Renal & Urology News Sept-Oct 2017 issue

SE P T E MBE R /O C T O BE R 2017

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VO L UME 16, IS SUE NUMBE R 5

Front-line mRCC Therapy to Shift Checkpoint inhibitors found superior to sunitinib

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IMMUNOTHERAPY VS SUNITINIB In the Checkmate-214 trial of patients with previously untreated metastatic renal cell carcinoma, those who received a checkpoint inhibitor combination of nivolumab and ipilimumab had a better objective response rate (ORR) and longer median progression-free survival (PFS) than those who received sunitinib.

Nivolumab/ipilimumab

Sunitinib

41.6%

BY JODY A. CHARNOW CLINICAL TRIAL findings presented at European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, could signal a major shift in the front-line treatment of metastatic renal cell carcinoma (mRCC).

The CheckMate-214 trial demonstrated that combined immunotherapy with the checkpoint inhibitors nivolumab and ipilimumab results in superior outcomes—including significantly better objective response rate (ORR), progression-free survival

IN THIS ISSUE 5 10

Proximal PSA predicts PCa metastasis risk Methylene blue may improve BTX-A injection technique

12

PSA screening decreases the risk of PCa-related death

15

Active surveillance for very lowrisk PCa is underused

24

High-risk PCa has favorableand unfavorable-risk subgroups A hospital emergency department discharge with AKI predicts poor outcomes.

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(PFS), and overall survival (OS)— compared with sunitinib among patients with previously untreated intermediate- and poor-risk mRCC. Sunitinib is the current standard of care for this patient population.

Bernard Escudier, MD, of Institut Gustave Roussy, Villejuif, France, who presented the study’s fi ndings, said nivolumab/ipilimumab will become the new standard of care for the frontline treatment of these patients.

The trial included 1096 patients randomly assigned to receive nivolumab/ ipilimumab (550 patients) or suni-

11.6 mo.

26.5%

8.4 mo.

0

ORR (%)

10

20

0 30

Median PFS (mo.)

Source: Escudier B, Tannir N, McDermott D, et al. CheckMate 214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. LBA5. Presented at the European Society for Medical Oncology 2017 congress in Madrid, Spain.

tinib (546 patients). With a minimum follow-up of about 17.5 months, the ORR was 41.6% in the nivolumab/ipilimumab arm compared with 26.5% among sunitinib recipients among patients with intermediate- and poorrisk disease. In addition, 9.4% of

patients in the combination therapy arm achieved a complete response compared with 1.2% of patients in the sunitinib arm. Median PFS was 11.6 months in the immunotherapy arm compared with 8.4% in the sunitinib continued on page 11

NMIBC Recurrence, CKD Linked NLR Predicts mRCC Therapy BY NATASHA PERSAUD NMIBC,” lead investigator Tetsutaro CHRONIC KIDNEY disease (CKD) Hayashi, MD, PhD, of Hiroshima Outcomes may increase the risk for recurrence and University in Hiroshima City, Japan,

BY JODY A. CHARNOW CHANGES IN NEUTROPHIL-tolymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma (mRCC) independently predicts outcomes, investigators reported at the European Society for Medical Oncology 2017 Congress in Madrid, Spain.

In a study of 142 patients with mRCC who received anti-PD-1/ PD-L1 immune checkpoint blockade (ICB), Aly-Khan A. Lalani, MD, and colleagues at the Dana-Farber Cancer Institute in Boston found that higher 6-week NLR was independently continued on page 11

progression of non-muscle invasive bladder cancer (NMIBC) following transurethral resection, according to researchers.

In a study of 418 Japanese patients who underwent transurethral resection of NMIBC, patients with CKD stage G3b–5 had a nearly 2-fold increased risk of recurrence and 3-fold increased risk of progression compared with those who had a CKD stage less than G3b, investigators reported in the International Journal of Urology (2017;24:594-600).

“CKD is an independent predictor of recurrence and progression in primary

told Renal & Urology News. “Adding CKD stage to the conventional risk factors could improve the accuracy of risk stratification.”

Of the 418 patients, 68.7% had stage G1–2, 23.4% had G3a, and 7.9% had G3b–5 CKD, defined, respectively, as an estimated glomerular fi ltration rate (mL/min/1.73 m2) of 60 or higher, 45–59, and less than 45.

Results showed that 57% and 7.7% of patients experienced recurrence and progression, respectively. Over continued on page 11

STRATEGIES FOR LEAVING INDEPENDENT PRACTICE

Options for mergers and partnerships have their pros and cons.

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Study: Cystectomy Complication Rate Not Improving PERIOPERATIVE complication rates following radical cystectomy (RC) for bladder cancer have not declined despite enhanced recovery protocols, but hospital length of stay (LOS) and need for blood transfusions have declined, data suggest.

Using the National Surgical Quality Improvement Program (SQIP), Scott

C. Johnson, MD, and colleagues at the University of Chicago identified 6510 patients who underwent RC from 2010 to 2015. Of these, 31.5% experienced a complication within 30 days. The complication rate was 28%, 32%, 31%, 32%, 32%, and 31% in 2010, 2011, 2012, 2013, 2014, and

2015, respectively, according to findings published online ahead of print in Urologic Oncology.

Infections were the most common complication (16.7%), followed by wound (14.3%) and pulmonary complications (5.7%). Overall, 5.6% of patients required reoperation (Clavien

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III), and 8.7% had a life-threatening (Clavien IV) complication. The 30-day mortality rate (Clavien V) was 1.8%.

The proportion of patients requiring blood transfusion declined significantly from 40% in 2010 to 37% in 2015.

Hospital LOS dropped from 10.6 to 9.2 days during the study period. n

www.renalandurologynews.com SEPTEMBER/OCTOBER 2017

Renal & Urology News 5

Proximal PSA Found to Predict PCa Metastasis Risk

BY JODY A. CHARNOW PROXIMAL PSA levels of 10 ng/mL or higher in men with biochemically recurrent prostate cancer (PCa) after radical prostatectomy and a PSA doubling time (PSADT) less than 12 months independently predicts imminent development of metastasis, according to study

findings presented at the European Society for Medical Oncology 2017 Congress in Madrid, Spain.

A team led by Mark C. Markowski, MD, PhD, of Johns Hopkins University in Baltimore, studied 513 men with biochemically recurrent PCa—defined as a PSA level higher than 0.2 ng/mL after

radical prostatectomy—and a PSADT less than 12 months. They defined proximal PSA as the most recent PSA value at least 6 months prior to the development of metastatic disease.

Results showed that a proximal PSA of 10 ng/mL or higher versus less than 10 ng/mL was associated with a

significant 2.7-fold increased risk of metastasis.

“These data allow clinicians to counsel their patients regarding risk of metastasis and treatment considerations,” Dr Markowski told Renal & Urology News. “Most important, these data provide critical information for selecting patients for clinical trials.”

The median metastasis-free survival (MFS) times differed significantly by PSADT subgroups. Among patients with a PSADT of 6.01 to 12 months, the median MFS was 20 years for those with a proximal PSA less than 10 ng/ mL compared with 5 years for men with a proximal PSA of 10 ng/mL or higher. The corresponding median MFS for men with a PSADT of 3.01 to 6 months was 7 and 3 years, respectively. The median MFS for men with a PSADT of 3 months or less did not differ significantly by proximal PSA value.

New finding has implications for patient counseling about treatment.

The study was a collaboration of Johns Hopkins, the Center for Prostate Disease Research in Rockville, Maryland, and the Department of Surgery at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. At enrollment, the study participants had not received adjuvant or salvage androgen deprivation therapy or radiotherapy. The investigators prospectively followed up the men until radiologic evidence of metastasis. Metastases developed in 218 men (42.5%) during a median follow-up of 9 years. Shorter PSADT was associated with an elevated risk for distant metastasis. Compared with a PSADT of 10.5 to 12 months, a PSADT of 4.01 to 7.5, 4.51 to 6.0, 3.01 to 4.51, and 3 months or less was associated with a 2.2, 2.6, 3.9, and 4.8-fold increased risk of distant metastasis, respectively.

Results also showed that patients with a pathologic Gleason sum of 7 and 8–10 had a 2- and 3-fold higher risk of distant metastases, respectively, compared with those who had a Gleason sum of 6 or less. Patients with pathologic pT3 versus pT2 disease had a 64% increased risk. Surgical margin status was not significantly associated with distant metastasis risk. n

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SEPTEMBER/OCTOBER 2017 www.renalandurologynews.com

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD

Nephrology-Urology Teamwork Sensible

A

number of patients referred to my faculty ambulatory clinic at the University of California Irvine have urologic disorders, including some who underwent partial or radical nephrectomy.

Many patients do not comprehend the distinction between nephrologist and urologist, and refer to both as “kidney doctor.” I often educate these patients, explaining that a urologist is a surgeon who repairs urinary tract plumbing and structure, whereas a nephrologist is an internist who attends to kidney function and provides dialysis and kidney transplantation care. Notwithstanding the inherent distinctions between urology and nephrology, there are areas in which a teamwork approach can enhance patient care tremendously.

Our post-nephrectomy kidney health care is a relevant example in that solitary kidney function following radical nephrectomy is watched closely by the nephrologist, whereas the urologist continues with periodic imaging surveillance for malignancy and urinary tract patency.

Kidney stone management also lends itself to collaboration between nephrologists and urologists, with urologists removing stones and nephrologists preventing stone recurrence by focusing on dietary and pharmacologic management of nephrolithiasis. High protein intake, especially animal protein such as red meat and seafood, may increase uric acid levels and decrease urinary citrate, predisposing patients to kidney stones, whereas non-oxalate-containing vegan food can oppose these effects. As renal nutrition therapy has been gaining in importance in nephrology practices for the conservative management of CKD, dietary modulation of kidney stones can be handled more effectively by nephrologists and their associated renal dietitians.

Further, kidney stones, as well as bladder and prostate tumors, may lead to acute kidney injury from urinary tract obstruction. The nephrology care team may depend on urologist assessment and placement of urinary tract stents. Another setting where urology and nephrology can work together is in the management of pyelonephritis in children.

In these cases, pyelonephritis frequently is related to reflux disease, which is co-managed by pediatric urologists via anti-reflux surgeries.

Since urologists and nephrologists are “kidney doctors,” at least in the minds of many patients, and they provide complementary care in certain clinical scenarios, it certainly makes a lot of sense to collaborate in what could be called centers of excellence for kidney health.

As medical tourism gains in popularity and increasing numbers of patients seek holistic kidney care, there may indeed be a place for such comprehensive centers where both urologists and nephrologists work hand-to-hand to provide better care to patients and their kidneys.

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 President, Cleveland Clinic Regional Hospitals & Family Health Centers Professor & Horvitz/Miller Distinguished Chair in Urological Oncology Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California Irvine

Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc.

