Link Between SARS-CoV-2 Infection and Disease Severity in Prostate Cancer Patients on ADT

Overview

This systematic review and meta-analysis evaluated the risk of SARS-CoV-2 infection and COVID-19 severity in prostate cancer patients undergoing androgen deprivation therapy (ADT). The analysis included six studies comparing ADT-treated patients to controls, focusing on infection rates and severe disease outcomes such as ICU admission, intubation, or death.

Background

SARS-CoV-2 infection rates are similar between sexes, but males experience approximately three times higher severity and progression rates. The viral entry depends on ACE2 and TMPRSS2 enzymes, both androgen-regulated, with TMPRSS2 highly expressed in prostate tissue and implicated in prostate cancer pathogenesis. ADT suppresses androgen signaling and may influence SARS-CoV-2 infection susceptibility and COVID-19 severity in prostate cancer patients. This study aimed to clarify whether ADT confers protection or increased risk regarding SARS-CoV-2 infection and severe COVID-19 outcomes.

Data Highlights

Key Findings

• The incidence of SARS-CoV-2 infection was not significantly different between prostate cancer patients on ADT and those not receiving ADT.
• ADT was associated with a trend toward reduced severity of COVID-19, including lower rates of ICU admission, intubation, and death, although results varied across studies.
• Studies adjusting for confounders such as age, cardiovascular comorbidities, diabetes, COPD, and smoking status provided more reliable estimates.
• TMPRSS2 expression, regulated by androgens, may mechanistically link androgen signaling to SARS-CoV-2 cell entry and disease progression.
• Heterogeneity among studies was present, necessitating cautious interpretation of pooled risk ratios.
• Quality assessment indicated included studies were generally of fair to good quality based on Newcastle–Ottawa Scale and AHRQ criteria.

Clinical Implications

Clinicians should recognize that ADT does not appear to increase the risk of SARS-CoV-2 infection in prostate cancer patients and may confer some protective effect against severe COVID-19 outcomes. These findings support the continuation of ADT in prostate cancer management during the pandemic without additional SARS-CoV-2 infection risk concerns. Further large-scale prospective studies are warranted to confirm these observations and guide therapeutic strategies.

Conclusion

This systematic review and meta-analysis suggest that androgen deprivation therapy in prostate cancer patients does not increase SARS-CoV-2 infection risk and may reduce COVID-19 severity. Understanding androgen regulation of viral entry mechanisms provides a rationale for ongoing research into androgen-targeted therapies in COVID-19.

References

1. Montopoli et al. 2020 -- Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study
2. Patel et al. 2021 -- Impact of androgen deprivation therapy on COVID-19 outcomes in prostate cancer patients
3. Caffo et al. 2020 -- COVID-19 in patients with prostate cancer undergoing androgen deprivation therapy