Influence of androgen deprivation therapy on the severity of COVID‐19 in prostate cancer patients
Estíbaliz Jiménez‐alcaide, Clara García‐fuentes, MD Virginia Hernández, MD Enrique De La Peña, Elia Pérez‐fernández, MD Alejandro Castro, Begoña Caballero‐perea, MD Ana Guijarro, MD Carlos Llorente
The Prostate, doi:10.1002/pros.24232
Background: The TMPRSS2 protein has been involved in severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). The production is regulated by the androgen receptor (AR). It is speculated that androgen deprivation therapy (ADT) may protect patients affected by prostate cancer (PC) from SARS-CoV-2 infection. Methods: This is a retrospective study of patients treated for COVID-19 in our institution who had a previous diagnosis of PC. We analyzed the influence of exposure of ADT on the presence of severe course of COVID-19. Results: A total of 2280 patients were treated in our center for COVID-19 with a worse course of disease in males (higher rates of hospitalization, intense care unit [ICU] admission, and death). Out of 1349 subjects registered in our PC database, 156 were on ADT and 1193 were not. Out of those, 61 (4.52%) PC patients suffered from COVID-19, 11 (18.0%) belonged to the ADT group, and 50 (82.0%) to the non-ADT group. Regarding the influence of ADT on the course of the disease, statistically significant differences were found neither in the death rate (27.3% vs. 34%; p = 0.481), nor in the presence of severe COVID-19: need for intubation or ICU admission (0% vs. 6.3%; p = 0.561) and need for corticoid treatment, interferon beta, or tocilizumab (60% vs. 34.7%; p = 0.128). Multivariate analysis adjusted for clinically relevant comorbidities did not find that ADT was a protective factor for worse clinical evolution (risk ratio [RR] 1.08; 95% confidence interval [CI], 0.64-1.83; p = 0.77) or death (RR, 0.67; 95% CI, 0.26-1.74; p = 0.41). Conclusions: Our study confirms that COVID-19 is more severe in men. However, the use of ADT in patients with PC was not shown to prevent the risk of severe COVID-19.
CONFLICT OF INTERESTS The authors declare that there are no conflict of interests.
References
Arora, Schenkein, Murali, Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade, Cell
Bugge, Antalis, Wu, Type II transmembrane serine proteases, J Biol Chem
Caffo, Zagonel, Baldessari, On the relationship between androgen-deprivation therapy for prostate cancer and risk of infection by SARS-CoV-2, Ann Oncol,
doi:10.1016/j.annonc.2020.06.005Choi, Bertram, Glowacka, Park, Pohlmann, Type II transmembrane serine proteases in cancer and viral infections, Trends Mol Med
Guan, Ni, Hu, Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med
Huang, Wang, Li, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Jiménez-Alcaide, García-Fuentes, Hernández, Influence of androgen deprivation therapy on the severity of COVID-19 in prostate cancer patients, The Prostate
Klein, Flanagan, Sex differences in immune responses, Nat Rev Immunol
Klein, Li, Milinovich, Androgen deprivation therapy in men with prostate cancer does not affect risk of infection with SARS-CoV-2, J Urol,
doi:10.1097/JU.0000000000001338Lucas, Heinlein, Kim, The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis, Cancer Discov
Lucas, True, Hawley, The androgen-regulated type II serine protease TMPRSS2 is differentially expressed and mislocalized in prostate adenocarcinoma, J Pathol
Matsuyama, Nao, Shirato, Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells, Proc Natl Acad Sci
Mikkonen, Pihlajamaa, Sahu, Zhang, Janne, Androgen receptor and androgen-dependent gene expression in lung, Mol Cell Endocrinol
Montopoli, Zumerle, Vettor, Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a populationbased study (N = 4532), Ann Oncol
Shaw, Whitaker, Corcoran, The early effects of rapid androgen deprivation on human prostate cancer, Eur Urol
Shaw, Whitaker, Corcoran, The early effects of rapid androgen deprivation on human prostate cancer, Eur Urol
Shin, Seong, Type II transmembrane serine proteases as potential target for anti-influenza drug discovery, Expert Opin Drug Discov
Zhang, Xie, Hashimoto, Current status of potential therapeutic candidates for the COVID-19 crisis, Brain Behav Immun,
doi:10.1016/j.bbi.2020.04.046Zhou, Yang, Wang, A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
Zhu, Zhang, Wang, A novel coronavirus from patients with pneumonia in China, 2019, N Engl J Med
Zou, A modified Poisson regression approach to prospective studies with binary data, Am J Epidemiol
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