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

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

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

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

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

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

Renal & Urology News Staff Editor Web editor Production editor

Jody A. Charnow Natasha Persaud Kim Daigneau

Group art director, Haymarket Medical

Jennifer Dvoretz

Production manager

Krassi Varbanov

Production director Circulation manager National accounts manager Group Publisher Editorial director

Kam Kalantar-Zadeh, MD, MPH, PhD Chief, Division of Nephrology & Hypertension Professor Medicine, Pediatrics and Public Health University of California Irvine School of Medicine Orange, California

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

Kathleen Millea Grinder Paul Silver William Canning Chad Holloway Kathleen Walsh Tulley

General manager, medical communications

Jim Burke, RPh

CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 16, Number 5. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. Periodicals postage paid at New York, NY, and an additional mailing office. The subscription rates for one year are, in the U.S., $75.00; in Canada, $85.00; all other foreign countries, $110.00. Single issues, $20.00. www.renalandurologynews.com. Postmaster: Send address changes to Renal & Urology News, c/o DMD Data Inc., 2340 River Road, Des Plaines, IL 60018. Copyright: 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 © 2017.

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Renal & Urology News 7

Upfront Cabozantinib Improves RCC Outcomes CABOZANTINIB DECREASES the risk of disease progression or death compared with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC), according to updated results from the CABOSUN (CABOzantinib versus SUNitinib) phase 2 trial presented at the European

Society for Medical Oncology 2017 Congress in Madrid, Spain.

Investigators randomly assigned 157 patients with intermediate- or poor-risk advanced RCC to receive cabozantinib 60 mg once daily (79 patients) or sunitinib 50 mg once daily, 4 weeks on followed by 2 weeks off (78 patients).

The latest analysis, presented by Toni K. Choueiri, MD, Director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, included an assessment by a blinded independent radiology review committee showing that cabozantinib was associated with a

S:7”

clinically meaningful and statistically significant 52% decreased risk of disease progression or death compared with sunitinib, the current standard of care for the first-line treatment of advanced RCC. Median progressionfree survival (PFS) was 8.6 months for cabozantinib-treated patients compared with 5.3 months for sunitinib recipients, a statistically significant 3.3 month difference between the groups, according to the investigators.

“These updated analyses from CABOSUN consistently show that cabozantinib provided a statistically significant decrease in the rate of disease progression or death compared to sunitinib, a current standard of care— potentially offering a new treatment option for physicians to treat patients in the first-line advanced renal cell carcinoma setting,” Dr Choueiri said.

Patients in the trial had locally advanced or metastatic clear-cell RCC, an ECOG performance status of 0–2, intermediate- or poor-risk disease based on IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) criteria. n

CKD May Increase Risk of Tinnitus CHRONIC KIDNEY disease (CKD) is associated with a greater risk of tinnitus, researchers reported online in PLoS One. Using 2000–2010 data from the Taiwan National Insurance Research Database, Cheng-Ping Shih, MD, of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, and colleagues compared 185,430 patients with CKD and 556,290 controls without CKD. In adjusted analyses, CKD patients had a significant 3-fold higher risk of tinnitus than non-CKD patients. CKD patients with heart failure and those with diabetes mellitus had a significant 10-fold and 3.7-fold greater risk, respectively. Compared with non-CKD patients, dialysis-dependent CKD patients had a 4.6-fold increased risk of tinnitus, whereas non-dialysis CKD patients had a 2.5-fold increased risk. n

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Contents

SEPTEMBER/ OCTOBER 2017 ■ VOLUME 16, ISSUE NUMBER 5

Urology 7

ONLINE

23

this month at renalandurologynews.com 24

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

25

HIPAA Compliance How to balance security with employee access to information.

Drug Information

7

Timing of PSA Nadir After RP May Predict BCR Risk Patients who have both a detectable PSA nadir and a shorter time to nadir are at higher risk for biochemical recurrence of disease.

Racial Disparity in PCa Therapy Identified At most US medical facilities, white men are more likely than black men to receive definitive treatment for intermediate- or high-risk prostate cancer.

CKD May Increase Risk of Tinnitus Patients with CKD, especially those on dialysis, have a significant 3-fold higher risk of tinnitus than patients without CKD, according to a new study.

20

Arteriovenous Fistulas Not Always Best for HD In a recent meta-analysis, only 26% of AVFs were mature by 6 months, and 21% were abandoned without use.

22

Liraglutide Decreases Diabetic Nephropathy Risk Patients treated with liraglutide had a significant 26% reduction in the risk of macroalbuminuria compared with patients who received placebo.

24

Cancer Drug May Inhibit ADPKD Cysts In a phase 2 study, patients with autosomal dominant polycystic kidney disease treated with bosutinib experienced a 66% reduction in the annual rate of kidney enlargement.

Job Board

News Coverage Visit our website for daily reports from Kidney Week in New Orleans, November 1-5.

Prostate Atrophy Linked to Lower PCa Risk Prostate atrophy and chronic prostate inflammation in baseline biopsies are associated with lower prostate cancer risk and grade.

Nephrology

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

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

Upfront Cabozantinib Improves RCC Outcomes Cabozantinib decreases the risk of disease progression or death compared with sunitinib in patients with previously untreated advanced renal cell carcinoma.

Participants in multicenter clinical trials are willing

and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators.

See our story on page 22

CALENDAR American Society of Nephrology Kidney Week 2017 New Orleans October 31–November 5 Genitourinary Cancers Symposium San Francisco February 8–10, 2018 Annual Dialysis Conference Orlando, Florida March 3–6 European Association of Urology 2018 Congress Copenhagen, Denmark March 16–20.

National Kidney Foundation Spring Clinical Meeting Austin, Texas April 10–14 American Urological Association Annual Meeting San Francisco, CA May 18–21 Canadian Urological Association Annual Meeting Halifax, Nova Scotia June 23–26.

26

Departments 6

From the Medical Director More collaboration needed between nephrologists and urologists

10

News in Brief Serum uromodulin may predict CKD development

26

Practice Management How to create a culture of HIPAA compliance

10 Renal & Urology News

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News in Brief

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

Short Takes Serum Uromodulin May Predict CKD Development

cure or improvement in symptoms and

UROMODULIN may be a novel

end of treatment compared with 94%

predictive serum biomarker marker

of patients who received piperacillin/

for chronic kidney disease (CKD),

tazobactam, according to an FDA news

researchers reported online in the

release. About 7 days after completing

Journal of Hypertension.

treatment, some 77% of Vabomere

had a negative urine culture test at the

In a study of 529 patients, Andreas

recipients experienced resolution of

Leiherer, MD, of the Vorarlberg Institute

symptoms and had a negative urine

for Vascular Investigation and Treat-

culture compared with 73% of those

ment, Feldkirch, Austria, and colleagues

treated with piperacillin/tazobactam.

found that serum uromodulin concentradevelopment of CKD, and it significantly

Study Links Subclinical CAC to Nephrolithiasis

improved the performance of a predic-

NEPHROLITHIASIS is associated with

tion model for CKD.

coronary artery calcification (CAC) in

tion was inversely associated with the

adults without known coronary heart

FDA Approves Drug For Complicated UTIs

disease (CHD), researchers reported

THE FDA HAS approved Vabomere

Journal of Kidney Diseases.

online ahead of print in the American

(Rempex Pharmaceuticals), an intra-

Seolhye Kim, MD, MSc, and col-

venous antibiotic, for the treatment

leagues at Sungkyunkwan University

of complicated urinary tract infec-

School of Medicine in Seoul, South

tions (UTIs), including pyelonephritis,

Korea, studied 62,091 asymptomatic

in adults.

adults without known CHD. Individuals

The drug contains meropenem and

who had nephrolithiasis had a higher

vaborbactam. In a clinical trial that

prevalence of CAC than those who

included 545 adults with complicated

did not (19.1% vs 12.8%). In adjusted

UTIs, including some with pyelone-

analyses, the CAC score ratio compar-

phritis, approximately 98% of patients

ing individuals with and without nephro-

treated with Vabomere experienced

lithiasis was 1.31.

Cardiovascular Disease in CKD Among individuals aged 66 years and older, cardiovascular disease (CVD) is present in a higher proportion of patients with chronic kidney disease (CKD) than those without CKD (68% vs 34.1%). The proportions vary by race and sex, as shown here.

69.8%

72.4% 64.7%

n Whites n Male n Blacks n Female

65.5%

35%

CKD Source: U.S. Renal Data System.

37.4% 30.4%

No CKD

31.6%

Methylene Blue Improves BTX-A Injection Technique A

dding methylene blue to onabotulinum toxin A (BTX-A) solution for the treatment of overactive bladder (OAB) facilitates observation of the procedure and assessment of drug distribution, researchers reported online ahead of print in the Scandinavian Journal of Urology.

Michal Szczypior, MD, and colleagues at the Medical University of Gdansk in Poland tested this approach in 30 patients (24 women and 6 men) with OAB who qualified for BTX-A injections. Each patients received 100 IU of BTX-A dissolved in 9.5 mL of 0.9% sodium chloride solution, with 0.5 mL of methylene blue added.

Over the course of 600 injections, the investigators reported that they were unable to observe the exact distribution of the solution in only 43 injections in 7 patients.

They found no pharmacologic interactions between methylene blue and BTX-A.

Marijuana Use Not Linked To Renal Impairment M

arijuana use is not associated with decreased renal function in healthy young adults, researchers reported online in the Clinical Journal of the American Society of Nephrology (CJASN).

In a study using data from 3765 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3131 (83%) reported past or current marijuana use. Over the following 10 years, 504 individuals experienced rapid decline in estimated glomerular filtration (eGFR) rate as measured using cystatin C, and over the following 15 years, albuminuria developed in 426. Multivariable analysis showed that marijuana use was not significantly associated with eGFR change, rapid eGFR decline, or prevalent albuminuria.

In a press release from the American Society of Nephrology, which publishes CJASN, lead investigator Julie H. Ishida, MD, of the University of California San Francisco, said the results “may not translate into a clinically meaningful difference and may be insufficient to inform decision-making concerning marijuana use.”

Men with PCa Most Likely To Die From Other Causes T

he 10-year overall mortality rate among men with non-metastatic prostate cancer (PCa) is about 3 times higher than PCa-specific mortality (PCSM), according to investigators in Norway.

Using data from the Norwegian Prostate Cancer Registry, Kirsti Aas, MD, of Baerum Hospital in Drammen, and colleagues calculated the 10-year overall mortality and PCSM rates among 3449 men diagnosed with non-metastatic PCa during 2004-2005. Of these, 913 underwent radical prostatectomy, 1334 underwent radiotherapy, and 1202 had no local treatment. The 10-year overall mortality and PCSM rates were 25.5% and 8.5%, respectively, the investigators reported online ahead of print in Urology. Among low-risk and high-risk patients, the likelihood of dying from causes other than PCa was 8-fold and 2-fold higher compared with death from PCa. “Patients with high-risk factors seemed to benefit the most from local treatment,” the researchers wrote.

www.renalandurologynews.com

Front-line mRCC therapy continued from page 1

arm. Compared with sunitinib, the nivolumab/ipilimumab combination decreased the risk of disease progression by a significant 18%.

