Ten-year outcomes of a phase III, multicenter, randomized controlled trial (SHIP0804) with three-month neoadjuvant androgen deprivation prior to 125I-seed transperineal prostate brachytherapy followed by nil versus nine-month adjuvant hormonal therapy in patients with intermediate-risk prostate cancer.

Purpose: To analyze the effects of adjuvant hormonal therapy (AHT) on time to event following neoadjuvant androgen deprivation therapy (ADT) and ¹²⁵I-transperineal prostate brachytherapy (TPPB), compared with neoadjuvant ADT and TPPB only, in patients with intermediate-risk prostate cancer (IRPC).

Patients and methods: In this multicenter, open-label, phase III randomized controlled trial (SHIP0804), 421 patients with IRPC were randomized to either nine-month AHT (AHT arm) or no AHT (non-AHT arm) after three months of neoadjuvant ADT and TPPB. The primary endpoint was biochemical progression-free survival (BPFS), and secondary endpoints included overall survival (OS) and clinical progression-free survival (CPFS). Prostatic biopsy results 36 months after treatment were evaluated in a correlative investigation (SHIP36B).

Results: With a median follow-up of over 11 years, the 10-year BPFS rates were comparable: 82.9% in the AHT group and 78.4% in the non-AHT group (P = 0.51). Results were consistent across key prognostic indicators such as age at randomization, baseline prostate-specific antigen level, clinical stage, Gleason grade group, number of National Comprehensive Cancer Network intermediate-risk factors, and prostatic volume. The secondary endpoints, including OS and CPFS, were also comparable between the two arms. Grade 3 or higher AEs occurred in 5.4% and 1.4% of patients in the AHT and non-AHT arms, respectively. At 36-month post-TPPB prostate biopsy, only 3.1% of biopsied patients tested positive for residual tumors. There were no deaths due to prostate cancer in either group.

Conclusions: Adding nine-month AHT to TPPB after three-month neoadjuvant ADT did not improve long-term outcomes in patients with IRPC. These findings suggest that moderate-term AHT may not offer substantial benefits and thus should not be considered a standard treatment in this population with IRPC.