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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer (Adenocarcinoma); Localized Prostate Cancer; Dose Escalation: Solid Tumors; Stereotactic Body Radiation Therapy (SBRT); Prostate Brachytherapy
• Intervention / Treatment: Radiation: Stereotactic Body Radiotherapy (SBRT) Monotherapy; Drug: Androgen Deprivation Therapy (ADT); Radiation: External Beam Radiotherapy (EBRT) Backbone; Radiation: High-Dose-Rate Brachytherapy Boost; Radiation: Low-Dose-Rate Brachytherapy Boost; Radiation: Stereotactic Body Radiotherapy (SBRT) Boost

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 or locally advanced prostate cancer staged as cN0/cM0 on mandatory baseline prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT).

Scientific Background and Rationale Radiobiological and clinical evidence supports the concept that prostate cancer is sensitive to hypofractionation and dose escalation. Multiple randomized and prospective studies have shown that higher biologically effective radiation doses delivered to the prostate can improve biochemical control and delay disease progression. Modern dose-escalation techniques, including high-dose-rate (HDR) brachytherapy boost, low-dose-rate (LDR) brachytherapy boost, and stereotactic boost strategies, allow intraprostatic dose intensification while limiting dose to surrounding organs at risk.

Brachytherapy boost strategies enable delivery of very high biologically effective doses to the prostate. HDR boost offers optimized dose distribution and rapid dose fall-off, whereas LDR brachytherapy provides continuous low-dose radiation exposure over time through permanent seed implantation. SBRT boost is a non-invasive alternative capable of delivering a highly conformal ablative dose in a single fraction.

Although these approaches are used in clinical practice and have individually demonstrated favorable oncologic outcomes, direct prospective randomized comparison within a uniform treatment framework remains limited. In addition, many prior dose-escalation studies were conducted before the widespread use of PSMA PET/CT, which may have resulted in inclusion of patients with occult nodal or distant metastatic disease. PRO-BOOST-LC is designed to evaluate prostate dose-escalation strategies in a contemporary population staged with mandatory PSMA PET/CT.

Study Hypothesis The central hypothesis is that assignment to a whole-gland ablative boost strategy following a standardized ultrahypofractionated external beam radiotherapy backbone will improve failure-free survival compared with SBRT monotherapy, without an unacceptable increase in clinically significant toxicity or deterioration in patient-reported quality of life.

Overall Study Design PRO-BOOST-LC is a prospective, multicenter, randomized, controlled, multi-arm, multi-stage phase II/III trial with a seamless internal safety and feasibility stage.

Eligible patients are randomized using a centralized capability-based allocation procedure. The patient-level randomization set is determined before allocation according to center credentialing and technical suitability for the individual patient. The protocol-defined treatment strategies are:

SBRT monotherapy as the control strategy. Ultrahypofractionated external beam radiotherapy followed by HDR brachytherapy boost.

Ultrahypofractionated external beam radiotherapy followed by LDR brachytherapy boost.

Ultrahypofractionated external beam radiotherapy followed by single-fraction SBRT boost.

The primary comparison is pooled whole-gland boost strategy versus SBRT monotherapy. Comparisons among individual boost modalities are exploratory.

Seamless Phase II/III Structure The trial includes an internal phase II safety and feasibility component. During this stage, treatment delivery compliance, acute toxicity, technical feasibility, and major radiotherapy protocol deviations are prospectively monitored. Predefined safety and feasibility thresholds are reviewed by the Data Safety Monitoring Board. An experimental treatment arm may be continued, modified, temporarily suspended, or discontinued based on safety, feasibility, or protocol-compliance findings. Arms meeting predefined criteria proceed into the confirmatory phase III stage without interruption of accrual.

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 and non-metastatic disease.

The ultrahypofractionated external beam radiotherapy backbone consists of five high-dose fractions delivered using intensity-modulated radiotherapy or volumetric modulated arc therapy with daily image guidance. This backbone serves as a standardized platform across experimental boost arms.

Whole-gland boost delivery differs by modality. HDR brachytherapy boost consists of a single high-dose fraction delivered through temporary transperineal catheter implantation under image guidance. LDR brachytherapy boost consists of permanent seed implantation. 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.

Androgen deprivation therapy is administered according to contemporary guideline-based risk stratification. Protocol-planned androgen receptor pathway inhibitors may be used in selected very high-risk or locally advanced patients when declared before randomization and handled according to the protocol and statistical analysis plan.