PD-L1 expression a factor The beneficial effect of nivolumab/ ipilimumab over sunitinib was more pronounced among intermediate- and poor-risk patients having baseline PD-L1 expression of 1% or greater.

In these patients, the ORR was 58% in the combination arm versus 25% among sunitinib recipients, and the median PFS was 22.8 months versus 5.9 months. The combination therapy decreased the risk of disease progression by 52% compared with sunitinib.

Of the 550 patients treated with

NLR predicts outcomes continued from page 1

associated with reduced objective response rate (ORR, partial or complete response) and shorter progression-free survival (PFS) and overall survival (OS).

The study, which was presented by Dr Lalani, showed that compared with patients who had no change in NLR from baseline to 6 weeks, those who experienced a 25% or greater relative decrease in NLR during that period had a 52% increased likelihood of responding to treatment, a 45% decreased risk of radiographic or clinical progression, and 67% decreased risk of death, in adjusted analyses.

Patients who experienced a 25% or greater increase in NLR from baseline

NMIBC, CKD linked continued from page 1

a median of 40 months, the researchers observed higher proportions of T1 tumors in patients with worse renal function (29.6%, 43.9%, and 51.4% of patients with G1–2, G3a, and G3b–5 CKD, respectively). Patients with CKD stage G3a and G3b–5 had significantly higher proportions of histologic grade 3 tumors than those with CKD stage G1–2 (43.9% and 36.4% vs 17.8%).

Upcoming News

SEPTEMBER/OCTOBER 2017

Renal & Urology News 11

nivolumab/ipilimumab, 159 (28.9%) died during follow-up compared with 202 (36.9%) of the 546 sunitinib recipients, Dr Escudier’s group reported.

Among intermediate- and poor-risk patients, median OS was 26 months in the sunitinib group and not yet reached in the combination arm. Among patients in all risk groups, median OS was 32.9 months among sunitinib recipients and not yet reached in the combination arm.

Moshe Ornstein, MD, a genitourinary oncologist at the Cleveland Clinic Taussig Cancer Institute, who was not part of the Checkmate-214 research team, noted that the results of the study presented at the ESMO congress “represent the first phase 3 data to support the use of checkpoint inhibitors in the front-line setting for metastatic renal cell carcinoma.”

“The superior objective response rates and overall survival of combined ipilimumab and nivolumab compared to sunitinib in patients with intermediate- and poor-risk mRCC will

likely usher in an era in which this combination of checkpoint inhibitors become the standard of care for frontline mRCC,” Dr Ornstein told Renal & Urology News.

The ORR and OS rates also favored the nivolumab/ipilimumab combination in the intention-to-treat popula-

Dual regimen well-tolerated A primary concern of the nivolumab/ ipilimumab combination is the perceived toxicity, Dr Ornstein said.

Although the combination was very well tolerated overall, 25% of patients who received the treatment discontinued it because of drug toxicity compared with only 12% of sunitinibtreated patients. He pointed out, however, that 79% of the patients in the ipilimumab/nivolumab arm successfully received all 4 doses of ipilimumab as called for in the trial protocol. ■

to 6 weeks had a 55% decreased likelihood of responding to treatment, a 2.6 times increased risk of radiographic or clinical progression, and 1.57 times increased risk of death.

“The results of analyses at 6-weeks on ICB therapy are informative for

both patients and physicians given that this time point typically coincides with the first set of re-staging scans after initiation of treatment,” Dr Lalani, a Genitourinary Oncology

Fellow at Dana-Farber’s Lank Center for Genitourinary Oncology, told Renal & Urology News. “For example, if a patient presents at 6-weeks on ICB therapy with stable or slightly progressive disease on imaging and a simultaneous decline in NLR, this may be reassuring to continue treatment assuming it is otherwise clinically suitable. Taken together, our data suggest that NLR appears to be a readily available, prognostic marker in mRCC patients treated with conventional ICB, and warrants larger, prospective validation.”

The study, whose senior author was Toni K. Choueiri, MD, Director of Lank Center for Genitourinary Oncology, demonstrated that NLR at 6 weeks was a significantly stronger predictor of ORR, PFS, and OS than baseline NLR.

Previous studies have demonstrated that an elevated NLR is associated with a poor prognosis among patients with various types of solid tumors. The prognostic value of NLR in the current era of ICB has been evaluated in small subsets of patients, such as those with lung, melanoma, and bladder malignancies, but its utility in the context of contemporary immunotherapy for mRCC has not been well defined, Dr Lalani said.

Of the 142 patients in the study, 53.5% received monotherapy and 46.5% received combination therapy. Based on IMDC (International Metastatic Renal Cell Carcinoma Database) criteria, 18.3%, 59.9%, and 21.8% of patients had favorable-, intermediate-, and poor-risk disease at the start of treatment. ■

Higher-stage CKD patients had worse recurrence-free and progressionfree survival and significantly shorter times to recurrence and progression.

On multivariate analysis, CKD stage G3b–5 was associated with a significant 1.87 and 2.96 times increased risk of recurrence and progression, respectively, compared with a CKD stage less than G3b. Patients with grade 3 tumors had a significant 2.4-fold greater risk of progression than those with grade 1–2 tumors. The team also found that

CKD stage correlated well with bladder cancer risk groups based on criteria in the European Association of Urology guidelines.

Among plausible mechanisms linking CKD with NMIBC outcomes, the team speculated that cytokeratin 18, active in inflammation, might increase cancer activity. They also considered the possibility that CKD reflects other factors, such as aging, diabetes, and hypertension. Proteinuria assessed by dipstick testing did not appear pre-

dictive in this study. Chronic urinary retention was not assessed.

In a discussion of study limitations, the authors noted that their investigation was retrospective and included a “fairly limited” number of patients.

The study included only 9 patients with CKD stage G4–5. “Thus, until future prospective studies certify the relationship between CKD and NMIBC, CKD might not yet be considered an authentic risk factor with only the present results,” the authors stated. ■

Disease progression risk associated with change in NLR from baseline to 6 weeks.

Immunotherapy superiority observed in intermediate- and poor-risk patients.

tion (patients with favorable-, intermediate-, and poor-risk disease), suggesting that this combination also may become a new standard of care as front-line mRCC treatment for all patients, regardless of risk group, Dr Ornstein said.

Renal & Urology News will be providing onsite coverage of the Genitourinary Cancers Symposium 2018 in San Francisco, February 8 – 10. Go to www.renalandurologynews.com for daily reports on noteworthy studies.

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PSA Screening Lowers Prostate Cancer Death Risk

BY JODY A. CHARNOW SCREENING FOR prostate cancer (PCa) decreases the risk of dying from the malignancy, researchers concluded based on a new analysis of data from 2 randomized trials that came to conflicting conclusions about the survival benefit.

The ERSPC (European Randomized Study of Screening for Prostate Cancer) trial found that screening decreased the risk of PCa mortality by 21%, whereas the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer) screening trial, which was conducted in the United States, found no survival benefit. In the ­current analysis, a team led by Ruth Etzioni, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, attempted to reconcile the effects of screening on PCa mortality in these trials.

After accounting for differences in implementation and practice settings, the investigators found that ­screening reduced the risk of PCa mortality by an estimated 25% to 31% in the ERSPC trial and 27% to 32% in the

Researchers attempt to reconcile findings from the PCLO and ERSPC trials.

PCLO trial, according to a paper published online ahead of print in the Annals of Internal Medicine.

“Our estimation of the common effect of screening suggests that it can significantly reduce the risk for prostate cancer death,” the investigators concluded.

“However, as for all interventions, the benefit of screening must be weighed against its potential harms for informed clinical and shared decision making.”

The ERSPC trial included men aged 55 to 69 years at randomization. The trial had 72,473 men in a screening arm and 88,921 in a control arm. The PCLO trial included men aged 55 to 74 years at randomization, with 38,340 men in a screening arm and 38,343 in a control arm. The screening interval was longer in the ERSPC trial compared with the PLCO trial (every 2–4 years vs annually). The PLCO trial had a higher PSA threshold for biopsy than the ERSPC trial (4.0 vs 3.0 ng/mL in most ERSPC centers and screening rounds).

“Rather than comparing the trial groups as if they represented screened and nonscreened populations,” the

authors explained, “this study estimated the intensity of screening in each group relative to no screening.

This allowed us to formally assess whether screening effects differed between the trials when we accounted for differential screening intensity between groups in each trial.”

Using mean lead times (MLTs), the researchers accounted for increased PCa incidence due to screening and diagnostic work-up in each group.

MLTs usually are defined as the average time by which diagnosis is advanced by screening to the date of diagnosis without screening, Dr Etzioni’s team

noted. MLTs reflect the magnitude of increased PCa incidence relative to a baseline level expected in the absence of screening, they explained. Dr Etzioni and her colleagues estimated that screening conferred a 7% to 9% reduction in the risk for PCa mortality per year of MLT.

www.renalandurologynews.com SEPTEMBER/OCTOBER 2017

In an editorial accompanying the new study, Andrew J. Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York, said he hopes the researchers “have finally put to rest the question of whether PSA screening reduces prostate cancer mortality.

I say this not to close debate but to refocus it. Screening with PSA testing does good by saving lives, but it also causes harm in terms of overdiagnosis

and overtreatment. Thus, we need to determine how to screen so that the benefits outweigh the harms.”

Dr Vickers also commented, “The controversy about PSA-based screening should no longer be whether it can do good but whether we can change our behavior so that it does more good than harm.”

Neal D. Shore, MD, President of the Large Urology Group Practice

Association, based in Schaumburg, Illinois, said the new analysis was well conducted, but noted that for some it may not settle the issue of whether PCa screening saves lives.

“If you’re a proponent of appropriate screening as well as the appropriate use of the information from that screening, then you would read Dr Etzione’s paper as highly informative,” said Dr Shore, Director, CPI, Carolina

Renal & Urology News 13

Urologic Research Center, Myrtle Beach, South Carolina.

“It should give anyone who’s been on the screening fence additional evidence from extremely reputable researchers that screening, when used appropriately, will diagnose men [with PCa] who would otherwise have been missed. The use of PSA should be part of a thorough patient-physician discuscontinued on page 14

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PSA screening

continued from page 13

sion, and especially for populations that are risk for prostate cancer.” These at-risk populations include men with a significant family history of prostate, colon, breast, and ovarian cancer, as well as African American men.

Based on the new study, Dr Shore said, the U.S. Preventive Services Task

Force (USPSTF) should rethink its position on PSA screening. In 2012, USPSTF recommended against PSAbased screening for men of any age based on an assessment of potential benefits and harms, Dr Shore said.

“Many of us have intuitively felt that if you stopped screening, especially the at-risk populations…there would naturally follow an increase in metastatic disease presentation and thus

an increase in cause specific prostate cancer deaths,” Dr Shore said.

In a draft document now under review, USPSTF recommends that clinicians inform men aged 55 to 69 years about the potential benefits and harms of PSA screening.

