J U L Y /A U G U S T 2 0 2 1
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VOLUME 20, ISSUE NUMBER 4
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Novel Radiotherapy Beneficial in mCRPC Lutetium-177-PSMA-617 improved survival of men whose disease progressed after previous treatment IMPROVED SURVIVAL OUTCOMES Use of 177Lu-PSMA-617 in combination with standard of care (SOC) improved survival of men with metastatic castration-resistant prostate cancer compared with SOC alone, a study found. Shown here are median survival times in months.
© KATERYNA KON / SCIENCE PHOTO LIBRARY / GETTY IMAGES
■ Progression-free survival
■ Overall survival
months Lu-PSMA-617 plus SOC
Source: Morris MJ, De Bono JS, Chi KN, et al. Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). J Clin Oncol. 39, 2021 (suppl 15; abstr LBA4).
PCa Care Dipped in Pandemic BY NATASHA PERSAUD ACCESS TO MEDICAL care for men with prostate cancer (PCa) was sharply reduced last year during the COVID-19 pandemic, according to real-world data from Verana Health and the American Urological Association (AUA) presented at the American Society of Clinical Oncology 2021 virtual annual meeting. A total of 267,691 patients with PCa visited 158 US urology providers within the AUA’s Quality (AQUA) registry during 2019 and 2020. From March 2 to November 1, 2020 (week 10 to week 44) the magnitude of the decline and recovery in health care visits, including telehealth, varied by PCa risk category, with the steepest drops observed for lowrisk PCa, Matthew R. Cooperberg, MD,
MPH, of the University of California, San Francisco, and colleagues reported. For the first 9 weeks of 2020, health care providers had 25.6 mean visits per day, similar to 2019. Visits declined from weeks 10 to 14 (early March to the first week of April) to 18.03 per day — a 31% drop compared with the same period in 2019. Visits recovered to 2019 levels by week 23 (early June 2020), then declined to 11.89 per day by week 44 — a 58% drop from the same period in 2019, Dr Cooperberg and colleagues reported. The most surprising finding was the depth of the second decline in prostate cancer visits in October to early November after the initial continued on page 9
BY JODY A. CHARNOW A NOVEL radiotherapy that targets cells expressing prostate-specific membrane antigen (PSMA) could become an important new treatment option for men with late-stage metastatic castration-resistant prostate cancer (mCRPC), investigators reported at the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting. The radiotherapy, lutetium-177-PSMA617 (177Lu-PSMA-617), added to the current standard of care (SOC), improved survival outcomes in men whose cancer progressed after prior treatment. The medication binds to PSMA, an enzyme highly expressed on the surface of prostate cancer cells. “PSMA617 targets PSMA with high affinity
Pembro After RCC Surgery Prolongs DFS BY JODY A. CHARNOW PEMBROLIZUMAB following surgery for clear cell renal cell carcinoma (RCC) improves disease-free survival (DFS) and may offer a potential new standard of care, according to study findings presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. The phase 3 KEYNOTE-564 trial included 994 patients with intermediate high-risk or high-risk cancer or those who had no evidence of disease after primary tumor and soft tissue metastases were completely resected up to 1 year after nephrectomy. All patients underwent surgery at least 12 weeks prior to trial randomization. The study investigators found that adjuvant immunotherapy with pembrolizumab was significantly associated with a 32% decreased risk of disease recurrence compared with placebo after a median follow-up duration of 24 months. The 24-month estimated DFS continued on page 9
and delivers a payload of 177lutetium, a beta-particle-emitting radioactive metal,” lead investigator Michael J. Morris, MD, of Memorial Sloan Kettering Cancer in New York, New York, explained during an ASCO press conference. “When the drug carrying the 177lutetium payload binds to PSMA, the whole molecule is internalized by the cell, and the cell is then exposed to a lethal dose of radiation and dies.” Dr Morris and his colleagues conducted a randomized, open-label phase 3 trial (VISION), which enrolled 831 men with PSMA-positive mCRPC who were previously treated with androgen receptor pathway inhibitors and 1 or 2 taxane regimens. Investigators continued on page 9
IN THIS ISSUE 7
Recurrence of NMIBC is not associated with smoking status
Obese patients with mCRPC have better survival outcomes
Guideline-based kidney cancer treatment for women less likely
Timing of BCG induction does not affect therapeutic response
Nocturnal polyuria is highly prevalent in men and women
Low testosterone in men with COVID-19 ups their death risk
Kidney stone risk is higher for men compared with women Bluetooth-enabled devices may be vulnerable to attacks by cyber criminals. PAGE 36
J U LY / A U G U S T 2 0 2 1
this month at renalandurologynews.com Clinical Quiz Test your knowledge by taking our latest quiz at renalandurologynews.com/ run-quiz
HIPAA Compliance Read timely articles on various issues related to keeping protected health information secure.
Drug Information Search a comprehensive drug database for prescribing and other information on more than 4000 drugs.
Nocturnal Polyuria Highly Prevalent in the US By one measure, nocturnal polyuria was present in 39.1% of men and 49.9% of women, a study found. Pandemic’s Legacy: Innovations in Cancer Care and Research What clinicians have learned from their experiences during the COVID-19 crisis may change how they manage patients.
Hospitalizations May Predict ESKD Risk Intermediate and high utilizers have a 1.5- and 1.8-fold higher risk of end-stage kidney disease compared with low utilizers, data show.
Living Donor Transplantation Declining The proportion of patients undergoing living donor kidney transplantation decreased from 37% in 2010 to 29% in 2019, according to the investigators.
Switching to Twice-Weekly HD Can Be Done Safely Converting selected patients from thriceweekly to twice-weekly hemodialysis resulted in no significant changes in potassium, phosphorus, hemoglobin, or parathyroid hormone levels, a study found.
News Coverage Visit our website for daily reports on the latest developments in clinical research.
Metformin Possibly Beneficial in Advanced Prostate Cancer In a randomized controlled trial, use of the drug in combination with standard of care delayed development of castrationresistant disease.
Job Board Be sure to check our latest listings for professional openings across the United States.
Obesity May Lower mCRPC Death Risk A study found that obesity was significantly associated with a 29% and 35% decreased risk of all-cause and cancer-specific mortality.
Intradialytic Cycling Has CV Benefits In a study, exercise cycling during hemodialysis sessions was associated with a reduction in left ventricular mass.
Our member institutions pivoted to telehealth
very quickly. Clinicians worked together to figure out clinical pathways to minimize risk and maximize benefit. See our story on page 32
Renal & Urology News 1
VOLUME 20, ISSUE NUMB E R 4
CALENDAR American Urological Association Annual Meeting Las Vegas, Nevada September 10–13 International Continence Society Annual Meeting Melbourne, Australia October 12–15 American Society for Radiation Oncology (ASTRO) Annual Meeting Chicago, IL October 24–27 American Society of Nephrology Kidney Week San Diego, CA November 2–7 Large Urology Group Practice Association Annual Meeting Chicago, IL November 12–13 Society of Urologic Oncology Annual Meeting Orlando, FL December 1–3
From the Editor The pandemic has opened new research frontiers
News in Brief Burnout afflicts 47% of urology residents
Ethical Issues in Medicine Promote a “just culture” to improve patient safety
Practice Management Bluetooth-connected devices are a potential target for hackers
2 Renal & Urology News
JULY/AUGUST 2021 www.renalandurologynews.com
FROM THE EDITOR EDITORIAL ADVISORY BOARD
Health Care Interrupted: Research Frontiers Beckon
or years after the COVID-19 pandemic ends, researchers from every academic discipline will probe the long-term effects of the crisis. Sociologists, anthropologists, and psychologists surely will examine how months of social isolation affected human behavior. Economists will analyze the pandemic’s influence on the stock market and consumer spending patterns and the effect of the trillions of dollars the federal government spent to buttress the economy and provide financial relief for households. And medical researchers will study the clinical consequences of the pandemic, especially the ramifications of delayed care. For a few months early in the pandemic, states across the nation mandated the cessation of non-urgent medical services, bringing routine screening and testing to a halt or nearly so. Even when the mandates lifted, patients remained reluctant to make emergency department visits or regular in-person doctor appointments out of fear of contracting COVID-19. This interruption in care raises a number of important research questions. Did the delay in routine screening and testing result in an increase in the number of patients presenting with more advanced cancers, as some investigators have predicted? Does a delay of a few months in performing such services as surveillance cystoscopies for patients with bladder cancer or per-protocol PSA tests for men on active surveillance for prostate cancer make a difference in outcome? Can clinicians safely prolong the interval between these and other such services to make patients’ lives easier and reduce health care costs? Telehealth will be another area ripe for scientific inquiry. Unable to have non-urgent in-person encounters with patients, clinicians across specialties turned en masse to telehealth. This migration to virtual encounters was facilitated by the Centers for Medicare & Medicaid Services, which allowed Medicare to pay physicians and other health care providers for telehealth visits at the same rate as regular in-person visits and under a broader range of circumstances. Will the increased prominence of telehealth during the pandemic remain after the crisis ends? What is the level of patient and physician acceptance of telehealth? How does telehealth impact the physician-patient relationship? To lower the risk of COVID-19 transmission, some dialysis facilities tested a strategy of converting patients who met certain criteria from thrice-weekly to twice-weekly in-center hemodialysis sessions (a controversial topic in nephrology) or to home hemodialysis. Physicians have switched from intravenous to oral drugs and from shorter- to longer-duration injection formulations of drugs to reduce the number of in-person visits. How did these strategies work out? If outcomes were not adversely affected, could these approaches be used more widely? These are only a sampling of the numerous research questions likely to be explored. The answers could change the practice of medicine. Jody A. Charnow Editor
Medical Director, Urology
Medical Director, Nephrology
Robert G. Uzzo, MD, MBA, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman Department of Surgery Fox Chase Cancer Center Temple University School of Medicine Philadelphia
Kamyar Kalantar-Zadeh, MD, PhD, MPH Professor & Chief, Division of Nephrology, Hypertension & Kidney Transplantation UC Irvine School of Medicine Orange, CA
Nephrologists Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, NC
Urologists Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City
David S. Goldfarb, MD Professor, Department of Medicine Clinical Chief New York University Langone Medical Center Chief of Nephrology NY Harbor VA Medical Center
R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto
Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center Memphis
Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD Chief Executive Officer Inova Health System Falls Church, VA Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology (ret.) Cleveland Clinic Lerner College of Medicine Cleveland Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology UC Irvine School of Medicine Orange, CA James M. McKiernan, MD John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology Columbia University College of Physicians and Surgeons New York Kenneth Pace, MD, MSc Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Vancouver, Canada
Edgar V. Lerma, MD Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA Chief Medical Officer, DaVita Inc. Denver Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Associate Professor of Medicine Wayne State University School of Medicine Detroit Vice President of Medical Affairs, DaVita Healthcare Denver Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital Teaneck, NJ
Renal & Urology News Staff
Editor Jody A. Charnow Web editor Natasha Persaud Production editor Kim Daigneau Group creative director Jennifer Dvoretz Production manager Brian Wask
Vice president, sales operations and production Louise Morrin Boyle
National accounts manager William Canning Editorial director, Haymarket Oncology Lauren Burke
Vice president, content, medical communications Kathleen Walsh Tulley
Chief commercial officer James Burke, RPh President, medical communications Michael Graziani Chairman & CEO, Haymarket Media Inc. Lee Maniscalco
Renal & Urology News (ISSN 1550-9478) Volume 20, Number 4. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). For reprint/licensing requests, contact Customer Service at firstname.lastname@example.org. Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2021.
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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 Survey: Burnout Afflicts 47% of Urology Residents
and 81% among patients treated with
A recent survey found that 47% of US
LP and HP laser lithotripsy, a team led
urology residents, including 65% of
by Olivier Traxer, MD, of Assistance-
second-year residents, met criteria
Publique Hôpitaux de Paris, Hôpital
for professional burnout, investigators
Tenon, Sorbonne Université, Paris,
reported in Urology.
reported online ahead of print in the
The pooled stone-free rate was 82%
Journal of Endourology. Complica-
In addition, 17% of the 415 survey respondents regretted their overall
tion rates did not differ between the
career choice, according to Kevin Kim,
procedures. Mean operative time was
MD, MPH, of Mayo Clinic in Rochester,
significantly faster for HP procedures
Minnesota, and colleagues. The cross-
(32.9 vs 62.7 minutes). Mean stone
sectional study examined urology
volume was significantly larger in the
residents’ responses to the 22-item
LP group (2604 vs 1217 mm3).
Maslach Burnout Inventory and choice regret from the 2019 American
FDA Approves Once-Daily Torsemide Formulation
Urological Association census.
The Food and Drug Administration in
questions about career and specialty
Regarding unmet needs, 62% of
June approved Soaanze, a once-a-day
respondents prioritized the ability to
improved formulation of the oral loop
attend personal health appointments,
diuretic torsemide, for the treatment
with the majority experiencing difficulty
of edema associated with heart failure
in attending such appointments.
or renal disease in adults. It provides a longer duration of peak effects without
HP Laser Lithotripsy Not More Effective
causing excessive urination, accord-
Both low-power (LP) and high-power
Pharmaceuticals, the drug’s maker.