Imaging Integration Baseline staging requires PSMA PET/CT and multiparametric MRI within protocol-defined timeframes before randomization. Imaging is used to confirm cN0/cM0 status and to support radiotherapy planning.

Follow-up imaging is performed when clinically indicated. PSMA PET/CT is prioritized for evaluation of suspected recurrence or distant metastatic progression. Local recurrence requires radiologic progression confirmation and is not defined solely by PSA kinetics or isolated biopsy findings.

Endpoint Strategy

The primary endpoint is failure-free survival (FFS). Failure-free survival includes biochemical recurrence, radiologically documented local, regional, or distant progression, progression-driven salvage treatment, or death from any cause.

Metastasis-free survival (MFS) is a key hierarchical confirmatory endpoint and is tested only if the primary failure-free survival comparison is statistically significant. Secondary and exploratory analyses evaluate local and regional control, treatment-related toxicity, patient-reported quality of life, PSA kinetics, time to salvage therapy, cancer-specific survival, and overall survival.

Patient-Reported Outcomes Patient-reported outcomes are a core component of the study. Validated questionnaires are used to assess urinary, bowel, sexual, hormonal, and general health-related quality of life domains at baseline and during follow-up. These assessments are intended to determine whether improved oncologic control can be achieved while preserving long-term function and quality of life.

Toxicity Monitoring Adverse events are graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. Acute toxicity is defined as adverse events occurring within 90 days after completion of protocol radiotherapy. Late toxicity includes adverse events occurring beyond 90 days.

Genitourinary, gastrointestinal, sexual, systemic therapy-related, and procedure-related adverse events are recorded prospectively. For clinically significant events, the maximum grade, attribution, onset date, resolution or improvement date, ongoing status, and relationship to treatment components are documented. Safety data are reviewed periodically by the Data Safety Monitoring Board.

Statistical Considerations The study is powered for the primary comparison of pooled whole-gland boost strategies versus SBRT monotherapy for failure-free survival. Time-to-event analyses will use prespecified statistical methods including Kaplan-Meier estimation and Cox proportional hazards modeling. The hierarchical endpoint strategy is designed to preserve the overall type I error rate.

Clinical Significance By integrating PSMA PET/CT staging, contemporary ultrahypofractionated radiotherapy, brachytherapy boost, SBRT boost, standardized radiotherapy quality assurance, toxicity monitoring, and patient-reported outcomes, PRO-BOOST-LC aims to generate high-quality evidence on how best to use prostate dose escalation in localized and locally advanced prostate cancer.

The study is intended to clarify which modern radiotherapy dose-escalation strategy provides the most favorable balance between durable cancer control, treatment-related toxicity, and long-term preservation of urinary, bowel, sexual, and overall quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Mateusz Edward Bilski, MD, PhD; Phone Number: 048 84 535 99 10; Email: bilskimat@gmail.com

Study Locations

• Poland
  • Lublin Voivodeship
    • Zamość, Lublin Voivodeship, Poland, 22-400
      • Recruiting
      • Affidea Nu-Med, Center of Oncological Diagnostics and Therapy
      • Contact: Mateusz Edward Bilski, MD, PhD; Phone Number: 048 84 535 99 10; Email: bilskimat@gmail.com
      • Principal Investigator: Mateusz Edward Bilski, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male patients aged ≥18 years.
• Histologically confirmed adenocarcinoma of the prostate.
• Localized or locally advanced prostate cancer classified as cT1-4, cN0, cM0.
• Negative pelvic nodal and distant metastatic disease on baseline PSMA PET.
• NCCN favourbale or unfavourbale intermediate-, high-, or very high-risk disease.
• Candidate for definitive radiotherapy with curative intent.
• ECOG performance status 0-2.
• Baseline PSA available prior to randomization.
• Ability to undergo external beam radiotherapy and brachytherapy or SBRT according to protocol.
• Planned androgen deprivation therapy (ADT) permitted according to protocol-defined risk group.
• Ability to understand and willingness to sign written informed consent.