In Dr Shore’s opinion, obtaining baseline PSA values is reasonable for all men aged 50 to 75 years as well T:6.75”men who have as younger and older

either hereditary risk factors or an actuarial significant life expectancy.

“Having at least a baseline PSA and the ability at some point to get it repeated again, looking at changes over time, and then having shared decision making, will allow the patients to best decide, with the help of their primary care physician or their urologist, whether or not to proceed to prostate biopsy.” n

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Prostate Cancer AS Use Low, But Increasing DESPITE National Comprehensive Cancer Network (NCCN) guidelines that recommend active surveillance (AS) for men with very low-risk prostate cancer, overall use of AS, although increasing, remains low, investigators reported online ahead of print in Cancer Medicine.

In a study of 2010–2013 data from the National Cancer Data Base (NCDB), Rahul R. Parikh, MD, of the Department of Radiation Oncology at Rutgers Cancer Institute of New Jersey in New Brunswick, and colleagues found that only 14.2% of men with very low-risk prostateT:6.75” cancer (PCa) were

managed with AS. They identified a rising trend, however, with the proportion of men placed on AS increasing from 11.6% in 2010 to 27.3% in 2013.

For the study, the researchers identified men with biopsy-proven very lowrisk PCa as defined by Epstein criteria (stage T1c or less disease, Gleason score

of 6 or less, PSA less than 10 ng/mL, and 2 or fewer [or less than 33%] positive biopsy cores). Of 448,773 patients in the NCDB, 40,838 patients met these criteria. AS was prescribed for 5798 of them. Among patients who opted for treatment, 52.2% underwent radical prostatectomy. ■

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Intensive BP Control in CKD May Lower Death Risk

BY NATASHA PERSAUD MORE INTENSIVE LOWERING of systolic blood pressure (SBP) in patients with chronic kidney disease (CKD) not on dialysis may provide a survival benefit, new research confirms. The optimal SBP target remains unclear, however, and may vary by CKD stage.

In a systematic review and metaanalysis, published online before print in JAMA Internal Medicine, Rakesh Malhotra, MD, MPH, of the University of California in San Diego, and colleagues pooled data from 15,924 patients with stages 3 to 5 CKD T:6.75” (estimated glomerular filtration rate

below 60 mL/min/1.73 m2) enrolled in 18 randomized controlled trials up to June 2016, including SPRINT (Systolic Blood Pressure Intervention Trial).

Nine trials supplied fresh, unpublished data.

The patients had an average SBP of 148 mm Hg at baseline. This fell 16 and

8 mm Hg, respectively, in the more and less intensively treated groups. What was considered “more” or “less” intensive varied by study.

Over a median 3.6 years of follow up, 1293 patients died. Results showed a 14% lower risk for all-cause mortality with more intensive treatment. This advantage held in subgroup analyses and in a sensitivity analysis that excluded SPRINT data. The investigators observed no significant heterogeneity among studies.

“Although additional studies and intensive monitoring for safety are warranted, these data support that the net benefits may outweigh the net harms of more intensive BP lowering in persons with CKD,” Dr Malhotra and colleagues concluded.

Still, the mean SBP in the intensive group fell to just 132 mm Hg—above the less than 120 mm Hg target considered physiologically normal.

Targeting lower SBP reduced CKD patient death risk by 14%, meta-analysis shows.

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Due to a lack of data, the reviewers could not examine all-cause mortality and SBP by CKD severity, which was a study limitation.

In an accompanying editorial, Csaba K. Kovesdy, MD, Fred Hatch Professor of Medicine at the University of Tennessee Health Science Center in Memphis, a Renal & Urology News editorial advisory board member, noted that the mean overall intensive SBP of 132 mm Hg in the meta-analysis actually falls within the clinical target recommended by most current guidelines (less than 140 mm Hg) and is also within the range that has been associated with the best outcomes in large observational studies.

“One could therefore interpret the results of this meta-analysis as solidifying existing evidence about the benefits of lowering BP to a range of 130 to 140 mm Hg but not as proof that truly intensive BP lowering (ie, to a target <120 mm Hg) is beneficial,” wrote Dr Kovesdy, Chief of Nephrology at Memphis VA Medical Center. He emphasized that there are many outstanding questions that warrant research, including outcomes for advanced CKD patients. n

www.renalandurologynews.com SEPTEMBER/OCTOBER 2017

Renal & Urology News 17

n SPECIAL FEATURE

Evaluating Practice Options in the Shifting Health Care Landscape Weighing pros and cons carefully can help ensure a successful partnership or merger

© SMILE STUDIO / SHUTTERSTOCK

BY ROBERT PROVENZANO, MD, FACP, FASN, MARK HOVERMANN, MBA, AND LANNY TEETS

Editor’s note: This article is the second of a 3-part series.

A

s a growing number of physicians consider divesting their practices to adapt to today’s practice environment, there are many factors to consider. It is a big decision that impacts both job satisfaction and the ability to meet future challenges. Considering personal short- and long-term goals, as well as the various pros and cons that correspond with different options, will help you make a decision that is personally and professionally satisfying.

In Part 1, we discussed how several challenges—including the shift away from fee-for-service to value-based payments—are pushing physicians to consider different business models.

Partnering with another organization may provide multiple benefits, includ-

ing support for participating in new value-based agreements, infrastructure to comply with increasingly complex and burdensome regulations and, most importantly, access to the capital needed to fund technological investments and growth.

Should you consider a strategic partnership? Here are a few questions to help guide your thought process: • Are you working harder to maintain your current level of annual income?

• Have you had to sacrifice work-life balance to maintain your income goals?

• Have you become disillusioned with the complexity of managing your practice, and is this impacting your satisfaction?

independence, or your current processes—clinical or administrative.

If the answer to any of the above questions is “yes,” it is worth further examining new practice models.

Before we dive into the various pros and cons of different options, however, it is important to note that this is a highly individualized decision that hinges on both personal preferences and local market dynamics. Consider the competitive landscape in your market. Is there a large health system or nephrology group that could employ you? Is there interest from large dialysis providers? How about independent groups in the community that might be interested in consolidating? Depending on the answers to these questions, not all of the following options will be available to every nephrologist.

PROS: If you decide to partner with a hospital, your practice will likely remain in an existing network, with little or no disruption for your current patients.

In addition, you will likely have a stable referral base. Finally, being part of a larger organization may include additional benefits, such as access to capital and more leverage in contract negotiations.

Option 1: Do nothing— stay independent PROS: It may be tempting to do nothing.

After all, it keeps the status quo intact, meaning no change in accountability,

CONS: Given the current environment, this could be a risky proposition that results in your practice losing value over time.

With the shift to value-based payments, size matters. For instance, if your practice is too small, it could negatively impact your leverage in negotiating contracts. In addition, remaining independent may hinder your ability to recruit new physicians as they consider the long-term viability of your practice.

Robert Provenzano, MD

Option 2: Partner with a hospital

CONS: Patients with kidney disease can require complex, expensive treatment. As such, nephrologists are often viewed by hospitals as “cost containers,” rather than big revenue generators, which more typically describes cardiologists and oncologists. This dynamic can have several important implications in a hospital partnership.

• Compared with other specialties, nephrology may not experience the same flow of revenue from shared savings agreements, which are becoming increasingly popular as reimbursement shifts to value-based payments.

Mark Hovermann, MBA

Lanny Teets

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Urologist Ownership of IMRT Ups Its Use MEN WITH newly diagnosed prostate cancer are significantly more likely to receive intensity-modulated radiation therapy (IMRT) if their care is managed in a single-specialty urology practice that has an ownership interest in a facility that offers IMRT, according to a new study.

Brent K. Hollenbeck, MD, of the Dow Division for Health Services Research in the Department of Urology at the University of Michigan in Ann Arbor, and collaborators retrospectively analyzed data from a cohort of Medicare beneficiaries with PCa diagnosed between 2010 and 2012. The proportion of patients who underwent IMRT was 43% among men managed in a urology practice with an IMRT ownership compared with 30% among those managed

in a practice without such ownership, regardless of practice size, the researchers reported online in European Urology.

In addition, among patients at very high risk of death from causes other than cancer within 10 years of diagnosis, IMRT use and overall treatment were significantly more likely among those treated by practices with IMRT ownership than without (42% vs 26% and 53% vs 44%, respectively).

“Our findings are consistent with previous research suggesting that physicians are most responsive to financial incentives in clinical settings where treatment benefit is uncertain as opposed to circumstances where it is clear-cut,” Dr Hollenbeck’s team wrote. “In this context, the greatest gap in use of curative

treatment among IMRT owners versus nonowners occurred in the patients with the highest risk of noncancer mortality, where treatment benefit is least certain.”

The authors noted that their study has implications for practicing clinicians.

“Referring physicians should carefully consider the practice structure of the urology group to which they send their patients, as this is likely to importantly influence how their patients are managed.”

Although their study design prevented them from establishing a causal link between ownership and utilization, the researchers noted that “prior longitudinal studies on the topic and strong relationships between ownership and utilization in other contexts support that possibility.” n

Preeclampsia Risk Lowered

By Aspirin TREATMENT WITH low-dose aspirin may lower the risk of preterm preeclampsia among pregnant women at high risk for the condition, new study findings suggest.

In a study, the odds of preeclampsia developing before 37 weeks of gestation were 62% lower among women who took 150 mg of aspirin daily during pregnancy compared with women who took placebo, Daniel L. Rolnik, MD, of Homerton University Hospital in London, and colleagues reported in the New England Journal of Medicine

Practice options continued from page 17

• Since hospitals encompass many different providers, nephrology’s voice at the table may be diluted.

• Although hospitals may have more leverage in contract negotiations, they have to balance the needs and economics of multiple specialties.

This may result in agreements that benefit the larger revenue generators at the expense of nephrologists.

• The future of hospital partnerships is unclear. In some parts of the country, hospitals are in the midst of divesting nephrology practices they had previously acquired.

Option 3: Partner with a kidney care provider This is a newer and growing option that solves for unique subspecialty needs, much like The US Oncology Network.

PROS: • Partnering with a kidney-centric entity can provide specialized insights for your practice—both through tailored data reports and renal-specific management teams.

• It may be easier to access capital for growth and strategic investments.

• Your practice governance remains generally intact and integrated into a broader strategic team.

• When it comes to negotiating contracts, kidney disease remains the sole focus, meaning that nephrology does not have to compete with other specialties for attention (or dollars).

• There may be enhanced kidney care revenue opportunities, as well as cost savings associated with the economies of scale and purchasing power that national providers can bring to the table.

CONS: • The practice, although functionally independent, exists within a structured framework, where the practice is accountable to the nephrology partner.

• Along with increased access to regulatory and legal expertise comes another layer of bureaucracy. While some practices find this oversight invaluable, it can also slow some processes and decisions.

It is also worth considering that a shift away from private practice often can represent a shift in compensation. This can have both advantages and disadvantages. Today’s reimbursement models increasingly require physicians to take on some risk. That risk is mitigated in an employment model, though potential future upside is often shared.

