Ten-Year Outcomes of a Phase 3, Multicenter, Randomized Controlled Trial (SHIP0804) With 3-Month Neoadjuvant Androgen Deprivation Prior to 125I-Seed Transperineal Prostate Brachytherapy Followed by Nil Versus 9-Month Adjuvant Hormonal Therapy in Patients With Intermediate-Risk Prostate Cancer

Wataru Fukuokaya; Kenta Miki; Manabu Aoki; Hiroyuki Takahashi; Shiro Saito; Atsunori Yorozu; Takashi Kikuchi; Takushi Dokiya; Shin Egawa; SHIP Collaborative Group

doi:10.1016/j.ijrobp.2024.11.010

Ten-Year Outcomes of a Phase 3, Multicenter, Randomized Controlled Trial (SHIP0804) With 3-Month Neoadjuvant Androgen Deprivation Prior to ¹²⁵I-Seed Transperineal Prostate Brachytherapy Followed by Nil Versus 9-Month Adjuvant Hormonal Therapy in Patients With Intermediate-Risk Prostate Cancer

Int J Radiat Oncol Biol Phys. 2024 Nov 16:S0360-3016(24)03584-3. doi: 10.1016/j.ijrobp.2024.11.010. Online ahead of print.

Authors

Wataru Fukuokaya¹, Kenta Miki¹, Manabu Aoki², Hiroyuki Takahashi³, Shiro Saito⁴, Atsunori Yorozu⁵, Takashi Kikuchi⁶, Takushi Dokiya⁷, Shin Egawa⁸; SHIP Collaborative Group

Collaborators

SHIP Collaborative Group:
Tetsuo Momma, Hideyasu Tsumura, Takashi Fukagai, Kumiko Karasawa, Koji Masui, Katsuyoshi Hashine, Nobumichi Tanaka, Satoshi Katayama, Yoshito Kusuhara, Masatoshi Eto, Koji Iinuma, Narihiko Hayashi, Mikio Sugimoto, Kazuhiro Suzuki, Ryoichi Imamura, Junji Yonese

Affiliations

¹ Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
² Department of Radiology, The Jikei University School of Medicine, Tokyo, Japan.
³ Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
⁴ Department of Urology, Ofuna Chuo Hospital, Kamakura, Japan.
⁵ Department of Radiation Oncology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
⁶ Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation, Translational Research Informatics Center, Kobe, Japan.
⁷ The Japan Foundation for Prostate Research, Tokyo, Japan.
⁸ Department of Exploratory Liquid Biopsy in Malignant Tumors, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: [email protected].

PMID: 39551103
DOI: 10.1016/j.ijrobp.2024.11.010

Abstract

Purpose: To analyze the effects of adjuvant hormonal therapy (AHT) on time to event after 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).

Methods and materials: In this multicenter, open-label, phase 3 randomized controlled trial (SHIP0804), 421 patients with IRPC were randomly assigned to either 9-month AHT (AHT arm) or no AHT (non-AHT arm) after 3 months of neoadjuvant ADT and TPPB. The primary endpoint was biochemical progression-free survival, and secondary endpoints included overall survival and clinical progression-free survival. 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 biochemical progression-free survival rates were comparable: 82.9% in the AHT group and 78.4% in the non-AHT group (P = .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 overall survival and clinical progression-free survival, were also comparable between the 2 arms. Grade 3 or higher adverse events 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 9-month AHT to TPPB after 3-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.