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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Failure-Free Survival (FFS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients aged ≥18 years.
- •Histologically confirmed adenocarcinoma of the prostate.
- •Localized or locally advanced prostate cancer classified as cT1-4, cN0, cM
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Stereotactic Body Radiotherapy (SBRT) Monotherapy (Radiation)
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.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
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.
干预措施: External Beam Radiotherapy (EBRT) Backbone (Radiation)
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.
干预措施: High-Dose-Rate Brachytherapy Boost (Radiation)
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.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
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.
干预措施: External Beam Radiotherapy (EBRT) Backbone (Radiation)
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.
干预措施: Low-Dose-Rate Brachytherapy Boost (Radiation)
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.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
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.
干预措施: External Beam Radiotherapy (EBRT) Backbone (Radiation)
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.
干预措施: Stereotactic Body Radiotherapy (SBRT) Boost (Radiation)
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.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
结局指标
主要结局
Failure-Free Survival (FFS)
时间窗: 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
时间窗: 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.
次要结局
- Acute Genitourinary and Gastrointestinal Toxicity(From start of radiotherapy to 90 days after completion)
- Late Genitourinary and Gastrointestinal Toxicity(More than 90 days after completion of radiotherapy up to 10 years)
- Intraprostatic Local Control (iLC)(From randomization up to 10 years)
- PSA Nadir(From randomization up to 10 years)
- Regional Pelvic Nodal Control (rNC)(From randomization up to 10 years)
- Late Genitourinary and Gastrointestinal Toxicity(From start of radiotherapy to 90 days after completion)
- Expanded Prostate Cancer Index Composite-26 (EPIC-26)(From baseline up to 10 years)
- EORTC QLQ-C30 Global Health Status Score(From baseline up to 10 years)
- Time to Initiation of Salvage Therapy(From randomization up to 10 years)
- Cancer-Specific Survival (CSS)(From randomization up to 10 years)
- Overall Survival (OS)(From randomization up to 10 years)
- International Prostate Symptom Score (IPSS)(Time Frame: From baseline up to 10 years)
- EORTC QLQ-PR25 Prostate Cancer Module(From baseline up to 10 years)
- Time to PSA Nadir(Up to 10 years)
- PSA Doubling Time(Up to 10 years)
- PSA Bounce(Up to 10 years)
研究者
Mateusz Bilski
Medical Director and Head of Radiotherapy Department, MD, PhD
Affidea Nu-med Center of Oncological DIagnostics and Therapy