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Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Given the higher COVID-19–related mortality rate observed among men than among women, is androgen deprivation therapy associated with decreased rate of 30-day mortality from COVID-19 among patients with prostate cancer?

Findings  In this cohort study of 1106 patients, no statistically significant difference was found in the rates of all cause 30-day mortality following COVID-19 infection among men with prostate cancer receiving androgen deprivation therapy (15%) vs those not receiving androgen deprivation therapy (14%).

Meaning  The findings of this cohort study do not support an association between androgen deprivation therapy and 30-day mortality among patients with COVID-19 infection.

Abstract

Importance  Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2).

Objective  To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer.

Design, Setting, and Participants  This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease.

Exposures  Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19.

Main Outcomes and Measures  The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching.

Results  After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42).

Conclusions and Relevance  Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.

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Article Information

Accepted for Publication: September 15, 2021.

Published: November 12, 2021. doi:10.1001/jamanetworkopen.2021.34330

Correction: This article was corrected on December 28, 2021, to add group name, author, author affiliation, academic degrees, nonauthor collaborators, disclosure, and grant/support information.

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Schmidt AL et al. JAMA Network Open.

Corresponding Author: Rana R. McKay, MD, Genitourinary Oncology Lead, Moores Cancer Center, University of California, San Diego, 3855 Health Sciences Drive, No. 0987, La Jolla, CA 92093 (rmckay@ucsd.edu).

Author Contributions: Drs Shyr and Warner had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Schmidt and Tucker contributed equally and are considered co–first authors. Drs Gupta and McKay contributed equally and are considered co–senior authors.

Concept and design: Schmidt, Tucker, Bakouny, Labaki, Connell, Gartrell, Joshi, Menon, D. P. Shah, Shaya, Schweizer, Wulff-Burchfield, Rini, Warner, Zhang, Choueiri, Gupta, McKay.

Acquisition, analysis, or interpretation of data: Schmidt, Tucker, Bakouny, Labaki, Hsu, Shyr, Armstrong, Beer, Bijjula, Bilen, Dawsey, Faller, Gao, Gartrell, Gill, Gulati, Halabi, Hwang, Joshi, Khaki, Menon, Morris, Puc, Russell, D. P. Shah, N. J. Shah, Sharifi, Shaya, Schweizer, Steinharter, Wulff-Burchfield, Xu, Zhu, Mishra, Grivas, Warner, Zhang, Gupta, McKay.

Drafting of the manuscript: Schmidt, Tucker, Bakouny, Labaki, Hsu, Armstrong, Beer, Bilen, Gulati, Rini, Warner, McKay.

Critical revision of the manuscript for important intellectual content: Schmidt, Tucker, Bakouny, Labaki, Shyr, Armstrong, Beer, Bijjula, Bilen, Connell, Dawsey, Faller, Gao, Gartrell, Gill, Gulati, Halabi, Hwang, Joshi, Khaki, Menon, Morris, Puc, Russell, D. P. Shah, N. J. Shah, Sharifi, Shaya, Schweizer, Steinharter, Wulff-Burchfield, Xu, Zhu, Mishra, Grivas, Rini, Warner, Zhang, Choueiri, Gupta, McKay.

Statistical analysis: Schmidt, Bakouny, Labaki, Hsu, Shyr, Beer, Halabi, D. P. Shah, N. J. Shah, Zhu, Warner.

Obtained funding: D. P. Shah, Warner.

Administrative, technical, or material support: Tucker, Labaki, Armstrong, Dawsey, Gao, Hwang, Morris, Russell, Mishra, Rini, Warner, Choueiri, Gupta, McKay.

Supervision: Schmidt, Shyr, Armstrong, Bilen, Faller, Joshi, N. J. Shah, Steinharter, Grivas, Rini, Choueiri, McKay.

