Abstract
BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) presents a challenge for clinicians in determining the optimal treatment sequence because of the lack of direct head-to-head comparisons, which is further complicated by the now-widespread use of androgen receptor pathway inhibitors (ARPIs) in metastatic hormone-sensitive prostate cancer (mHSPC). OBJECTIVE: This study is a Bayesian network meta-analysis (NMA) intended to provide a comprehensive evaluation and comparison of the efficacy of mCRPC treatments across different treatment lines. PATIENTS AND METHODS: We performed a systematic search of ClinicalTrials.gov, extracted information, assessed the risk of bias, and reconstructed missing outcomes. We performed an NMA to evaluate treatment efficacy for overall survival (OS) and progression-free survival (PFS) in first and subsequent lines. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) NMA guidelines and was registered with PROSPERO (CRD42024499607). RESULTS: The NMA included 43 trials with 33,494 patients. ARPI-based therapies, particularly in combination with poly(ADP-ribose) polymerase inhibitors, demonstrated the most significant benefits for OS and PFS in first-line mCRPC treatment, followed by chemotherapy regimens. However, ARPI re-treatment showed limited effectiveness in subsequent lines, leading to weaker OS and PFS benefits. CONCLUSIONS: This NMA highlights the superiority of ARPI-based therapies and chemotherapies as first-line options for mCRPC while emphasizing the need for treatment class switching after ARPI failure. To refine treatment sequencing and enable precision care, future research should integrate individual participant data to better address patient-level heterogeneity and identify biomarkers for personalized therapy.