PSMA PET-Staged Comprehensive Progression-Directed Radiotherapy for Limited Progression in Prostate Cancer

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.

Sex

Male

Minimum age

18 Years

* 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.
* Qualifying baseline PSMA PET/CT or PSMA PET/MRI with review of relevant anatomical imaging.
* Metachronous, repeat, or induced oligoprogression or limited progression according to the protocol framework.
* Retrospective cases treated before June 26, 2026: 1-5 qualifying progressing metastatic lesions.
* Prospective cases enrolled before the site-specific amendment effective date: 1-5 qualifying progressing metastatic lesions.
* Prospective cases enrolled after the site-specific amendment effective date: 1-10 qualifying progressing metastatic lesions, prespecified as 1-5 or 6-10.
* Intraprostatic or prostate-bed progressing foci are recorded separately from the metastatic-lesion count and must also be technically amenable to comprehensive PDRT.
* Every qualifying metastatic and local progressing site is judged technically amenable to comprehensive definitive-intent PDRT before prospective analytic-cohort enrollment.
* For post-amendment prospective enrollment, qualifying PSMA PET performed within 60 days before enrollment and index PDRT planned to begin within 60 days after the scan.
* Availability of the qualifying PET date, systemic-therapy dates, locked metastatic-lesion count, separate local-site count, lesion map, and eligibility decision. For retrospective inclusion, PDRT exposure and at least one outcome or censoring time must also be determinable.

Exclusion Criteria

* 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.
* Any known active metastatic or local progressing site that cannot be included in the comprehensive PDRT plan.
* Clinical deterioration or an urgent systemic-treatment indication that makes comprehensive PDRT inappropriate or unsafe.
* Radiotherapy delivered solely with palliative symptom-control intent rather than definitive progression-directed local-control intent.
* For prospective participation, inability to complete the approved consent process.
* For retrospective cases, missing baseline imaging or core dates such that metastatic burden, PDRT exposure, or at least one outcome or censoring time cannot be determined reliably.

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