Androgen deprivation and SARS-CoV-2 in men with prostate cancer

Abstract

Androgen deprivation and SARS-CoV-2 in men with prostate cancerWe read with great interest the very recent article by Montopoli et al., 1 which reports men with prostate cancer tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Veneto, Italy, by 1 April 2020. The authors suggest that androgen deprivation therapy (ADT) could partially protect from SARS-CoV-2 infection. 1 The biological premise for this observation is the androgen receptormediated regulation of TMPRSS2, 2 a type II transmembrane serine protease that is important for SARS-CoV-2 entry to host cells. 3 Indeed, androgens regulate TMPRSS2 expression also in a lung carcinoma cell line. 4 Encouraged by the findings of Montopoli et al., 1 we examined the health care records of patients with prostate cancer [International Classification of Diseases (ICD)-10 code C61] in the Hospital District of Helsinki and Uusimaa, Finland, using automated text mining with manual verification and structured diagnostic codes. Altogether, 352 such men were tested for SARS-CoV-2 between 7 March and 14 May 2020. A patient was classified to be on ADT if he had a history of orchiectomy, or a valid prescription for a gonadotropin-releasing hormone (GnRH) analogue, GnRH antagonist, and/or antiandrogens (flutamide, bicalutamide, enzalutamide) or the CYP17 inhibitor abiraterone before his SARS-CoV-2 test (n ¼ 134) [38%, 95% confidence interval (CI): 33%e43%]. The mean age of these 134 men was 78.4 years AE 8.1 standard deviation (range 58e96 years). The frequency of being on ADT was in agreement with that observed in a survey of a large cohort of UK men with prostate cancer. 5 Conversely, a patient was classified not to be on ADT if no records of the above conditions were found or ADT had been ceased before a SARS-CoV-2 test (n ¼ 218; mean age 76.5 years AE 9.4 standard deviation, range 51e96 years). The presence of SARS-CoV-2 RNA in nasopharyngeal swab samples was analyzed by RT-PCR (details available upon request). This study was based on register data, provided by the registry holder, Helsinki University Hospital, and therefore no ethical permission was required according to the Finnish Medical Research Act.Of the 352 prostate cancer patients, 17 (4.8%, 95% CI: 2.6%e7.0%) tested positive for SARS-CoV-2, and 6 (35%, 95% CI: 13%e58%) of them were on ADT. However, the frequency of being positive for SARS-CoV-2 was not associated with ADT [6/134 on ADT versus 11/218 not on ADT; odds ratio (OR) 0.88; 95% CI 0.32e2.44, P ¼ 0.81]. ADT was not associated with the severity of the disease, as assessed by occurrence of death or the need of intensive care (1/6 in the ADT-positive group versus 3/11 in the ADT-negative group; OR 0.53; 95% CI 0.04e6.66, P ¼ 0.63). There were no differences in possible confounding comorbidities on Letters to the Editor

Androgen-deprivation therapy and SARS-CoV-2 in men with prostate cancer: findings from the University of California Health System registry

“… 3 A registry study reported by Montopoli et al 1 demonstrated that ADT was associated with decreased COVID-19 incidence in Venetian men with prostate cancer. However, this relationship was not observed by Koskinen et al 2 in a study of Finnish men. This relationship has not been examined in a diverse population.…”

“…We read with great interest two studies on the association of androgen deprivation therapy (ADT), a widespread therapy for advanced prostate cancer, and COVID-19 published in the Annals . 1 , 2 SARS-CoV-2 entry into host cells is facilitated by the transmembrane protease TMPRSS2, whose expression can be modulated by the androgen receptor. 3 Pre-clinical data suggests that ADT may protect from SARS-CoV-2 infection and decrease COVID-19 severity.…”

Association of Circulating Sex Hormones With Inflammation and Disease Severity in Patients With COVID-19

“…47,48 However, impaired mobility associated with sarcopenia induced by androgen deprivation therapy may have decreased their risk of exposure to SARS-CoV-2 virus. Other studies 49,50 have not confirmed an association between androgen deprivation therapy and SARS-CoV-2 infection or COVID-19 illness.…”

Cancerona: Challenges of Cancer Management in Times of COVID-19 Pandemic

“…A study by Montopoli et al [ 70 ] supported this finding by showing that prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT. In contrast, Koskinen et al [ 71 ] results did not support a role of ADT in decreasing the risk of SARS-CoV-2 infection in men with prostate cancer via ADT-mediated decrease in the expression of TMPRSS2. This discrepancy was explained by methodological differences mainly the region of data acquisition.…”