Quantitative Morphometric Response to Neoadjuvant Androgen-Deprivation Therapy and Its Prognostic Role After Radical Prostatectomy

Background: Neoadjuvant Androgen-Deprivation Therapy (Nadt) Prior to Radical Prostatectomy (Rp) Induces Heterogeneous Morphological Responses in Prostate Cancer (Pca). Complete Pathological Response Is Rare, Therefore, Quantitative Assessment of Residual Viable Tumor May Provide Additional Prognostic Information Beyond Conventional Clinicopathological Parameters. Materials and Methods: In this retrospective single-center study conducted between 2015 and 2021, 84 patients with localized and locally advanced PCa treated with NADT followed by RP were analyzed. Residual tumor burden (RTB) and residual tumor area (RTA) were quantified using calibrated digital morphometry. Optimal cut-off values for biochemical recurrence (BCR) were determined using ROC analysis. Biochemical recurrence-free survival (BCRFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis and Cox proportional hazards regression models. Results: During a median follow-up of 56 months, 62 BCR events and 12 deaths were observed. ROC analysis identified cut-off values of 32.5% for RTB and 50.5 mm 2 for RTA. In univariable analysis, high RTB (HR 1.93, 95% CI 1.14– 3.23, p=0.010) and high RTA (HR 2.11, 95% CI 1.24– 3.62, p=0.006) were significantly associated with inferior BCRFS. However, in multivariable analysis, cribriform architecture (HR 1.85, 95% CI 1.05– 3.27, p=0.035) and high NCCN risk category (HR 1.95, 95% CI 1.07– 3.54, p=0.028) remained independent predictors of BCR, whereas RTB and RTA did not retain independent significance. No independent association between morphometric parameters and OS was observed. Discussion and conclusion: Quantitative assessment of residual viable tumor following NADT is associated with BCR risk, however, their prognostic impact appears largely driven by intrinsic tumor biology, particularly cribriform architecture and baseline risk stratification. Morphometric assessment may complement postoperative risk evaluation but should not be used as a standalone prognostic marker. Keywords: prostate cancer, neoadjuvant androgen-deprivation therapy, radical prostatectomy, treatment response, oncological outcomes