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

3230 - PRO-BOOST-N: Phase II/III Trial of Prostate-First vs. Combined Prostate and Nodal Dose Escalation in PSMA PET-Staged Node-Positive 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, L. Kuncman4, M. Pedrani5, G. Salfi6, J. Fijuth7, D. Garmol8, L. Jaroszewska8, L. D. Nicosia9, F. Alongi10, T. Zilli11, B. A. Jereczek-Fossa12, and A. U. Kishan13,14; 1Affidea Nu-med Center of Oncology 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, 4Copernicus Memorial Hospital in Lodz Comprehensive Cancer Center and Traumatology, Lodz, Poland, 5Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland, 6Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Institute of Oncology Research, Bellinzona, Switzerland, 7Department of External Beam Radiotherapy, Copernicus Memorial Hospital in Lodz Comprehensive Cancer Center and Traumatology, Lódz, Poland, 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, 12Division of Radiation Oncology, IEO, European Institute of Oncology IRCCS, Via Ripamonti 435, I 20132, Milano, Italy, 13Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 14University of California Los Angeles, Department of Radiation Oncology, Los Angeles, CA

Purpose/Objective(s): Patients with PSMA PET–staged node-positive (cN1M0) prostate cancer remain at high risk of distant progression despite whole-pelvis radiotherapy (WPRT) combined with long-term androgen deprivation therapy (ADT) ± androgen receptor pathway inhibitors (ARPI). While intraprostatic dose escalation improves outcomes in high-risk disease, and nodal boost strategies are increasingly implemented, their relative contribution to metastasis-free survival (MFS) in the molecular imaging era remains undefined. No randomized trial has prospectively dissected prostate-first versus combined prostate and nodal dose escalation within a unified ultrahypofractionated pelvic platform. PRO-BOOST-N evaluates whether ablative prostate dose escalation improves MFS and whether intensified PSMA PET–positive nodal boost doses provide incremental systemic benefit in the context of modern systemic therapy integration.

Materials/Methods: PRO-BOOST-N is a prospective, multicenter, seamless phase II/III randomized trial using a 2×2 factorial design with hierarchical testing. Eligible patients are men =18 years with histologically confirmed cT1–4 cN1 cM0 prostate adenocarcinoma staged with mandatory PSMA PET/CT and multiparametric MRI. All patients receive ultrahypofractionated WPRT (25 Gy in 5 fractions) with long-term ADT (24 months with ARPI or 36 months without; ARPI permitted but not randomized). Randomization is stratified by ARPI use, ISUP grade group, cT stage, number of PSMA PET–positive nodes, and center.

Factor A (Primary Comparison – Prostate Dose Escalation): A0: Prostate SIB to 36.25 Gy/5 fractions A1: WPRT 25 Gy/5 fractions followed by ablative prostate boost (HDR 15 Gy×1, LDR 110 Gy, or SBRT 15 Gy×1; capability-based with optional sub-randomization)

Factor B (Key Secondary – Nodal Dose Escalation): B1: PSMA PET–positive nodes 27.75 Gy/5 fractions (~56 Gy EQD2) B2: 30 Gy/5 fractions (~64–65 Gy EQD2) with protocol-defined OAR-driven de-escalation permitted only in this arm.

The primary endpoint is metastasis free-survival (MFS) (prostate boost vs no boost). The nodal dose comparison is hierarchically tested. Secondary endpoints include overall survival (OS), radiographic (rPFS) (PSMA PET–based), CRPC-free survival, time to next systemic therapy (TTNS), intraprostatic and regional nodal control, CTCAE v5.0 toxicity, and PROMs (EPIC-26, IPSS, IIEF-5, EORTC QLQ-C30/PR25). The seamless phase II component evaluates feasibility and early safety prior to continuation into the phase III efficacy stage.

Results: Recruiting.

Conclusion: PRO-BOOST-N is the first randomized trial to formally separate prostate and nodal dose intensification within a PSMA PET–guided ultrahypofractionated WPRT platform integrated with contemporary systemic therapy. The study is designed to define whether durable intraprostatic control or nodal escalation is the dominant determinant of metastasis prevention in cN1 disease.

Trial registration: ClinicalTrials.gov NCT07426055.