Prostate Radiotherapy and Metastasis-Directed Therapy in Synchronous Oligometastatic Prostate Cancer

SynSABR-PC is a multicenter, observational, ambispective real-world evidence registry designed to evaluate outcomes and patterns of failure in patients with synchronous de novo oligometastatic prostate cancer treated with comprehensive local and metastasis-directed radiotherapy.

Synchronous de novo oligometastatic prostate cancer represents an intermediate clinical state between localized prostate cancer and widely disseminated metastatic disease. In this study, eligible patients have up to 10 extraregional metastatic lesions detected at baseline staging, with metastatic disease diagnosed at initial presentation or within 6 months of the primary prostate cancer diagnosis. Baseline staging may include prostate-specific membrane antigen positron emission tomography/computed tomography, prostate-specific membrane antigen positron emission tomography/magnetic resonance imaging, conventional imaging, choline positron emission tomography, or other imaging used for routine clinical decision-making.

The central concept of the registry is comprehensive treatment of all visible disease. Included patients are treated with definitive prostate-directed radiotherapy and stereotactic body radiotherapy to all identified extraregional metastatic lesions. Prostate-directed radiotherapy may consist of external-beam radiotherapy, moderately hypofractionated radiotherapy, ultra-hypofractionated prostate radiotherapy, external-beam radiotherapy with brachytherapy boost, or definitive prostate brachytherapy monotherapy in selected patients according to institutional practice. Elective or definitive pelvic lymph node irradiation and dose escalation to involved pelvic lymph nodes may be used according to local standards. Metastasis-directed therapy is delivered with ablative intent to all baseline extraregional metastatic lesions. Treatment of selected metastatic lesions only, while leaving other baseline metastatic sites untreated, is not consistent with the comprehensive treatment strategy of this registry. This study is non-interventional. The registry does not assign radiotherapy, brachytherapy, metastasis-directed therapy, systemic therapy, imaging, or follow-up schedules. All clinical decisions are made by the treating physicians and multidisciplinary teams according to institutional standards, available imaging, patient characteristics, and routine clinical practice. Systemic therapy, including androgen deprivation therapy, androgen receptor pathway inhibitors, docetaxel, or other systemic treatments, is recorded as part of real-world care and will be analyzed as a treatment-related covariate rather than as a protocol-assigned intervention. The study has an ambispective design. The historical retrospective cohort includes eligible patients treated before registry activation, with baseline, treatment, follow-up, outcome, and adverse event data abstracted from available medical records. The ambispective follow-up cohort includes eligible patients treated before registry activation who remain under follow-up, with retrospective baseline and treatment data and prospective updates of follow-up, imaging, progression, subsequent treatment, adverse events, and survival. The prospective enrollment cohort includes newly eligible patients identified from the registry activation date onward and entered prospectively before, during, or shortly after routine clinical decision-making for definitive prostate-directed radiotherapy and metastasis-directed therapy.

The primary objective is to characterize radiographic outcomes and patterns of first disease progression after definitive prostate-directed radiotherapy and stereotactic body radiotherapy to all visible metastatic lesions. The registry will evaluate the timing of first radiographic progression and the anatomical pattern of first failure, including local recurrence in the prostate or seminal vesicles, regional pelvic nodal recurrence, progression at previously treated metastatic sites, distant extraregional recurrence, and combined patterns of recurrence.

Secondary and exploratory objectives include evaluation of time to first radiographic progression, time to polymetastatic progression, time to initiation of the next line of systemic therapy, overall survival, and treatment-related adverse events graded according to the Common Terminology Criteria for Adverse Events version 5.0. The registry will also explore whether outcomes differ according to baseline metastatic burden, imaging modality, anatomical distribution of metastatic disease, prostate-directed radiotherapy modality, use of brachytherapy boost or brachytherapy monotherapy, pelvic lymph node irradiation, nodal boost, metastasis-directed radiotherapy dose and fractionation, systemic therapy intensity, and treatment sequence.

For time-to-event analyses, time zero is defined as the start date of the first radiotherapy course, corresponding to the earliest initiation date of metastasis-directed stereotactic body radiotherapy, prostate external-beam radiotherapy, or prostate brachytherapy delivered as boost or monotherapy. This approach is intended to provide a consistent time origin across patients and to minimize immortal time bias in a real-world setting where treatment sequencing may vary. Adverse events will be assessed using CTCAE version 5.0. Acute adverse events are defined as events occurring within 90 days from the start date of the first radiotherapy course. Late adverse events are defined as events occurring more than 90 days after the start date of the first radiotherapy course. Genitourinary and gastrointestinal adverse events will be summarized separately, and grade 3 or higher adverse events will be recorded with event date and clinical description where available.

Data will be collected in a centralized, de-identified registry. No direct patient identifiers will be transferred to the coordinating center. Data elements include baseline demographic and clinical characteristics, staging and imaging modality, prostate-directed radiotherapy details, brachytherapy details where applicable, pelvic lymph node irradiation, metastasis-directed stereotactic body radiotherapy, systemic therapy, radiographic progression, pattern of failure, repeat oligoprogression, transition to polymetastatic disease, subsequent metastasis-directed therapy, systemic therapy escalation, adverse events, vital status, and date of last known follow-up. Because this is an observational real-world registry, analyses will be primarily descriptive and exploratory. The registry is intended to improve understanding of outcomes after comprehensive treatment of synchronous de novo oligometastatic prostate cancer and to generate hypotheses for future prospective trials.

• Time to Polymetastatic Progression [Срок оценки: From start of first radiotherapy course to polymetastatic progression or last follow-up, up to 36 months]
• Time to Next-Line Systemic Therapy [Срок оценки: From start of first radiotherapy course to next-line systemic therapy or last follow-up, up to 36 months]
• Overall Survival [Срок оценки: From start of first radiotherapy course to death or last known follow-up, up to 60 months]
• Treatment-Related Adverse Events [Срок оценки: From start of first radiotherapy course to last follow-up, up to 36 months]