Option 4: Merge with another independent nephrology group

organization that is specifically focused on kidney disease.

CONS: Mergers of any kind can be tricky, and this is especially true with physician practices that were previously competitors. Add to that potential cultural differences, and things can get contentious.

Here are some questions to consider: • Will this partnership help establish best practices?

• How is the potential partner viewed by others in the market?

• How will the new organization be governed?

• How will your practice be valued?

• Who will be make staffing decisions, and how will duplicative functions be addressed?

(2017;377:613-622).

The investigators enrolled 1776 women with singleton pregnancies determined to be at high risk for preeclampsia by means of first trimester screening. The researchers randomly assigned patients to receive aspirin at a dose of 150 mg per day or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. After 152 patients withdrew consent during the trial and the loss of 4 patients to follow up, 798 women in the aspirin group and 822 in the placebo group remained in the trial.

Preterm preeclampsia developed in 13 women (1.6%) in the aspirin

Pursuing a strategic partnership is a big decision that should not be rushed.

Nonetheless, carefully weighing the pros and cons, as well as knowing the right questions to ask, will help ensure that you make the best decision for you and your patients.

In the final chapter of the divestiture series next month, we cover in depth what to expect when choosing to partner with a large dialysis provider. n

group versus 35 (4.3%) in the placebo group, a statistically significant difference in incidence. The aspirin and placebo groups were similar with respect to the incidence of neonatal adverse outcomes or other adverse events.

“Unlike previous trials of strategies to reduce the risk of preeclampsia among high-risk women, we identified women at high risk for

PROS: Consolidating with another nephrology group in your community can provide multiple advantages, including increasing your leverage in contract negotiations and allowing you to capitalize on economies of scale. Merging with another nephrology group also allows you to partner locally with another

Robert Provenzano, MD, is vice president for medical affairs at DaVita Kidney Care in Denver. He also is on the editorial advisory board of Renal & Urology News. Mark Hovermann, MBA, is Senior Director, Corporate Development, and Lanny Teets is Director, Transactions & Growth Initiatives, at Nephrology Practice Solutions.

preterm preeclampsia by means of combined screening with maternal demographic characteristics and historical factors and biomarkers— a strategy that has been shown to be superior to other currently used methods,” Dr Rolnik’s group wrote. n

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Arteriovenous Fistulas Not Always Best for HD

BY NATASHA PERSAUD ARTERIOVENOUS fistulas (AVFs) are widely considered the optimal form of vascular access for hemodialysis (HD) patients, but new findings suggest AVFs are not appropriate for all HD patients.

In a paper published online ahead of print in the European Journal of

Vascular Endovascular Surgery, Jeffrey Lawson, MD, PhD, of Humacyte in Morrisville, North Carolina, and collaborators reported results from a meta-analysis of 318 studies spanning 20 years that involved 62,712 accesses. AVFs displayed a high risk of maturation failure and abandonment.

Only 26% of AVFs were mature by 6 months, and 21% were abandoned without use. The average time to maturation was 3.5 months, and 66% of patients required a bridging catheter. The primary unassisted, primary assisted, and secondary patency rates at 1 year were 64%, 73%, and 79%,

respectively. The AVF patients had an overall infection risk of 4.1%.

“Reported fistula patency rates may overstate their potential clinical utility when time to maturation, maturation rate, abandonment and infection are considered,” Dr Lawson’s team concluded. “Protracted maturation times, abandonment and infection all have a significant impact on evaluating the clinical utility of fistula creation.”

In other findings, the meta-analysis showed that AVFs created in the United States were abandoned more frequently than in other developed nations (27% vs 16%). Higher abandonment rates were found among women than men (43% vs 33%). Accesses placed in the upper arm were abandoned less frequently than those in the forearm (16% vs. 23%).

Meta-analysis shows approximately 1 in 5 AVFs are abandoned without use.

Dr Lawson and his colleagues noted that the National Kidney Foundation recommends AVF placement at least 6 months prior to HD initiation to allow sufficient time for access creation and evaluation, vein maturation, and, if necessary, maturation-enhancing interventions before cannulation.

Therefore, it is recommended that patients with stages 4 and 5 chronic kidney disease be educated on vascular access modalities to allow sufficient time for access placement.

“While this is a noble goal,” the investigators wrote, “it has been difficult to implement because of the unpredictability of renal failure progression, patient referral patterns, and financial disincentives for early fistula creation. It is common for patients to progress to ESRD and initiate HD before the fistula has either been created or matured.”

In an editorial accompanying the report by Dr Lawson and his colleagues, Jan H.M. Tordoir, MD, PhD, of the Department of Vascular Surgery at Maastricht University Medical Centre in Maastricht, the Netherlands, noted that “implementation of preoperative ultrasonographic vessel examination reduces the number of early AVF failures by improved selection of the most suitable vessels and site for AVF creation.” ■

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AVFs Not Always Best for HD Patients Meta-analysis showed that only 26% of arteriovenous fistulas were mature by 6 months

BY NATASHA PERSAUD ARTERIOVENOUS fistulas (AVFs) are widely considered the optimal form of vascular access for hemodialysis (HD) patients, but new findings suggest AVFs are not appropriate for all HD patients.

In a paper published online ahead of print in the European Journal of Vascular Endovascular Surgery, Jeffrey Lawson, MD, PhD, of Humacyte in Morrisville, North Carolina, and collaborators reported results from a meta-analysis of 318 studies spanning 20 years that involved 62,712 accesses. AVFs displayed a high risk of maturation failure and abandonment.

Only 26% of AVFs were mature by 6 months, and 21% were abandoned without use. The average time to maturation was 3.5 months, and 66% of patients required a bridging catheter. The primary unassisted, primary

assisted, and secondary patency rates at 1 year were 64%, 73%, and 79%, respectively. The AVF patients had an overall infection risk of 4.1%.

“Reported fistula patency rates may overstate their potential clinical utility when time to maturation, maturation

Primary unassisted and assisted patency rates at 1 year were 64% and 73%. rate, abandonment and infection are considered,” Dr Lawson’s team concluded. “Protracted maturation times, abandonment and infection all have a significant impact on evaluating the clinical utility of fistula creation.”

MIBC Patients Fare Better With Radical Cystectomy OVERALL SURVIVAL is greater for

more narrowly defined with adjust-

patients with stage 2 to 3 muscle-

ment for confounders. In multivariate

invasive bladder cancer (MIBC) who

analysis, any EBRT, definitive EBRT, and

undergo radical cystectomy (RC) versus

definitive EBRT with chemotherapy were

bladder preservation therapy (BPT), a

associated with 2.1, 1.9, and 1.6 times

new study finds.

increased risk of death, respectively.

Of 32,300 patients from the National

Based on propensity score matching,

Cancer Data Base (2004–2013),

the risk of death was 2.0, 1.6, and 1.4

22,680 underwent RC and 9620 had

times greater, respectively.

BPT. The BPT patients underwent trans-

“There is an ongoing need to charac-

urethral resection and received either

terize survival outcomes to distinguish

any form of external beam radiation

who can benefit from bladder-sparing

therapy (EBRT), definitive EBRT (50–80

approaches and avoid the morbidity of

Gy), or definitive EBRT plus chemother-

radical cystectomy,” lead author David

apy. In the BPT group, 2540 patients

B. Cahn, DO, MBS, a urologic oncol-

(26.4%) had definitive EBRT and 1489

ogy fellow at Fox Chase Cancer Center

patients (15.5%) had definitive EBRT

in Philadelphia, told Renal & Urology

with concurrent chemotherapy. Only

News. “The results of the current study

14% of RC patients had neoadjuvant

suggest that BPT may produce accept-

chemotherapy (NAC).

able oncologic outcomes in appropri-

BPT was associated with significantly reduced overall survival compared

ately selected patients.”

Generally, BPT candidates include

with RC, according to results published

those with node-negative, non-meta-

online ahead of print in Cancer. The

static stage 2 to 3 urothelial carcinoma

5-year overall survival (OS) rates were

of the bladder, no carcinoma in situ, uni-

30% in the BPT cohort compared with

focal lesions, and no hydronephrosis,

48% in the RC cohort. The survival

who are likely to have complete TURBT,

advantage of RC diminished as BPT was

according to the investigators. ■

In other findings, the meta-analysis showed that AVFs created in the United States were abandoned more frequently than in other developed nations (27% vs 16%). Higher abandonment rates were found among women than men (43% vs 33%). Accesses placed in the upper arm were abandoned less frequently than those in the forearm (16% vs. 23%).

Dr Lawson and his colleagues noted that the National Kidney Foundation recommends AVF placement at least 6 months prior to HD initiation to allow sufficient time for access creation and evaluation, vein maturation, and, if necessary, maturation-enhancing interventions before cannulation.

Therefore, it is recommended that patients with stages 4 and 5 chronic kidney disease be educated on vascular access modalities to allow sufficient time for access placement.

NSAID Users Have Lower Risk of PCa USE OF non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased risk of prostate cancer (PCa), according to researchers. The protective effect is more pronounced among men with a history of prostatitis.

An analysis of data from the EPICAP (EPIdemiology of Prostate CAncer) case-control study showed that overall users of NSAIDs had a significant 23% decreased risk of PCa compared with men non-users, investigators reported online in Cancer Medicine. The investigators adjusted for age, race, family history of cancer in first-degree relatives, educational level, history of prostatitis, and waist-to-hip ratio.

Men who used NSAIDs that preferentially inhibited COX-2 activity had a significant 52% decreased risk. Use of non-aspirin NSAIDs was associated with a significant 28% decreased risk of PCa overall and a 51% decreased risk of high-grade PCa, defined as Gleason score 7 (4 + 3) or higher.

Compared with men who did not use NSAIDs, those who took 1 or more NSAID pills per day had a 62% decreased risk of PCa.

“While this is a noble goal,” the investigators wrote, “it has been difficult to implement because of the unpredictability of renal failure progression, patient referral patterns, and financial disincentives for early fistula creation. It is common for patients to progress to ESRD and initiate HD before the fistula has either been created or matured.”

In an editorial accompanying the study by Dr Lawson’s team, Jan H.M. Tordoir, MD, PhD, of the Department of Vascular Surgery, Maastricht University Medical Centre in Maastricht, the Netherlands, suggested that pre-operative ultrasonographic vessel examination and vascular access training centers of excellence might better identify appropriate patients for AVF placement and reduce AVF failure. ■

The study also found that the protective effect of NSAIDs was greater among men with a history of prostatitis. In these patients, use of any NSAIDs and use of non-aspirin NSAIDs were associated with a 68% and 79% decreased risk of PCa, respectively, compared with nonuse. By comparison, among men without a history of prostatitis, the use of any NSAIDs and use of non-aspirin NSAIDs were associated with a 15% and 18% decreased risk of PCa, respectively.