(HP) laser lithotripsy are associated
The formulation has an extended
with similar results, according to a
duration of action that lasts approxi-
recent systematic review and meta-
mately 6 to 8 hours, with a peak effect
analysis that included 6403 patients.
that occurs within the first 4 hours.
ing to a press release from Sarfez
CKD in Patients With Cancer A study by investigators in Romania found that the prevalence of chronic kidney disease (CKD) among patients with cancer is higher than that of the general population, and the prevalence varies by cancer type, as shown below. 48.7%
Source: Ciorcan M, Chisavu L, Gadalean F, et al. Chronic kidney disease in neoplasia patients, the analysis of a large cancer database. Presented at: 58th ERA-EDTA 2021 virtual congress. Abstract MO525.
NMIBC Therapies Vary in Side Effects, Tolerability P
atient-reported side effects and tolerability of various intravesical therapies for nonmuscle-invasive bladder cancer differ significantly, according to survey findings published in Urology. A team led by Brian R. Lane, MD, of Spectrum Health Hospital System in Grand Rapids, Michigan, analyzed responses to 592 completed surveys filled out by patients prior to repeat instillation of full-dose and high-dose bacillus CalmetteGuérin (BCG) and gemcitabine. Patients reported symptoms of any kind in 463 surveys (78%), the most common being bladder symptoms (59%), fatigue (52%), body aches (26%), and hematuria (18%). Patients were able to hold full-dose BCG, reduced-dose BCG, and gemcitabine for the protocol-specified duration 87%, 95%, and 71% of the time, respectively. The prevalence, severity, and duration of body aches were highest with gemcitabine, whereas the prevalence and duration of hematuria were higher with BCG. Reduced-dose BCG had the lowest prevalence, severity, and duration of fatigue.
MRAs May Decrease Death Risk in Dialysis Patients M
ineralocorticoid receptor antagonists (MRAs) appear to lower mortality risks in patients receiving dialysis without substantially increasing the risk for hyperkalemia, investigators reported in the Clinical Journal of the American Society of Nephrology. Chih-Chin Kao, MD, of Taipei Medical University Hospital in Taipei, Taiwan, and colleagues conducted a systematic review and meta-analysis of MRA trials published up to 2020. The review included 13 trials of spironolactone and 1 trial of eplerenone and involved a total of 1309 patients on dialysis for kidney failure (mean age 53-70 years). MRA use was significantly associated with a 59% lower risk for cardiovascular mortality and a 56% lower risk for all-cause mortality, according to researchers. In a meta-analysis of 7 of the trials, the MRA group had a nonsignificant 12% increased risk for hyperkalemia compared with the control group.
Adjuvant Nivolumab Improves Outcomes in High-Risk UC A
djuvant nivolumab following radical surgery for high-risk muscle-invasive urothelial carcinoma (UC) is associated with improved disease-free survival compared with placebo, according to study findings published in the New England Journal of Medicine. Researcher randomly assigned 353 patients to receive nivolumab 240 mg intravenously and 356 to receive placebo every 2 weeks for 1 year. All patients had undergone radical surgery within 120 days of randomization. The median disease-free survival in the intention-to-treat population was 20.8 months with nivolumab and 10.8 months with placebo, Dean F. Bajorin, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues reported. The proportion of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo. Nivolumab was significantly associated with a 30% decreased risk for disease recurrence or death compared with placebo.
www.renalandurologynews.com JULY/AUGUST 2021
Renal & Urology News 7
NMIBC Recurrence Not Tied to Smoking Investigators find a lack of an association in a cohort of mostly patients with high-risk disease SMOKING IS A known risk factor for bladder cancer, but a recent study suggests that smoking status is not significantly associated with recurrence of nonmuscle-invasive bladder cancer (NMIBC) among patients managed with photodynamic enhanced (blue light) cystoscopy. The study included 723 adults with NMIBC (11.5% with primary and 88.5% with recurrent NMIBC). Almost 73% of patients had high-risk disease, 52.6% were former smokers, and 12.7% were smokers at the time of entry into the multi-institutional registry used for the study. Of the 723 patients, 259 (35.8%) experienced recurrence during a 3-year study period. The 1- and 3-year probability of recurrence was 19% and 44%, respectively, Richard S. Matulewicz, MD, of New York University Grossman
School of Medicine in New York City, and colleagues reported online in Urologic Oncology. After adjusting for clinical and demographic factors, smokers were not at significantly increased risk for recurrence compared with never smokers.
Obesity May Lower mCRPC Death Risk
MD, of Vita-Salute San Raffaele University in Milan, Italy, reported. Each 1 kg/m 2 increase in BMI was significantly associated with a 4% decreased risk of all-cause mortality and 6% decreased risk of CSM. Dr Cirulli and colleagues examined interactions between BMI and chemotherapy (docetaxel) dose to exclude any possible effect attributable to higher dose of chemotherapy and found no association. The latest study adds to previous findings by other investigators suggesting a protective effect of obesity in men with prostate cancer. In a previous study of 1129 men with nonmetastatic CRPC identified using the Shared Equal Access Regional Cancer Hospital (SEARCH) database, Adriana C. Vidal, PhD, and colleagues found that obesity (BMI of 30 kg/m 2 or higher) was significantly associated with a 21% decreased risk for death from any cause compared with normal weight (BMI 21-24.9 kg/m 2) patients, but was not associated with PCSM (BJU Int. 2018;122:76-82). A study of 1226 men with metastatic CRPC by Susan Halabi, PhD, and colleagues showed that compared with normal weight men (BMI 18.5-24.9 kg/m2), both overweight (BMI 25-29.9 kg/m2) and obese (30 kg/m 2 or higher) men had a significant 20% decreased risk for death (Cancer. 2007;100:1478-1484). ■
OBESITY IN MEN with metastatic castration-resistant prostate cancer (mCRPC) is associated with better survival outcomes, investigators reported at the European Association of Urology 36th congress. The finding emerged from a study of 1577 men with mCRPC who enrolled in the control arm of 3 randomized controlled phase 3 trials (ASCENT2, MAINSAL, and VENICE). Patients had a median age of 69 years and median body mass index (BMI) of 28 kg/m2. Of the study population, 655 had died by the end of the studies. The median follow-up for survivors was 12 months. The investigators defined obesity as a BMI higher than 30 kg/ m2 and normal weight and overweight as a BMI of 20-25 and 25-30 kg/m2, respectively. Obesity was significantly associated with a 29% decreased risk for death from any cause and a 35% decreased risk for prostate cancer-specific mortality (PCSM) compared with overweight and normal weight patients, investigator Giuseppe Ottone Cirulli,
The study included 723 adults managed with photodynamic enhanced cystoscopy. Still, the importance of smoking cessation should not be dismissed, according to the investigators. “Our findings should not be used to minimize the need for urologists to educate and counsel smokers who
are diagnosed with bladder cancer,” Dr Matulewicz’s team cautioned. “Smoking cessation is critically important given the myriad health benefits of smoking cessation and all urologists should be screening for tobacco use during visits and improving how they help patients quit.” The latest study is not the first to provide evidence that smoking cessation after NMIBC diagnosis has no significant effect on disease recurrence. A prospective study of 722 patients with NMIBC (103 never smokers, 266 former smokers, 186 continuing smokers, 150 former smokers who started again, and 17 who quit smoking after diagnosis) showed that smoking cessation after diagnosis did not decrease recurrence risk compared with continued smoking (Cancer Causes Control. 2018;29:675– 683). A study of 963 patients with
NMIBC (181 never smokers, 490 f ormer smokers, and 292 current smokers) found no significant difference in the risk for recurrence and smoking status at the time of diagnosis (Urol Oncol. 2015:33:e9-17). In a study of 390 patients with recurrent NMIBC who underwent transurethral resection (91 never smokers, 192 former smokers, and 107 current smokers), investigators found no difference in recurrence risk among the 3 groups (J Urol. 2012;188:2121-2127). Other studies, however, arrived at different conclusions. For example, a study of 718 patients with NMIBC who underwent transurethral resection found that ex-smokers and current smokers had a significantly shorter recurrence-free survival compared with nonsmokers (Eur Urol. 2011;60:713-720). The study was supported by Photocure, Inc. ■
Semaglutide Improves Renal Outcomes in High-Risk DKD SEMAGLUTIDE MARKEDLY improves
occurred in only 5% of patients taking
albuminuria and other important renal
insulin, and rapid insulin requirement
and metabolic parameters in patients
declined by 25%. Mean weight also
with diabetic kidney disease (DKD) at
significantly declined from 98.5 to
high risk for progression, according to
91.5 kg, representing a more than 5%
real-world data presented at the 58th
weight loss for 69% of patients.
European Renal Association−European
Systolic blood pressure significantly
Dialysis and Transplant Association
declined from 129.95 to 120.09 mm Hg
and diastolic blood pressure from 77.05
Beatriz Avilé, MD, PhD, of Hospital
to 71.12 mm Hg. LDL cholesterol and
Costa del Sol in Málaga, Spain, and
triglyceridemia significantly decreased
colleagues studied 122 patients with
by 10.79 mg/dL and 29.15 mg/dL,
an estimated glomerular filtration rate
(eGFR) higher than 15 but less than
Semaglutide was discontinued in 5%
60 mL/min/1.73 m or urinary albumin
of patients, commonly due to gastroin-
to creatinine ratio (UACR) exceeding
30 mg/g treated with semaglutide, a
“Our real-world study shows a
glucagon-like peptide-1 (GLP-1) recep-
significant reduction in albuminuria and
tor agonist. Over 12 months, semaglu-
weight with semaglutide treatment in
tide significantly decreased mean UACR
patients with type 2 diabetes at high
from 349.5 to 187.3 mg/g, Dr Avilés
risk for kidney disease progression,”
and colleagues reported. Mean eGFR
Dr Avilé told Renal & Urology News.
remained relatively stable with a slight
“Hyperglycemia improved with only 5%
increase of 2.2 mL/min/1.73 m .
of patients experiencing mild hypo-
Mean hemoglobin A1c significantly
glycemia with lower need of insulin.
decreased from 7.6% to 6.8%, which is
Semaglutide is safe and well tolerated
within target range. Mild hypoglycemia
and can ameliorate renal prognosis.” ■
8 Renal & Urology News
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Women vs Men Less Likely to Receive Guideline-Based Kidney Cancer Care They had lower odds of undertreatment and higher odds of overtreatment
Customized PCa Ablation Is Feasible CUSTOMIZED prostate ablation with magnetic resonance imaging (MRI)-
WOMEN ARE MORE likely than men and Blacks and Hispanics are more likely than Whites to receive kidney cancer treatments that deviate from accepted clinical guidelines, according to a recent study. Compared with men, women had significant 18% lower odds of undertreatment and 27% higher odds of overtreatment in adjusted analyses, Jeffrey M. Howard, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues reported in JAMA Network Open. “One might question whether there are underlying clinician-driven or patient-driven reasons for this disparity,” the investigators wrote. “For example, there may be a tendency of clinicians to perceive female patients as having greater potential longevity and therefore warranting more aggressive cancer treatment. Alternately or concurrently, there may be a systematic preference among female patients for more aggressive treatment.” Compared with White patients, Black and Hispanic patients had significant 42% and 20% increased odds of
undertreatment, respectively, and 9% and 6% higher odds of overtreatment. In addition, patients who were uninsured had significant 2.6-fold higher adjusted odds of undertreatment and 28% lower odds of overtreatment compared with insured patients.
Uninsured vs insured patients had 2.6-fold higher adjusted odds of undertreatment. “We found that female patients had higher odds of receiving more aggressive treatment than men, which was associated with increased rates of overtreatment for small kidney masses and potentially increased risk for unjustified complications,” Dr Howard and colleagues concluded. “Black race and Hispanic ethnicity were associated with higher odds of undertreatment and overtreatment, highlighting the bidirectional nature of inequities in treatment.”
Using 2010-2017 data from the National Cancer Database, the investigators studied 158,445 patients treated for localized kidney cancer, of whom 99,563 (62.8%) were men, 120,001 (75.7%) were White, and 91,218 (57.6%) had private insurance. Of the study cohort, 3893 patients (2.5%) were undertreated and 44,651 (28.2%) were overtreated. Dr Howard and colleagues assigned patients to 1 of 4 tumor classifications based on tumor size and clinical stage and categorized patients as receiving guideline-based treatment or under- or overtreatment. For tumors less than 2 cm in diameter, guideline-based treatment would be surveillance and overtreatment would be ablation or partial or radical nephrectomy. For tumors 2-4 cm in diameter, guideline-based treatment would be surveillance, ablation, or partial nephrectomy, and overtreatment would be radical nephrectomy. For tumors 4-7 cm and larger than 7 cm, partial or radical nephrectomy would be guideline-based treatment and surveillance or ablation would be undertreatment. ■
guided transurethral ultrasound ablation (TULSA) offers “favorable and promising” early MRI and PSA results for men with prostate cancer (PCa), according to study findings published in Urologic Oncology. The procedure is a feasible combination therapy for patients who have PCa and concurrent benign prostatic hyperplasia (BPH), they concluded. “This first real-world series of customized prostate ablation using TULSA demonstrated the safety and early efficacy of partial through wholegland ablation in men with low- to highrisk localized prostate cancer, as well as symptom relief in men with concurrent cancer and BPH,” a team led by Rolf Muschter, MD, of ALTA Klinic in Bielefeld, Germany, concluded. The investigators studied 52 consecutive patients with localized PCa who underwent TULSA. Of these, 47 had not previously received treatment and 5 underwent salvage therapy for recurrent PCa. Of the 52 patients, 41 (78.8%) underwent partial ablation, whereas the remainder
Hospitalization Pattern May Predict ESKD Risk
received whole-gland ablation.
