The primary end point used in the study was OS, defined as the time from PCa diagnosis to date of death from any cause. Patients without events were censored at their last date of follow-up. We evaluated the association of several exposure variables of interest with OS: markers of systemic inflammation (baseline neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and albumin), baseline hemoglobin, baseline testosterone levels and prostate-specific antigen (PSA) metrics (50% PSA decrease, PSA percentage change from baseline, PSA nadir <0.1 ng/mL). These exposure variables were selected because they are readily available from laboratory tests and have been implicated in the prognosis of prostate cancer [22,23,24,29,30]. Of note, all laboratory tests were performed in the 3 months preceding the index date. If the test was not available prior to the index date, then we used a test value available within 2 months following the index date but no more than 5 days after ADT initiation. In either case, the test value that was closest to the index date was selected. In a sensitivity analysis, we considered laboratory tests performed in the 6 months preceding the index date. As an exploratory analysis, we evaluated the association of these laboratory markers with time to emergence of castrate resistance.

The study population was described at baseline, using a set of variables that included sociodemographic characteristics (age, socioeconomic status, Local Health Integration Network (LHIN), rurality, PCa attributes such as PSA at diagnosis, Gleason score and health status (Charlson Comorbidity Index, history of key comorbid conditions other than PCa, including diabetes, myocardial infarction, congestive heart failure, and liver or kidney disease), as well as healthcare use (number of general practitioner (GP) visits, status of being a long-term care (LTC) resident and history of hospitalizations). Details on each variable are briefly presented in Table A2.

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