Main Session
Sep 29
PQA 06 - Genitourinary Cancer, Gynecological Cancer, and Health Care Access and Engagement

3229 - PRO-BOOST-LC: Phase II/III Trial of Whole-Gland Boost Strategies vs. SBRT Monotherapy in PSMA-Staged Localized and Locally Advanced Prostate Cancer

02:15pm - 03:30pm ET
Poster Hall - Exhibit Hall A
Screen: 6
POSTER

Presenter(s)

Mateusz Bilski, MD, PhD Headshot
Mateusz Bilski, MD, PhD - Lublin Region Oncology Center, Lublin, lubelskie

M. Bilski1,2, F. Mastroleo3,4, L. Kuncman5, M. Pedrani6, G. Salfi7, D. Garmol8, L. Jaroszewska8, L. D. Nicosia9, J. Fijuth5, F. Alongi10, T. Zilli11,12, B. A. Jereczek-Fossa13, and A. U. Kishan14; 1Affidea Nu-med Center of Cancer Diagnostics and Therapy, Zamosc, Poland, 2Department of Radiotherapy, Medical University of Lublin, Lublin, Poland, 3Division of Radiation Oncology, IEO, European Institute of Oncology, IRCCS, Milan, Italy, 4Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 5Department of External Beam Radiotherapy, Copernicus Memorial Hospital in Lodz Comprehensive Cancer Center and Traumatology, Lódz, Poland, 6Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland, 7Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Institute of Oncology Research, Bellinzona, Switzerland, 8Radiotherapy Department, Affidea Nu-med Center of Oncological Diagnostics and Therapy, Zamosc, Poland, 9Department of Advanced Radiation Oncology, IRCCS "Sacro Cuore Don Calabria Hospital" Cancer Care Center, Negrar di Valpolicella (VR), Italy, 10Varian, Milpitas, CA, Uganda, 11Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland, 12Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland, 13Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, I 20132, Milano, Italy, 14Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA

Purpose/Objective(s): Prostate dose escalation beyond conventional external beam radiotherapy improves biochemical and relapse-free outcomes in intermediate- and high-risk disease. Randomized trials support low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy boost strategies, while stereotactic body radiotherapy (SBRT) has emerged as a non-invasive ablative approach capable of delivering biologically effective doses exceeding 100 Gy (a/ß=1.5) with favorable toxicity profiles. Ultrahypofractionated regimens (5×5 Gy) have demonstrated feasibility and encouraging control rates. Despite robust data for each modality individually, no prospective randomized trial has directly compared HDR, LDR, and SBRT boost strategies using a uniform ultrahypofractionated backbone in the era of mandatory PSMA PET staging. Molecular imaging refines risk stratification and patterns of failure and may influence the magnitude of benefit derived from intraprostatic dose escalation. PRO-BOOST-LC addresses this gap by comparing three whole-gland ablative boost modalities following a standardized 5×5 Gy VMAT backbone versus SBRT monotherapy in PSMA-staged cN0/cM0 prostate cancer.

Materials/Methods: PRO-BOOST-LC is a prospective, multicenter, multi-arm, multi-stage randomized phase II/III trial with a seamless adaptive design. An initial phase II safety stage allows discontinuation of experimental arms for unacceptable toxicity or infeasibility, followed by confirmatory phase III efficacy evaluation. Eligible patients are men =18 years with NCCN-defined favorable intermediate-, unfavorable intermediate-, high-, or very high-risk prostate cancer, staged cT1–T4, cN0, cM0 on mandatory baseline PSMA PET/CT and multiparametric MRI within 12 weeks before randomization. Selected cT3b–T4 tumors are eligible if definitive ablative radiotherapy is technically feasible.

Patients are randomized 1:1:1:1 (capability-based allocation) to:

Arm A: SBRT monotherapy 36.25–40 Gy in 5 fractions Arm B: EBRT 25 Gy/5 fractions + HDR boost 15 Gy ×1 Arm C: EBRT 25 Gy/5 fractions + LDR boost 110 Gy Arm D: EBRT 25 Gy/5 fractions + SBRT boost 15 Gy ×1

ADT duration is risk-adapted and identical across arms; ARPI use is permitted in very high-risk disease if declared before randomization. The primary endpoint follows a hierarchical strategy: failure-free survival (FFS), followed by metastasis-free survival (MFS) if FFS is significant. Secondary endpoints include intraprostatic local control, CTCAE v5.0 toxicity, PSA kinetics, time to salvage therapy, overall survival, and longitudinal patient-reported outcomes (EPIC-26, IPSS, EORTC QLQ-C30/PR25, IIEF-5). The capability-based randomization framework enhances external validity while preserving internal validity through stratification, reflecting real-world international practice in boost delivery.

Results: Recruiting.

Conclusion: -

Trial registration: ClinicalTrials.gov NCT07426055 (Registered 20th Feb 2026).