NCT07426055

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

PRO-BOOST-LC: A Prospective, Multi-arm Phase II/III Clinical Trial Evaluating the Efficacy and Safety of Whole-Gland Boost Using HDR Brachytherapy, LDR Brachytherapy, or Single-Fraction SBRT Following an Ultrahypofractionated EBRT (VMAT) Backbone (5 Gy x 5 Fractions) Compared to Standard SBRT Monotherapy in Patients With Localized and Locally Advanced Prostate Cancer Staged With PSMA PET/CT

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 1,200 (estimated)
• Sponsor: Affidea Nu-med Center of Oncological DIagnostics and Therapy · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

PRO-BOOST-LC is a prospective, multicenter, randomized clinical trial designed for patients with localized prostate cancer who do not have evidence of lymph node or distant metastases based on modern PSMA PET imaging. Prostate cancer is one of the most common cancers in men. For patients with disease confined to the prostate, radiotherapy is a well-established and effective curative treatment option. Over the past decades, research has shown that delivering higher radiation doses to the prostate can improve cancer control and reduce the risk of disease recurrence. However, higher radiation doses may also increase the risk of side effects affecting urinary, bowel, and sexual function. For this reason, different radiation techniques have been developed to safely deliver higher doses while protecting surrounding healthy organs. Several approaches to radiation dose escalation are currently used in clinical practice. These include stereotactic body radiotherapy (SBRT), which delivers radiation in a small number of highly precise treatments, as well as brachytherapy, where radioactive sources are placed directly inside the prostate for a short time (high-dose-rate brachytherapy) or permanently (low-dose-rate brachytherapy). Although all these approaches are accepted and widely used, it is not known which strategy provides the best balance between cancer control, treatment-related side effects, and long-term quality of life, particularly when modern imaging techniques are used to accurately stage the disease. The PRO-BOOST-LC study aims to directly compare different radiation dose escalation strategies using a standardized treatment framework. All participants enrolled in the study will have localized prostate cancer staged with PSMA PET imaging to exclude metastatic disease. Participants will then be randomly assigned to one of four treatment groups. One group will receive SBRT alone to the prostate. The other three groups will receive a short course of external beam radiotherapy followed by an additional focused radiation boost delivered using one of three methods: high-dose-rate brachytherapy, low-dose-rate brachytherapy, or SBRT. All treatment approaches used in this study are established methods routinely applied in clinical practice. Randomization ensures that each participant has an equal chance of being assigned to any of the treatment groups. This allows the study to fairly compare outcomes between the different strategies. The main objective of the trial is to determine whether adding a radiation boost improves treatment outcomes compared with SBRT alone. The primary outcome measure is failure-free survival, which includes cancer recurrence, disease progression, the need for additional cancer treatment, or death from any cause. Secondary outcomes include the development of distant metastases, overall survival, treatment-related side effects, and patient-reported quality of life. Participants will be closely monitored throughout the study. Before treatment, patients will undergo clinical evaluation, blood tests including prostate-specific antigen (PSA), imaging studies, and quality-of-life assessments. During and after treatment, participants will attend regular follow-up visits. These visits will include clinical examinations, PSA testing, assessment of treatment-related side effects, and completion of standardized questionnaires evaluating urinary, bowel, and sexual function, as well as overall quality of life. Imaging studies, including PSMA PET scans, will be performed when clinically indicated to assess for possible disease recurrence or progression. The study is designed to follow participants for many years in order to capture both early and long-term outcomes. By using modern radiotherapy techniques, standardized treatment protocols, and comprehensive follow-up, PRO-BOOST-LC aims to generate high-quality evidence that will help guide future treatment decisions for patients with localized prostate cancer. The results of this trial are expected to improve understanding of how best to use radiation dose escalation to maximize cancer control while minimizing side effects and preserving quality of life in the era of advanced imaging and precision radiotherapy. Participation in this study does not involve experimental or unproven treatments. All radiation techniques used in PRO-BOOST-LC are approved, widely available, and considered standard of care in many treatment centers worldwide. The study focuses on optimizing how these existing techniques are combined and delivered, rather than introducing new drugs or devices. Participation may involve additional follow-up assessments and questionnaires compared with routine care, but treatment decisions are made within established clinical practice guidelines. Patients may or may not directly benefit from participation, but the information gained from this study may help improve future treatment strategies for men with localized prostate cancer.

