Neoadjuvant Hormonal Therapy Before Radical Prostatectomy: Favorable Pathological and PSA Outcomes Do Not Guarantee Favorable Oncological Outcomes

ABSTRACT Background To evaluate the impact of neoadjuvant hormonal therapy (Neo‐HT) on postoperative pathological and prostate‐specific antigen (PSA) outcomes after radical prostatectomy (RP) and oncological outcomes in patients with favorable postoperative outcomes (pT0‐2N0, negative surgical margin and undetectable PSA). Methods A total of 1099 prostate cancer (PCa) patients who underwent RP were divided into the direct RP group or the Neo‐RP group (Neo‐HT before RP). We compared the proportions achieving favorable postoperative outcomes. Oncological endpoints included biochemical progression‐free survival (bPFS), local recurrence‐free survival (LRFS), and metastasis‐free survival (MFS). Predictors of biochemical recurrence (BCR) were identified using multivariable Cox regression. Propensity score matching (PSM) was applied to balance baseline characteristics. Results Neo‐HT increased the proportions achieving favorable postoperative outcomes among both low‐to‐intermediate and high‐risk patients (42.02% vs. 23.63%, p < 0.001). Among 362 patients with favorable postoperative outcomes, unadjusted 3‐year bPFS was worse in the Neo‐RP group (81.5% vs. 93.6%, p = 0.008), with similar patterns for LRFS and MFS. Baseline PSA > 20 ng/ml, Gleason score 8–10, and cT2c‐4 were independent predictors of BCR, and no statistically significant differences in bPFS, LRFS, or MFS were observed in the PSM cohort. Conclusions Neo‐HT enables more PCa patients to achieve favorable postoperative outcomes. Among patients with favorable postoperative outcomes, those with high‐risk baseline features are more likely to experience BCR irrespective of Neo‐HT. The apparent improvements in postoperative pathological and PSA outcomes after Neo‐HT may obscure recurrence risk, underscoring the need to incorporate baseline characteristics into postoperative risk stratification and management.