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

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.