Descriptive statistics (counts (%); mean and standard deviation (SD) or median with inter-quartile range (IQR)) were reported for the baseline patient characteristics. Median was used to describe years, as well as PSA, at diagnosis (due to its non-normal nature). Overall survival (OS) (median with IQR) for the entire cohort was calculated by using the Kaplan–Meier method.

Utilizing a complete case analysis, we fitted a Cox proportional hazard model to assess the association between each of the exposure variables and OS. Hazard ratios (HRs) and their associated 95% confidence intervals (CI) were computed. We first examined the relationship between each exposure lab test and overall survival by using restricted cubic splines (RCS) with 5 knots to assess for non-linearity. We identified significant non-linearity, and, to provide clinically interpretable estimates, the exposure variables were categorized into quintiles, with the lowest quintile (Q1) used as the reference. We also tested a binary categorization of the non-ratio type of exposure variables, i.e., “normal vs. below normal” for albumin, hemoglobin, testosterone and “yes vs. no” for 50% PSA decrease and PSA nadir <0.1 ng/mL. The models were compared by using negative log-likelihood (NLL) values. Results for all the models were reported. The assumption of proportionality was tested by the examination of Schoenfeld residuals.

Each Cox model was adjusted for baseline characteristics. All the characteristics were introduced to the models as dichotomized or categorical independent variables, with the exception of GP visits (continuous) and PSA (splines). For the latter, the baseline PSA values were transformed by using restricted cubic splines (RCS) with 5 knots to account for non-linearity. Table A3 provides more detail on categorization of the independent covariates, including the exposure variables. There was no evidence of multicollinearity between the covariates in the model. All analyses were conducted in SAS. The study received research ethics approval from Advarra IRB (Pro00037601).

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