We read with great interest two studies on the association between androgen-deprivation therapy (ADT), a widespread therapy for advanced prostate cancer, and coronavirus disease 2019 (COVID-19) published in the Annals.1 , 2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into host cells is facilitated by the transmembrane protease TMPRSS2, whose expression can be modulated by the androgen receptor.3 Preclinical data suggest that ADT may protect from SARS-CoV-2 infection and decrease COVID-19 severity.3 A registry study reported by Montopoli et al.1 demonstrated that ADT was associated with decreased COVID-19 incidence in Venetian men with prostate cancer. However, this relationship was not observed by Koskinen et al.2 in a study of Finnish men. This relationship has not been examined in a diverse population.
We sought to determine the association between ADT and COVID-19 incidence in men with prostate cancer in the University of California Health System (UCHS) in California, USA. The UC Health COVID Research Data Set, which includes electronic health data of all patients who underwent testing for SARS-CoV-2 at five UCHS academic medical centers and 12 affiliated hospitals across California, was used for men tested between 1 February 2020 and 20 December 2020.4 Association of SARS-CoV-2 positivity with ADT [GnRH (gonadotropin-releasing hormone) agonist/antagonist] within 6 months of COVID-19 testing was determined using the chi-square test. Multivariable logistic regression to predict SARS-CoV-2 infection based on ADT, race/ethnicity, birth year, and comorbidities was performed. This study was approved by the University of California, San Francisco Institutional Review Board.
Overall, 5211 men with prostate cancer who underwent SARS-CoV-2 testing were identified, of whom 97 (1.9%) tested positive. Of these men, 3812 (73%) were white; 369 (7%) black or African-American; 350 (7%) Asian, American Indian/Alaska Native, or Native Hawaiian/Pacific-Islander; 238 (5%) Other/Multiple race; and 442 (8%) Unknown race. There were 385 (7%) Hispanic/Latinx men.
Of 799 men who received ADT, 18 (2.3%) tested positive. Of 4412 men who did not receive ADT, 79 (1.8%) tested positive (odds ratio 1.30, 95% confidence interval 0.78-2.19, P = 0.31). No statistically significant association between ADT and SARS-CoV-2 infection was found within the race/ethnicity subgroups. Multivariable logistic regression revealed that ADT was not independently associated with SARS-CoV-2 infection (Table 1 ). By contrast, known risk factors (diabetes, black race, Other/Multiple race, and Hispanic/Latinx ethnicity) were associated with infection.
Table 1.
Multivariable logistic regression of SARS-CoV-2 infection in men with prostate cancer
| Characteristic | N | Odds ratio | 95% confidence interval | P value |
|---|---|---|---|---|
| ADT | ||||
| Received | 799 | 1.18 | (0.70-1.99) | 0.541 |
| Birth year | ||||
| ≤1955 | 3999 | 0.91 | (0.57-1.45) | 0.680 |
| Race | ||||
| White | 3812 | Reference | ||
| Black or African-American | 369 | 1.96 | (1.04-3.68) | 0.037 |
| Asian, Native Hawaiian/Pacific Islander, or American Indian/Alaska Native | 350 | 0.34 | (0.08-1.41) | 0.136 |
| Other or Multiple | 238 | 2.16 | (1.03-4.50) | 0.041 |
| Unknown | 442 | 1.59 | (0.83-3.05) | 0.165 |
| Ethnicity | ||||
| Hispanic/Latinx | 385 | 1.94 | (1.04-3.63) | 0.038 |
| Comorbidities | ||||
| Diabetes mellitus | 763 | 1.86 | (1.13-3.06) | 0.015 |
| Chronic kidney disease | 658 | 1.08 | (0.61-1.92) | 0.800 |
| Chronic obstructive pulmonary disease | 321 | 1.60 | (0.82-3.15) | 0.171 |
| Coronary artery disease | 243 | 1.36 | (0.62-3.02) | 0.444 |
| Congestive heart failure | 334 | 0.99 | (0.46-2.10) | 0.974 |
| Obesity | 340 | 1.22 | (0.62-2.44) | 0.569 |
ADT, androgen-deprivation therapy; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Among 97 COVID-19-positive men with prostate cancer, 1/19 men (5.3%) who received ADT died, versus 7/78 men who did not (9.0%; odds ratio 0.56, 95% confidence interval 0.07-4.88, P = 0.60).
Our results do not suggest a benefit of ADT for SARS-CoV-2 infection or mortality, though deaths were few. Differences between our study and those in Italy and Finland are exclusion of oral anti-androgen therapies and COVID-19 community prevalence. Other factors such as socioeconomic determinants, stage, chemotherapy use, and ADT duration are unreported potential confounders. ADT duration may be important, as Patel et al.5 recently reported that longer ADT duration was associated with decreased mortality.
In conclusion, no association between ADT and SARS-CoV-2 infection was identified in this large, diverse population of men with prostate cancer. Racial/ethnic disparities in SARS-CoV-2 infection rates described in the United States are also observed in men with prostate cancer.
Acknowledgments
Acknowledgements
HTB, RRA, and FWH are funded by the Prostate Cancer Foundation.
Funding
None declared (no grant number).
Disclosure
RRA reports receiving honoraria from Clovis Oncology; performing consulting or advisory role for AstraZeneca, Dendreon, Advanced Accelerator Applications, Clovis Oncology, Axiom Biotechnologies; research funding (for institution) from Zenith Epigenetics, Novartis, Xynomic Pharma, Cancer Targeted Technology, Janssen, Merck, AbbVie, Amgen, AstraZeneca, BioXcel Therapeutics. AJB is a cofounder and consultant to Personalis and NuMedii; consultant to Samsung, Mango Tree Corporation, and in the recent past, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Facebook, Alphabet (Google), Microsoft, Amazon, Snap, Snowflake, 10x Genomics, Illumina, Nuna Health, Assay Depot (Scientist.com), Vet24seven, Regeneron, Sanofi, Royalty Pharma, Pfizer, BioNTech, AstraZeneca, Moderna, Biogen, Twist Bioscience, Pacific Biosciences, Editas Medicine, Invitae, and Sutro, and several other nonhealth-related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, several investment and venture capital firms, many academic institutions, medical or disease-specific foundations and associations, and health systems; receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. his research has been funded by NIH, Northrup Grumman (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor's Office of Planning and Research, California Institute for Regenerative Medicine, L'Oréal, and Progenity. FWH has stock or other ownership in GlaxoSmithKline and AbbVie. All remaining authors have declared no conflicts of interest.
References
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