The study, led by Florence Menegaux, MD, PhD, of the Center for Research in Epidemiology and Population Health, INSERM, Team Cancer and Environment, Villejuif, France, enrolled 819 men aged less than 75 years with newly diagnosed PCa and 879 age-matched controls.

The researcher concluded that their study “provides convincing evidence” that frequent and chronic use of NSAIDs decreases the risk of PCa, especially aggressive PCa. The decreased risk observed among men with a history of prostatitis is additional evidence that targeting chronic inflammation may help prevent prostate carcinogenesis, they noted.

For the study, the investigators defined overall users of NSAIDs as men who took aspirin or non-aspirin NSAIDs at least once a month. They considered men who never took NSAIDs or took them less frequently than once a month to be non-users. ■

www.renalandurologynews.com SEPTEMBER/OCTOBER 2017

ED Discharge With AKI Predicts Poor Outcomes Study reveals 60% higher 30-day death risk versus no AKI on discharge mation about urine output was not available in their data sources.

The investigators matched 4379 discharged patients to 4379 who were hospitalized from the ED with similar AKI stage. They also matched 6188 discharged patients to 6188 patients discharged home from the ED with

© OLESIA BILKEI / SHUTTERSTOCK

PATIENTS DISCHARGED home from an emergency department (ED) with acute kidney injury (AKI) are at risk of poor 30-day outcomes, new findings suggest.

In a study of emergency department visits in Ontario, Canada, researchers found that patients discharged home

In a study of emergency department visits in Ontario, Canada, 16% of patients discharged with acute kidney injury (AKI) required hospitalization within 30 days.

with a diagnosis of AKI had a 60% higher risk of all-cause mortality within 30 days than those discharged home without an AKI diagnosis, according to a paper published online ahead of print in the Clinical Journal of the American Society of Nephrology.

“Our results suggest there is an opportunity to explore health system strategies to improve the identification and management of patients discharged home from the ED with AKI,” Rey R. Acedillo, MD, of London Health Sciences Centre in London, Ontario, and colleagues concluded.

The study included 6346 ED discharges with AKI. Patients had a mean age of 69 years and 6012 patients (95%) had stage 1, 290 (5%) had stage 2, and 44 (0.7%) had stage 3 AKI. The researchers defined AKI as a relative increase in serum creatinine by 50% or more or an absolute increase of 0.3 mg/dL or higher from the pre-ED baseline. They staged AKI severity based on the 2012 Kidney Disease: Improving Global Outcomes guidelines. The authors noted that infor-

no AKI. The patients discharged with AKI had a significantly higher 30-day all-cause mortality rate than those discharged with no AKI (2% vs 1%) and a significantly lower 30-day all-cause mortality rate compared with patients hospitalized with AKI (3% vs 12%).

Of the 6346 patients discharged with AKI, 1032 (16%) required hospitalization within 30 days, a rate similar to the 30-day readmission rates among AKI survivors after hospitalization found in previous studies, the authors noted.

The mean age of the patients discharged home was 69 years, and 47% were women. The most common preexisting comorbidities were hypertension, which was present in 75% of patients, followed by diabetes (38%) and coronary artery disease (34%).

Dr Acedillo’s team noted that several rapid access clinics for patients discharged from the ED with chest pain, heart failure, or a transient ischemic attack have been shown to improve patient outcomes. The researchers cited a study showing that AKI survi-

vors discharged after hospitalization appear to benefit from follow-up clinics. That study, which was published in Kidney International (2013;83:901-908), included patients hospitalized with AKI who received temporary inpatient dialysis and survived for 90 days following discharge independent from dialysis. The incidence of all-cause mortality was lower for patients who had early nephrology follow-up care—defined as a visit with a nephrologist within 90 days of discharge—compared with those who did not. “A similar model could be adopted for patients discharged home from the ED with AKI, supported by an automated surveillance system to aid in the identification of AKI,” Dr Acedillo and colleagues wrote.

In an acknowledgement of study limitations, the investigators noted that they were unable to capture patients who had baseline pre-ED serum creatinine measurements in other outpatient laboratories or hospitals. Also, use of an administrative database limited their ability to ascertain information regarding AKI awareness by ED physicians, according to the researchers. “For many patients, we suspect that AKI was in fact recognized, appropriately managed, and deemed safe for discharge home.”

In an editorial accompanying the paper by Dr Acedillo and colleagues, Jay L. Koyner, MD, of the University of Chicago, noted that the new study “emphasizes that every patient with an incident case of AKI is an opportunity to improve patient care and prevent morbidity and mortality, regardless of the AKI setting or severity.”

Importantly, Dr Koyner stated, the results highlight that “the treating ED physicians were able to identify, manage, treat, and discharge home a cohort of patients with AKI in the setting of other acute on chronic medical issues and risk stratify them as lower risk for morbidity and mortality compared with the other patients who were admitted to the hospital from the ED with AKI.” The study also highlights that “ED-based AKI, although it was almost exclusively stage 1, carries a significant degree of morbidity and mortality, which often go under-recognized by physicians all over the hospital, not just in the ED.” n

Renal & Urology News 21

‘Purge’ PTx May Be a New SHPT Option PURGE parathyroidectomy (PTx) may represent a new option in the treatment of secondary hyperparathyroidism (SHPT) refractory to medical therapy.

Cheng-Xiang Shan, MD, Nian-Cun Qiu, MD, and Si-Luo Zha, MD, of Chang Zheng Hospital in Shanghai, China, and colleagues reported online in the International Journal of Surgery that 9 patients were treated successfully with purge PTx. To be included in the study, patients had to have shown no response to medical therapy and have sustained serum parathyroid hormone (PTH) levels higher than 800 pg/mL. Preoperatively, patients had PTH levels ranging from 1062 to 2879 pg/mL. On the first postoperative day, PTH levels ranged from 12.35 to 72.69 pg/mL. The operation was performed in 95 to 135 minutes, with blood loss of 20 to 40 mL. No patients experienced major bleeding or died during the procedure.

The procedure involves removing more than the main parathyroid glands.

About 2% to 20% of SHPT patients experience recurrent or persistent SHPT within 2 years of conventional PTx procedures, including total PTx, likely due to residual parathyroid tissue, the authors noted. The investigators proposed that microparathyroid tissues and cells could exist in odd places and escape detection, contributing to high PTH after surgery.

Purge PTx was designed to eliminate these invisible “seeds” by removing their “soil.” The procedure removes more than the main parathyroid glands.

According to the team, it involves a comprehensive resection of cervical fibrofatty tissues within the region surrounded by the thyroid cartilage, bilateral carotid artery sheath, and the brachiocephalic artery.

Pathology reports showed that 3 patients had ectopic parathyroid tissues in areas unknown to contain such cells.

Overall, the surgeons resected 37 parathyroid glands from the 9 patients.

None of the patients experienced SHPT recurrence or persistence during the short follow-up period. n

22 Renal & Urology News

SEPTEMBER/OCTOBER 2017 www.renalandurologynews.com

CA Patient Self-Reporting Reliable Prostate cancer patients accurately report their comorbidities, according to investigators MEN WITH newly diagnosed prostate cancer (PCa) can reliably report their comorbidities, and participants in cancer clinical trials “are willing and able” to report symptomatic adverse events (AEs), according to the findings of separate studies published in JAMA Oncology.

The new findings could have implications for therapeutic decision making, cutting study-related data collection costs, and improving reporting of toxic events in clinical trials.

In a study of a population-based cohort of 881 men with newly diagnosed localized PCa, Fan Ye, MD, MPH, and colleagues at the University of North Carolina at Chapel Hill compared the presence or absence of 20 medical conditions based on patient reports versus medical records. For 16 of the 20 conditions, patient reports agreed with medical records for more than 90% of patients.

Agreement was lowest for arthritis (66%) and hyperlipidemia (68%). Nonwhite race and lower educational level were not associated with lower patient versus physician report agreement.

On multivariate analysis, researchers found that older age was associated with lower overall agreement for multiple conditions. For example, compared with patients younger than 60 years, those older than 70 years had significantly lower overall agreement for

myocardial infarction, cerebrovascular disease, kidney disease, coronary artery disease, and arrhythmia.

“Patient reporting provides information similar to medical record abstraction and may be a less costly method for assessing comorbid conditions for observational comparative effectiveness research,” Dr Ye and colleagues wrote.

Accurate assessment of comorbidities is important, they researchers noted, because patients’ baseline comorbidities directly affect PCa treatment decision making. “In the United States, younger and healthier patients commonly undergo prostatectomy, whereas older patients and those with more comorbid conditions receive radiation or conservative management.”

The study cohort was part of the North Carolina Prostate Cancer Comparative Effectiveness & Survivorship Study. Patients had a median age of 65 years (range 41–80 years). Of the 881 men, 633 (71.9%) were white. Investigators assessed conditions by patient report via telephone survey and by medical record abstraction at the time of study enrollment.

For the other study, Ethan Basch, MD, MSc, of the University of North Carolina at Chapel Hill, and colleagues examined patient reporting of symptomatic AEs in 9 US multicenter cancer clinical tri-

Patients in cancer clinical trials report more adverse events than investigators.

als. The study enrolled 285 patients with a median age of 57 years. Of these, 151 (53%) had breast cancer, 16 (5.6%) had colorectal cancer, 10 (3.5%) had lung cancer, 14 (4.9%) had PCa, and 94 (33%) were receiving supportive care.

Patients completed self-reports at 1202 (93.9%) of 1280 visits during which they had an opportunity to selfreport. Patient-investigator agreement was moderate or worse for most symptoms, with investigators reporting fewer AEs than patients across symptoms, Dr Basch’s team stated. The study also showed that 93% of patients found the

reporting system easy to use and useful; 94% and 83.2% of investigators considered patient-reported AEs to be useful and accurate, respectively.

“Participants in multicenter clinical trials are willing and able to report their own symptomatic AEs at most clinic visits and report more AEs than investigators,” Dr Basch and his colleagues concluded. “This approach may improve the precision of AE reporting in cancer trials.”

In an editorial accompanying both studies, Zaina P. Qureshi, PhD, MPH, MS, of the University of South Carolina in Columbia, and coauthors said the studies “take important first steps in showing us that it is feasible to obtain expanded information about patient experiences, comorbid conditions, and toxic effects that occur among patients with cancer.”

The editorial writers commented that the study by Dr Ye and colleagues “provides support for the reliability of reported comorbid illnesses by men with localized prostate cancer when compared with the medical record.

Furthermore, hypothesized factors of race and education were not relevant predictors of the accuracy of self-report.

The feasibility of this approach has implications for evaluating patterns of care and outcomes for men with localized prostate cancer.” n

BY NATASHA PERSAUD DIABETIC KIDNEY DISEASE is less likely to develop or progress in patients with type 2 diabetes treated with liraglutide, a glucagon-like peptide 1 (GLP-1) agonist, according to a secondary analysis of the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial.

For the study, investigators randomly assigned 9340 patients with type 2 diabetes and a high risk of cardiovascular disease to receive, in addition to usual care, liraglutide or placebo.

