Evaluating Treatment Efficacy in Metastatic Hormone-sensitive Prostate Cancer Patients with Visceral Disease: A Systematic Review and Network Meta-analysis

Background and objective: Metastatic hormone-sensitive prostate cancer (mHSPC) patients with visceral disease (VD) represent a high-risk subgroup associated with poor prognosis. Despite the introduction of treatment intensification strategies, the optimal systemic therapy for these patients remains unclear. This network meta-analysis (NMA) aims to evaluate the efficacy of the current therapeutic combinations in terms of overall survival (OS) in the subgroup of patients with VD. Methods: A systematic review and NMA was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (PROSPERO: CRD42025642120). Phase 3 randomised controlled trials assessing systemic therapies for mHSPC were identified through the PubMed, Cochrane, and Embase databases. Only studies reporting OS outcomes for patients with VD were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and analysed using a frequentist NMA framework. The risk of bias was assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. Key findings and limitations: Eight phase 3 trials (7944 patients, 1189 with VD) were included. The androgen deprivation therapy (ADT) + docetaxel + darolutamide combination was the most effective regimen (HR = 0.42, 95% CI: 0.21-0.82). Among doublets, ADT + docetaxel (HR = 0.53, 95% CI: 0.30-0.93) and ADT + abiraterone (HR = 0.58, 95% CI: 0.41-0.83) showed superior efficacy to other androgen receptor pathway inhibitor-based doublet regimens, including combinations with enzalutamide, apalutamide, and darolutamide. The absence of individual patient data and the lack of efficacy data stratified by metastatic site (liver or lung involvement) were the key limitations. Conclusions and clinical implications: Treatment intensification with triplet therapy (ADT + docetaxel + darolutamide) provides the greatest OS benefit in mHSPC patients with VD. Doublet regimens incorporating chemotherapy or abiraterone remain viable alternatives. Further prospective studies are needed to refine treatment selection based on VD-specific biology and organ-specific metastatic patterns.