The role of androgen deprivation therapy on the clinical course of COVID-19 infection in men with prostate cancer.

Abstract

41 Background: TMPRSS2, a cell surface protease which is commonly upregulated in prostate cancer (PC) and regulated by androgens, is a necessary component for SARS-CoV2 cellular entry into respiratory epithelial cells. PC patients receiving ADT were reported to have a lower risk of SARS-CoV-2 infection. However, whether ADT may have an impact on the severity of COVID-19 illness in this population is poorly understood. Methods: In this study performed across 7 US medical centers, we retrospectively evaluated patients with active PC and SARS-COV-2 viral detection by PCR between 03/01/20 and 05/31/20. We collected information on demographics; medical comorbidities; medications; PC Gleason score at initial diagnosis; presence of active disease, metastases, and castration resistance; ADT use as defined by GnRH analog or antagonist within 3 months or castration levels of testosterone < 50 ng/dL within 6 months of COVID-19 diagnosis, or history of bilateral orchiectomy; active non-ADT systemic therapies including, but not limited to, androgen-receptor-targeted therapies and chemotherapy; and COVID-19-related outcomes including hospitalization, supplemental oxygen use, mechanical ventilation requirement, WHO COVID-19 ordinal scale for clinical improvement, follow-up duration, and vital status. Multivariable mixed-effect logistic regression was performed to evaluate any difference in COVID-19 clinical outcomes between patients on and not on ADT. Survival analysis was done using adjusted Cox proportion-hazards regression model. All tests were two-sided at 0.05 significance level. Results: We identified 465 evaluable patients with median age of 71 (61-81) years. Median duration of follow-up was 60 (12-114.2) days. In this follow up period, there were 195 (41.9%) hospitalizations and 111 (23.9%) deaths. When adjusted for age, BMI, and PC clinical disease state, overall survival (HR 1.28 [95%CI 0.79-2.08], P = 0.32), hospitalization status (HR 1.07 [0.61-1.87], P = 0.82), supplemental oxygen use (HR 1.29 [0.77-2.17], P = 0.34), and use of mechanical ventilation (HR 1.07 [0.51-2.23], P = 0.87) were not statistically different between ADT and non-ADT cohorts. Similarly, in subgroup analysis, no statistical difference in overall survival was found between ADT and non-ADT cohorts for hospitalized patients (HR 1.42 [0.82-2.47], P = 0.21) and those receiving supplemental oxygen (HR 1.10 [0.65-1.85], P = 0.73). Conclusions: In this retrospective cohort of PC patients, use of ADT prior to COVID-19 diagnosis does not protect against severe COVID-19 illness as defined by hospitalization, supplemental oxygen use, or death. Further preclinical work in understanding TMPRSS2 expression and androgen regulation in respiratory epithelial cells is needed. As well, longer clinical follow-up and additional clinical studies inclusive of prospective data are warranted to fully address this question.

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.…”

Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis

“…1. After applying the inclusion and exclusion criteria six studies (Patel et al updated their study in 2021 [18,21]) were included for systematic review; Caffo et al was excluded from the meta-analysis due to the lack of a control group [22].…”

“…Table 2 illustrates the characteristics of the five included studies. Four and five studies reported the risk of SARS-CoV-2 infection and severe COVID-19, respectively [16][17][18][19][20][21]. The reported outcomes including the odds ratio or hazard ratio of the SARS-CoV-2 infection and severe disease risks from the included studies are mentioned in Table 3.…”

Severe acute respiratory syndrome coronavirus 2 infection in patients with prostate cancer: A critical review

“…A search of the PubMed and Scopus databases and the proceedings of ASCO, ESMO, AUA, and EAU meetings from 1 January 2020 to 1 September 2021 identified 14 studies reporting the outcomes of PC patients with SARS-CoV-2 infection: five were published in the form of full papers (Caffo et al, 2020a;Di Lorenzo et al, 2020;Jimenez-Alcaide et al, 2021;Klein et al, 2021;Montopoli et al, 2020), and the others as letters (5) (Caffo et al, 2020b;Dalla Volta et al, 2020;Koskinen et al, 2020;Kwon et al, 2021;Patel et al, 2020) or meeting abstracts (4) (Duarte et al, 2021;Patel et al, 2021;Sbrana et al, 2020;Tucker et al, 2021). The results are summarised in Table 1.…”

“…Two studies investigated infection severity in terms of mortality and intensive care unit (ICU) admissions and, in these cases, severe outcomes were recorded in respectively 16.6 % and 25 % of patients (Koskinen et al, 2020;Montopoli et al, 2020). Comparison of infection severity by ADT use did not reveal any statistically significant difference in mortality in most cases (Jimenez-Alcaide et al, 2021;Koskinen et al, 2020;Kwon et al, 2021;Montopoli et al, 2020;Patel et al, 2020Patel et al, , 2021; the only one that suggested ADT had a statistically significant favourable impact on mortality only evaluated the outcomes of hospitalised patients (Duarte et al, 2021).…”