PRO-BOOST-N: Prostate-First Versus Combined Prostate and Nodal Dose Escalation in PSMA PET-Staged Node-Positive Prostate Cancer

Condition(s) studied

Investigational drug(s) / intervention(s)

Ultrahypofractionated Whole-Pelvis Radiotherapy: Whole-pelvis external beam radiotherapy delivered using VMAT or IMRT techniques to elective pelvic lymph node volumes and the prostate. Treatment is prescribed as 25 Gy in 5 fractions and delivered with daily image guidance, serving as the standardized radiotherapy backbone for all study arms.

SBRT-Based Prostate Radiotherapy (No Boost): Definitive prostate radiotherapy delivered as a simultaneous integrated boost within the ultrahypofractionated whole-pelvis radiotherapy plan. The prostate receives a total dose of 36.25 Gy in 5 fractions without additional prostate boost beyond this dose.

Ablative Prostate Boost: Ablative whole-gland prostate dose escalation delivered after completion of ultrahypofractionated whole-pelvis radiotherapy. The prostate boost modality is prospectively assigned before main randomization. If two or more protocol-defined boost modalities are available and technically suitable, the modality is assigned by embedded subrandomization; if only one modality is feasible, that modality is assigned as the single feasible option. Boost modalities include high-dose-rate brachytherapy (15 Gy in 1 fraction), low-dose-rate brachytherapy (110 Gy permanent implant), or single-fraction SBRT boost (15 Gy in 1 fraction).

Intermediate Nodal Dose Escalation: Dose escalation to PSMA PET-positive pelvic lymph nodes delivered using a simultaneous integrated boost technique within the ultrahypofractionated whole-pelvis radiotherapy plan. The prescribed nodal boost dose is 27.75 Gy in 5 fractions.

Higher Nodal Dose Escalation: Dose escalation to PSMA PET-positive pelvic lymph nodes delivered using a simultaneous integrated boost technique within the ultrahypofractionated whole-pelvis radiotherapy plan. The prescribed nodal boost dose is 30 Gy in 5 fractions, with protocol-defined organ-at-risk-driven dose de-escalation permitted if required.

Androgen Deprivation Therapy (ADT): Androgen deprivation therapy administered as long-term systemic treatment in all study arms. ADT is delivered using luteinizing hormone-releasing hormone (LHRH) agonists or antagonists according to institutional practice and protocol-defined duration. ADT is initiated before or during radiotherapy and continued after completion of radiotherapy as specified in the study protocol.

Androgen Receptor Pathway Inhibitors (ARPIs): Androgen receptor pathway inhibitors may be administered in combination with androgen deprivation therapy according to contemporary clinical practice, local availability, and patient-specific considerations. The use of ARPIs is permitted but not randomized and includes approved agents targeting androgen receptor signaling.

Study summary

PRO-BOOST-N is a prospective, multicenter, randomized phase II/III clinical trial for patients with prostate cancer and pelvic lymph node involvement (cN1M0) confirmed by PSMA PET/CT, without distant metastatic disease.

Patients with PSMA PET-staged node-positive prostate cancer are potentially curable, but remain at substantial risk of distant progression despite contemporary treatment with radiotherapy, long-term androgen deprivation therapy, and, when appropriate, androgen receptor pathway inhibitors. The optimal way to intensify radiotherapy to the prostate and PSMA PET-positive pelvic lymph nodes remains uncertain in the era of modern molecular imaging.

All participants receive a standardized ultrahypofractionated whole-pelvis radiotherapy backbone delivered in five fractions, combined with long-term systemic therapy according to contemporary clinical practice. The study uses a 2 x 2 factorial randomized design to evaluate two treatment questions.

The primary comparison evaluates whether prostate dose escalation improves metastasis-free survival compared with no additional prostate boost. Patients assigned to prostate boost receive one of three protocol-defined boost techniques: high-dose-rate brachytherapy, low-dose-rate brachytherapy, or single-fraction SBRT. If more than one prostate boost technique is available at the treating center and technically suitable for the patient, the boost technique is assigned by embedded subrandomization.

The key secondary, hierarchically tested comparison evaluates nodal dose escalation by comparing two predefined dose levels to PSMA PET-positive pelvic lymph nodes. Organ-at-risk-driven nodal dose de-escalation is permitted within the higher-dose arm when required for patient safety and protocol compliance.

The primary endpoint is metastasis-free survival (MFS) . Secondary endpoints include overall survival (OS), radiographic progression-free survival (rPFS), intraprostatic and regional nodal control, time to castration-resistant prostate cancer, time to next systemic therapy, treatment-related adverse events graded according to CTCAE version 6.0, and patient-reported quality of life, including urinary, bowel, sexual, and global health domains.

PRO-BOOST-N aims to determine the optimal radiotherapy intensification strategy for patients with PSMA PET-staged node-positive prostate cancer by prospectively evaluating prostate-directed and nodal-directed dose escalation within a modern, standardized radiotherapy platform.

Eligibility

Primary outcome measure(s)

• Metastasis-Free Survival (MFS) — Up to 10 years from randomization
  Metastasis-free survival is defined as the time from randomization to the first occurrence of distant metastatic disease or death from any cause, whichever occurs first. Distant metastases include non-regional lymph node, bone, or visceral metastases confirmed by PSMA PET imaging or other clinically indicated imaging modalities. Pelvic nodal progression alone does not constitute a metastasis-free survival event.

Trial sites (1)

More Affidea Nu-med Center of Oncological DIagnostics and Therapy trials in Poland

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