Clinical trials

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.

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.

This is an ambispective, multicenter, observational real-world registry of patients with synchronous de novo oligometastatic prostate cancer, defined as prostate cancer with up to 10 extraregional metastatic lesions diagnosed at initial presentation or within 6 months of the primary diagnosis. The study will evaluate outcomes after comprehensive local and metastasis-directed treatment. Eligible patients receive definitive prostate-directed radiotherapy, which may include external-beam radiotherapy, external-beam radiotherapy with brachytherapy boost, or definitive prostate brachytherapy monotherapy in selected patients, together with stereotactic body radiotherapy to all identified extraregional metastatic lesions. Systemic therapy is given according to routine clinical practice and local multidisciplinary decisions. The registry is non-interventional. Participants are not assigned to treatment by the study protocol, and no experimental treatment, randomization, or protocol-mandated imaging schedule is used. The study collects de-identified data from routine medical records, including baseline disease characteristics, imaging, radiotherapy details, systemic therapy, radiographic progression, patterns of failure, subsequent treatments, adverse events, and survival. The study includes historical retrospective data, prospective follow-up of previously treated eligible patients, and prospective enrollment of newly eligible patients from the registry activation date. The main goal is to describe where and when prostate cancer progresses after comprehensive treatment of the prostate and all visible metastatic lesions, and to identify clinical and treatment-related factors associated with disease control and adverse events.

PSMA-OLIGO-PRO is a multicenter ambispective observational real-world registry evaluating outcomes after PSMA PET-guided progression-directed radiotherapy for oligoprogressive prostate cancer. The registry includes retrospectively identified patients treated before June 26, 2026 and prospectively enrolled patients from June 26, 2026 onward. Eligible patients have metastatic hormone-sensitive or castration-resistant prostate cancer, are receiving active systemic therapy, and develop a limited number of new or regrowing lesions while the remaining disease sites are controlled. Oligoprogression is primarily defined by PSMA PET/CT or PSMA PET/MR, with MRI used when clinically appropriate, particularly for intraprostatic, local, or prostate-bed progression. Participants are not assigned to treatment by the registry protocol. All imaging, systemic therapy, radiotherapy modality, dose, fractionation, and follow-up decisions are made by treating physicians as part of routine clinical care. Progression-directed radiotherapy may include stereotactic body radiotherapy for nodal, bone, visceral, or local lesions, moderately hypofractionated external beam radiotherapy when clinically selected, and brachytherapy when appropriate for intraprostatic, prostate-bed, or selected metastatic oligoprogressive lesions. The registry evaluates whether treating all identifiable oligoprogressive lesions can delay escalation to a new systemic therapy line, preserve the oligometastatic state, maintain local control, and provide acceptable safety in contemporary PSMA PET-guided practice.

REGYNERA(dia)TION is an international, multicenter, ambispective observational patient registry of adults with recurrent gynecologic malignancies after prior radiotherapy who are treated or planned for reirradiation and/or total ablative strategies as part of routine clinical care. The registry does not assign treatment. Radiotherapy technique, dose, systemic therapy, surgery, metastasis-directed therapy, imaging, and follow-up are selected by the treating multidisciplinary team according to local standards and patient-specific factors. The registry will collect harmonized retrospective and prospective data on disease characteristics, prior radiotherapy, recurrence pattern, reirradiation or ablative treatment exposure, response, progression, survival, severe treatment-related morbidity, fistula events, and patient-reported outcomes where available.