PRO-BOOST-LC: Whole-Gland Boost Strategies Versus SBRT Monotherapy in PSMA-Staged Localized and Locally Advanced Prostate Cancer

Condition(s) studied

Investigational drug(s) / intervention(s)

Stereotactic Body Radiotherapy (SBRT) Monotherapy: Stereotactic body radiotherapy (SBRT) delivered to the prostate as definitive monotherapy using an ultrahypofractionated schedule. Treatment is planned with highly conformal techniques and daily image guidance according to protocol-defined target coverage objectives and organ-at-risk constraints. This intervention represents a non-invasive definitive radiotherapy strategy without additional intraprostatic boost.

External Beam Radiotherapy (EBRT) Backbone: Ultrahypofractionated external beam radiotherapy delivered to the prostate using volumetric modulated arc therapy (VMAT) or equivalent intensity-modulated techniques. This intervention serves as a standardized treatment backbone prior to intraprostatic dose escalation and is delivered according to protocol-defined target volumes, margins, and dose constraints.

High-Dose-Rate Brachytherapy Boost: Intraprostatic high-dose-rate brachytherapy delivered as a single-fraction boost following completion of external beam radiotherapy. The procedure involves transperineal catheter placement with afterloading and is performed according to protocol-defined technical, dosimetric, and safety criteria to achieve focal dose escalation while respecting organ-at-risk constraints.

Low-Dose-Rate Brachytherapy Boost: Intraprostatic low-dose-rate permanent seed brachytherapy delivered as a boost following completion of external beam radiotherapy. Radioactive seeds are implanted transperineally according to protocol-defined planning and implantation guidelines to provide continuous low-dose-rate irradiation while maintaining predefined target coverage and organ-at-risk constraints.

Stereotactic Body Radiotherapy (SBRT) Boost: Intraprostatic stereotactic body radiotherapy delivered as a single-fraction boost following completion of external beam radiotherapy. This intervention provides non-invasive dose escalation using highly conformal planning and image guidance according to protocol-defined coverage objectives and organ-at-risk constraints.

Androgen Deprivation Therapy (ADT): Androgen deprivation therapy (ADT) administered according to protocol-defined risk group and standard clinical practice. ADT may include luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, with or without short-course antiandrogens, delivered as neoadjuvant, concurrent, and/or adjuvant therapy in accordance with contemporary clinical guidelines. ADT is not randomized and is applied uniformly within each risk group across all treatment arms.

Study summary

PRO-BOOST-LC is a prospective, multicenter, randomized phase II/III clinical trial for men with localized or locally advanced prostate cancer without lymph node or distant metastases, confirmed using prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT).

Radiotherapy is an established curative treatment option for prostate cancer. Several modern radiotherapy strategies can safely deliver high radiation doses to the prostate while limiting dose to surrounding organs. These include stereotactic body radiotherapy (SBRT), high-dose-rate (HDR) brachytherapy, low-dose-rate (LDR) brachytherapy, and combinations of external beam radiotherapy with a prostate boost. However, the optimal dose-escalation strategy for balancing cancer control, treatment-related toxicity, and long-term quality of life remains uncertain in patients staged with modern PSMA PET imaging.

The aim of PRO-BOOST-LC is to compare definitive SBRT monotherapy with whole-gland prostate boost strategies delivered after a short course of external beam radiotherapy. Participants will be randomly assigned, according to center capability and patient-level technical suitability, to one of the protocol-defined treatment options. The control group receives SBRT monotherapy. The experimental groups receive external beam radiotherapy followed by one of three whole-gland boost techniques: HDR brachytherapy, LDR brachytherapy, or single-fraction SBRT boost.

The primary objective is to determine whether assignment to a prostate boost strategy improves failure-free survival compared with SBRT monotherapy. Failure-free survival includes biochemical recurrence, local or regional progression, distant metastases, progression-driven salvage treatment, or death from any cause. Key secondary outcomes include metastasis-free survival, overall survival, physician-reported treatment-related toxicity, and patient-reported quality of life, including urinary, bowel, and sexual function.

Participants will undergo baseline clinical evaluation, PSA testing, prostate MRI, PSMA PET/CT, and quality-of-life assessments. After treatment, participants will be followed regularly with clinical assessments, PSA testing, toxicity evaluation, patient questionnaires, and imaging when clinically indicated. The study is designed to provide long-term evidence on how best to use modern radiotherapy dose escalation for patients with PSMA-staged localized or locally advanced prostate cancer.

Eligibility

Primary outcome measure(s)

• Failure-Free Survival (FFS) — From randomization up to 10 years
  Failure-Free Survival (FFS) is defined as the time from randomization to the earliest occurrence of any of the following events: biochemical recurrence according to the Phoenix definition (PSA nadir + 2 ng/mL), confirmed local recurrence within the prostate, regional pelvic nodal progression, distant metastatic disease, initiation of salvage therapy, or death from any cause. Local recurrence is defined by radiologic progression on multiparametric MRI or PSMA PET/CT confirmed on repeat imaging ≥6 months later, or biopsy-proven viable adenocarcinoma in the presence of radiologic progression. Regional nodal progression includes pelvic nodal relapse (obturator, internal iliac, external iliac, presacral nodes). Patients without an event will be censored at the date of last disease assessment.
• Metastasis-Free Survival (MFS) hierarchical — From randomization up to 10 years
  Metastasis-Free Survival (MFS) is defined as the time from randomization to the occurrence of distant metastatic disease or death from any cause, whichever occurs first. Distant metastases are defined as non-pelvic nodal disease (including common iliac nodes) or visceral or bone metastases detected preferentially by PSMA PET/CT and confirmed according to protocol-defined imaging criteria. MFS is analyzed as a key confirmatory endpoint within a hierarchical testing strategy and will be formally tested only if the primary comparison for Failure-Free Survival is statistically significant. MFS is assessed in accordance with EAU/ASTRO/STRATOS consensus definitions and is recognized as a validated surrogate for overall survival in localized and locally advanced prostate cancer.

Trial sites (1)

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

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