Neoadjuvant androgen receptor pathway inhibition for patients with high-risk localized prostate cancer: 5-year survival update and PSMA PET correlatives of the randomized NeoPRO trial.

5119 Background: Patients with high-risk prostate cancer remain at elevated risk of recurrence after local therapy. Ongoing trials are investigating neoadjuvant strategies using androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPI). Methods: This phase II trial randomized patients with Gleason ≥ 8 and/or cT3N0-1 and/or PSA ≥ 20 ng/mL to receive either goserelin (ADT) plus abiraterone acetate and prednisone (AAP arm) or AAP plus apalutamide (A-APA arm) prior to radical prostatectomy. The primary endpoint was the rate of pathological complete response (pCR) or minimal residual disease (tumor ≤ 0.5 cm). Here we present updated survival data after a median follow-up of 59 months. Biochemical-free survival (BFS) was defined as the time from randomization to PSA > 0.1 ng/mL, metastasis, or death. Metastasis-free survival (MFS) was defined as the time from randomization to metastasis or death. Kaplan-Meier method and log-rank tests were used for time-to-event analyses. Results: Sixty-two patients were randomized (AAP = 31; A-APA = 31). Previous results showed no significant difference in the primary endpoint (Bastos D, et al. ASCO 2022). A total of 35 patients experienced biochemical recurrence. No significant difference was observed between the AAP and A-APA arms in 5-year BFS (48% vs 35%, p = 0.55) or MFS (83% vs 84%, p = 0.88). Achieving complete PSMA response on PSMA PET prior to surgery was a significant prognostic factor for improved 5-year BFS (28% vs 66%, p = 0.003) and MFS (74% vs 100%, p = 0.009). A trend toward higher 5-year overall survival (OS) was also observed among those with complete PSMA response (87% vs 100%, p = 0.09). Residual cancer burden ≤ 0.25 cm³ was associated with better 5-year BFS (32% vs 77%, p = 0.008), but not with MFS (79% vs 100%, p = 0.06) or OS (89% vs 100%, p = 0.22). Conclusions: No difference in 5-year BFS or MFS was observed between AAP and A-APA. Complete PSMA response on PSMA PET is a promising prognostic marker and may serve as a surrogate for BFS and MFS after neoadjuvant treatment in high-risk prostate cancer. Clinical trial information: NCT02789878 .