented in almost all of the large academic cohorts that have longitudinally studied patients on active surveillance, making it difficult to directly compare outcomes over time for patients who choose this approach. In the absence of direct study, the suitability of active surveillance has been estimated using other surrogate endpoints, such as the likelihood of pathologic upgrading or upstaging in patients treated with radical prostatectomy. In a cohort of men with very-low risk prostate cancer (defined by Gleason 3+3, PSA density 0.15 ng/mL/cm3 or less, clinical

Dr Reese: I do not think that more frequent follow-up studies are indicated, but I do think efforts are needed to ensure that men on surveillance are compliant with follow up. Data from our institution show relatively high rates of noncompliance with suggested PSA testing and surveillance biopsies for both Caucasian and African-American men on active surveillance. Given the potential increased risk of disease reclassification in African-American men, failure to comply with follow-up could allow for unrecognized disease progression and potentially compromise oncologic outcomes. ■

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Renal & Urology News 23

Ethical Issues in Medicine What is a physician’s obligation to answer calls for help in public places? BY DAVID J. ALFANDRE, MD

Unique status A profession like medicine has unique status in modern society because of its specialized, complex body of knowledge that is used in the service of others. The profession has achieved its societal position through what has been termed a “social contract.”1 In exchange for providing

evidence-based medicine, and establishing and following codes of ethics. The professional obligation to promote the health and wellbeing of the members of society is central to the legitimacy and integrity of the profession and to maintaining the social contract. Society expects and relies on the medical profession to advocate for and promote its health. Indeed, as a central defining principle of medical practice, the AMA Code of Ethics states in its preamble, “A physician shall recognize a responsibility to participate in activities contributing to the improvement of the community and the betterment of public health.”

Know your limitations Identifying where professional and ethical obligations begin is easier because they are based on professional practice standards and codes of ethics, but pinpointing where these obligations end for individual physicians can be more challenging. What are individual physicians responsible for and can reasonable limits be set? In answering this question, physician scholars make a distinction between professional obligations and aspirations.2 Physicians should not be obligated to provide services to their community

The professional obligation to promote the health and wellbeing of the members of society is central to the legitimacy and integrity of the profession. necessary expert services and committing itself to competence, integrity, and altruism, the social contract between society and the profession grants the profession a high level of prestige, a monopoly on its service, and autonomy in its practice, the latter usually enacted through the privilege of self-regulation. The profession maintains its accountability with the public (thus strengthening the social contract) by acting according to a transparent set of rigorously derived standards. These include developing and adhering to clinical practice guidelines, practicing

that exceed their ability to intervene. It might be laudatory and aspirational to do so, but it is not an ethical duty. For example, a physician’s role in promoting human health encompasses not just the medical aspects of illness, but also its social determinants. A patient’s kidney disease can progress if it is not treated adequately by his physician, but if the patient does not have health insurance or sufficient access to a nephrologist, the effect of these socioeconomic factors will be greater. Therefore, assisting patients with improving their access to

he call comes over the commuter train loudspeaker. “If there is a medical professional on-board, please come to the rear car to assist with a sick passenger.” In deciding whether to respond, a physician might silently ask him or herself a series of ethically charged questions. What obligation do I have to respond in such a situation? This example, and others like it, may prompt physicians to consider the scope of their professional and ethical obligations. What are physicians’ professional obligation to advance the health of the community they serve? Are they obligated to enhance access to care for underserved communities by donating their time to a local free clinic? We can begin to address some of these questions by considering the framework of ethical commitments that professions historically have had to society.

care may fall within a professional’s obligation. However, addressing broader economic and educational disparities related to health (such as reducing poverty or improving education) would be aspirational, but not obligatory. This is because there is less direct causality between those socioeconomic conditions and health. Should every physician be obligated to serve their community? Yes, and no. All physicians should contribute to that ideal and provide support where they can consistent with their skills, abilities, and expertise. But this collective professional obligation to society does not require every member of the profession to fulfill that responsibility. At the same time, consider that if individual physicians continually fail to rise to that obligation, the profession can eventually lose the trust of the public. The profession may be a diffuse entity, but it is still made up of individual members with ethical commitments.

Context matters Returning to the earlier case discussed, what are medical professionals’ obligations to respond to a medical emergency outside of a hospital setting?3 In this case, as with many ethical challenges, the context matters. An obstetrician may not be best suited to manage a seizure disorder when it occurs on the subway, but he or she may be skilled in managing clinical emergencies and can

help establish calm and a normalizing presence for a public that might be unfamiliar and frightened by witnessing acute illness. If you can help, you should. Still, for all of the ethical analysis, one of the most convincing reasons for taking the opportunity to provide a service to those in need is that it feels right and good, the same reason physicians originally entered the field of medicine. Providing care for those who need it and seeing their appreciation for your expertise and service often provides its own motivation. That can be an easy answer to a complex problem. ■ David J. Alfandre MD, MSPH, is a health care ethicist for the National Center for Ethics in Health Care (NCEHC) at the Department of Veterans Affairs (VA) and an Associate Professor in the Department of Medicine and the Department of Population Health at the NYU School of Medicine in New York. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the NCEHC or the VA. REFERENCES 1. Cruess SR, Johnston S, Cruess RL. “Profession”: a working definition for medical educators. Teach Learn Med. 2004;16:74-76. Review. 2. Gruen RL, Pearson SD, Brennan TA. Physiciancitizens—public roles and professional obligations. JAMA. 2004;291:94-98. 3. Eastwood GL. What should I do when I hear the call for medical assistance in a plane? JAMA. 2017;318:907–908.

