Influence of androgen deprivation therapy on the severity of COVID‐19 in prostate cancer patients

Abstract

Background The TMPRSS2 protein has been involved in severe acute respiratory syndrome caused by coronavirus 2 (SARS‐CoV‐2). The production is regulated by the androgen receptor (AR). It is speculated that androgen deprivation therapy (ADT) may protect patients affected by prostate cancer (PC) from SARS‐CoV‐2 infection. Methods This is a retrospective study of patients treated for COVID‐19 in our institution who had a previous diagnosis of PC. We analyzed the influence of exposure of ADT on the presence of severe course of COVID‐19. Results A total of 2280 patients were treated in our center for COVID‐19 with a worse course of disease in males (higher rates of hospitalization, intense care unit [ICU] admission, and death). Out of 1349 subjects registered in our PC database, 156 were on ADT and 1193 were not. Out of those, 61 (4.52%) PC patients suffered from COVID‐19, 11 (18.0%) belonged to the ADT group, and 50 (82.0%) to the non‐ADT group. Regarding the influence of ADT on the course of the disease, statistically significant differences were found neither in the death rate (27.3% vs. 34%; p = 0.481), nor in the presence of severe COVID‐19: need for intubation or ICU admission (0% vs. 6.3%; p = 0.561) and need for corticoid treatment, interferon beta, or tocilizumab (60% vs. 34.7%; p = 0.128). Multivariate analysis adjusted for clinically relevant comorbidities did not find that ADT was a protective factor for worse clinical evolution (risk ratio [RR] 1.08; 95% confidence interval [CI], 0.64–1.83; p = 0.77) or death (RR, 0.67; 95% CI, 0.26–1.74; p = 0.41). Conclusions Our study confirms that COVID‐19 is more severe in men. However, the use of ADT in patients with PC was not shown to prevent the risk of severe COVID‐19.

The Transmembrane Protease TMPRSS2 as a Therapeutic Target for COVID-19 Treatment

“…Patients undergoing ADT have been reported to express lower levels of TMPRSS2, and may be less affected by COVID-19 [103]. Montopoli and colleagues reported an association between ADT and reduced occurrence of SARS-CoV-2 infection, whereas others found no beneficial effect of ADT on SARS-CoV-2 infection or COVID-19 progression [177][178][179][180][181][182]. However, the fact that the study cohorts consisted of men suffering from prostate cancer limits the applicability of the results to non-cancer patients with COVID-19.…”

Examining Male Predominance of Severe COVID-19 Outcomes: A Systematic Review

“… 59 However, these data largely stand in isolation as more recent studies of mixed sample sizes report data that refute this finding. 60 , 61 Further, the results from the single study are potentially confounded by the likelihood that men with known PCa managed with ADT may have less energy at baseline or may have taken greater precautions to social distance and follow recommended health guidelines, as compared with the general population.…”

Susceptibility to SARS‐Cov‐2 infection and risk for severe COVID‐19 in patients with prostate cancer on androgen deprivation therapy

“…33 More recent noninterventional studies from other settings have not supported a protective effect of ADT on COVID-19 outcomes. [34][35][36] In a prior study among men with prostate cancer from Sweden, we compared relative excess mortality between those using ADT vs not using ADT between two time periods-during the first wave of the COVID-19 pandemic (March-June 2020) and the corresponding months in 2015 to 2019, 37 These three studies are consistent in suggesting against an association between use of ADT and risk of COVID-19. No evidence of a protective effect was observed.…”

“…33 More recent noninterventional studies from other settings have not supported a protective effect of ADT on COVID‐19 outcomes. 34 , 35 , 36 …”