Efficacy of Neoadjuvant Hormone Therapy Combined with Radical Prostatectomy in Improving Oncological Outcomes for Patients with cT3 Prostate Cancer: A Systematic Review and Meta-Analysis.

Introduction: This comprehensive review and meta-analysis investigates the effectiveness of neoadjuvant hormone therapy (NHT) in conjunction with radical prostatectomy (RP) for patients diagnosed with clinical stage T3 (cT3) prostate cancer (PCa) patients. Our objective is to evaluate its influence on cancer-related outcomes.

Methods: In accordance with PRISMA standards, we conducted an analysis of 10 randomized controlled trials (RCTs) sourced from PubMed, Embase, Web of Science, and Cochrane databases, with a cutoff date of May 17, 2025. The main outcomes assessed included rates of positive surgical margins (PSMs) rates and prostate-specific antigen progression-free survival (PSA-PFS). Additional outcomes evaluated were pathologic complete response (pCR), minimal residual disease (MRD), and metastasis-free survival (MFS). We aggregated risk ratios (RRs), hazard ratios (HRs), and mean differences along with 95% confidence intervals (CI) utilizing either fixed or random-effects models.

Results: The combination of NHT and RP led to a notable decrease in PSM rates when compared to RP alone (RR = 0.75, 95% CI: 0.60-0.94, p = 0.01), particularly evident in Asian demographics (RR = 0.47, p = 0.001) and for NHT durations of 6 months or more (RR = 0.75, p = 0.01). Additionally, PSA-PFS showed significant enhancement (HR = 0.25, 95% CI: 0.22-0.28). While there was no overall advantage in achieving pCR or MRD, certain subgroups in North America and those undergoing extended NHT experienced benefits. MFS did not show any significant changes (RR = 0.99, 95% CI: 0.89-1.10).

Conclusion: The combination of NHT and RP enhances immediate surgical and biochemical results in patients with cT3 PCa, especially among those of Asian descent, and leads to a longer duration of NHT. However, the long-term survival advantages are still not established, highlighting the need for standardized RCTs to refine treatment protocols.