Detailed description

The PRO-BOOST-LC study is a prospective, multicenter, randomized phase II/III clinical trial designed to evaluate whether biologically intensified whole-gland prostate dose escalation improves clinically meaningful oncologic outcomes compared with contemporary stereotactic body radiotherapy (SBRT) monotherapy in patients with localized and locally advanced prostate cancer staged as cN0/cM0 on mandatory baseline PSMA PET/CT. Scientific Background and Rationale Radiobiological and clinical evidence supports the concept that prostate cancer exhibits a low alpha/beta ratio, suggesting enhanced sensitivity to hypofractionation and dose escalation. Multiple randomized and prospective studies have demonstrated that higher biologically effective doses delivered to the prostate are associated with improved biochemical control and delayed disease progression. Modern dose-escalation techniques-including high-dose-rate (HDR) brachytherapy boost, low-dose-rate (LDR) brachytherapy boost, and stereotactic boost strategies-enable intraprostatic dose intensification beyond what is typically achievable with external beam radiotherapy alone. Brachytherapy boost strategies allow delivery of ablative-equivalent dose levels exceeding 100 Gy EQD2 (α/β=1.5), resulting in durable biochemical control improvements in intermediate- and high-risk populations. HDR boost approaches offer the advantage of optimized dose distribution and rapid dose fall-off, whereas LDR brachytherapy provides continuous low-dose radiation exposure over time. SBRT boost strategies represent a non-invasive alternative capable of delivering highly conformal, ablative single-fraction treatments. Although these modalities have individually demonstrated favorable oncologic outcomes, direct head-to-head comparison using a uniform external beam backbone has not been performed in a prospective randomized setting. Additionally, prior trials were conducted largely in the pre-PSMA staging era, potentially including occult nodal or distant disease. Modern PSMA PET/CT allows improved staging accuracy and may refine the therapeutic benefit of local dose intensification. The PRO-BOOST-LC trial is designed to address this evidence gap by directly comparing three whole-gland boost modalities delivered after a standardized ultrahypofractionated external beam backbone against SBRT monotherapy in a contemporary, PSMA-staged population. Study Hypothesis The central hypothesis is that the addition of a whole-gland ablative boost following a standardized ultrahypofractionated external beam backbone will improve failure-free survival and metastasis-free survival compared with SBRT monotherapy, without unacceptable increases in clinically significant toxicity or deterioration in quality of life. Overall Study Design This is a prospective, multicenter, randomized, controlled, multi-arm, multi-stage phase II/III trial employing a seamless adaptive design. Eligible patients are randomized to one of four treatment strategies: SBRT monotherapy (control arm), or Ultrahypofractionated external beam radiotherapy backbone followed by HDR brachytherapy boost, Ultrahypofractionated external beam radiotherapy backbone followed by LDR brachytherapy boost, or Ultrahypofractionated external beam radiotherapy backbone followed by single-fraction SBRT boost. Randomization is centralized and stratified to ensure balance of major prognostic factors across arms. Seamless Phase II/III Structure The trial incorporates an initial safety and feasibility stage (phase II component) across all experimental boost arms. During this stage, treatment delivery compliance, acute toxicity, and technical feasibility are prospectively monitored. Predefined safety thresholds and feasibility criteria are applied. If an experimental arm demonstrates unacceptable toxicity, inadequate compliance, or operational infeasibility, that arm may be discontinued upon recommendation of the Data Safety Monitoring Board. Arms meeting predefined criteria proceed seamlessly into the confirmatory phase III stage without interruption of accrual. This adaptive structure preserves statistical integrity while allowing early optimization of the investigational platform. Treatment Principles All treatments are delivered with curative intent using contemporary image-guided radiotherapy techniques. Multiparametric MRI-based planning is mandatory for all patients. Baseline PSMA PET/CT is mandatory for staging confirmation of node-negative, non-metastatic disease. The ultrahypofractionated external