Background: Treatment decision-making for metastatic castration-sensitive prostate cancer (mCSPC) is complicated by the unclear comparative effectiveness and widely varying costs of competing strategies. Objective: To compare the effectiveness and safety of systemic treatments for mCSPC. Methods: We searched bibliographic databases, regulatory documents, and trial registries for randomized controlled trials testing active drugs added to androgen deprivation therapy (ADT) for mCSPC. We used Cochrane risk-of-bias tool (version 2) to assess trial quality and Bayesian network meta-analysis (NMA) to estimate the relative effects of competing treatments. In addition to combing published time-invariant hazard ratios (HRs), we reconstructed survival data from Kaplan Meier curves to enable parametric survival NMA that allows time-varying HR. Results: Seven trials with 7,236 patients were included comparing six treatments (Table). Risk of bias is a concern for trials with open label (N=4), missing data (N=3), or unprespecified analysis (N=3). Ordered from the most to the least effective, treatments significantly improving overall survival (OS) include abiraterone acetate, apalutamide, and docetaxel; treatments significantly improving radiographic progression-free survival (rPFS) include enzalutamide, abiraterone, apalutamide, and docetaxel. (see HRs in Table) Allowing time-varying HR produced similar treatment rankings. Serious adverse events (SAE) were substantially increased for docetaxel (odds ratio [OR] 104.17, 95% credible interval [CI] 24.85-1012.32) and slightly increased for abiraterone (OR 1.42, 95% CI 1.11-1.83). Conclusions: Abiraterone provided the largest OS benefit with slightly increased risk of SAE. Apalutamide offered comparable OS benefit with abiraterone without increasing SAE risk. Although enzalutamide delayed rPFS to the greatest extent, longer follow-up is needed to examine its OS benefit.