Results of a retrospective study that included men with prostate cancer infected with the SARS-CoV-2 virus suggested that use of androgen-deprivation therapy (ADT) may be protective against infection with SARS-CoV-2. These findings were published in Annals of Oncology.1
TMPRSS2, a serine protease that is highly expressed in localized and metastatic prostate cancer, is encoded by TMPRSS2, the most frequently altered gene in primary prostate cancer. Transcription of TMPRSS2 in the prostateis upregulated by activated androgen receptor (AR), and there is also evidence for similar AR-related regulation of TMPRSS2 transcription in other tissues, including the lung.
Notably, TMPRSS2 has also been identified as a key component of the process through which the SARS-CoV-2 virus is able to successfully replicate within host cells. Specifically, results of recent studies have provided evidence that viral entry of SARS-CoV-2 mediated by the angiotensin-converting-enzyme 2 receptor on host cells, and subsequent proteolytic activation of its S protein by TMPRSS2 are essential steps in the process through which the coronavirus infects its hosts.2,3
Given that inhibition of AR through the use of ADT is a common therapeutic approach used in the treatment of patients with prostate cancer, the authors hypothesized that the risk of SARS-CoV-2 infection would be lower in that population of patients. Hence, one of the primary endpoints of the study was determination of the frequency and severity of COVID-19 in patients with prostate cancer treated with and without ADT.
Information on patient-, disease-, and treatment-related factors including history of cancer and cancer diagnosis, use of ADT, sex, history of hospitalization and intensive care treatment, and date of death, if applicable, for 9280 patients in the Veneto region of Italy with confirmed COVID-19 infection was accessed from several large databases.
Of the 4532 men included in this study, 118 (2.6%) had a previous diagnosis of prostate cancer for which 4 and 114 had received treatment with and without ADT, respectively.
A key finding of this study was that, compared with men with prostate cancer receiving ADT, the odds ratio for COVID-19 infection in those with prostate cancer not treated with ADT was 4.05 (95% CI, 1.55-10.59; P =.0059).
Possible study limitations included the potential for higher levels of social distancing practiced by patients receiving ADT.
Based on these results, the study authors proposed the possibility that “AR antagonists could be used to block or decrease the severity of SARS-CoV-2 infection in male patients.” They also mentioned a potential for using these types of therapeutic approaches in combination with other agents that either work through a different mechanism of action to oppose the action of AR on TMPRSS2, or block the virus from entering cells and/or replicating within them.
However, they cautioned that “these data need to be further validated in additional large cohorts of SARS-CoV-2-infected patients and corrected for multiple variables.”
1. Montopoli M, Zumerle S, Vettor R, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (n=4532) [published online May 4, 2020]. Ann Oncol. doi: 10.1016/j.annonc.2020.04.479
2. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.
3. Matsuyama S, Nao N, Shirato K, et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci USA. 2020;117(13):7001-7003.