PATIENTS WITH CHRONIC kidney disease (CKD) who are more frequently hospitalized are more likely progress to end-stage kidney disease (ESKD) or die compared with patients who are rarely hospitalized, independent of traditional risk factors, a new study finds. Among 3012 individuals with CKD stages 2 to 4 in the Chronic Renal Insufficiency Cohort (CRIC) study, 5658 hospitalizations occurred within 4 years. The high-, intermediate-, and low-utilizer groups had a mean 6.3, 2.2, and 0 all-cause hospitalizations, respectively, over the period, Anand Srivastava, MD, MPH, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, and colleagues reported in Kidney International Reports. For both high and intermediate utilizers, the top 5 reasons for hospitalization were circulatory system disorders, infectious diseases, endocrine disorders, musculoskeletal system d isorders,
various factors, including location and
and injury and poisoning. High utilizers had a significantly longer hospital stay compared with intermediate and low utilizers: 1.6 vs 0.5 vs 0 days, respectively, according to the investigators. After the 4 year period, 544 ESKD events and 437 ESKD-censored deaths occurred during a median follow-up duration of 5.1 years. In adjusted analyses, intermediate and high utilizers had a 1.5- and 1.8-fold higher risk of ESKD, respectively, compared with low utilizers, Dr Srivastava’s team reported. Intermediate and high utilizers also had a 1.5- and 2.6-fold higher risk of ESKD-censored death, respectively. Intermediate and high utilizers were more likely than low utilizers to be female and Black and have lower income, diabetes, cardiovascular disease, lower serum albumin, lower hemoglobin, higher body mass index, proteinuria, and lower estimated glomerular filtration rate.
“Collectively, our results suggest that trajectories of cumulative all-cause hospitalization identify high-risk individuals with CKD who have rapidly declining health, as suggested by their need for increased health care resource utilization,” Dr Srivastava and colleagues wrote. They suggested that hospitalization trajectories could be a simple severity of illness marker that treating physicians could review in a patient’s electronic medical record. In an accompanying editorial, Stuart L. Goldstein, MD, of the Center for Acute Care Nephrology, Cincinnati Children’s Hospital, University of Cincinnati College of Medicine in Cincinnati, Ohio, wrote, “Finally, and obviously, our goal should be to slow CKD progression and reduce mortality risk. The utilization groups not only identify patients who may require more clinical attention but can enrich the CKD population to direct novel interventions to the most at-risk patient.” ■
The investigators said they customized ablation volume based on Gleason score of the primary lesion, presence of secondary lesions, a diagnosis of BPH, and patient preference. Both PCa and BPH were present in 23 patients in the treatment-naïve group and 1 patient in the salvage therapy group. The median follow-up duration was 16 months. The early treatment success rate, defined as negative multiparametric MRI findings and lack of PSA recurrence, was 88%, Dr Muschter and colleagues reported. The median PSA level following primary treatment was 1.1 ng/mL. A single repeat TULSA was performed in 9 patients. All 37 patients who were potent prior to TULSA maintained potency. Of the patients who also had BPH, 83% reported improvement in symptoms. ■
www.renalandurologynews.com JULY/AUGUST 2021
Novel radiotherapy continued from page 1
randomly assigned 551 men to receive 177 Lu-PSMA-617 plus standard of care (SOC) and 280 to receive SOC alone. The median study follow-up duration was 20.9 months. The men who received 177Lu-PSMA617 plus SOC experienced significantly longer radiographic progression-free survival (median 8.7 vs 3.4 months), overall survival (median 15.3 vs 11.3 months), and time to first symptomatic skeletal event (SSE, median 11.5 vs 6.8 months) compared with those who received SOC alone, Dr Morris reported. Patients in the radiotherapy-SOC arm had a significant 60% decreased risk for disease progression, 38% decreased risk for death, and 50% decreased risk for a first SSE compared with the SOC-only arm. Although the radiotherapy arm experienced a higher rate of high-grade treatment-emergent adverse events (52.7% vs 38.0%), the combination of radiotherapy and SOC was well tolerated, Dr Morris and colleagues reported. “These findings do warrant adoption of lutetium-PSMA as a new treatment option in this patient population, pending FDA review,” Dr Morris said, adding that 177Lu-PSMA-617 is being studied for use in patients with earlier-stage prostate cancer.
PCa care dip continued from page 1
drop in March and recovery in June, Dr Cooperberg told Renal & Urology News. “Clearly as a country we have struggled to restore access to cancer care to prepandemic levels, even more so in the
Visits to urologists declined twice from January to November 2020 vs 2019. latter half of 2020 than in the first half,” he said. “We have multiple guidelines, developed in the past year, to help decide which patients’ cancer care can and cannot be safely deferred, but based largely on expert opinion. It will take time and attention to measure the impact of COVID-related delays on outcomes.” For low-risk PCa, mean visits per day declined from 6.57 at week 10 to 4.49 at week 14, rebounded to a peak
Commenting on the study’s fi ndings, ASCO President Lori J. Pierce, MD, stated, “Use of this PSMA radioligand therapy, if it obtains regulatory approval, could indeed become an important treatment option for these patients with refractory disease.” “I am excited about the future possibilities of combining this new therapy with other treatments and using it even earlier in the disease management,” said Stephen J. Freedland, MD, director of the Center for Integrated Research in Cancer and Lifestyle at CedarsSinai Medical Center in Los Angeles, California, who was not part of the study. He pointed out, however, that not all men would qualify for the treatment because they would need to have a PSMA-positive PET scan. Dr Freedland, who is affiliated with the Durham VA Medical Center in Durham, North Carolina, noted that the control arm of the study might not have been the best comparison group. Patients already had been treated with novel hormone therapy, such as enzalutamide, apalutamide, or abiraterone, and at least 1 chemotherapy, and SOC was not allowed to include chemotherapy or radium-223. “Thus, I am guessing most of the men received [an] alternative novel hormonal therapy, which multiple studies show is not a great choice.” Endocyte, Inc., a Novartis company, provided funding for the VISION trial. ■
of 7.04, then declined again to a new low of 3.62 at week 44. Intermediaterisk PCa visits followed the same temporal trend. Mean visits per day declined from 9.68 at week 10 to 7.36 at week 14, rebounded to a peak of 10.04, then declined to 5.65 at week 44. High-risk PCa visits showed less fluctuation but also declined twice. Mean visits per day declined from 6.31 at week 10 to 5.24 at week 13, rebounded to a peak of 6.45, then dropped to 4.31 at week 41, Dr Cooperberg’s team reported.
Early Detection Critical “For urologists and genitourinary cancer patients, early detection and treatment are critical to successful outcomes,” David F. Penson, MD, MPH, chair of the AUA Science and Quality Council, stated in a news release from Verana Health and the AUA. “Thanks to our collaboration with Verana Health, we now have a better understanding about changes in care due to the COVID-19 pandemic that we can study to gauge the long-term impact of delayed diagnoses and treatments for prostate cancer.” ■
Renal & Urology News 9
Metformin Possibly Beneficial in Advanced Prostate Cancer USING METFORMIN in combination
The investigators found a beneficial
with standard of care (SOC) for high-
effect of metformin among some sub-
risk locally advanced or metastatic
groups. For example, among patients
hormone-sensitive prostate cancer
with high-risk locally advanced disease,
(mHSPC) may improve outcomes
the median CRPC-FS was not reached
in selected patients, according to
in the metformin arm and 25 months
in the SOC arm. Among patients with
In a randomized controlled trial (RCT),
metastatic low-tumor-volume disease,
patients who received the combination
the median CRPC-FS was not reached
therapy experienced a significant delay in
in the metformin arm and 15 months
the development of castration-resistant
in the SOC arm. CRPC-FS did not dif-
disease compared with patients who
fer significantly between study arms
received SOC alone, Reham Alghandour,
among patients with metastatic high-
MD, and colleagues from Mansoura
University in Mansoura, Egypt, reported online in Urologic Oncology. The trial included 124 patients randomly assigned to receive metformin
The study arms did not differ significantly with regard to overall survival and PSA response. Metformin did not show significant
850 mg twice daily plus SOC (androgen
adverse events except self-limited
deprivation therapy [ADT] or chemo-
diarrhea in 3 patients, according to the
therapy) or SOC alone. The primary
endpoint was castration-resistant prostate cancer-free survival (CRPC-FS). Over a median follow-up of 22 months,
Dr Alghandour and colleagues said that to the best of their knowledge, “our study is the first RCT that con-
the metformin group had significantly
firmed that metformin use in combina-
longer median CRPC-FS compared with
tion with ADT prolonged the CRPC-FS
the SOC group (29 vs 20 months).
in HSPC.” ■
Pembro prolongs DFS continued from page 1
rate was 77.3% among the patients treated with pembrolizumab compared with 68.1% for placebo recipients, lead investigator Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts, reported during an ASCO presscast. The estimated preliminary overall
Adjuvant treatment was associated with a 32% lower risk for disease recurrence. s urvival rate at 24 months was 96.6% for those who received pembrolizumab and 93.5% for placebo. Approximately half of patients who undergo surgery for kidney cancer experience disease recurrence, Dr Choueiri said, adding that there is no globally accepted standard
a djuvant therapy to prevent recurrence supported by high-level evidence. “Pembrolizumab is a potential new standard of care for patients with renal cell cancer in the adjuvant setting,” Dr Choueiri said. Grade 3 to 5 all-cause adverse events occurred among more patients in the pembrolizumab group (32.4%) compared with the placebo group (17.7%). No treatment-related deaths occurred in the pembrolizumab group, according to the investigators. “Despite surgery, recurrence is common in clear cell renal cell carcinoma, and if it does recur, there are limited curative treatment options,” commented ASCO Chief Medical Officer and Executive Vice President Julie R. Gralow, MD. “The results of the KEYNOTE-564 trial support consideration of pembrolizumab as a potential new standard of care in the adjuvant setting to reduce disease recurrence in certain patients with kidney cancer.” Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, funded the trial. ■
14 Renal & Urology News
Half of Hospitalized COVID-19 Patients Have Complications
BCG Timing Not a Factor in Response
Male sex, increasing age, and preexisting conditions increase the risk
THE TIME INTERVAL from transurethral resection of bladder tumor (TURBT) to onset of bacillus Calmette– Guérin (BCG) induction does not affect therapeutic response, according to data presented at the European Association Urology 36th congress. BCG induction is conventionally administered after a recovery interval following TURBT to avoid complications related to systemic absorption, but timing of BCG instillation after TURBT has never formally been studied, and there exist no data to inform appropriate intervals after TURBT to administer induction BCG, said investigator Patrick Hensley, MD, of MD Anderson Cancer Center in Houston, Texas, who reported study findings.
COMPLICATIONS IN various organ systems develop in half of adults admitted to the hospital with COVID-19, even in young, previously healthy individuals, a new study finds. Of 73,197 patients aged 19 years or older admitted to UK hospitals with severe COVID-19 from January 17 to August 4, 2020, 49.7% had 1 or more in-hospital complications within 28 days, particularly those requiring critical care (82.4%) or mechanical ventilation (91.7%), Ewen M. Harrison, MBChB, PhD, MSc, of the University of Edinburgh, Scotland, and colleagues reported in The Lancet. Overall, 31.5% of patients died, including 40.1% with any complication.
Every Age Group Affected The incidence of in-hospital complications increased with age, from 39% of those aged 19-49 years to 51% of those aged 50 years and older, the investigators reported. Specifically, a complication developed in 27%, 37%, and 43% of patients aged 19-29, 30-39, and 40-49 years hospitalized with COVID-19, respectively. By comparison, a complication developed in 49%, 54%, 52%, 51%, and 50% of older patients aged 50-59, 60-69, 70-79, 80-89, and 90 years or more, respectively. Men, who comprised 56% of the cohort, were more likely than women to experience a complication, particularly older men: 49% vs 37% of those younger than 60 years and 55% vs 48% of those aged 60 years or older. White, South Asian, and East Asian ethnic groups had similar rates of complications, but rates were highest among Black adults: 58% Black vs 49% White patients. According to Dr Harrison’s team, in-hospital complication rates with COVID-19 seem the same or higher than with influenza, and appear to be driven by noninfectious complications. The most common complications included renal (24.3%), complex respiratory (18.4%), and systemic complications
(16.3%), but cardiovascular (12.3%), gastrointestinal (GI) and liver (10.8%), and neurological (4.3%) complications were also reported. Acute kidney injury (AKI; 15.6%), probable acute respiratory distress syndrome (15.6%), liver injury (11.3%), anemia (9.0%), and cardiac arrhythmia (4.8%) were the most prevalent conditions (data reflect patients with no preexisting illnesses). The investigators found that increasing age and male sex predicted the development of any and all organ-specific complications, except for GI and liver complications, which were more likely to affect younger patients. The presence of any and multiple complications increased the odds of poor survival. For example, more patients with than without cardiovascular or respiratory complications died.
