PURPOSE: Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT). METHODS: We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I2 statistic, respectively. RESULTS: Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68). CONCLUSION: We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.

2nd Faculty of Medicine Department of Urology Charles University Prague Czech Republic

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Center Montreal Canada

Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Währinger Gürtel 18 20 1090 Vienna Austria

Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Men's Health and Reproductive Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran

The National Center for Diabetes Endocrinology and Genetics The University of Jordan Amman Jordan

World J Urol. 2023 Dec 22;42(1):4. doi: 10.1007/s00345-023-04755-8. PubMed

See more in PubMed

O’Hearn M, Liu J, Cudhea F, et al. Coronavirus Disease 2019 hospitalizations attributable to cardiometabolic conditions in the united states: a comparative risk assessment analysis. J Am Heart Assoc. 2021 doi: 10.1161/JAHA.120.019259. PubMed DOI PMC

Peckham H, de Gruijter NM, Raine C, et al. Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. Nat Commun. 2020;11:6317. doi: 10.1038/s41467-020-19741-6. PubMed DOI PMC

Rajwa P, Przydacz M, Krajewski W, et al. Changing patterns of urologic emergency visits and admissions during the COVID-19 pandemic: a retrospective, multicenter, nationwide study. Arch Med Sci. 2020 doi: 10.5114/aoms.2020.98364. PubMed DOI PMC

Thunders M, Delahunt B. Gene of the month: TMPRSS2 (transmembrane serine protease 2) J Clin Pathol. 2020;73:773–776. doi: 10.1136/jclinpath-2020-206987. PubMed DOI

Roshandel MR, Nateqi M, Lak R, et al. Diagnostic and methodological evaluation of studies on the urinary shedding of SARS-CoV-2, compared to stool and serum: a systematic review and meta-analysis. Cell Mol Biol. 2020;66:148–156. doi: 10.14715/cmb/2020.66.6.26. PubMed DOI

Compérat E, Wasinger G, Oszwald A, et al. The genetic complexity of prostate cancer. Genes. 2020;11:1396. doi: 10.3390/genes11121396. PubMed DOI PMC

Kumar-Sinha C, Tomlins SA, Chinnaiyan AM. Recurrent gene fusions in prostate cancer. Nat Rev Cancer. 2008;8:497–511. doi: 10.1038/nrc2402. PubMed DOI PMC

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2021) A phase ii trial to promote recovery from COVID-19 with endocrine therapy. clinicaltrials.gov

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (2021) COMBO trial: camostat with bicalutamide for COVID-19. clinicaltrials.gov

Josefsson A (2020) A prospective, multicenter, randomized phase ii clinical trial of enzalutamide treatment to decrease the morbidity in patients with corona virus disease 2019 (COVID-19). clinicaltrials.gov PubMed PMC

Corpometria Institute (2021) Early antiandrogen treatment (EAT) with dutasteride for COVID-19 (EAT-DUTA AndroCoV Trial). clinicaltrials.gov

Applied Biology, Inc. (2021) Anti-androgen treatment for COVID-19. clinicaltrials.gov

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–560. doi: 10.1136/bmj.327.7414.557. PubMed DOI PMC

Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–605. doi: 10.1007/s10654-010-9491-z. PubMed DOI

Agency for Healthcare Research and Quality (AHRQ). https://www.ahrq.gov/. Accessed 1 Apr 2021

Koskinen M, Carpen O, Honkanen V, et al. Androgen deprivation and SARS-CoV-2 in men with prostate cancer. Ann Oncol. 2020;31:1417. doi: 10.1016/j.annonc.2020.06.015. PubMed DOI PMC

Kwon DH, Vashisht R, Borno HT, et al. Androgen deprivation therapy and SARS-CoV-2 in men with prostate cancer: findings from the University of California Health System registry. Ann Oncol. 2021 doi: 10.1016/j.annonc.2021.01.067. PubMed DOI PMC

Patel VG, Zhong X, Liaw B, et al. Does androgen deprivation therapy protect against severe complications from COVID-19? Ann Oncol. 2020;31:1419–1420. doi: 10.1016/j.annonc.2020.06.023. PubMed DOI PMC