Exclusion Criteria:

• Evidence of pelvic nodal (cN1) or distant metastatic disease (cM1) on baseline imaging.
• Prior definitive local treatment for prostate cancer, including prostatectomy, brachytherapy, or definitive external beam radiotherapy.
• Prior pelvic radiotherapy for any malignancy.
• Prior systemic therapy for prostate cancer other than protocol-allowed neoadjuvant ADT.
• History of other active malignancy requiring systemic treatment (except adequately treated non-melanoma skin cancer).
• Contraindications to radiotherapy or anesthesia required for brachytherapy procedures.
• Severe uncontrolled comorbidities that would preclude protocol treatment.
• Inability to comply with study procedures or follow-up schedule.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SBRT Monotherapy; Patients assigned to this arm receive definitive stereotactic body radiotherapy (SBRT) delivered to the prostate as monotherapy, without any additional intraprostatic boost. Treatment is administered using an ultrahypofractionated regimen with highly conformal dose delivery, daily image guidance, and motion management according to protocol-defined standards. Target volumes and organs at risk are contoured following centralized guidelines, and treatment planning adheres to predefined coverage objectives and dose constraints. This arm represents a contemporary, non-invasive definitive radiotherapy strategy for localized prostate cancer and serves as the active comparator for all boost-based dose escalation approaches evaluated in the study. Androgen deprivation therapy may be administered according to protocol-defined risk group and current clinical practice guidelines.	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.; 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.
Experimental: EBRT With HDR Brachytherapy Boost; Patients assigned to this arm receive a standardized ultrahypofractionated external beam radiotherapy (EBRT) backbone delivered to the prostate using modern image-guided techniques, followed by an intraprostatic boost delivered with high-dose-rate (HDR) brachytherapy. The EBRT component provides uniform baseline irradiation, after which a single-fraction HDR brachytherapy boost is administered using transperineal catheter placement and afterloading according to protocol-defined technical and dosimetric criteria. This approach enables delivery of a very high biologically effective dose to the prostate while maintaining strict organ-at-risk constraints. Target coverage objectives, applicator placement principles, and dose limits are standardized across centers. Androgen deprivation therapy may be administered according to protocol-defined risk group and standard clinical practice.	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.; 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.
Experimental: EBRT With LDR Brachytherapy Boost; Patients assigned to this arm receive a standardized ultrahypofractionated external beam radiotherapy (EBRT) backbone delivered to the prostate, followed by an intraprostatic boost using low-dose-rate (LDR) permanent seed brachytherapy. After completion of EBRT, LDR brachytherapy is performed with transperineal implantation of radioactive seeds according to protocol-defined planning, implantation, and post-implant dosimetric criteria. This strategy achieves dose escalation through continuous low-dose-rate irradiation while respecting predefined target coverage goals and organ-at-risk constraints. Implant quality and dosimetry are centrally specified to ensure consistency across participating centers. Androgen deprivation therapy may be administered based on protocol-defined risk group and standard clinical practice.	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.; 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: 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.
Experimental: EBRT With SBRT Boost; Patients assigned to this arm receive a standardized ultrahypofractionated external beam radiotherapy (EBRT) backbone delivered to the prostate, followed by an intraprostatic stereotactic body radiotherapy (SBRT) boost. The EBRT component establishes baseline target coverage, after which a highly conformal SBRT boost is delivered in a single fraction using advanced image guidance and motion management. This arm represents a fully non-invasive dose escalation strategy that avoids brachytherapy while enabling delivery of a high biologically effective intraprostatic dose. Treatment planning and delivery follow protocol-defined target coverage objectives and organ-at-risk constraints to ensure safety and consistency. Androgen deprivation therapy may be administered according to protocol-defined criteria.	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.; 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: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-Free Survival (FFS)	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.	From randomization up to 10 years
Metastasis-Free Survival (MFS) hierarchical	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.	From randomization up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraprostatic Local Control (iLC)	Intraprostatic local control is defined as the time from randomization to confirmed local recurrence within the prostate gland. Local recurrence is determined by radiologic progression on multiparametric MRI or PSMA PET/CT confirmed on repeat imaging performed at least 6 months later, or by biopsy-proven viable adenocarcinoma in the presence of radiologic progression. This endpoint evaluates the effectiveness of intraprostatic dose escalation strategies.	From randomization up to 10 years
Regional Pelvic Nodal Control (rNC)	Regional pelvic nodal control is defined as the time from randomization to pelvic nodal progression detected on imaging. Pelvic nodal progression includes involvement of obturator, internal iliac, external iliac, or presacral lymph nodes. Progression in common iliac lymph nodes is classified as distant metastatic disease and is not considered a regional nodal event. Nodal progression must be confirmed on imaging according to protocol-defined criteria.	From randomization up to 10 years
Expanded Prostate Cancer Index Composite-26 (EPIC-26)	Change from baseline in Expanded Prostate Cancer Index Composite-26 (EPIC-26) domain scores. EPIC-26 assesses urinary, bowel, sexual, and hormonal domains. Each domain score ranges from 0 to 100. Higher scores indicate better quality of life (fewer symptoms and better function).	From baseline up to 10 years
EORTC QLQ-C30 Global Health Status Score	Change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status score. Scores range from 0 to 100. Higher scores indicate better global health-related quality of life.	From baseline up to 10 years
PSA Nadir	Lowest prostate-specific antigen value recorded after completion of radiotherapy. Measured in ng/mL. Lower values indicate better biochemical response.	From randomization up to 10 years
Time to Initiation of Salvage Therapy	Time from randomization to initiation of salvage treatment, including re-initiation of androgen deprivation therapy, initiation of androgen receptor pathway inhibitors, local salvage therapies, or systemic therapy for metastatic disease.	From randomization up to 10 years
Cancer-Specific Survival (CSS)	Time from randomization to death attributable to prostate cancer.	From randomization up to 10 years
Overall Survival (OS)	Time from randomization to death from any cause.	From randomization up to 10 years
International Prostate Symptom Score (IPSS)	Change from baseline in International Prostate Symptom Score (IPSS). IPSS ranges from 0 to 35. Higher scores indicate worse urinary symptoms.	Time Frame: From baseline up to 10 years
EORTC QLQ-PR25 Prostate Cancer Module	Change from baseline in European Organisation for Research and Treatment of Cancer Prostate Cancer Module (EORTC QLQ-PR25) domain scores. Scores range from 0 to 100. For functional scales, higher scores indicate better functioning. For symptom scales, higher scores indicate worse symptoms.	From baseline up to 10 years
Time to PSA Nadir	Time from completion of radiotherapy to lowest PSA value. Measured in months.	Up to 10 years
PSA Doubling Time	PSA doubling time calculated using at least three consecutive PSA values after nadir. Measured in months. Shorter doubling time indicates more aggressive disease.	Up to 10 years
PSA Bounce	Incidence of PSA bounce defined as a rise ≥0.2 ng/mL above nadir followed by spontaneous decline without intervention. Measured as proportion of patients experiencing bounce.	Up to 10 years
Acute Genitourinary and Gastrointestinal Toxicity	Acute genitourinary (GU) and gastrointestinal (GI) toxicity is defined as treatment-related adverse events occurring within 90 days from completion of radiotherapy. Toxicity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 6.0. The incidence and severity of acute adverse events will be systematically recorded at scheduled follow-up visits.	From start of radiotherapy to 90 days after completion
Late Genitourinary and Gastrointestinal Toxicity	Late genitourinary (GU) and gastrointestinal (GI) toxicity is defined as treatment-related adverse events occurring more than 90 days after completion of radiotherapy. Toxicity will be graded using CTCAE version 6.0. This endpoint assesses long-term safety and tolerability of dose-escalated and boost-based radiotherapy strategies.	More than 90 days after completion of radiotherapy up to 10 years