Complications worsen patients’ ability to self-care after discharge. The predefined categories used in the study limited capture of some important complications, such as pulmonary embolism and deep vein thrombosis.
Comorbidities Play a Role Among the hospitalized patients, 81% had an underlying health condition. Chronic cardiac disease, chronic pulmonary disease, and chronic kidney disease (CKD) were the most common. Complication rates increased with the number of comorbidities from 38% to 47% to 55% in patients with 0, 1, and 2 or more comorbidities, respectively. The investigators found that patients with a preexisting condition affecting a specific organ had a higher risk of having a complication involving that same organ. A cardiac complication, for
example, more frequently developed in patients with than without preexisting cardiac disease (19.9% vs 8.9%). AKI developed in more patients with than without CKD (39.8% vs 21.6%). Liver injury was more common in patients with preexisting moderate to severe liver disease compared with those without liver problems (22.4% vs 6.2%).
Self-Care Hindered Among survivors, having an acute complication was associated with 2.4-fold increased odds of worse self-care ability after hospital discharge. Even 13% of patients aged 19-29 years and 16% of those aged 30-39 years were less able to perform self-care at discharge, the investigators reported. In descending order, neurological, respiratory, cardiovascular, renal, and GI complications were associated with significant 4.4-, 3.6-, 2.2-, 2.1-, and 2.0-fold increased odds of worse self-care ability. “We found respiratory and cardiovascular complications were associated with greatest [COVID-19] severity and acute kidney injury was one of the most common,” Dr Harrison’s team stated. “Treatments such as enhanced monitoring and early treatment for patients for cardiac arrhythmias that might lead to further problems such as stroke or cardiac arrest might, therefore, be useful. Similarly, for acute kidney injury, optimising fluid balance to ensure adequate renal perfusion in patients with less severe respiratory disease might lessen the impact of acute kidney injury.” In an accompanying editorial, Xiaoying Gu, MD, and Bin Cao, MD, of the National Clinical Research Center for Respiratory Diseases in Beijing, China, commented, “Comprehensively understanding the health effects of COVID-19 from its acute to chronic stages is important, not only for the preparation of further waves of the pandemic, but also for assessing the burden on health-care systems due to COVID-19 consequences.” ■
Early administration is safe in properly selected patients, according to a study. He and his colleagues studied 518 patients with nonmuscle-invasive bladder cancer who received adequate BCG therapy at a median 26 days from TURBT. BCG intolerance developed in 45 patients (9%) at a median 12th instillation. When time from TUR to BCG instillation was stratified into quartiles, the investigators found no significant difference in recurrence-free survival (RFS), progressionfree survival (PFS), and BCG intolerance. For patients in the first (6-19 days), second (20-26 days), third (27-34 days), and fourth quartile (35-188 days) of time from TURBT to BCG induction, median RFS times were 77, 111, 65, and 59 months, respectively. On multivariate analysis, time from TURBT to BCG induction was not a significant predictor of RFS and PFS either when analyzed by quartile or as a continuous variable. Dr Hensley concluded that early administration in properly selected patients is safe, and delays do not affect therapeutic response. ■
Renal & Urology News will cover the 2021 annual meeting of the American Urological Association, September 10 to 13. Go to www.renalandurologynews.com for daily reports on noteworthy studies.
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Renal & Urology News 15
COVID-19 Care of Transplant Patients Evolved During Crisis Therapies used to treat the disease in SOT recipients shifted since the pandemic began BY JODY A. CHARNOW
uch has been learned about COVID-19 since the White House declared it to be a national emergency on March 13, 2020. Researchers have conducted thousands of studies that have characterized myriad aspects of the disease, including populations at high risk for infection and predictors of disease severity and outcomes. Particular interest has centered on solid organ transplant (SOT) recipients, who are prone to infection because of the immunosuppressive medications they must take to prevent organ rejection. Some of the latest research findings, including those presented at the 2021 American Transplant Congress (ATC) in June, document an evolution in the understanding and management of COVID-19 in this patient population.
© MORSA IMAGES / GETTY IMAGES
Shift in Therapies For example, Madeleine R. Heldman, MD, and colleagues at the University of Washington in Seattle presented study results at the ATC demonstrating a shift in therapies as the pandemic progressed. In their analysis of 946 SOT recipients hospitalized with COVID-19, they compared medications prescribed during an early period in the pandemic (patients diagnosed up to June 19, 2020) and a late period (patients diagnosed during June 20 to December 31, 2020). Between the early and late period, the proportion of patients treated with hydroxychloroquine plummeted from 60% to 1%, Dr Heldman reported. Remdesivir use jumped from 9% to 52% of patients and corticosteroid use increased from 11% to 62% of patients. Patients diagnosed in the late period had significant 32% decreased
odds of 28-day mortality compared with those diagnosed in the early period after adjusting for comorbidities, according to Dr Heldman. “This provides indirect evidence that novel therapies for COVID-19 may [positively] impact SOC recipients,” she said. In a separate study of 157 SOT recipients presented at the congress, investigators from the Miami Transplant Institute of the University of MiamiJackson Health System in Miami, Florida, concluded that remdesivir and convalescent plasma are safe to use in SOT recipients. Of the 157 patients, 64 (40.8%) and 41 (26.1%) received remdesivir and convalescent plasma, respectively. Liver function test abnormalities developed in 5 (7.8%) of the remdesivir recipients, but none of the patients required cessation of treatment, according to Anmary Fernandez, MD, a transplant infectious disease fellow who reported study findings. She and
her colleagues observed no infusion reactions among patients who received convalescent plasma. Acute rejection occurred in 2 patients (4.9%) within 9 days after infusion, but this rate was similar to that of patients who did not receive the plasma, Dr Fernandez said. Transplant infectious disease specialist Robin K. Avery, MD, professor of medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland, who was not involved with the study, said the research findings presented by Dr Heldman and Dr Fernandez are encouraging. “There had been questions early on in the pandemic as to whether these newer therapies were going to be okay for transplant recipients, like whether remdesivir was going to be okay for patients with renal dysfunction or [on] dialysis [and] whether convalescent plasma was going to cause alloimmune responses and rejection later on,” Dr Avery told
Solid organ transplant recipients are especially vulnerable to COVID-19 infection.
Renal & Urology News. “This [study by Dr Fernandez and colleagues] and some other studies have underscored the fact that these therapies seem to be safe in our organ transplant recipients.”
Epidemiologic Insight Novel epidemiologic findings also emerged. A study by Gaurav Agarwal, MD, of the University of Alabama at Birmingham, and colleagues revealed that kidney transplant recipients are at higher risk for COVID-19 than other SOT recipients. In a study of 19,031 SOT recipients, of whom 2183 tested positive and 16,848 tested negative for SARS-CoV-2, 71.8% of patients who tested positive had a kidney transplant compared with 57.4% of those who tested negative. In addition, patients who tested negative were more likely to be of Hispanic or Latino ethnicity (17.3% vs 10.4%). Compared with patients who tested negative, those who tested positive were significantly more likely to be Hispanic or Latino (17.3% vs 10.4%) and to have hypertension (86.7% vs 81.1%), diabetes (64.5% vs 59.0%), coronary artery disease (71.2% vs 67.6%), chronic kidney disease (76.3% vs 70.2%), and peripheral vascular disease (28.5% vs 23.2%), Dr Agarwal’s team reported. The study also characterized complications in SOT recipients following a COVID-19 diagnosis: 13.7% experienced major adverse cardiac events, 3.8% had graft rejection, and 3.4% had graft loss during the study period, according to the investigators. Zeroing in on which therapies are effective for SOT recipients with COVID-19 is critical because the disease course in these individuals can
16 Renal & Urology News
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Obesity Shown to Increase COVID-19 Death Risk in Kidney Transplant Recipients Obesity, Black and Hispanic race, and high functional status increase the risk of dying from COVID-19 among kidney transplant recipients (KTRs), data presented at the virtual 2021 American Transplant Congress suggest. In a study of 1804 KTRs in the 11 United Network for Organ Sharing (UNOS)
Patients aged 65 years or older had significant 41% decreased odds of dying from COVID-19 compared with younger patients, according to the investigators. Dr Goli, who presented study findings in a video presentation, said obese KTRs tend to be at higher risk for a COVID-19-related death because of multiple comor-
regions who died, Karthik Goli, MD, of Baylor College of Medicine in Houston,
bidities, he said. “Additionally, patients who have higher functional status and are
Texas, and colleagues found that patients who had a body mass index (BMI) of
thus more active may be more likely to get exposed to COVID-19 while on immuno-
30 kg/m2 or higher had significant 1.70-fold increased odds of death from COVID-
suppression. In contrast, the elderly who are under immunosuppression may be
19 than those with a lower BMI. Black and Hispanic race were significantly associ-
more likely to remain at home and limit exposure to COVID-19.”
ated with 2.9- and 3.7-fold increased odds of COVID-19-related death, respectively,
The investigators also reported variation among UNOS regions in the percentage
compared with White race. KTRs who had a functional status of 90% at follow-up
of deaths due to COVID-19, which ranged from 11.1% in region 8 (Colorado, Iowa,
had significant 2.2-fold increased odds of dying from COVID-19 compared with
Kansas, Missouri, Nebraska, and Wyoming) to 57.5% in region 9 (New York State
those who had a lower functional status.
and western Vermont).
be particularly severe. For example, an analysis of retrospective data from the TANGO International Transplant Consortium by Leonardo V. Riella, MD, of Massachusetts General Hospital in Boston, and colleagues found that 44 (30%) of 145 kidney transplant recipients (KTRs) hospitalized with COVID-19 in March and April 2020 died after a median follow-up of 10 days following hospital admission for COVID-19. AKI developed in 46% of cases, and respiratory failure requiring intubation occurred in 29% of cases, the investigators reported. The study, which was described during the American Society of Nephrology’s 2020 Kidney Week conference, included 9697 KTRs followed at 11 transplant centers, of whom 145 (1.5%) were hospitalized with COVID-19. Of the 145 patients, 55% were older than 60 years and 65% were male. The median time since receiving a transplant was 5 years. Only 16% had received a transplant less than 1 year from presentation.
Novel Research Approach Besides stimulating research that has provided information that can guide management decisions, the pandemic spurred innovation in how research itself is conducted. For example, transplant surgeon Dorry L. Segev, MD, PhD, professor of surgery and epidemiology at Johns Hopkins University, described to ATC attendees how he and colleagues conducted largescale COVID-19 vaccine studies with SOT recipients while keeping participants safe. “We launched this study during what was the third wave of the pandemic in the United States,” he said. “It was dangerous for transplant patients to leave the house, let alone go to a health care
center, enroll in a study, do exams, do lab work, and things like that.” The mRNA vaccines became available for use in the United States in December 2020. Knowing that SOT recipients would be scattered across the country, his team used social media to openly enroll any transplant recipient
the 2 FDA approved mRNA vaccines (Moderna and Pfizer-BioNTech) in SOT recipients without a prior COVID19 diagnosis. The vaccines are designed to stimulate an immune response to the spike protein of SARS-CoV-2, the novel coronavirus that causes COVID19. At the congress, Dr Segev reported
Researchers developed innovative methods for conducting a clinical trial, including sending patients blood collection devices. who wanted to participate and who had access to the vaccine starting in December. “By March, we were even already able to quantify responses to the vaccine,” Dr Segev related. Thousands of patients participated in the study “and we’ve never met any of them in person,” Dr Segev said. “Everything has been done online, over the phone, remotely.” One of the novel approaches used in conducting the study was to send patients automated blood collection devices they could attach to their upper arm and painlessly draw about 200 microliters of blood. The team made an instructional video to educate patients how to use the devices. Patients would then use a return mailer to send the devices containing the sample back to Johns Hopkins.
Updated Findings Dr Segev and colleagues originally published findings from these studies in research letters in JAMA, one on March 15 and another on May 5. These reports described the effects of the first dose and second dose, respectively, of
updated findings from larger numbers of patients. The March 15 research letter discussed findings from 436 transplant patients, of whom 76 (17%) had detectable antibodies at a median of 20 days after receiving the first vaccine dose. The updated findings, based on 1112 patients, showed that 208 (19%) developed antibodies at a median of 21 days after the first dose. The May 5 report described results from 658 patients, of whom 357 (54%) had detectable antibodies at a median of 29 days after the second dose. Updated findings from 873 patients showed that antibodies developed in 495 (57%) at a median of 30 days after the second dose. Based on the latest findings, Dr Segev concluded that the mRNA vaccines are safe in SOT recipients, but they elicit poor anti-spike protein antibody responses. SOT recipients, he said, may be at higher risk for COVID-19 despite vaccination, but he cautioned that the studies only looked at antibody response, which at best is a surrogate measure of protection against SARSCoV-2 and may not accurately reflect patients’ level of protection.
