Tumor regression after neoadjuvant hormonal therapy in high risk prostate cancer: pathological outcomes from a randomized phase II trial.

Purpose: High-risk localized prostate cancer (HRLPC) commonly progresses to metastatic disease after local treatment. Neoadjuvant androgen deprivation therapy (nADT) before radical prostatectomy (RP) has recently been suggested to improve early oncological outcomes in HRLPC. We aimed to perform an exploratory analysis of the pathological outcomes from a prospective trial testing nADT before RP.

Methods: Prospective, single-centered, phase II, randomized trial performed between October 2018 and July 2021. Random assignment (1:1) for nADT modalities: goserelin (10.8 mg) plus abiraterone acetate (1000 mg/d) plus prednisone (5 mg/d), with or without apalutamide (240 mg/d) for 12 weeks, followed by RP (within 30 days) and extended lymph node dissection. Baseline clinical and pathological variables were assessed in needle biopsies before nADT. Tumor regression was histologically evaluated in surgical specimens using the residual cancer burden index (RCB).

Results: Sixty-two patients reached the surgical phase. Good response (RCB ≤ 0.25 cm³) was achieved in 14 patients (22.5%). Overall stage migration rate between baseline status (MRI before nADT) and final status (after surgery) was 27.4%. Late stage detection (high tumor burden, perineural invasion) and altered PTEN/ERG immunostatus showed significant association with poor response in univariate analysis. Higher baseline tumor burden was the only independent factor related to poor response in multivariate analysis.

Conclusions: There are subgroups of patients, such as those with low baseline cancer burden and PTEN/ERG wild-type status, more likely to achieve good response with nADT. In the case of long term oncological benefit to be proven, nADT might be an additional therapeutic resource for these patients.