Liraglutide-treated patients had a significant 22% lower risk of a composite renal outcome of new-onset persistent macroalbuminuria (urinary albumin excretion greater than 300 mg/day), persistent doubling of serum creatinine, end-stage renal disease (ESRD),

and death due to renal disease compared with patients who received placebo. The composite renal outcome occurred in 268 (5.7%) of 4668 liraglutide patients and 337 (7.2%) of

Decreased risk was mostly due to fewer cases of persistent macroalbuminuria.

4672 placebo recipients over a median 3.8 years of follow-up.

The decreased risk of the composite outcome was attributable mainly to fewer instances of persistent macroalbuminuria among the liraglutide group (161 liraglutide vs 215 placebo), Johannes F.E. Mann, MD, of the KfH Kidney Center

in Munich, reported in the New England Journal of Medicine. Liraglutide was associated with a significant 26% reduction in the risk of macroalbuminuria. The investigators found no significant reduction in the risk for persistent doubling of serum creatinine or ESRD. The liraglutide and placebo groups had similar rates of adverse events overall: 15.1 vs 16.5 events per 1000 patientyears, respectively.

“It appears to be unlikely that the moderate between-group differences in systolic blood pressure and body weight can fully explain the effect on renal outcomes,” Dr Mann’s team stated. “In an analysis that took into account those differences, the composite renal outcome still occurred less frequently with liraglutide than with placebo. The mechanisms behind the renal effects of liraglutide are probably multifactorial.”

In a previous study published in the New England Journal of Medicine (2016;375:323-334), treatment with empagliflozin, an inhibitor of sodium– glucose cotransporter 2 (SGLT2), was associated with slower progression of kidney disease and lower rates of clinically relevant events compared with placebo when added to standard care among patients with type 2 diabetes at high cardiovascular risk.

In an accompanying editorial, Ian H. de Boer, MD, of the University of Washington in Seattle, stated: “Currently, it is logical to consider including a GLP-1 agonist or SGLT2 inhibitor in the glucose-lowering regimen of patients with type 2 diabetes and mild-to-moderate diabetic kidney disease, with the anticipation of salutary renal and, particularly, cardiovascular effects.” n

© WAVEBREAKMEDIA / GETTY IMAGES

Liraglutide Decreases Diabetic Nephropathy Risk

www.renalandurologynews.com SEPTEMBER/OCTOBER 2017

Renal & Urology News 23

Prostate Abnormalities Linked to Lower Odds of PCa PROSTATE ATROPHY (PA) and chronic prostate inflammation (CPI) in baseline biopsies, especially when these findings occur together, are associated with lower prostate cancer risk and grade, according to a recent study.

A team led by Daniel M. Moreira, MD, of the University of Illinois at Chicago, retrospectively studied 6132 men aged 50 to 75 years who underwent 2-year repeat prostate biopsies after a negative baseline biopsy for prostate cancer (PCa) in the REDUCE (REduction by DUtasteride for prostate Cancer Events) trial. The investigators evaluated the association of baseline PA and CPI with 2-year repeat biopsy cancer status and grade.

PA, CPI, and both were detected in 583 (9.5%), 1063 (17.4%), and 3675 (59.9%) baseline biopsies, respectively.

Compared with biopsies with neither PA nor CPI, the presence of PA, CPI, and both was associated with a signifi-

Prostate atrophy and chronic prostate inflammation reduce PCa diagnosis risk. cant 21%, 29%, and 36% lower odds of PCa in the 2-year repeat biopsy, respectively, in multivariable analysis, Dr Moreira and his colleagues reported online ahead of print in Prostate Cancer and Prostatic Diseases. Among patients with both PA and CPI, those with both findings in the same core had a significant 27% lower odds of PCa in multivariable analysis.

Multivariable analyses included adjustments for baseline age, race, PSA, digital rectal examination findings, body mass index, prostate volume (PV), among other potential confounders.

In addition, compared with the absence of both PA and CPI, the presence of CPI, either alone or occurring together with prostate atrophy in the same biopsy, was associated with 42% lower odds of high-grade PCa, defined as Gleason score 7–10.

Dr Moreira’s group noted that the biologic mechanisms linking prostate atrophy and chronic prostate inflammation to prostate carcinogenesis remain unclear, although a number of studies have demonstrated an association between both of these findings and larger prostate volumes. Increased prostate volumes have been correlated with

a lower likelihood of a PCa diagnosis in prostate biopsies. “Thus, it is plausible that PV could be a mediator between PA, CPI and PCa,” they wrote.

In a previously published paper in Urology (2017;103:161-166), Dr Moreira and colleagues reported findings from a separate retrospective analysis of

3165 men in the REDUCE trial showing that the extent of baseline PA is independently associated with lower PCa risk in a dose-dependent fashion.

Compared with men without PA, those with 1%–25%, 26%–50%, 51%–75%, and greater than 75% core involvement had 35%, 40%, 44%, and 65% lower

ds of PCa. In addition, men with PA in more cores had a lower incidence of both low-grade (Gleason 2–6) and high-grade (Gleason 7–10) PCa, they reported. More extensive PA was associated with older age, lower PSA, larger prostate volume, and greater prevalence of acute and chronic inflammations. ■

24 Renal & Urology News

SEPTEMBER/OCTOBER 2017 www.renalandurologynews.com

Not All High-Risk PCa Is the Same Men with 1 high-risk factor have better treatment outcomes than those with 2 or 3 high-risk factors RESEARCHERS HAVE identified distinct subgroups of men with high-risk prostate cancer (PCa) who experience different outcomes following treatment with a combination of high-dose radiation therapy and androgen-deprivation therapy (ADT), according to a new report in BMC Urology (2017;17:60).

In a study of 547 patients, Daniel N. Cagney, MD, of St. Luke’s Radiation Oncology Network in Dublin, Ireland, and colleagues found that patients with a single high-risk factor (favorable highrisk subgroup) had better outcomes than those with multiple high-risk factors (unfavorable high-risk subgroup) following treatment with a combination of external beam radiation therapy (EBRT) and ADT. The favorable high-risk subgroup had a 5-year distant metastasisfree survival (DMFS) rate similar to that of patients with intermediate-risk PCa. The 2015 National Comprehensive Cancer Network (NCCN) guidelines define high-risk PCa as a biopsy Gleason score of 8–10, a PSA level greater than

Cancer Drug May Inhibit ADPKD Cysts IN A PHASE 2 STUDY, bosutinib, an oral drug approved for treating certain cases of chronic myeloid leukemia, slowed cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD).

In the 2-year placebo-controlled study, patients treated with bosutinib 200 mg/day experienced a significant 66% reduction in the annual rate of kidney enlargement compared with placebo recipients (1.63% vs 4.74%).

The change in median kidney volume from baseline to end of treatment was about 100 mL smaller in the bosutinib 200 mg/day group compared with placebo recipients (62.7 vs 168.1 mL), researchers reported online ahead of print in the Journal of the American Society of Nephrology.

The pathogenesis of ADPKD has been linked to overactivation of Src, and bosutinib is a dual Src/Bcr-Abl tyrosine kinase inhibitor, noted a research team led by Vladimir Tesar, PhD, of Charles

Favorable vs Unfavorable High-Risk Prostate Cancer In a study of men with high-risk prostate cancer treated with high-dose radiation therapy plus androgen-deprivation therapy, those with 1 high-risk factor had better 5-year biochemical recurrence-free survival (bRFS) and distant metastasis-free survival (DMFS) rates than those with 2–3 high-risk factors, as shown below.

100

60

n bRFS

88%

80

69.2%

66.2%

81.2%

n DMFS

40 20 0

1 high-risk factor

2–3 high-risk factors

Source: Cagney DN et al. Heterogeneity in high-risk prostate cancer treated with high-dose radiation therapy and androgen deprivation therapy. BMC Urol. 2017;17:60.

20 ng/mL, or clinical stage T3a disease.

In the new study, all patients underwent EBRT and 98% received ADT. The investigators defined 4 subgroups based on NCCN criteria: patients with 1 high-risk factor (favorable risk subgroup); patients with 2–3 high-risk factors (unfavorable risk subgroup); patients with 2–3 NCCN criteria for

University and General University Hospital in Prague, Czech Republic.

“The study offers evidence that Src kinase inhibitors may have the potential to retard the growth of cysts and kidney volume in ADPKD but the long-term benefit remains to be determined,” the researchers concluded.

Dr Tesar and his colleagues enrolled 172 patients with ADPKD. Of these, 169 receive at least 1 study dose. The study consisted of 4 groups: 58 patients who received bosutinib 200 mg/day; 31 who received bosutinib 400 mg/day; 24 who initially received bosutinib 400 mg/day but were later switched to 200 mg/day (400/200 mg/day group), and 56 who received placebo.

When the investigators compared pooled bosutinib results with placebo, the annual rate of kidney enlargement was reduced by 82% (0.84% vs 4.74%).

The researchers observed no significant change in estimated glomerular filtration rate between the study arms during the treatment period.

The most frequent toxicities were gastrointestinal (GI) and liver-related adverse events, but the overall GI and liver toxicity profile was consistent with the profile demonstrated in previous studies of bosutinib. The researchers identified no new toxicities. n

intermediate-risk disease; and patients with very high-risk disease. The main outcomes were biochemical recurrencefree survival (bRFS) and DMFS. For the entire study population, the median EBRT dose was 74 Gy, and the median ADT duration was 8 months.

The median follow-up was 62.3 months.

The 2-year bRFS rate was 87%; the 2-

and 5-year DMFS rates were 95% and 85%, respectively.

For the favorable, unfavorable, and very high-risk subgroups, the estimated 2-year bRFS rates were 91.6%, 78.8%, and 79.4%, respectively, Dr Cagney and his colleagues reported. The 5-year bRFS rates for the favorable, unfavorable, and very high-risk subgroups were 69.2%, 66.2%, and 58.2%. The 5-year rates of DMFS were 88.0%, 81.2%, 78.4%, and 93.7% for the favorable, unfavorable, very high-risk, and intermediate-risk patients. The estimated 10-year DMFS rates were 66.7% and 54.5% for the favorable and unfavorable subgroups. The estimated 5- and 10-year DMFS rates for the very highrisk group were 78.4% and 57.4%.

“These results highlight the heterogeneity within high-risk prostate cancer,” the authors wrote. “This is one of the first series from Europe in patients with highrisk prostate cancer treated with radiotherapy that has sought to sub-classify high-risk disease.” n

Timing of PSA Nadir After RP May Predict BCR Risk FOLLOWING RADICAL prostatectomy

respectively, Dr Freedland and his col-

(RP) for prostate cancer, patients who

leagues reported online ahead of print

have both a detectable PSA nadir and

in Urology. Additionally, among patients

a shorter time to nadir (TTN) are at

who had detectable PSA at 1–3

higher risk for biochemical recurrence

months, 53% had a lower follow-up PSA

of disease, a new study suggests.

3–6 months after RP, with 32% having

A team led by Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, conducted a retrospec-

undetectable levels and 21% having lower but still detectable levels.