Pandemic’s Lessons The Johns Hopkins COVID-19 vaccine studies, which were designed in response to the exigencies presented by the pandemic, have shown what can be achieved by streamlining large-scale studies, Dr Avery said. Investigators were able to get answers more quickly by enrolling patients online, providing ways for patients to send in blood samples by mail, and communicating remotely. This is important because “the whole thing with pandemic science is the faster we get answers, the better we can implement interventions for these patients,” she said. Transplant recipients typically are excluded from initial randomized trials of new treatments, and the pandemic underscored the need to find out quickly which therapies are effective in this population, she said. Physicians learned a lot about managing immunosuppression in SOT recipients hospitalized with COVID-19, such as the need to withhold mycophenolate to allow the immune system to control the virus, Dr Avery noted. “However, we’ve also learned that you need to have some immunosuppression on board because you still want to mitigate the inflammatory phase [of COVID-19].” Another consequence of the pandemic was that transplant center physicians and nurses became more adept at managing larger numbers of transplant recipients as outpatients to avoid exposing them to possible infection during in-person visits, she said. They have gained proficiency in the use of telehealth encounters and remote monitoring, she said. “We’ve learned a lot from this pandemic,” Dr Avery said. “My hope is that on a societal level we are better prepared in terms of hospital resources, ability to ramp up production of drugs and vaccines rapidly, and things of that nature.” n
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Renal & Urology News 17
Apalutamide Found to Increase Survival Among Men With mCSPC Regardless of Disease Volume Investigators report findings from a final analysis of the phase 3 TITAN trial APALUTAMIDE ADDED TO androgen deprivation therapy (ADT) for metastatic castration-sensitive prostate cancer (mCSPC) prolongs survival regardless of disease volume, according to a final analysis of data from the TITAN phase 3 trial presented at the 36th annual European Association of Urology congress. The TITAN trial included 1052 men with mCSPC randomly assigned to receive apalutamide 240 mg/d or placebo plus ADT. Findings from the first interim analysis of TITAN after a median 22.7 months of follow-up, which were published in The New England Journal of Medicine in 2019, showed apalutamide-treated patients had a significant 52% decreased risk for radiographic progression and 33% decreased risk for death compared with placebo.
Study Links Hyponatremia To COVID-19 COVID-19 MAY induce hyponatremia, investigators reported at the European Renal Association-European Dialysis and Transplant Association 2021 congress. Keiko Tanoue, MD, of the SelfDefense Forces Central Hospital in Tokyo, Japan, and colleagues studied 98 patients hospitalized with COVID19, of whom 53 (54%) were male and 39 (40%) had a smoking history. Patients had a mean age of 50.8 years.
Low sodium levels at hospitalization increased the risk of needing oxygen. At admission, hyponatremia (serum sodium level less than 135 mEq/L) was present in 11 patients (11.2%), whereas the remaining 87 patients had normonatremia (serum sodium level of 135-145 mEq/L). Twenty-seven patients (27.6%) received oxygen and 4 (4.1%) died during hospitalization.
In a final analysis focusing on outcomes according to disease volume, Simon Chowdhury, MD, of Guy’s and St. Thomas’ NHS Foundation Trust in London, UK, and colleagues found that,
Benefits persisted after a median follow-up period of 44 months. at a median follow-up of 22.7 months, apalutamide-treated patients with highand low-volume disease had a significant 48% and 64% improvement in radiographic progression-free survival, respectively, compared with placebo recipients.
Hyponatremia at admission was significantly associated with 41.2-fold increased odds for requiring oxygen and 32.3-fold increased odds for death, Dr Tanoue reported in an oral slide presentation. The lower the serum sodium level at admission, the higher probability of requiring oxygen during hospitalization, Dr Tanoue reported. “Irrespective of hyponatremia at admission, serum sodium levels increased with improvement in disease activity,” she said. Patients admitted around 7-8 days after disease onset had the lowest serum sodium levels and highest serum C-reactive protein (CRP) levels at admission. In addition, in both cross-sectional and longitudinal analyses, serum sodium levels were negatively correlated with serum CRP levels after adjusting for age, sex, estimated glomerular filtration rate, body mass index, and smoking history, which suggests that serum sodium levels may reflect COVID-19 activity. Hyponatremia in COVID-19 may occur secondarily to COVID-19 and a condition called “COVID-19-induced hyponatremia” might exist, Dr Tanoue concluded. Previous studies have found that hyponatremia is a complication and a predictor of COVID-19 severity and mortality, but no studies had looked at longitudinal changes in serum sodium levels during the course of COVID-19 infection. ■
At a median follow-up of 44 months, apalutamide-treated patients with high- and low-volume disease had a significant 30% and 47% decreased risk for death, respectively, compared with the placebo group, Dr Chowdhury reported in an oral presentation. In addition, compared with placebo recipients, apalutamide-treated patients with high- and low-volume disease had a significant 68% and 85% decreased risk for PSA progression, respectively, and 60% and 77% decreased risk for development of castration-resistant disease, respectively. The investigators noted that the longterm treatment effect of apalutamide was observed even though around 40% of patients crossed over from placebo to apalutamide after unblinding.
At baseline, 63% of patients had highvolume disease and 37% had low-volume disease. The apalutamide group had 325 patients with high-volume disease and 200 with low-volume disease; the placebo group had 335 patients with high-volume disease and 192 with low-volume disease. The investigators defined high-volume disease as the presence of visceral metastases and 1 or more bone lesions or 4 or more bone lesions with 1 or more outside the vertebral column or pelvis; they defined low-volume disease as the presence of bone lesions not meeting the high-volume definition. The safety profile of apalutamide in patients with high- and low-volume disease was consistent with the safety profile in the intent-to-treat population as described in earlier reports. ■
Renal Mass Size May Predict Synchronous Lung Metastasis RENAL MASS SIZE predicts the likeli-
metastasis based upon the initial renal
hood of harboring synchronous lung
mass size,” Dr Jamil said.
metastasis, a finding that could help
A 4-cm cutoff would result in a nearly
physicians decide whether chest imag-
50% reduction in unnecessary imaging
ing is warranted, according to study
in all patients presenting with a renal
data presented at the 36th European
tumor, Dr Jamil said.
Association of Urology congress. The lungs are the most common site
The researchers identified the study population using the National Cancer
of synchronous metastasis in patients
Database. Of the 253,838 patients,
with renal tumors, said investigator
120,386 (47%) had a renal mass less
Marcus Jamil, MD, of the Vattikuti
than 4 cm and 14,524 (5.7%) had
Urology Institute at Henry Ford Hospital
synchronous lung metastases at diag-
in Detroit, who presented study findings.
nosis. Of the 120,386 patients, 1135
All guidelines recommend chest imaging
(0.9%) had synchronous lung metasta-
as part of the staging evaluation.
ses. These 1135 patients made up 8%
The study, which included 253,838 patients with a renal mass who underwent staging chest imaging from
of the 14,524 patients with synchronous lung metastases. Thus, in patients with a tumor size
2011-2016, showed that the likelihood
less than 4 cm, a 4-cm cutoff for
of synchronous lung metastases
performing chest imaging would risk
increases along with renal mass size,
missing 0.9% of synchronous lung
but these metastases occur in less
metastases, according to Dr Jamil.
than 1% of patients with renal masses smaller than 4 cm in diameter. “Our findings provide physicians with
The 4-cm threshold could be useful in counseling patients about the benefits and risks of undergoing staging chest
the necessary information to assess
imaging and possibly reduce unneces-
a patient’s risk of synchronous lung
sary radiation exposure, he said. ■
22 Renal & Urology News
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Newer Therapies Underused in mCSPC Physician prescribing practices do not follow clinical guideline recommendations, a study found BY JODY A. CHARNOW MOST MEN WITH metastatic castration-sensitive prostate cancer (mCSPC) in 2018 did not receive advanced therapies in addition to androgen deprivation therapy (ADT) as first-line treatment for their disease as recommended by clinical practice guidelines, according to real-world data presented at the 2021 annual meeting of the American Society of Clinical Oncology. This lack of therapeutic intensification was more pronounced among Black men than non-Hispanic White men. Possible reasons for the underuse of advanced therapies include patient or disease characteristics, physician awareness, therapeutic inertia, and cost, according to investigators led by Stephen J. Freedland, MD, of CedarsSinai Medical Center in Los Angeles and Durham VA Medical Center in Durham, North Carolina. “For years, we’ve known that ADT is the standard treatment for mCSPC,” Dr Freedland said in a video presentation. “However, in more recent years, randomized trials have shown that
Finerenone Approved for CKD in T2D BAYER HAS received FDA approval for finerenone (Kerendia), a first-inclass nonsteroidal selective mineralocorticoid receptor antagonist, as a treatment for chronic kidney disease (CKD) in patients with type 2 diabetes. The approval follows the FDA’s granting of priority review to the New
Guidelines Not Followed Only in a minority of cases are advanced therapies added to ADT for the first-line treatment of metastatic castration-sensitive prostate cancer, as recommended by clinical guidelines, a study found.
KEY ADT = androgen deprivation therapy
12.4% ADT alone
ADT plus NHT
17.4% 4.1% ADT plus DOC
NHT = novel hormonal therapy DOC = docetaxel
ADT plus NSAAs
NSAA = nonsteroidal antiandrogens
Source: Freedland SJ, Agarwal N, Ramaswamy K, et al. Real-world utilization of advanced therapies and racial disparity among patients with metastatic castration-sensitive prostate cancer: a Medicare database analysis. Presented at: ASCO 2021 virtual annual meeting held June 4-8. Poster 5073.