Conflict of Interest Disclosures: Dr Bakouny reported grants from Genentech/imCORE; nonfinancial support from Bristol Myers Squibb; and personal fees from UpToDate outside the submitted work. Dr Shyr reported grants from the National Cancer Institute during the conduct of the study. Dr Armstrong reported grants from Bayer, Janssen, and Pfizer/Astellas; and personal fees from Bayer, Janssen, and Pfizer/Astellas outside the submitted work. Dr Beer reported grants paid to his institution from Alliance Foundation Trials, Astellas Pharma, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Endocyte Inc, Freenome, Grail Inc, Harpoon Therapeutics, Janssen Research and Development, Medivation Inc, Sotio, Theraclone Sciences/OncoResponse, and Zenith Epigenetics; personal fees from Arvinas, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squib, Clovis Oncology, Constellation, GlaxoSmithKline, Grail Inc, Janssen, Merck & Co, Myovant Sciences, Novartis, Pfizer, Sanofi, and Tolero; and stock ownership in Arvinas Inc and Salarius Pharmaceuticals outside the submitted work. Dr Bilen reported grants to his institution from AAA, AstraZeneca, Bayer, Bristol Myers Squibb, Genentech/Roche, Genome and Company, Incyte, Nektar, Peloton Therapeutics, Pfizer, SeaGen, Tricon Pharmaceuticals, and Xencor outside the submitted work; and personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Calithera Biosciences, Eisai, EMD Serono, Exelixis, Genomic Health, Janssen, Nektar, Pfizer, Sanofi, and SeaGen outside the submitted work. Dr Gill reported personal fees from Amgen and personal fees from Pfizer outside the submitted work. Dr Gulati reported grants to her institution from AstraZeneca outside the submitted work. Dr Hwang reported funding from the Henry Ford Cancer Institute; grants from AstraZeneca, Bayer, and Merck & Co; grants to her institution from AstraZeneca, Bausch, Bayer, Dendreon, Exelixis, Genentech, and Merck & Co; personal fees from Astellas, Bayer, Bristol Myers Squibb, Dendreon, EMD Sorono, Exelixis, Genentech, Janssen Scientific, Medivation, and Sanofi/Genzyme outside the submitted work; and stock ownership in Johnson and Johnson by an immediate family member. Dr Joshi reported grants from AstraZeneca and Pfizer; grants to his institution from Bayer, Endocyte, Corcept, Janssen, Progenics, and Roche/Genentech; personal fees from Bayer and Sanofi outside the submitted work; personal fees from Athenex, Curium, Exelexis, and ORIC; and being an uncompensated consultant for Advanced Accelerator Applications, Bayer, Endocyte, Janssen, Lantheus, Norvartis, and Progenics and an advisory board member for Seagen. Dr Khaki reported stock ownership in Merck & Co and Sanofi stock outside the submitted work. Dr Morris reported personal fees from AstraZeneca, Athenex, Curium, Exelixis, and Oric Pharmaceuticals outside the submitted work. Dr D. P. Shah reported grants from the American Cancer Society and the Hope Foundation for Cancer Research during the conduct of the study. Dr N. J. Shah reported grants from Aravive; and personal fees from Merck & Co outside the submitted work. Dr Schweizer reported funds to his institution from AstraZeneca, Bristol Myers Squibb, Elevate Bio, Hoffmann-La Roche, Immunomedics, Janssen, Madison Vaccines, Merck & Co, Pfizer, Tmunity, and Zenith Epigenetics; and personal fees from AstraZeneca, Janssen, PharmaIn, and Resverlogix outside the submitted work. Dr Wulff-Burchfield reported personal fees from Astellas, Bristol Myers Squibb; being on the advisory board for Exelixis; grants from Pfizer outside the submitted work; grants from Pfizer Global Medical; family members with stock ownership in Immunomedics and Nektar. Dr Xu reported grants from The ASCO Conquer Cancer Foundation outside the submitted work. Dr Mishra reported grants from National Cancer Institute during the conduct of the study; and personal fees from National Geographic outside the submitted work. Dr Grivas reported grants to his institution from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, GlaxoSmithKline, Immunomedics, Kure It Cancer Research, Merck & Co, Mirati Therapeutics, Pfizer, and QED Therapeutics; and personal fees from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Clovis Oncology, Dyania Health, Driver, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Guardant Health, Heron Therapeutics, Immunomedics/Gilead, Infinity Pharmaceuticals, Janssen, Merck & Co, Mirati Therapeutics, Pfizer, QED Therapeutics, Regeneron Pharmaceuticals, Seattle Genetics, and 4D Pharma PLC outside the submitted work. Dr Warner reported grants from the National Institute of Cancer during the conduct of the study; grants from AACR; personal fees from Roche and Westat; and ownership of HemOnc.org LLC outside the submitted work. Dr Zhang reported grants to his institution from AbbVie/Stemcentrx, Acerta, Astellas, Merck & Co, Janssen, Merrimack, Mirati Therapeutics, Novartis, OmniSeq, PGDx, Pfizer, and Regeneron outside the submitted work; having a spouse who is a stockholder/employee for Capio Biosciences and Archimmune Therapeutics and a stockholder/consultant for Nanorobotics; consulting/speaking with Genomic Health and Sanofi Aventis; consulting/advisory board with Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Dendreon, Foundation Medicine, Janssen, MJH Associates, and Pfizer; and personal fees from Aptitude Health, Aravive, Bristol Myers Squibb, Dendreon, Eisai, Exelixis, Janssen, Merck & Co, MJH Associates, Pacific Genuity, Pfizer, QED Therapeutics, Sanofi-Aventis, and SeaGen outside the submitted work. Dr Choueiri reported nonfinancial support from COVID-19 and Cancer Consortium (CCC19) steering committee, and ESMO-CoCare steering committee during the conduct of the study; personal fees from Bristol Myers Squibb, Eli Lilly and Company, Exelixis, Merck & Co, Novartis, Pfizer, Roche/Genentech, and UptoDate; and participating in the European Society for Medical Oncology and the American Society of Clinical Oncology planning committees and the Genitourinary Steering Committee of the National Institute of Cancer. Dr Gupta reported grants to her institution from AstraZeneca and Isoray; and personal fees from AstraZeneca, Bristol Myers Squibb, Exelixis, Janssen, Merck & Co, Pfizer, and Seattle Genetics outside the submitted work. Dr McKay reported research funding from Bayer, Pfizer, and Tempus; and personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Caris, Dendreon, Exelixis, Janssen, Johnson and Johnson, Merck & Co, Myovant, Novartis, Pfizer, Sanofi, Sorrento Therapeutics, Tempus, and Vividion. No other disclosures were reported.

Funding/Support: Vanderbilt Institute for Clinical and Translational Research developed and supports REDCap through grant UL1 TR000445 from the National Center for Advancing Translational Sciences. This study was partly supported by the National Cancer Institute grant P30 CA068485 to Drs Hsu, Rini, Warner, Mishra, and Shyr. This study was partly supported by grants from the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and the National Institutes of Heath (P30CA054174) to Dr D. P. Shah. This study was supported by Henry Ford Cancer Institute research funds to Dr Rini.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The members of the COVID-19 and Cancer Consortium are listed in Supplement 2.

Meeting Presentation: This paper was presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium; February 11, 2021; virtual.

Additional Contributions: We thank all members of the CCC19 steering committee: Toni K. Choueiri, Narjust Duma, Dimitrios Farmakiotis, Petros Grivas, Gilberto de Lima Lopes Jr, Corrie A. Painter, Solange Peters, Brian I. Rini, Dimpy P. Shah, Michael A. Thompson, and Jeremy L. Warner, for their invaluable guidance of the CCC19.

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