Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19

Abstract

IMPORTANCEAndrogen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissuebased expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). OBJECTIVE To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. EXPOSURES Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. MAIN OUTCOMES AND MEASURESThe primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. RESULTSAfter exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42).

The Transmembrane Protease TMPRSS2 as a Therapeutic Target for COVID-19 Treatment

“…Patients undergoing ADT have been reported to express lower levels of TMPRSS2, and may be less affected by COVID-19 [103]. Montopoli and colleagues reported an association between ADT and reduced occurrence of SARS-CoV-2 infection, whereas others found no beneficial effect of ADT on SARS-CoV-2 infection or COVID-19 progression [177][178][179][180][181][182]. However, the fact that the study cohorts consisted of men suffering from prostate cancer limits the applicability of the results to non-cancer patients with COVID-19.…”

Neurological complications associated with Covid‐19; molecular mechanisms and therapeutic approaches

“…Several experiments support the role of co‐receptors and attachment factors such as transmembrane serine protease 2 (TMPRSS2), basigin (BSG) (also known as CD147), GRP78, some toll‐like receptors (TLRs) and c‐type lectin receptors (CLRs), heparan sulfate, and sialic acids, which facilitate and enhance the entry of the virus in the presence of ACE2. 26 , 33 , 36 Nevertheless, these co‐receptors may not be sufficient for virus entry into some specific cells not expressing ACE2 although deletion of co‐receptors may reduce infection. 26 , 33 , 37 , 38 , 39 Furthermore, Neuropilin 1 (NRP1) mainly facilitates the regulation of angiogenesis, gangliogenesis, and vascular permeability, and similarly, enhances viral infectivity and acts as a co‐receptor for cell entry.…”

The adverse impact of COVID-19 on men's health

“…An early study from Montopoli et al examined 4,532 male patients and found that prostate cancer patients on ADT had lower risk of COVID-19 infection compared to those not on ADT (OR 4.05) [14]. However, newer data from Schmidt et al queried the Cancer Consortium registry and found no difference in 30-day mortality among COVID-19 patients who did and did not receive ADT [12]. Consistent with these data, two recent meta-analysis found no protective effect of ADT against COVID-19 infection or disease severity [33,34].…”