Collaborators and Investigators

• Sponsor: Affidea Nu-med Center of Oncological DIagnostics and Therapy
• Investigators: Principal Investigator: Mateusz Bilski, MD PhD, Affidea Nu-Med, Center of Oncological Diagnostics and Therapy, Zamość, Poland

Publications and helpful links

General Publications

• Rodda S, Tyldesley S, Morris WJ, Keyes M, Halperin R, Pai H, McKenzie M, Duncan G, Morton G, Hamm J, Murray N. ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):286-295. doi: 10.1016/j.ijrobp.2017.01.008. Epub 2017 Jan 6.
• Morris WJ, Tyldesley S, Rodda S, Halperin R, Pai H, McKenzie M, Duncan G, Morton G, Hamm J, Murray N. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):275-285. doi: 10.1016/j.ijrobp.2016.11.026. Epub 2016 Nov 24.
• Gorovets D, Hopkins M, Kollmeier M, Moore A, Goel A, Shasha D, Brennan V, McBride S, Cohen G, Damato AL, Zelefsky MJ. Early outcomes of high-dose-rate brachytherapy combined with ultra-hypofractionated radiation in higher-risk prostate cancer. Brachytherapy. 2021 Nov-Dec;20(6):1099-1106. doi: 10.1016/j.brachy.2021.08.006. Epub 2021 Sep 26.
• Bilski M, Lelek P, Stankiewicz M, Miszczyk M, Burchardt W, Kluska A, Napieralska A, Kukielka A, Cisek P, Konat-Baska K, Stando R, Dec M, Piliszczuk E, Matys R, Bajon T, Trojanowski M, Moll M, Gomez-Iturriaga A, Chichel A, Wojcieszek P, Shariat SF, Chyrek AJ. MUlticentre REtrospective comparison of definitive EBRT with or without HDR BRAchytherapy boost in patients with locally-advanced prostate cancer and regional lymph NOde metastases (MUREBRANO) - A propensity score matched analysis. Radiother Oncol. 2025 Nov;212:111112. doi: 10.1016/j.radonc.2025.111112. Epub 2025 Aug 27.
• National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version current at study initiation. Available at: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
• Sidibe I, Beaudry MM, Carignan D, Froment MA, Foster W, Bachand F, Vigneault E, Magnan S, Aubin S, Morrier J, Poulin E, Lacroix F, Lavallee MC, Beaulieu L, Martin AG. Ultra-hypofractionated radiotherapy combined with HDR brachytherapy: An optimized treatment. Radiother Oncol. 2026 Jan;214:111199. doi: 10.1016/j.radonc.2025.111199. Epub 2025 Oct 9.
• Mendez LC, Crook J, Martell K, Schaly B, Hoover DA, Dhar A, Velker V, Ahmad B, Lock M, Halperin R, Warner A, Bauman GS, D'Souza DP. Is Ultrahypofractionated Whole Pelvis Radiation Therapy (WPRT) as Well Tolerated as Conventionally Fractionated WPRT in Patients With Prostate Cancer? Early Results From the HOPE Trial. Int J Radiat Oncol Biol Phys. 2024 Jul 1;119(3):803-812. doi: 10.1016/j.ijrobp.2023.11.058. Epub 2023 Dec 8.
• Beaudry MM, Carignan D, Foster W, Lavallee MC, Aubin S, Lacroix F, Poulin E, Lachance B, Despres P, Beaulieu L, Vigneault E, Martin AG. Comparison of four-year toxicities and local control of ultra-hypofractionated vs moderate-hypofractionated image guided prostate radiation with HDR brachytherapy boost: A phase I-II single institution trial. Clin Transl Radiat Oncol. 2023 Feb 8;40:100593. doi: 10.1016/j.ctro.2023.100593. eCollection 2023 May.
