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

Koskinen et al., Annals of Oncology, doi:10.1016/j.annonc.2020.06.015
Jun 2020  
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Mortality 46% Improvement Relative Risk Death/ICU 46% Case 11% Antiandrogens  Koskinen et al.  Prophylaxis Is prophylaxis with antiandrogens beneficial for COVID-19? Retrospective 352 patients in Finland Study underpowered to detect differences Koskinen et al., Annals of Oncology, Jun 2020 Favorsvarious Favorscontrol 0 0.5 1 1.5 2+
7th treatment shown to reduce risk in September 2020
*, now with p = 0.000000056 from 49 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
Retrospective 352 prostate cancer patients in Finland, showing no significant differences in COVID-19 with ADT.
Although the 46% lower mortality is not statistically significant, it is consistent with the significant 37% lower mortality [21‑50%] from meta analysis of the 32 mortality results to date.
risk of death, 45.8% lower, RR 0.54, p = 1.00, treatment 1 of 134 (0.7%), control 3 of 218 (1.4%), NNT 159.
risk of death/ICU, 45.8% lower, RR 0.54, p = 1.00, treatment 1 of 134 (0.7%), control 3 of 218 (1.4%), NNT 159.
risk of case, 11.3% lower, RR 0.89, p = 1.00, treatment 6 of 134 (4.5%), control 11 of 218 (5.0%), NNT 176.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Koskinen et al., 29 Jun 2020, retrospective, Finland, peer-reviewed, 7 authors.
This PaperAntiandrogensAll
Abstract: Annals of Oncology Letters to the Editor Androgen deprivation and SARS-CoV-2 in men with prostate cancer We 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  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  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 Volume 31 - Issue 10 - 2020 Table 1. The presence of potential confounding factors on COVID-19 severity in SARS-CoV-2 tested patients with prostate cancer classified on the basis of being on androgen deprivation therapy Age > 65 years Hypertensionb Coronary artery diseasec COPDd Diabetese Cardiac arrhythmiaf Current smoker No ADT (n [ 218) On ADT (n [ 134) P valuea 191 47 30 12 17 41 17 125 30 21 8 16 30 18 0.10 0.89 0.64 1.0 0.26 0.42 0.10 The distributions of diagnoses from 2015 to 2 weeks before the SARS-CoV-2 test are shown. Smoking status was extracted by using automated text mining and manual verification. The data denote the..
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