a dding either docetaxel or novel hormonal therapies — such as apalutamide, abiraterone, and enzalutamide — to ADT can significantly improve survival.” Although National Comprehensive Cancer Network® (NCCN®) treatment guidelines recommend ADT in combination with docetaxel (DOC) or novel hormonal therapies (NHTs) for patients with mCSPC, data on real-world utilization
of mCSPC therapies and survival after DOC and NHT introduction are limited, as is evidence of potential racial disparities, Dr Freedland’s team noted. The investigators analyzed data from 35,209 men with mCSPC in the Medicare database (2010 to 2018). Overall, 24,459 (69.5%) received ADT alone, 1060 (3.0%) received ADT plus NHTs, 1244 (3.5%) received ADT
plus DOC, and 8446 (24%) received ADT plus nonsteroidal antiandrogens (NSAAs) as first-line treatment. In 2018, despite the NCCN guideline recommendations, the vast majority (66%) of patients received ADT alone as first-line treatment, whereas only 12.4% of patients received ADT plus NHT, 4.1% received ADT plus DOC, and 17.4% received ADT plus NSAAs. The rate of treatment intensification with ADT plus NHT varied by race and ethnicity. The rate was higher among non-Hispanic White men (increasing from 6.2% in 2017 to 13.0% in 2018) and Hispanic men (increasing from 6.2% in 2017 to 12.4% in 2018) compared with Black men (increasing from 6.3% in 2017 to 8.3% in 2018). The odds of treatment intensification were 40% lower among Black men and 32% lower among Hispanic men compared with non-Hispanic White men. The study population included 27,643 White non-Hispanic men (78.5%), 4,136 Black men (11.7%), 1862 Hispanic men (5.3%), and 1568 men of other races (4.5%). ■
Living Donor Transplantation Declining ADULT LIVING DONOR kidney transplantation (LDKT) declined significantly from 2010 to 2019, investigators reported at the 2021 American Transplant Congress. Using the United Network for Organ Sharing database, Nyingi Kemmer, MD, MPH, MSc, and colleagues from Tampa General Hospital in Tampa, Florida, identified 178,125 adult patients who underwent kidney transplants and 66,719 who underwent liver transplants during 2010 to 2019. Results showed that 31.8% of the kidney transplant patients
and 4.0% of liver transplant patients received organs from living donors. Although annual transplantation of both living- and deceased-donor kidneys rose from 16,152 to 23,641, the proportion of patients undergoing LDKT decreased from 37% in 2010 to 29% in 2019. The decline in LDKT was found among Black, White, and Hispanic recipients. Among Asian recipients, however, the proportion who underwent LDKT rose significantly from 27% to 33%. The number of liver transplants, both from living and deceased donors, dur-
ing the study period increased from 5731 to 8345, but in contrast to kidney transplantation, the proportion of patients undergoing living-donor liver transplantation increased from 3.8% to 5.3%. Study findings could increase community awareness about the important role of living donation in decreasing the long waiting time for a transplant and the ever-widening gap between the number of organ donors and the number of individuals in need of a transplant, said Dr Kemmer, medical director for the hospital’s liver transplant program. ■
Drug Application for finerenone in January 2021. The agency based its approval on results from the pivotal phase 3 FIDELIO-DKD trial, the results of which were published in the New England Journal of Medicine (2020;383:22192229). Data showed that finerenone treatment resulted in decreased risks for CKD progression and cardiovascular events compared with placebo. ■
Nocturnal Polyuria Highly Prevalent in the US NOCTURNAL POLYURIA is common among both men and women in the United States, according to new study findings presented during the 36th annual European Association of Urology congress. The findings are from the Epidemiology of Nocturnal Polyuria (EpiNP) study, which included
10,190 individuals aged 30 years and older who completed online surveys. Respondents were broadly representative of the US population (75% White; 14.5% Hispanic; 11.8% Black; 5.7% Asian). Using the Nocturnal Polyuria Index (NPI33) threshold of more than 0.33, nocturnal polyuria was present in
39.1% of men and 49.9% of women, Karin S. Coyne, PhD, MPH, vice president of Patient-Centered Research at Evidera in Bethesda, Maryland, reported on behalf of her team. Using nocturnal urine production of greater than 90 mL/h as a definition, nocturnal polyuria was present in 31.6% of men and 25.7% of women. ■
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Renal & Urology News 23
Kidney Stone Risk Higher Among Men The increased likelihood of stone formation among men compared with women is diminishing, however KIDNEY STONES ARE more likely to develop in men than women, and modifiable risk factors account for only a fraction of the difference, investigators reported at the 58th European Renal Association–European Dialysis and Transplant Association (ERAEDTA) congress. In an analysis of data from 268,553 individuals, Pietro Manuel Ferraro, MD, PhD, of Università Cattolica del Sacro Cuore in Rome, Italy, and colleagues found that the risk of kidney stones was consistently higher among men across age categories. A total of 10,302 incident stone events occurred during 5,872,249 person-years of followup. After age adjustment, men still had a significant 2.3-fold higher risk for kidney stones compared with women. The gap in kidney stone incidence between men and women appears to be narrowing
with time due to increasing risk among women, however, Dr Ferraro reported in a video presentation. Prior to 1990, men had a significant 2.7 times higher risk for kidney stones compared with women, but from 2010 onward, men had a significant 1.7 times higher risk. Differences in urinary composition, including volume, oxalate, pH, and citrate, explain a substantial fraction of the observed excess risk in men, according to the investigators. Non-urinary factors associated with excess stone risk among men included waist circumference, fluid intake, use of thiazide diuretics, sugar-sweetened beverages, dietary oxalate, and dietary calcium, according to Dr Ferraro. The study population consisted of participants in the Health Professionals Follow-Up Study (HPFS) and Nurses’
COVID-19 Is Linked With Low T in Men
with 33% increased odds of death, the investigators reported. The lower the testosterone levels, the greater the risk of death. In addition, results showed that the lower the testosterone levels, the higher the likelihood patients would need intensive care, be intubated, and remain in a hospital over a longer period. “At the start of the [COVID-19] pandemic, we were seeing far more men than women coming to hospital and suffering very severe forms of the
LOW TESTOSTERONE levels are highly prevalent among men at the time of hospital admission for COVID-19, and it is associated with more severe clinical outcomes, including death, investigators reported during the European Association Urology 36th Congress. In a case-control study that compared 286 men hospitalized with COVID-19 during the first wave of the pandemic with a control group of 281 healthy blood donors, investigators led by Andrea Salonia, MD, of San Raffaele University Hospital in Milan, Italy, found that 257 (89.8%) of the COVID19 patients had hypogonadism at hospital admission compared with 42 (14.9%) health controls. The investigators defined hypogonadism as a total testosterone level less than 9.2 nmol/L (265.1 ng/dL). On multivariable analysis, infection with SARS-CoV-2, the novel coronavirus that causes COVID-19, was significantly associated with nearly 6-fold increased odds of hypogonadism. After accounting for disease severity, hypogonadism was significantly associated
Hypogonadism was present in nearly 90% of COVID-19 patients at hospital admission. isease,” Dr Salonia said in an EAU d press statement. “We immediately thought this might be related to male hormone levels, particularly testosterone. But we never expected to see such a high proportion of [COVID19] patients with these extremely low levels of testosterone, in comparison to a similar group of healthy men. The relationship is very clear: the lower the testosterone, the higher the severity of the condition and likelihood of death. I’ve never seen anything like it in my 25 years in the field.” ■
Health Study I (NHS I) and NHS II. Dr Ferraro’s team excluded from their study patients who had kidney stones or cancer (except non-melanoma skin cancer) at baseline. Begun in 1986, the HPFS enrolled 51,529 men in various health professions, including dentists, pharmacists,
Researchers report findings from their analysis of data from 268,553 individuals. optometrists, osteopath physicians, podiatrists, and veterinarians. NHS I started in 1976 and enrolled 121,700 married women nurses aged 30 to 55. NHS II began in 1989 and enrolled
116,430 single and married nurses aged 25 to 42 years. All 3 studies are ongoing. In a separate study of data from 34,749 participants in the National Health and Nutrition Examination Survey (from 2007-2008 to 2017-2018) aged 20 years or older, investigators found a higher overall prevalence of kidney stones among men compared with women (10.9% vs 9.5%). The prevalence, however, increased over time among women, rising from 6.5% in the 2007-2008 survey to 9.4% in the 20172018 survey, but not in men, thereby narrowing the prevalence gap between the sexes, a team led by Shahrokh F. Shariat, MD, of the Medical University of Vienna, Austria, reported in European Urology Focus. The trends remained after adjusting for sociodemographic factors in both sexes. ■
Switching to Twice-Weekly HD Can Be Done Safely CONVERTING FROM thrice- to twice-
and nutrition status were comparable.
weekly maintenance hemodialysis
Dialysis adequacy was maintained.
(HD) is feasible for select patients with
Karnofsky Performance Status Scale
residual renal function, investigators
values also did not differ between
reported at the 58th European Renal
groups. Hospital admissions during
Association-European Dialysis and
the study period were no higher for the
Transplant Association congress.
patients who switched to the twice-
Of 71 patients on thrice-weekly HD,
7cpatients (9.8%) met criteria for conver-
In their community-based dialysis
sion to a twice-weekly schedule, includ-
program, the authors concluded, 10%
ing a residual renal function exceeding
of HD patients qualified for conversion
3 mL/min; urine output greater than
from thrice-weekly to twice-weekly
500 mL/d; intradialytic weight gain
maintenance HD without significant
less than 2.5 kg; hemoglobin greater
changes to their laboratory or clinical
than 8 g/dL; and manageable serum
phosphorus and potassium levels. Residual renal function of 3 mL/min
These observations should “stimulate discussion regarding increased
or higher was maintained for more than
application of incremental dialysis
200 days after HD initiation, Abutaleb
initiation strategies to preserve residual
Ejaz, MD, of the University of Florida,
renal function, increase dialysis-free
Gainesville, and colleagues reported.
days, alleviate transportation and care
The investigators observed no significant
provider-related burden to patients and
changes in serum potassium, serum
families, and lower costs,” Dr Ejaz told
phosphorus, hemoglobin, or parathyroid
Renal & Urology News.
hormone levels between the twice- and
HD compliance was better after the
thrice-weekly HD groups. Normalized
conversion, he noted, and patients
protein-to-creatinine ratio, albuminuria,
reported better quality of life. ■
24 Renal & Urology News
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COVID-19 in Cancer Patients Characterized Investigators zero in on mortality risk factors among patients with cancer who contracted COVID-19 IN LINE WITH previous COVID-19 research, older age, male gender, and increasing comorbidities are associated with a higher death risk among patients with cancer who become ill with COVID-19, according to a study of a large nationally representative cohort. Using the National COVID Cohort Collaborative (N3C) database, investigators identified 398,579 adult patients with cancer in the United States. The most common cancers were skin (14.9%), breast (14.2%), prostate (12.3%), hematologic (12.3%), and gastrointestinal (8.8%). Multisite tumors were present in 10.9%. Of the 63,413 patients who tested positive for COVID19, 24,799 were excluded because they did not meet inclusion criteria, leaving 38,614 patients with COVID-19 and 335,166 without COVID-19 (controls) in the analytical cohort. “Using N3C, we assembled the largest nationally representative cohort of patients with cancer and COVID-19 to date,” Noha Sharafeldin, MD, PhD, MSc, of The University of Alabama at Birmingham School of Medicine, and colleagues wrote in the Journal
of Clinical Oncology. “We identified demographic and clinical factors associated with increased all-cause mortality in patients with cancer.” Patients with COVID-19 had a significant 1.2-fold increased risk for all-cause mortality, compared with the control
Multisite tumors, recent cytotoxic therapy linked to higher death risk. group, according to the investigators. Among the patients with COVID-19, those aged 65 years or older had a significant 2.0-fold increased risk for death compared with patients aged 18-29 years in adjusted analyses. Women had a significant 10% decreased risk for death compared with men. Risk for death increased with the Charlson Comorbidity Index (CCI). Compared with a CCI of 0, a CCI of 2, 3, or 4 or more significantly increased the risk for death by 1.3-, 1.6-, and 2.0-fold, respectively.
The study also revealed geographical differences in death risk among patients with COVID-19. Compared with patients in the Northeast, those in the South and West had a significant 1.3- and 1.7-fold increased risk for death, respectively. Among the COVID-19 patients, hematologic malignancies, multitumor sites, and recent cytotoxic therapy were significantly associated with an increased risk for death, the investigators reported. “Consistent with previous literature, older age, male gender, and increasing comorbidities were associated with higher mortality in patients with cancer and COVID-19,” Dr Sharafeldin’s team concluded. “The N3C data set also confirmed that patients with cancer and COVID-19 who received recent immunotherapies or targeted therapies were not at higher risk for overall mortality.” The N3C is a centralized data resource representing the largest multicenter cohort of COVID-19 cases and controls nationwide, the investigators noted. The study cohort was limited to patients with COVID-19 who had
their earliest COVID-19 diagnosis within 21 days before the start of the index encounter (the critical visit with N3C) and up to 5 days after the start of the index encounter, the authors explained. “To the best of our knowledge, this is the first collaborative network study on patients with cancer and COVID-19 of this magnitude that demonstrates the feasibility of performing such large-scale observational research on the interaction of COVID-19 infection and cancer management across multiple healthcare sites nationwide,” the authors wrote. An important strength of the study was the inclusion of non-COVID controls, “allowing us to estimate independent effects of COVID-19 infection on mortality risk in patients with cancer,” the investigators stated. They pointed out, however, that identifying a single primary cancer diagnosis for the patients in their study cohort presented a challenge. “Some patients might be misclassified with cancer while they were in remission or they merely underwent workups for cancer rule-out.” ■
Policy Change May Widen KT Access Disparities CHANGES TO THE US kidney allocation system approved in 2019 could result in worsening geographic disparities in access to a kidney transplant (KT) when measured against the burden of endstage kidney disease (ESKD) in a particular region, according to investigators. “Paradoxically, the largely urban areas with much higher transplant rates gain from the new allocation policy, whereas rural areas with low transplant rates, vulnerable patient populations, and a much higher ESKD burden lose access to deceased donor organs,” Derek A. DuBay, MD, of the Medical University of South Carolina in Charleston, and colleagues concluded in a paper published in JAMA Surgery. As a result of the policy changes, Dr DuBay’s team estimates that New York City had the largest increase (124%) and Nevada had the greatest decrease (–74%) in allocation of deceased donor kidneys of any donor service area (DSA) in the United States in 2017. The probability of a patient
with ESKD receiving a deceased donor kidney transplant during 2017 ranged from 6.36% in West Virginia to 18.68% in the District of Columbia. The changes to allocation policy, which were approved by the Organ Procurement and Transplantation Network (OPTN), were meant to address geographic inequities in waiting time for a deceased donor kidney transplant. OPTN had argued that the allocation system failed to minimize geographic location in the prioritization of distribution of available organs, Dr DuBay and colleagues pointed out. Research has shown that geographic location remains the factor most associated with transplant access. Dr DuBay’s team conducted a crosssectional, population-based economic evaluation in a study that included 122,659 patients with ESKD. They estimated the probability of a patient with ESKD being placed on the transplant wait list or receiving a deceased donor kidney transplant. The investigators
compared states and DSAs with respect to gains and losses in rates of transplant kidneys under the revised allocation system. They normalized transplant rates for ESKD burden. “Our analysis demonstrates that states with the lowest transplant rates normalized for ESKD burden will not benefit from the changes by the OPTN, and
A study examined the effect of recent changes in the kidney allocation system. several are projected to experience significant decreases in kidney organ allocation volume,” the investigators wrote. They also observed, “Until the playing field is level, it is important for the OPTN to not create policies that potentially worsen disparities in access to transplant.”
In a statement issued in response to the study, the United Network for Organ Sharing (UNOS), a nonprofit organization that serves as the OPTN under contract with the federal government, said the organization strives “to improve the equitable allocation of organs to patients on the waiting list no matter where they live. The kidney allocation policy is expected to improve equity and access for candidates nationwide who are listed for kidney transplantation.” As the study authors point out, however, only local physicians and transplant centers can assess and list patients for transplantation, the UNOS statement reads. “Additionally, we agree with the authors that the ideal solution to mitigate disparities in access to transplantation is to improve health care infrastructure throughout the US. We support improving access to the waiting list and have initiated a significant research designed to identify factors that drive inequities in access to transplantation.” ■
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Renal & Urology News 31
Patiromer Allows Spironolactone Use In Diabetics, Non-Diabetics
Intradialytic Cycling Has CV Benefits
More patiromer than placebo recipients remained on spironolactone at week 12
EXERCISE CYCLING during hemodialysis (HD) sessions reduced left ventricular (LV) mass and improved other cardiovascular parameters compared with usual care in a study conducted in the United Kingdom. In the CYCLE-HD trial, investigators randomly assigned 130 patients from 3 dialysis centers to usual care (controls) or a 6-month progressive cycling program. Cycling was performed 3 times per week during dialysis with the goal of 30 minutes of continuous cycling at a rate of perceived exertion of 12 to 14, with resistance adjustments as needed. Of the 130 patients, 101 completed the trial protocol: 51 in the exercise group and 50 in the control arm. The primary outcome was a change in LV mass from baseline to 6 months as measured by cardiac magnetic resonance imaging. Over 6 months, LV mass declined by a significant 11.1 g in the exercise group, whereas it increased slightly in the control group, James O. Burton, DM, MBChB, of the University of Leicester in the United Kingdom and colleagues reported in Kidney International. Intradialytic cycling also significantly improved secondary outcomes associated with beneficial left ventricular remodeling, including native T1 mapping (–32.23 ms) and aortic pulse-wave velocity (–2.07 ms–1).
