The efficacy of neoadjuvant chemohormonal therapy in combination with radical prostatectomy for locally advanced prostate cancer: a systematic review and meta-analysis.

Objective: Locally advanced prostate cancer (clinical stage T3 or higher) causes significant harm to patients, including decreased quality of life, high mortality rates, and economic burden. Current multimodal management for locally advanced prostate cancer often includes radiotherapy combined with long-term androgen deprivation therapy (ADT), with radical prostatectomy (RP) reserved for selected patients. However, RP alone or with ADT has limitations such as high biochemical recurrence rates and high positive surgical margin (PSM) rates. Therefore, this study aims to explore new effective treatment strategies. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Embase, Web of Science and Cochrane databases up of August 19, 2025. We analyzed data from 10 studies. The main outcomes assessed included biochemical progression-free survival (BPFS), PSM rate, overall survival (OS) and metastasis-free survival (MFS). We pooled risk ratios (RR) with 95% confidence intervals (CI) using fixed- or random-effects models. Results: The results show that compared with RP alone, the combination of NCHT and RP significantly improved BPFS (RR = 0.60, 95% CI: 0.41-0.87, P = 0.008), despite significant heterogeneity (I² = 90%). In RCT subgroup analysis, the benefit remained significant (RR = 0.73, 95% CI: 0.62-0.86; P = 0.0002; I² = 0%). The NCHT+RP group also showed a significant reduction in PSM rate (RR = 0.49, 95% CI: 0.37-0.65, P < 0.00001). For OS, the pooled analysis showed an improvement (RR = 0.45, 95% CI: 0.24-0.84, P = 0.01); however, this effect was entirely driven by non-randomized studies (RR = 0.55, 95% CI: 0.31-0.99; P = 0.04), while the randomized controlled trials (RCT) subgroup did not confirm a significant benefit (RR = 0.43, 95% CI: 0.10-1.88, P = 0.26). No significant improvement was observed in MFS (RR = 0.82, 95% CI: 0.45-1.49, P = 0.51), although the single large RCT (Eastham et al.) favored NCHT+RP (RR = 0.78, 95% CI: 0.63-0.98; P = 0.03). Conclusion: In selected patients with locally advanced prostate cancer, NCHT combined with RP may improve BPFS and reduce PSM rates, with the BPFS benefit confirmed in the RCT subgroup. However, the apparent OS benefit was not observed in RCTs and likely reflects bias in observational studies. According to GRADE, the certainty of evidence for survival outcomes is very low. These positive findings should be interpreted with caution, and adequately powered RCT with modern agents are needed.