Metastatic Castration-Sensitive Prostate Cancer (mCSPC) requires systematic treatments. These multiple therapies affect overall survival and reduce serious adverse events (SAE). They also facilitate radiographic progression-free survival (RPFS) in patients. This study compares systemic trials on mCSPC patients to assess their safety and effectiveness.

A network meta-analysis relied on trial registries, regulatory documents, and bibliographic database searches. A total of 7 trials comparing six treatments for 7287 patients were eligible. They got randomized to evaluate the effectiveness of apalutamide, docetaxel, enzalutamide, and abiraterone acetate to androgen-deprivation therapy (ADT). Techniques like independent screening, consensus-based discrepancy resolution, Bayesian network meta-analysis, and survival models were applied. The Cochrane risk-of-bias trial quality assessment tool was also used, with Systematic Reviews and Meta-analyses guidelines for The Preferred Reporting Items.

The most to least effective overall survival ADT add-ons were abiraterone acetate, apalutamide, and docetaxel with hazard ratios (HR) of 0.61, 0.67, 0.79, respectively. RPFS improved due to enzalutamide, apalutamide, abiraterone acetate, and docetaxel with HR of 0.39, 0.48, 0.51, 0.67, respectively. Only Docetaxel and abiraterone acetate substantially or slightly increased SAEs with an odds ratio of 23.72 and 1.42, respectively. There were 4, 3, and 2 bias risk trials with open-label design, missing data, and potential un-pre-specified analyses, respectively.

The ADT add-ons abiraterone acetate and apalutamide ensure relatively low SAE risks and higher overall survival. Similarly, the enzalutamide with a longer follow-up can greatly enhance radiographic progression-free survival.