Background
Cell entry of SARS-CoV-2 depends on binding of the viral spike (S) proteins to ACE2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is upregulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections.
Materials and methods
We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the COVID-19 pandemic. The parameters used for each COVID-19 positive patient were gender, hospitalization, admission to intensive care unit (ICU), death, tumor diagnosis, prostate cancer diagnosis, and androgen-deprivation therapy (ADT).
Results
There were 9280 SARS-CoV-2 positive patients in the Veneto on April 1, 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 Million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2 positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared to patients who did not receive ADT (OR 4.05; 95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT to patients with any other type of cancer (OR 5.17; 95% CI 2.02-13.40).
Conclusion
Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections than non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.
The ongoing COVID-19 outbreak is a global public health challenge especially for patients with advanced cancer. They might be more susceptible to develop severe COVID-19 infection due to their potential cancer-related or treatment-related immunosuppressive state. Some studies have also suggested that the prevalence of COVID-19 infection was higher in cancer patients compared to the general population with a higher risk for severe respiratory events. This raised the question of the most adequate treatment in patients with advanced prostate cancer given that taxane chemotherapy and use of steroids could predispose patients to more severe infection due to their immunosuppressive effect. Thus, several panels of experts such as the Guidelines Office Rapid Reaction Group of the European Association of Urology or the National Comprehensive Cancer Network have published recommendations for adapting prostate cancer treatment during COVID19 pandemic. The impact of androgen deprivation suppression on COVID19 risk remains unclear. The estrogen pathway has been linked to better resistance to COVID 19, with an increased death rate in men compared with women. Moreover, TMPRSS2 which is implicated in prostate cancer dissemination process and is under the control of androgens, may be also involved in SARS-CoV infections. In vitro studies have suggested that androgen-regulation of TMPRSS2 and its inhibition may protect patients from SARS-CoV infection.
In the present article, the authors have used a population cohort of COVID19 infected Italian patients to assess the risk of COVID19-related death in patients treated by androgen depression therapy. From an initial cohort of 9280 patients, they confirmed that men were at higher risk of severe infection, compared with women (78% of ICU-hospitalized patients, 62% of COVID19-related deaths). Analyses also suggested that male patients with a cancer diagnosis developed more severe disease conditions (17% death rate) that men without cancer (7%). Last point, when focusing on COVID19 positive males with prostate cancer (n=118; among more than 42,000 exposed prostate cancer patients), they found that men under androgen deprivation therapy developed less severe infections compared to those without hormonal treatment (OR 4). No COVID19 death was reported in this sub-group of prostate cancer men. The estimated total of COVID19 positive cases / 100,000 was 76 in prostate cancer patients under androgen deprivation therapy, versus 318 in the remaining prostate cancer patients.
Globally, these population data suggest that androgen deprivation therapy could be protective against COVID19 infection and against severe forms of this disease. However, the link between androgen deprivation therapy, TMPRSS2, and COVID19 disease remains unclear, and needs to be further investigated in additional, large cohorts. The merit of this study is to highlight that at least androgen deprivation suppression does not lead to worse COVID19 outcomes and that such hormonal treatment can be safely pursued or initiated during COVID19 pandemic. Immediate treatment for newly diagnosed advanced prostate cancer can be safely maintained, allowing in some cases to postpone associated immunosuppressive treatments.