“Using both the PSA nadir value and the

tive analysis of 1939 men from the

time it takes to reach nadir can be valu-

SEARCH database who underwent RP

able tools in predicting a patient’s BCR

from 1998 to 2015 and had PSA nadir

risk and potential need for early second-

values determined by ultrasensitive

ary therapy,” the authors concluded.

assay within 1–6 months post-RP.

With regard to patients for whom early

Among men with an undetectable

post-operative PSA values are crucial in

PSA nadir, TTN was unrelated to bio-

deciding on adjuvant radiation therapy

chemical recurrence (BCR). Regardless

or not, and PSA is detectable but below

of TTN, however, men with detectable

the threshold for recurrence (0.2 ng/mL

nadir had a significantly increased risk

or less), Dr Freedland’s team noted that if

of BCR. Compared with men who had

their findings are confirmed in future stud-

an undetectable nadir and TTN of 3–6

ies, “it may be reasonable to give more

months, those who had a TTN of 3–6

time for the PSA to decline before docu-

months and 1–2.99 months had a 1.8

menting a nadir, which may spare some

and 3.7 times increased risk of BCR,

patients from needless radiation.” n

www.renalandurologynews.com SEPTEMBER/OCTOBER 2017

Olfactory Deficits May Explain Malnutrition in Kidney Disease Theophylline showed potential as a treatment in a pilot study PATIENTS WITH CHRONIC kidney disease (CKD) and end-stage renal disease (ESRD) have olfactory deficits that correlate with markers of malnutrition, and intranasal theophylline may hold promise as a way to improve olfaction, researchers reported.

Sagar U. Nigwekar, MD, of Massa­chu­ setts General Hospital in Boston, and colleagues quantified odor identification, odor threshold, and subjective odor perception in a cohort of 161 individuals, including 36 patients CKD, 100 with ESRD, and 25 controls. The mean odor identification score was significantly lower among patients with CKD (75.6%) and ESRD 66.8%) compared with controls (83.6%), the investigators reported online ahead of print in the Journal of the American Society of Nephrology. Patients with ESRD showed higher odor threshold than the other study participants.

The 3 groups had similar scores for subjective smell assessment. In multivariate analyses, kidney disease was associated with 4.8-fold increased odds of odor identification deficits.

The investigators assessed the association between olfaction and nutrition using by subjective global assessment

(SGA) score—a validated nutritional assessment tool—and serum levels of nutritional markers. A reduction in odor identification score was associated with higher SGA score and lower serum total cholesterol, LDL cholesterol, and albumin concentrations. They found no associations between odor threshold and nutritional parameters.

Study reveals defects in odor identification among patients with CKD and ESRD. “Our results highlight olfactory deficit as a potential novel mechanism to comprehend malnutrition, as patients with odor identification deficits in our study were noted to have a higher SGA score and lower levels of biochemical measures of nutritional status,” they wrote. “Our findings of patients with CKD demonstrating defects in odor identification and patients with ESRD demonstrating defects in odor identification and odor threshold may facilitate the development

of interventions tailored to the severity of underlying kidney disease.”

The study included a 6-week openlabel clinical trial in which 5 (71%) of 7 patients who received intranasal theophylline—an epithelial membrane transport and proton secretion activator—experienced an increase in odor identification score. The researchers concluded that the findings from this pilot study “support further testing of nasal theophylline to alleviate olfactory deficits and malnutrition in patients with kidney disease.”

Decreased capacity and impaired regeneration of olfactory epithelial cells in the presence of uremic toxins are among the possible explanations for olfactory deficits in patients with kidney disease, the authors noted.

In a discussion of study limitations, the investigators stated that residual confounding cannot be ruled out. In addition, most of the patients in the ESRD group were receiving in-center hemodialysis (HD) thrice weekly, so the study’s findings may not be generalizable to patients receiving peritoneal dialysis or an HD prescription different from that of patient in the study. n

Renal & Urology News 25

Researchers: Iron-based Binders Best

BY NATASHA PERSAUD FOR REDUCING SERUM phosphate levels associated with hyperphosphatemia, iron-based binders may be the most efficacious and safe, according to Chinese researchers.

Xiaolei Zhang, MD, of Linyi People’s Hospital in Shandong, China, and colleagues performed a network meta-analysis (NMA) of 7 phosphate binders versus placebo using randomized controlled trial data from 80 articles involving 16,382 hemodialysis cases. Calcium-based, iron-based, and magnesium-based phosphate-binders were compared directly and indirectly along with lanthanum carbonate, nonabsorbed metal-free polymer, colestilan, and nicotinic acid. Compared with placebo, all phosphate-binding agents reduced serum phosphate levels and serum calcium × phosphorus product, according to findings published online in the Journal of Parenteral and Enteral Nutrition. Based on this single biomarker, iron-based binders appeared the most effective.

Phosphate binders had the additional

Racial Disparity in PCa Therapy Identified

effect of reducing serum intact

AT MOST US medical facilities, white men are more likely than black men to receive definitive therapy for intermediate- or high-risk prostate cancer (PCa), according to a new study.

Researchers said their findings suggest that current PCa mortality differences between white and black men may be partially the result of “within” hospital quality of care variation rather than geographic “between” hospital disparities. The study appears to be the first to examine individual facility-level variation among white and black men, according to the investigators.

Using the National Cancer Data Base, David F. Friedlander, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues identified 223,873 white men and 59,262 black men aged 40 years or older receiving care at a US facility for biopsy confirmed localized intermediate- or high-risk PCa from January 2004

based phosphate-binding agents

to December 2013. Results showed that 83% of whites received definitive therapy compared with 74% of blacks during the study period, the researchers reported online ahead of print in European Urology. In addition, 39% of treating facilities showed significantly higher rates

Whites are more likely than blacks to receive definitive therapy, data show. of definitive therapy among white men compared with just 1% favoring black men. After adjusting for sociodemographic and clinical factors, most facilities favored definitive therapy for white versus black patients, the investigators reported.

The effect of race on receipt of definitive therapy varied in subgroup

analyses, especially by treating facility region. Compared with black men, for example, white men receive care at a facility in the South Atlantic region had 1.69-fold greater odds of receiving definitive therapy.

“These findings have major implications for ongoing efforts by federal health care agencies and national cancer organizations aimed at reducing racial disparities in both overall treatment rates and outcomes,” the investigators concluded. Ultimately, they added, such variation may partially explain the inferior survival data among black men receiving PCa care.

Dr Friedlander and his colleagues found a number of nonclinical factors that predicted receipt of definitive therapy, including income level and insurance type. “Individuals with lower income and public insurance were less likely to undergo definitive therapy,” they stated. n

parathyroid hormone levels.

“Our NMA suggested that ironwere the most optimal when considering efficacy and safety simultaneously, since it was the best option in serum phosphorus, all-cause discontinuation and it had a satisfactory ranking in other outcomes. In contrast, nicotinic acid was found to be the worst option with poor efficacy overall,” Dr Zhang and colleagues stated.

Compared with placebo, the iron-based phosphate-binding agents, colestilan, and nicotinic acid were associated with greater risks of adverse events, according to the investigators. Nicotinic acid appeared the most risky.

Mortality and discontinuation of treatment results were similar across binders in this study. n

26 Renal & Urology News

SEPTEMBER/OCTOBER 2017

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Practice Management Practices need to have comprehensive training program to create a culture of HIPAA compliance BY TAMMY WORTH

M

Zabel said she has seen practices misdirect faxes; mail test results to a patient and include another patient’s results as well; and a secretary who meant to send a coupon to patients, but instead sent a spreadsheet with patient data to 11,000 patients.

Should a breach occur, practices should immediately follow up with some sort of training that will help prevent such a breach from recurring, Zabel said. This training and any corrective actions taken to satisfy the Office for Civil Rights (OCR) should be documented, Zabel said. OCR knows that practices cannot always avoid human error, so the agency is just going to look at what steps are taken to make sure a breach does not happen again. ■ Online and instructor-led courses are among the options for HIPAA training.

modules for billing personnel, nurses, front desk staff, and physicians.

Practice managers need to consider how training will be delivered, the length of time it will take staff away

“Individuals responsible for HIPAA training cannot just pop in a $20 training video and expect everyone to get up to speed.”

“There is nothing worse for an organization than to have someone say after a breach, ‘No one ever told me I couldn’t take that laptop home.’”

Make it user friendly Training should be succinct, Hodes said.

Attention spans are relatively short and people forget pretty quickly what they read. He also recommends making training user friendly and pertinent across the full spectrum of the workforce. It is too complicated, he said, to create different

On The Web

from their normal duties, and how detailed the training will be.

Online training is an option. For practices that take this route, Hodes recommends implementing some kind of system to ensure staff understand the information presented. At some practices, employees must attest to reading each policy and procedure. At other practices, individuals responsible for HIPAA training score tests and require staff to get a certain grade to “pass.” Another strategy is to provide

personnel the answers to questions they miss before they move to the next question for positive reinforcement.

Instructor-led courses The challenge with online training, however, is that it is not interactive, said Laurie Zabel, director of Coding and Compliance for MedSafe, a healthcare compliance firm based in Wellesley, Massachusetts. In her view, the best option, if time allows and it is affordable, is to sponsor an instructorled course in which people can ask questions and interact. These classes can be held in person or via video conferencing.

Practices can provide continuous education even without having an instructor come on site. At staff meetings, someone can pick a HIPAA topic and discuss how to prevent breaches.

Practices can put monthly reminders on a bulletin board. IT staff can put a banner on computers that brings up a security reminder when staff log in the first time each month.

Tammy Worth is a freelance medical journalist based in Blue Springs, MO.

How to prevent data breaches To prevent accidental dissemination of protected health information, experts suggest: • Double-checking fax numbers and email addresses before sending any correspondence • Changing passwords regularly, and not sharing them with anyone • Running reports regularly to find out who is accessing information • Making sure staff have access only to necessary files • Keeping desks clear of all protected health information • Reminding staff what minimum necessary information means • Reminding staff to lock up and set the alarm when they leave at night

Want to improve your practice? Look for our tips on how to handle equipment issues, adjust to EHRs, comply with HIPAA, and more at www.renalandurologynews.com/practice.

© SOUTH_AGENCY / GETTY IMAGES

ost breaches of protected health information (PHI) are related to human error, underscoring the need for medical practices to develop and maintain rigorous training programs for employees so they comply with HIPAA regulations. Yet physician organizations simply are not doing a good enough job when it comes to training, according to Jay Hodes, president and founder of Colington Consulting, a HIPAA consulting firm based in Burke, Virginia.

Primarily, this is because HIPAA provides little guidance. Aside from broad parameters and a yearly requirement to train staff, practices are on their own.

Practices that want to create a culture of compliance need to have a comprehensive program, Hodes said.

Individuals responsible for HIPAA training cannot just pop in a $20 training video and expect everyone to get up to speed.

“At the end of training, the person should walk away feeling like they understand HIPAA better,” he said.