BY JOHN SCHIESZER PATIROMER, A POTASSIUM binder approved for the treatment of hyperkalemia, enables longer use of spironolactone in patients with chronic kidney disease (CKD) regardless of diabetes status, according to a recent subgroup analysis of the AMBER trial. The trial included 295 patients with CKD and resistant hypertension despite taking 3 or more antihyper-
with diabetes (72% vs 41%) and those without diabetes (56.6% vs 29.7%). “There were no surprises here. This was a more granular look at the original study,” Dr Agarwal said. He also observed, “Patiromer is the only sodium-free potassium binder approved in the United States and may be an agent of choice for patients with resistant hypertension that may be more sensitive to sodium.”
AMBER Trial Subgroup Analysis A subgroup analysis of the AMBER trial show confirmed findings from the original analysis showing that patiromer enabled longer treatment with spironolactone in patients with and without diabetes mellitus. Shown here are the percentages of patients remaining on spironolactone at week 12. 100 80
n Patiromer n Placebo
40 20 0
Source: Agarwal R, Rossignol P, Mayo, M, et al. Patiromer to enable spironolactone in patients with resistant hypertension and chronic kidney disease (AMBER). Clin J Am Soc Nephrol. Published online June 23, 2021.
tensive drugs. Investigators randomly assigned patients to receive open-label oral spironolactone 25 mg once daily and, in double-blind fashion, either patiromer 8.4 g once daily or placebo. In the original AMBER analysis, 66% of patients in the placebo group and 86% in the patiromer group remained on spironolactone at week 12, the primary study endpoint. In the diabetes subgroup, 65.3% of patients receiving placebo remained on spironolactone at week 12 compared with 83.6% receiving patiromer, Rajiv Agarwal, MD, of Indiana University and the Richard L. Roudebush VA Medical Center in Indianapolis, and colleagues reported in the Clinical Journal of the American Society of Nephrology. In the subgroup without diabetes, 67.1% of patients receiving placebo remained on spironolactone at week 12 compared with 87.8% receiving patiromer. Serum potassium levels of 5.5 mEq/L or higher occurred in a significantly higher proportion of the placebo group compared with the patiromer group among those
In the current analysis, the subgroup of 150 patients without diabetes included 76 in the placebo arm and 74 in the patiromer arm. The subgroup of 145 patients with diabetes included 72 in the placebo arm and 73 in the patiromer arm. In patients with diabetes, patiromer’s safety profile was consistent with previous reports. The authors noted that spironolactone is recommended in patients with resistant hypertension, including those with diabetes. Still, there are concerns that spironolactone may increase hyperkalemia risk, thus limiting its use in patients with diabetes.
Adverse Events Adverse events (AEs) occurred in about 60% of patients with diabetes and 61% of placebo recipients, and 60% of patiromer-treated patients. Serious AEs occurred in 3 placebo recipients and 1 patiromer-treated patient. Dr Agarwal noted that it remains unclear whether the enabling of spironolactone use with patiromer leads
to improved cardiovascular outcomes. “We need hard outcomes but I don’t know if we will get that. We need to look at survival and hospitalization,” Dr Agarwal said. “We need to know if you can prevent hospitalizations and heart attacks.”
Important Contribution Nephrologist Matthew B. Rivara, MD, an assistant professor of medicine in the division of nephrology at the University of Washington and Harborview Medical Center in Seattle, said the new findings are an important contribution to the literature given the challenges in treating resistant hypertension in patients with diabetes and coexisting CKD. “These findings may encourage more nephrologists and other treating clinicians to consider treating patients with resistant hypertension with spironolactone, despite coexisting CKD and diabetes,” Dr Rivara said. Many physicians are reluctant to use mineralocorticoid receptor antagonists (MRAs) such as spironolactone in patients with diabetes and/or CKD due to the risk of hyperkalemia, he said. There is an urgent need to determine the long-term benefits of prolonging spironolactone use with patiromer, “particularly with new clinical practice guidelines advocating lower blood pressure targets for patients with chronic kidney disease,” Dr Rivara said. “There is a need for more tools to be able to treat hypertension in these patients. Use of a potassium binding resin like patiromer in conjunction with an MRA is one such tool.” Ziyad Al-Aly, MD, director of the Clinical Epidemiology Center and chief of Research and Education Service at Veterans Affairs in St. Louis, Missouri, said that while adding patiromer to control potassium may enable use of spironolactone, clinicians need to look at it from a patient perspective because it adds to patients’ pill burden. “There is also the issue of cost, which for some patients may be a serious problem. Also very importantly, there is the question of whether this practice leads to improved outcomes and if so at what cost in terms of adverse events and economic costs,” Dr Al-Aly said. ■
Researchers observe a significant decline in LV mass from baseline to 6 months. “Taken together, these data suggest [intradialytic cycling] improves the cardiovascular health of patients on maintenance hemodialysis,” Dr Burton’s team wrote. Intradialytic cycling did not significantly improve physical function or quality of life over 6 months. Serious adverse events occurred in more patients in the intervention than control group (37 vs 14 patients, respectively) but none were considered related to the exercise. The investigators reported no increase in either ventricular ectopic beats or complex ventricular arrhythmias as a result of exercise. Approximately 11% of the intervention group had ischemic heart disease. ■
32 Renal & Urology News
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Pandemic’s Legacy: Innovations in Cancer Care and Research The COVID-19 crisis challenged physicians and trial investigators to rethink their strategies
ith increasing numbers of individuals getting vaccinated against COVID-19 and deaths from the disease declining in the United States, people are optimistic the pandemic that disrupted their lives since March 2020 is coming to an end. In recent months, news reports have pointed to signs that the nation’s economy is bouncing back. The stock market is surging, many restaurants are opening their doors for inside dining for the first time in more than a year, and air travel is returning to pre-pandemic levels. Whatever the long-term effect the pandemic will have on American life, it is already clear that a legacy of the crisis will be a rethinking of how health care is delivered and clinical research is conducted and a greater awareness of inequities in the delivery of care. Oncology is among the medical disciplines for which this rethinking is well along. Providers of cancer care hurriedly devised strategies to manage patients for whom treatment delays and interruptions could result in cancer progression and death, and, like health care providers in other specialties, had to do this while keeping patients safe from COVID-19. “The biggest lesson we learned is that we can respond and pivot quickly when faced with a new challenge,” said Crystal S. Denlinger, MD, Chief Scientific Officer for the National Comprehensive Cancer Network ® (NCCN®), an alliance of 31 cancer centers in the United States. “The pandemic hit and all of a sudden [and] very quickly, we had to work together to come up with alternative models of care and research, figure out how to risk stratify our patient population, and
The pandemic forced investigators to come up with novel ways to conduct clinical trials.
determine how to deliver care all in the setting of a novel and fairly unknown clinical environment, with an unknown threat [from] this new virus.” During the first month or so of the pandemic, many states issued mandates for medical practices and hospitals to stop providing all but the most essential health care services. Throughout much of the United States, routine screenings and testing and diagnostic evaluations dropped sharply. Caseloads across medical specialties plunged. Telehealth quickly became the norm for nonurgent consults. When the mandates lifted, caseloads rebounded as medical practices stepped up operations, albeit with safeguards to protect patients and staff from infection. Even after practices resumed providing routine care, however, many patients hesitated to make doctor visits. By May 2020, Dr Denlinger said, NCCN member institutions were “back
up and running” and continuing to provide cancer care with little disruption for patients on active therapy. “Our member institutions pivoted to telehealth very quickly,” she said. “Clinicians worked together to figure out clinical pathways to minimize risk and maximize benefit. The oncology community figured out that we could deliver care multiple different ways.” Instead of having a one-size-fits-all paradigm, Dr Denlinger said, providers across NCCN member institutions focused on individual patients and their specific cancer in the context of the pandemic to “come up with what we thought was the best treatment plan for them that was going to minimize risk. And while we’ve always done personalized care, I think we even took that to the next level by thinking not just about the patient and their cancer, but in the context of the larger public health emergency.”
The pandemic underscored for Dr Denlinger that “cancer patients really prioritize their cancer care.” Many stopped seeing family and friends and making visits to their primary care doctor, but they made sure to keep appointments with their oncologist, she said. COVID-19 also highlighted disparities in the delivery of care. “The pandemic laid bare a lot of inequities across multiple different sectors,” Dr Denlinger said, adding that the issues that surfaced were “more than just the traditional disparities that we have previously seen.” For example, she found that many older patients were more likely than their younger counterparts to have trouble using telehealth technology and patients in rural areas frequently lacked internet access to support video encounters. In addition, patients postponed non-urgent oncology visits because they were furloughed from their jobs and could not afford insurance copays, she noted. Racial disparities in prostate cancer treatment during the pandemic emerged in a study comparing radical prostatectomy (RP) rates in MarchMay 2020 — the initial phase of the pandemic — and March-May 2019. Early in the pandemic, “routine oncologic care was deferred to encourage stewardship of resources and prioritize safety,” a team led by Adrien N. Bernstein, MD, of Fox Chase Cancer Center in Philadelphia, Pennsylvania, noted in a poster presentation at the 2021 annual meeting of the American Society of Clinical Oncology. Hospital restrictions were unbalanced, the investigators noted, resulting in a disproportionate reduction in RPs in Black men with nonmetastatic prostate cancer.
© MORSA IMAGES / GETTY IMAGES
BY JODY A. CHARNOW
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Dr Bernstein and his colleagues studied a retrospective cohort of 647 patients: 269 during March-May 2020 and 378 during March-May 2019. Black men were less likely than White men to undergo RP for nonmetastatic prostate cancer during the initial pandemic period (1.3% vs 25.9%) despite having similar COVID-19 risk factors and biopsy Gleason grade groups, the investigators reported. By comparison, RP rates during the same period in 2019 did not differ significantly (17.7% vs 19.1%). During the initial pandemic period, Black patients had 94% decreased odds of RP compared with White patients after adjusting for covariates. “Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the pandemic in order to develop balanced mitigation strategies as viral rates continue to fluctuate,” the researchers concluded.
Tele-Oncology Myths Dispelled “There have been many lessons learned by all as a result of the pandemic,” Philippe Spiess, MD, Medical Director of Virtual Health, and Cristina Naso, Virtual Health Director, at Moffitt Cancer Center in Tampa, Florida, said in a joint email comment. “One of the most surprising things was the discovery of how many myths we had clung to regarding tele-oncology.” For example, providers at Moffitt believed patients must be younger to adopt the technology and that only patients who lived far away from the cancer center would be interested in this service, they noted. “All of these preconceived notions were upended with the rapid expansion of virtual care and specifically tele-oncology in the early days of the COVID-19 pandemic in March and April of 2020,” they said. “We have since learned quite convincingly that patients value their time, freedom, and choice for care delivery ultimately personalizing the care we deliver to patients and their families. Patients continue to request telemedicine appointments from their providers regardless of age, distance or diagnosis. The experience has taught us that patients should be the drivers of their care journey.” While in-person care can never, and should never, be replaced, they noted, “telemedicine can supplement the care journey to minimize disruption to patients’ lives. Providing the choice for a telemedicine visit honors the patient’s ability to choose and that is something
that should be encouraged and advocated for when clinically appropriate of course.”
Adapting Treatments to the Crisis As a result of the pandemic, physicians tried therapeutic approaches that differed from the norm, in part with help from the Food and Drug Administration (FDA). The agency loosened dosing requirements for immunotherapies, said Dr Denlinger, who specializes in the treatment of gastrointestinal (GI) cancers and was a clinical investigator at Fox Chase early in the pandemic. For example, instead of dosing pembrolizumab every 3 weeks and nivolumab every 2 weeks, physicians could now dose these medications every 6 weeks and every 4 weeks, respectively. “So for patients who were on these immunotherapy drugs, they were switched from an every 2- to 3-week schedule to an every 4- to 6-week schedule so that they didn’t have to come in as frequently for their immunotherapy infusion,” Dr Denlinger said. Many therapies for GI cancers involve a combination of pharmacologic therapies and surgery, she noted. Chemotherapy and radiation therapy might be delivered after surgery or surgery might be sandwiched between them. At Fox Chase, this approach changed during the pandemic. “We moved all of the therapy that would have been done after surgical resection to the neoadjuvant setting, so patients got a total neoadjuvant approach for rectal cancer and pancreas cancer,” Dr Denlinger related. “The data has been evolving to that model but we probably moved a little faster than the data has moved because of the fact that we couldn’t bring people in necessarily for a surgical resection, but we could bring them in for chemotherapy.” Another strategy put into place was switching from infusion to oral therapies when appropriate. For example, patients on a 5-fluorouracil infusion regimen who came to a center for treatment every 2 weeks were switched to capecitabine, an oral form of the drug, when possible.