Klein EA, Li J, Milinovich A, et al. Androgen deprivation therapy in men with prostate cancer does not affect risk of infection with SARS-CoV-2. J Urol. 2021;205:441–443. doi: 10.1097/JU.0000000000001338. PubMed DOI

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) Ann Oncol Off J Eur Soc Med Oncol. 2020;31:1040–1045. doi: 10.1016/j.annonc.2020.04.479. PubMed DOI PMC

Patel VG, Zhong X, Shah NJ, et al. The role of androgen deprivation therapy on the clinical course of COVID-19 infection in men with prostate cancer. J Clin Oncol. 2021;39:41–41. doi: 10.1200/JCO.2021.39.6_suppl.41. DOI

Caffo O, Gasparro D, Di Lorenzo G, et al. (2020) Incidence and outcomes of severe acute respiratory syndrome coronavirus 2 infection in patients with metastatic castration-resistant prostate cancer. Eur J Cancer Oxf Engl. 1990;140:140–146. doi: 10.1016/j.ejca.2020.09.018. PubMed DOI PMC

Sari Motlagh R, Quhal F, Mori K, et al. The risk of new onset dementia and/or Alzheimer disease among patients with prostate cancer treated with androgen deprivation therapy: a systematic review and meta-analysis. J Urol. 2021;205:60–67. doi: 10.1097/JU.0000000000001341. PubMed DOI

Abufaraj M, Iwata T, Kimura S, et al. Differential impact of gonadotropin-releasing hormone antagonist versus agonist on clinical safety and oncologic outcomes on patients with metastatic prostate cancer: a meta-analysis of randomized controlled trials. Eur Urol. 2021;79:44–53. doi: 10.1016/j.eururo.2020.06.002. PubMed DOI

Smith MR, Lee WC, Brandman J, et al. Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2005;23:7897–7903. doi: 10.1200/JCO.2004.00.6908. PubMed DOI

O’Callaghan ME, Jay A, Kichenadasse G, Moretti KL. Androgen deprivation therapy in unlikely to be effective for treatment of COVID-19. Ann Oncol. 2020;31:1780–1782. doi: 10.1016/j.annonc.2020.09.014. PubMed DOI PMC

Semaan L, Mander N, Cher ML, Chinni SR. TMPRSS2-ERG fusions confer efficacy of enzalutamide in an in vivo bone tumor growth model. BMC Cancer. 2019;19:972. doi: 10.1186/s12885-019-6185-0. PubMed DOI PMC

Blee AM, He Y, Yang Y, et al. TMPRSS2-ERG controls luminal epithelial lineage and antiandrogen sensitivity in PTEN and TP53-mutated prostate cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2018;24:4551–4565. doi: 10.1158/1078-0432.CCR-18-0653. PubMed DOI PMC

Cadegiani FA, McCoy J, Gustavo Wambier C, Goren A. Early antiandrogen therapy with dutasteride reduces viral shedding, inflammatory responses, and time-to-remission in males with COVID-19: a randomized, double-blind, placebo-controlled interventional trial (EAT-DUTA AndroCoV Trial—Biochemical) Cureus. 2021 doi: 10.7759/cureus.13047. PubMed DOI PMC

Goren A, Wambier CG, Herrera S, et al. Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men. J Eur Acad Dermatol Venereol JEADV. 2021;35:e13–e15. doi: 10.1111/jdv.16953. PubMed DOI PMC

Lazzeri M, Duga S, Azzolini E, et al. Impact of chronic exposure to 5-alpha reductase inhibitors on the risk of hospitalization for COVID-19: a case-control study in male population from two COVID-19 regional centers of Lombardy (Italy) Minerva Urol E Nefrol Ital J Urol Nephrol. 2021 doi: 10.23736/S0393-2249.20.04081-3. PubMed DOI

Radiation therapy compared to radical prostatectomy as first-line definitive therapy for patients with high-risk localised prostate cancer: An updated systematic review and meta-analysis