beam backbone consists of five high-dose fractions delivered using intensity-modulated arc therapy (VMAT) with daily image guidance. This backbone serves as a standardized platform across experimental arms. Whole-gland boost delivery differs by modality: HDR brachytherapy boost consists of a single high-dose fraction delivered via temporary transperineal catheter implantation under image guidance. LDR brachytherapy boost consists of permanent seed implantation delivering continuous low-dose radiation. SBRT boost consists of a single ablative stereotactic fraction delivered with dedicated immobilization and high-precision image guidance. The control arm consists of SBRT monotherapy delivered in five fractions using stereotactic technique. Androgen deprivation therapy is administered according to contemporary guideline-based risk stratification. The protocol allows incorporation of androgen receptor pathway inhibitors in selected very high-risk patients, provided declaration prior to randomization and appropriate stratification. Imaging Integration Baseline staging requires PSMA PET/CT and multiparametric MRI within protocol-defined timeframes prior to randomization. Imaging ensures accurate classification of cN0 and cM0 status. Follow-up imaging for disease assessment prioritizes PSMA PET/CT for confirmation of distant metastasis. Local recurrence requires radiologic progression confirmation and cannot be defined solely by PSA kinetics or isolated biopsy findings. Primary Endpoint Strategy The primary analysis follows a hierarchical confirmatory framework: Failure-Free Survival (FFS) Metastasis-Free Survival (MFS) Failure-Free Survival includes biochemical recurrence, radiologic progression (local, regional, or distant), initiation of salvage therapy, or death from any cause. Metastasis-Free Survival includes confirmed distant metastasis or death from any cause and is tested only if superiority in FFS is demonstrated. This hierarchical approach preserves type I error control while enabling earlier readout in a heterogeneous NCCN risk population. Secondary Objectives Secondary analyses evaluate: Intraprostatic local control Regional pelvic nodal control Acute and late genitourinary and gastrointestinal toxicity Patient-reported quality of life outcomes PSA kinetics parameters Time to salvage therapy Cancer-specific survival Overall survival Patient-reported outcomes are assessed using validated prostate cancer-specific and general health-related quality of life instruments. Toxicity Monitoring Adverse events are graded using CTCAE version 5.0. Acute toxicity is defined as events occurring within 90 days following completion of radiotherapy. Late toxicity includes events occurring beyond 90 days. The Data Safety Monitoring Board periodically reviews safety data and may recommend protocol modifications if necessary. Statistical Considerations The study is powered to detect clinically meaningful improvements in failure-free survival between pooled boost strategies and SBRT monotherapy. Secondary exploratory comparisons between individual boost modalities will also be conducted. Time-to-event analyses will use Kaplan-Meier and Cox proportional hazards modeling. Hierarchical testing preserves overall alpha allocation. Interim safety analyses are prespecified during the phase II stage. Clinical Significance By integrating PSMA-based staging, contemporary ultrahypofractionation, and direct comparison of three ablative boost strategies within a unified platform, PRO-BOOST-LC represents a next-generation dose-escalation trial. The study aims to determine which prostate dose-intensification strategy provides the optimal balance between durable oncologic control and long-term functional preservation in the modern era.

Conditions

• Prostate Cancer (Adenocarcinoma)
• Prostate Brachytherapy
• Stereotactic Body Radiation Therapy (SBRT)
• Dose Escalation: Solid Tumors
• Localized Prostate Cancer

Interventions

Type	Name	Description
RADIATION	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.
RADIATION	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.
RADIATION	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.
RADIATION	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.
RADIATION	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.
DRUG	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.

Timeline

• Start date: 2026-03-19
• Primary completion: 2033-12-01
• Completion: 2035-12-01
• First posted: 2026-02-23
• Last updated: 2026-03-23

Locations

1 site across 1 country: Poland