Research Protocols Questioned The pandemic also forced researchers to examine what really is necessary in clinical trial protocols, Dr Denlinger said. For example, many studies require research-only visits in which participants come to a study center for an adverse effect assessment, blood work, or physical examination. Now investigators are questioning whether this is
necessary for every protocol, she said. The experience during the pandemic suggests that many such visits can be eliminated without jeopardizing the integrity of the trial. Although some institutions completely discontinued enrollment in clinical trials during the initial phase of the pandemic, she and her colleagues at Fox Chase, like many other large tertiary care centers, took a more measured approach. For instance, they continued pragmatic trials likely to provide a strong benefit to patients, such as those in which patients in both study arms experience a therapeutic benefit rather than one arm receiving a placebo. She credits the National Cancer Institute and FDA for issuing guidance early in the pandemic that allowed relaxation of some regulations on protocol adherence. This gave investigators flexibility in obtaining necessary data without compromising patient safety. They used telehealth when possible and did remote data monitoring. In some cases, instead of having patients come to Fox Chase for scheduled blood work, researchers had them go to CLIAcertified commercial laboratories in their community for their blood draws. The laboratories would then report results to the investigators. Occasionally, investigators enlisted the help of local oncology providers to whom patients were already known. These providers would have trial participants make a local clinic visit to perform necessary assessments. A survey of clinical trial programs in the United States launched in March 2020 by the American Society of Clinical Oncology led investigators to conclude that the impact of the pandemic on clinical trials could lead to changes in how they are conducted after the crisis ends. “One of the early lessons has been that it is possible to conduct more streamlined or pragmatic trials,” David M. Waterhouse, MD, MPH, of Oncology Hematology Care in Cincinnati, Ohio, and collaborators wrote in a paper published in JCO Oncology Practice. “Many trials currently include tests, procedures, and strict data collection requirements and windows for assessment that are intended to maximize knowledge gained but may prove burdensome to both patients and trial programs.” The pandemic exposed shortcomings in the nation’s health care system and nudged medical providers and researchers to reconsider how they care for patients and conduct clinical trials. When the crisis recedes, the innovations it sparked may be among its legacies. ■
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COVID-19 Interrupted CA Testing ROUTINE CANCER screenings and testing decreased sharply early in the COVID-19 pandemic, according to researchers. A study examining real-time electronic pathology report data from population-based Surveillance, Epidemiology and End Results (SEER) cancer registries in Georgia and Louisiana found the number of cancer pathology reports declined by 10.2% in 2020 compared with 2019, K. Robin Yabroff, PhD, an epidemiologist and senior scientific director of health services research at the American Cancer Society, and colleagues reported in the Journal of the National Cancer Institute. The greatest decline occurred in April 2020, when the number of reports was at least 40% lower than in April 2019. The investigators observed sharp declines in the number of reports in 2020 compared with 2019 in early November and late December (26.8% and 32.0% lower, respectively). Individuals aged 18 years or younger made up the age group with the largest percentage decline (38.3%). With respect to cancer site, the researchers observed the biggest percentage declines in lung cancer (17.4%), followed by colorectal (12.0%), breast (9.0%), and prostate cancer (5.8%). “Findings suggest substantial delays in diagnosis and treatment services for cancers during the pandemic,” the authors concluded. “Ongoing evaluation can inform public health efforts to minimize any lasting adverse effects of the pandemic on cancer diagnosis, stage, treatment, and survival.” In a separate study, Ronald C. Chen, MD, of the University of Kansas in Kansas City, and colleagues found that screening for breast, colorectal, and prostate cancer declined by 90.8%, 79.3%, and 63.4%, respectively, in March through May 2020 compared with the same period in 2019, according to findings published online April 29, 2021 in JAMA Oncology. ■
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Ethical Issues in Medicine A
patient is inadvertently given the wrong dose of an intravenous medication during hemodialysis that results in the patient’s transfer to the emergency department. The error was related to a miscommunicated verbal order between gowned and masked staff in a loud, busy treatment suite. Although the patient was stabilized and discharged later that day, the event was unnerving for the staff at the dialysis center. The nurse who administered the medication was feeling guilty about the adverse event and worried about feeling blamed for the error. The physician who ordered the medication felt responsible for the error and worried if this will lead to legal liability or affect their employment. The medical director of the dialysis unit was unsure how to productively and effectively promote patient safety on the unit going forward.
Punishment Model For decades, health care staff have adopted an approach to make safety a critical priority and recognize the central role of system errors in adverse events. The “bad apple” approach that assigns blame to individuals for medical errors has diminished in significance as more health care institutions recognize its serious flaws. This so-called
promote patients’ best interests, should embrace and participate in patient safety quality improvement initiatives. How health care settings approach this goal matters because unproductive strategies may threaten staff and patient trust in health care. First, if a “culture of blame” is perpetuated where health care professionals do not speak up about patient safety because they are afraid they will be blamed for doing so, then it will be harder to identify and address patient safety concerns. Staff should be empowered to raise these concerns because patient safety is everyone’s responsibility. Second, a punishment model is more likely to drive safety issues underground where they cannot be addressed, rather than in an open environment where leaders can promote solutions with the input of front-line staff. Within the high reliability organizational model lies the concept of “just culture.” Just cultures balance the need for continuous quality improvement using a systems approach to patient safety with the importance of individual accountability. In other words, health care professionals should know they are accountable for their actions but also feel comfortable that they will not be blamed for systems errors that
Health care systems should embrace a patient safety model that does not dissuade health care providers from speaking up about errors. “punishment model” explicitly punishes health care providers for medical error, reduces the likelihood of open reporting of safety concerns, and may lead to staff internalizing blame when an error occurs. Although health care professionals know intellectually that people will always make errors, acknowledging that fact and managing that reality continues to challenge them.1 All health care professionals, as part of their obligation to avoid harm and
are beyond their control.2 If we lump all types of adverse events together, we miss the specificity needed to promote a just culture. To distinguish different types of adverse events and make the systemsbased responses to them actionable and justifiable, patient safety experts have specified error by the degree of personal intent. The 3 main categories include human error, at-risk behavior, and reckless behavior. These
© JIM FRAZIER / THEISPOT.COM
Promoting a ‘just culture’ can create a health care environment that improves patient safety BY DAVID J. ALFANDRE, MD, MSPH
A just culture can encourage a team approach to preventing medical errors.
distinctions help to differentiate the accountability of the main actors.
Tailored Responses For example, a root cause analysis may reveal that an adverse event involving a nurse or physician was the result of a systems problem (and therefore they are not accountable). Contrast that with a clinician who knowingly and deliberately tries to harm a patient (and thus is accountable). Individual coaching and system changes as part of quality improvement are the just culture response in the former case, while disciplinary action or punishment might be an appropriate response in the latter one. In between these scenarios lies the at-risk behavior whereby health care providers make unsafe choices, often knowing that it violates a rule, policy, or standard operating procedure. These providers should be accountable for their deliberate choices, but also should be counseled on the error, their role, and how following the existing standard practice is designed to protect patients. Repeated at-risk behavior requires an individualized approach. Large health systems in the US and internationally as well the Institute for Healthcare Improvement and other organizations have developed useful
algorithms to promote fairness and consistency in addressing adverse events by balancing accountability with a systems focus.3 Algorithms draw on information about intent, foresight, and comparison to similarly situated colleagues. Although some adverse events may never be able to be completely avoided, how health systems learn about and respond to them can create an environment where they become increasingly unlikely. ■ David J. Alfandre, MD, MSPH, is a health care ethicist and an Associate Professor in the Department of Population Health at the NYU School of Medicine in New York. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the VA National Center for Ethics in Health Care or the US Department of Veterans Affairs. REFERENCES 1. Boysen PG. Just culture: a foundation for balanced accountability and patient safety. Ochsner J. 2013;13:400-406. 2. Frankel AS, Leonard MW, Denham CR. Fair and just culture, team behavior, and leadership engagement: The tools to achieve high reliability. Health Serv Res. 2006;41(4 Pt 2):1690-1709. 3. Meadows S, Baker K, Butler J. The incident decision tree: Guidelines for action following patient safety incidents. In: Henriksen K, Battles JB, Marks ES, et al., editors. Advances in Patient Safety: From Research to Implementation. 2005.
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Practice Management I
n 2020, Google and Apple announced a joint effort to enable the use of Bluetooth technology to help governments and health agencies reduce the spread of COVID-19 “with user privacy and security central to the design,” according to Google. The company’s COVID-19 contact tracing app, however, reportedly had a significant security flaw, and individuals who used the app are suing Google for violating their privacy. Google and Apple launched the Exposure Notifications System to help combat the spread of the coronavirus. With this system, the Bluetooth function provides alerts to nearby individuals of potential exposure to COVID-19. It was unveiled on April 10, 2020, and it came on the market May 20, 2020. It was added to devices via a Google Play Services update on Android. Individuals who used California’s public health COVID-19 contact tracing app have filed a lawsuit against Google claiming the app exposed their data and violated privacy laws. “Google is not the only tech giant to face court action for perceived violations of privacy laws and exposing data of their users,” said Maya Levine, a technical marketing engineer for cloud security at Check Point Software. The real cost for these companies, according to
be intercepted and that a hack always requires some sort of user interaction. “The BlueBorne vulnerabilities proved both assumptions wrong, as merely having Bluetooth on a device switched on renders it vulnerable to an attack,” Levine said. Most people leave Bluetooth on their devices on constantly, but they should shift to enabling Bluetooth on devices only when needed. This is easier said than done, however, and unlikely to be widely adopted. “For example, many headphones nowadays are Bluetooth enabled. Are people willing to not listen to music at all in high-risk zones such as airports or public transit centers? I think what is important here is to educate both individuals and companies of the risks and allow them to make informed decisions,” Levine said. European countries have changed laws to put the responsibility of users’ data onto the tech companies and levy heavy fines for irresponsible practices, she said. “These tech companies have operated largely unregulated for a length of time,” Levine said. “I believe that this free rein is quickly coming to an end.” Before releasing a new feature, it should be vetted and tested against any possible vulnerability or attack scenario. It is impossible to have 100% protection
Merely having Bluetooth on a device that is switched on renders it vulnerable to an attack, according to a cybersecurity expert. Levine, is not just money or loss of public trust but mounting evidence calling for a shift in regulation.
‘BlueBorne Vulnerabilities’ Many devices are Bluetooth enabled, so companies and individuals need to be aware that Bluetooth functionality can be compromised because of what has been dubbed “BlueBorne” vulnerabilities, Levine said. It is widely and wrongly believed that Bluetooth cannot
against every type of attack, however, she said. Numerous studies have highlighted how expensive cybersecurity incidents can be for an organization. Usually it is the monetary cost that is highlighted, but another problem is that it significantly erodes public trust. “A common perception is that if an organization cannot appropriately safeguard sensitive user data, it raises questions regarding what other managerial processes within the organization
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Bluetooth-connected medical devices may be vulnerable to breaches of confidential patient information BY JOHN SCHIESZER
To protect private information, turn on Bluetooth-enabled devices only when needed.
may be flawed or broken,” said Victor Benjamin, PhD, an assistant professor in the Department of Information Systems in the W.P. Carey School of Business at Arizona State University in Tempe, Arizona.
Internal Security Audits Physicians can protect themselves and their patients’ privacy by conducting internal security audits. This includes examining the internal technology ecosystem and network within an organization and cross-referencing vulnerable databases to check for potential security flaws. “Organizations should work with suppliers to maintain cybersecurity consistency,” Dr Benjamin said. “Many recent attacks occurring against organizations actually originate from within the supply chain.” Organizations should consider partnering with so-called red teams, Dr Benjamin said. “Red teams are typically professional cybersecurity consultants who are versed in network penetration,” he said. These individuals are employed to try to exploit any potential security vulnerabilities within an organization’s system. This can help provide some level of real-world cyberattack simulation. All organizations should be practicing some level of cyber-risk mitigation
that includes technological safeguards and processes that ensure good cybersecurity posture, he said. The level of cybersecurity readiness that an organization should put in place is typically related to the value of the data requiring protection. In health care settings, the data in question is patient information, which is valuable and sensitive. Risk mitigation often begins by taking stock of what technology, software, devices, and networking equipment an organization uses to operationalize their IT infrastructure. “Bluetoothenabled devices should fall into this portfolio of technology that is examined and monitored,” Dr Benjamin said. “But what makes Bluetooth potentially more susceptible to attack is its incredibly useful nature of allowing for different devices to communicate over the air.” Cybersecurity experts highly recommended that clinicians partner with outside consultants who better understand the technology space, and let them recommend technologies for use in health care environments. “At least then the liability can be pushed to the consultant organization rather than the physician,” Dr Benjamin said. ■ John Schieszer is a freelance medical writer based in Seattle, Washington.