PSMA-OLIGO-PRO is a multicenter, ambispective, observational real-world evidence registry of adults with metastatic hormone-sensitive or metastatic castration-resistant prostate cancer who develop a limited number of progressing metastatic lesions during active systemic therapy and are considered for comprehensive progression-directed radiotherapy (PDRT) in routine clinical care. The registry includes retrospective cases treated before June 26, 2026, and prospective cases enrolled from June 26, 2026, onward. Before the site-specific protocol amendment takes effect, the metastatic-lesion ceiling is 1-5. After the amendment takes effect, prospective candidates with 1-10 qualifying progressing metastatic lesions on baseline PSMA PET/CT or PSMA PET/MRI may be included. Metastatic burden is prespecified as 1-5 lesions, representing classical oligoprogression, or 6-10 lesions, representing exploratory, PSMA PET-defined, limited progression. Intraprostatic and prostate-bed progressing foci are recorded separately from the metastatic count and must also be included in the comprehensive PDRT plan. Otherwise eligible local-only episodes form a separate descriptive stratum. All qualifying metastatic and locally progressing sites must be deemed technically amenable to definitive-intent PDRT before prospective analytic-cohort enrollment. The registry does not assign imaging, systemic therapy, or radiotherapy; these clinical decisions are made independently by the treating team in routine care. A qualifying baseline PSMA PET and documentation of comprehensive treatability are required for inclusion.
The primary endpoint is time to next systemic therapy in the continuation-plan treatment-start set. Key secondary outcomes include PDRT initiation and comprehensive implementation, time to widespread or non-PDRT-amenable progression, classical time to polymetastatic progression in the baseline 1-5 cohort, radiographic progression-free survival, lesion-level local control, overall survival, and treatment-related toxicity. The prespecified 1-5 versus 6-10 comparison is restricted to concurrent post-amendment prospective participants and is exploratory.
Age 18 years or older.
Histologically confirmed prostate adenocarcinoma.
Metastatic hormone-sensitive or metastatic castration-resistant prostate cancer.
Active systemic anticancer therapy at the qualifying limited-progression assessment.
Limited progression defined only by conventional CT, MRI, or bone scintigraphy without a qualifying PSMA PET examination.
More than five qualifying progressing metastatic lesions for retrospective or pre-amendment inclusion.
More than 10 qualifying progressing metastatic lesions after amendment activation.
Diffuse, non-enumerable, or rapidly progressive disease that is not considered suitable for comprehensive lesion-directed radiotherapy.
Adults with histologically confirmed prostate adenocarcinoma and metastatic hormone-sensitive or metastatic castration-resistant disease receiving active systemic therapy at participating centers. Before amendment activation, eligible metastatic progression is limited to 1-5 lesions. After site-specific amendment activation, prospective candidates have 1-10 qualifying progressing metastatic lesions on baseline PSMA PET and undergo formal review to determine whether every metastatic and local progressing site can be treated with comprehensive PDRT. Otherwise, eligible local-only cases form a separate descriptive stratum.
Cohort
Other
Comprehensive Progression-Directed Radiotherapy
RadiationObserved routine-care exposure includes definitive-intent radiotherapy planned for every qualifying metastatic site and for local or prostate-bed progressing sites identified in the index episode. Treatment may include stereotactic body radiotherapy, moderately hypofractionated external-beam radiotherapy, high-dose-rate or low-dose-rate brachytherapy, combined external-beam and brachytherapy, or mixed-modality radiotherapy. The registry does not assign treatment. Treatment modality, dose, fractionation, timing, site-level completion, and reasons for non-start or incomplete treatment are recorded.
Time to Next Systemic Therapy in the Continuation-Plan Treatment-Start Set
Time from the first PDRT fraction to initiation of the first new systemic anticancer therapy line among participants who receive at least one PDRT fraction, whose management plan documented before PDRT was continuation of the same systemic regimen, and who had not initiated a new systemic line before the first PDRT fraction. Death before initiation of a new line is treated as a competing event; otherwise, participants are censored at the last adequate assessment.
Classical Time to Polymetastatic Progression (TTPP-5)
Supportive endpoint restricted to participants with 1-5 qualifying progressing metastases at baseline. Time to more than five new or unequivocally regrowing qualifying metastatic lesions at one assessment or to disease that is no longer safely amenable to comprehensive PDRT. Participants entering with 6-10 metastases do not contribute. Death without the progression state is treated as a competing event.
Radiographic Progression-Free Survival
Time from the first index PDRT fraction to radiographic progression at any site or death from any cause, whichever occurs first. Imaging modality and assessment date are recorded. Progression based only on an unconfirmed change in PSMA uptake is not accepted unless it meets the protocol confirmation criteria.
Overall Survival
Time from the first index PDRT fraction to death from any cause. Participants alive at the last known follow-up are censored on that date.
Lesion-Level Local Control
Time from completion of PDRT for an individual treated lesion to unequivocal in-field progression of that lesion. Lesions are linked to participants and analyzed with methods that account for within-participant clustering. Death without local failure is treated as a competing event.
Disease Trajectory After Index PDRT
Number and proportion of participants whose first post-PDRT trajectory is repeat limited progression involving no more than 10 qualifying progressing metastases, crossing of the classical threshold of more than five progressing metastases, direct widespread or non-PDRT-amenable progression, or death without documented progression.
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