• Kollmeier MA, Gorovets D, Flynn J, McBride S, Brennan V, Beaudry J, Cohen G, Damato A, Zhang Z, Zelefsky MJ. Combined brachytherapy and ultra-hypofractionated radiotherapy for intermediate-risk prostate cancer: Comparison of toxicity outcomes using a high-dose-rate (HDR) versus low-dose-rate (LDR) brachytherapy boost. Brachytherapy. 2022 Sep-Oct;21(5):599-604. doi: 10.1016/j.brachy.2022.04.006. Epub 2022 Jun 17.
• Martin J, Keall P, Siva S, Greer P, Christie D, Moore K, Dowling J, Pryor D, Chong P, McLeod N, Raman A, Lynam J, Smart J, Oldmeadow C, Tang CI, Murphy DG, Millar J, Tai KH, Holloway L, Reeves P, Hayden A, Lim T, Holt T, Sidhom M. TROG 18.01 phase III randomised clinical trial of the Novel Integration of New prostate radiation schedules with adJuvant Androgen deprivation: NINJA study protocol. BMJ Open. 2019 Aug 20;9(8):e030731. doi: 10.1136/bmjopen-2019-030731.
• Wang SC, Ting WC, Chang YC, Yang CC, Lin LC, Ho HW, Chu SS, Lin YW. Whole Pelvic Radiotherapy With Stereotactic Body Radiotherapy Boost vs. Conventionally Fractionated Radiotherapy for Patients With High or Very High-Risk Prostate Cancer. Front Oncol. 2020 May 29;10:814. doi: 10.3389/fonc.2020.00814. eCollection 2020.
• Lischalk JW, Akerman M, Repka MC, Sanchez A, Mendez C, Santos VF, Carpenter T, Wise D, Corcoran A, Lepor H, Katz A, Haas JA. High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation. Front Oncol. 2024 Feb 6;14:1325200. doi: 10.3389/fonc.2024.1325200. eCollection 2024.
• Wegener E, Sidhom M, Pryor D, Bucci J, Yeoh K, Richardson M, Greer P, Wilton L, Gallagher S, Schmidt L, Arumugam S, Keats S, Brown S, Glyde A, Martin JM. Prostate Virtual High-dose-rate Brachytherapy Boost: 5-Year Results from the PROMETHEUS Prospective Multicentre Trial. Eur Urol Oncol. 2024 Oct;7(5):1042-1050. doi: 10.1016/j.euo.2024.01.008. Epub 2024 Feb 1.
• Miszczyk M, Magrowski L, Krzysztofiak T, Stando R, Majewski W, Stawiski K, Masri O, Ciepal J, Depowska G, Chimiak K, Bylica G, Czapla B, Masri M, Cichur F, Jablonska I, Gmerek M, Nowicka Z, Wojcieszek P, Sadowski J, Suwinski R, Rajwa P, Goldner G, Moll M. Brachytherapy boost improves survival and decreases risk of developing distant metastases compared to external beam radiotherapy alone in intermediate and high risk group prostate cancer patients. Radiother Oncol. 2023 Jun;183:109632. doi: 10.1016/j.radonc.2023.109632. Epub 2023 Mar 23.
• Strouthos I, Karagiannis E, Antorkas G, Roussakis Y, Cloconi C, Savva A, Christoforou A, Vrachimis A, Zamboglou C, Ferentinos K. Combined Hypofractionated Radiation Therapy and Brachytherapy for Managing Prostate-Specific Membrane Antigen Positron Emission Tomography-Staged Organ-Confined Prostate Cancer: Primary Endpoint Analysis of a Prospective Study. Pract Radiat Oncol. 2025 Nov-Dec;15(6):e606-e616. doi: 10.1016/j.prro.2025.03.013. Epub 2025 Jun 20.
• Hoskin PJ, Rojas AM, Ostler PJ, Bryant L, Lowe GJ. Randomised trial of external-beam radiotherapy alone or with high-dose-rate brachytherapy for prostate cancer: Mature 12-year results. Radiother Oncol. 2021 Jan;154:214-219. doi: 10.1016/j.radonc.2020.09.047. Epub 2020 Oct 2.
• Oh J, Tyldesley S, Pai H, McKenzie M, Halperin R, Duncan G, Morton G, Keyes M, Hamm J, Morris WJ. An Updated Analysis of the Survival Endpoints of ASCENDE-RT. Int J Radiat Oncol Biol Phys. 2023 Apr 1;115(5):1061-1070. doi: 10.1016/j.ijrobp.2022.11.005. Epub 2022 Dec 15.