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Practice Management K

idney stones are so painful that most people who have had one say they would do anything to avoid another. Anything, that is, except follow their doctor’s orders. Increasing fluid intake can reduce the odds of stone recurrence by up to 80%. Most doctors prescribe drinking 2 liters a day, but patients rarely do it, said Peter P. Reese, MD, a nephrologist at the Hospital of the University of Pennsylvania in Philadelphia. “Humans are flawed, and we know it,” he said. “What we can do is leverage those flaws by giving social or other incentives to get them to take their medication, exercise, or drink the fluid they ought to be drinking.”

Behavioral economics This leverage comes from a field known as behavioral economics, which relies on behavioral psychology to explain why people make economic decisions. It has moved to health care, where researchers are trying to determine why people make poor health decisions and how to correct this. The health care field is looking at behavioral economics because of the understanding that behavior is the “final pathway through which all of

barriers through incentives, typically social or financial. Much of this takes place on the research front, such as a study conducted by Dr Reese and his colleagues on immunosuppressant adherence among kidney transplant patients. Participants in the study, which was published in the American Journal of Kidney Diseases (2017;69:400-409), were given wireless pill bottles for their prescription of tacrolimus. One group just received the bottles, whereas a second group received customized reminders, such as texts or alarms, to take the medication. A third group received reminders, and providers were notified of patients’ progress. Adherence among the 3 groups was 55%, 78%, and 88%, respectively. For patients with kidney stones, Dr Tasian is working on a study known as the PUSH trial. In this, patients use a “smart” water bottle connected to a mobile device that measures how much water is consumed each day. Participants receive individualized “fluid prescriptions” over 2 years. If they meet their goal, they receive a small financial reward on randomly selected days. Those who do not will receive coaching to help reach their goals.

The goal of behavioral economics is to help patients overcome adherence barriers through incentives, typically social or financial. our interventions act,” said Gregory E. Tasian, MD, a urologist at Children’s Hospital of Philadelphia. “For decades, we had the naïve approach that if the medication we prescribed didn’t work, it was due to the failure of the medication or underlying biology of the disease,” Dr Tasian said. “But we’ve had a realization that … the end result is whether or not the patient is going to adhere to our recommendations.” The goal of behavioral economics is to help patients overcome adherence

“If you talk to most patients, they will tell you their goal is to have good blood pressure, no more kidney stones, and not get out of shape,” Dr Tasian said. “What we are trying to do is help support people by taking advantage of patterns in the way people make decisions.”

Behavior and rewards One important concept of behavioral modification is that immediate rewards are more effective than long-term ones. It is difficult to say no to a steak sitting in front of you if the reason you are not

Behavioral economics could be an effective way to improve adherence to treatment recommendations BY TAMMY WORTH

eating it is to lose 3 pounds by the end of the month. Behavioral economics, then, hopes to provide a quick incentive to overcome this “present bias.” Three behavioral economic principles can help patients meet treatment goals. The first is loss aversion. So, instead of offering people $2 a day to meet exercise goals, a stronger incentive might be to give them $60 and take away $2 every day they do not. “People don’t like the concept of losing something they thought they had,” Dr Reese said. “This might motivate them more.” The second principle is social rewards. For example, if someone meets their fluid intake goal, the wireless feature on their bottle could send a note to their social network or someone designated to know their information. That way, their network can either praise or encourage them to perform the task. Another option is using decision architecture to promote desired patient behavior. Here, providers offer a default option to encourage a particular choice. One study in this area worked with patients older than 70 years on dialysis admitted to an intensive care unit. An intervention group was told they had to receive information on palliative care, whereas a control group was given

traditional information. The goal was to see if making palliative care the default pushed patients toward that choice. “If you teach a patient something is the default, a lot more people are going to take it instead of just letting them raise their hand and say they want it,” Dr Reese said.

What we know Behavioral economics have achieved successes in smoking cessation and increasing walking. Weight loss and medication adherence have not been as successful. These results have left even Dr Reese giving a “lukewarm endorsement” of paying people to change behavior, despite the potential of behavior economics. Because behavior must be measured to be improved, Dr Reese said health monitors like glucometers and pedometers are going to play an important role. “What’s coming soon is expecting physicians to pay attention to see how many steps people walk a day,” he said. “Physicians can begin now, talking to their health systems to see if they have a plan for integrating this data into the EMRs and figuring out what to do with it.” ■ Tammy Worth is a freelance medical journalist based in Blue Springs, MO.