Helpful Links

• NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer, providing contemporary standards for risk stratification, imaging including PSMA PET, and multimodality radiotherapy strategies relevant to the PRO-BOOST-LC trial.
• European Association of Urology (EAU) Guidelines on Prostate Cancer, including recommendations on PSMA PET staging, definitions of metastasis-free survival, and contemporary management of localized and locally advanced disease.
• ClinicalTrials.gov registry providing public information on interventional clinical studies, including protocol structure, predefined endpoints, and transparency standards applied in the PRO-BOOST-LC trial.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2026
• Primary Completion (Estimated): December 1, 2033
• Study Completion (Estimated): December 1, 2035

Study Registration Dates

• First Submitted: February 7, 2026
• First Submitted That Met QC Criteria: February 15, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 18, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Radiotherapy; Brachytherapy; SBRT; Dose Escalation; Stereotactic Body Radiotherapy; PSMA PET; Prostate-Specific Membrane Antigen; High-Dose-Rate Brachytherapy; Ultrahypofractionation; Low-Dose-Rate Brachytherapy; Metastasis-Free Survival; Failure-Free Survival
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Prostatic Neoplasms; Adenocarcinoma; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Pharmacologic Actions; Chemical Actions and Uses; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Androgen Antagonists; Radiosurgery
• Other Study ID Numbers: PRO-BOOST-LC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) that underlie the results reported in publications arising from this study will be made available upon reasonable request. Shared data will include baseline characteristics, treatment allocation, dosimetric parameters, outcome variables, and follow-up data necessary to reproduce the primary and secondary analyses. Data will be shared in accordance with applicable data protection regulations and only after approval of a methodologically sound research proposal.
• IPD Sharing Time Frame: IPD and supporting documentation will become available beginning 6 months after publication of the primary results and will remain available for a minimum of 5 years following publication.
• IPD Sharing Access Criteria: Access to de-identified IPD will be granted to qualified researchers who submit a written request describing the research question, analysis plan, and intended use of the data. Requests will be reviewed by the study steering committee to ensure scientific merit, feasibility, and compliance with ethical and data protection requirements. Approved users will be required to sign a data use agreement prior to data release.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No