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.
PSMA-OLIGO-PRO is a multicenter, ambispective, observational real-world evidence registry of adults with metastatic prostate adenocarcinoma who develop limited progression during active systemic therapy and are considered for comprehensive progression-directed radiotherapy (PDRT) in routine clinical practice. The study does not assign imaging, systemic therapy, or radiotherapy. Decisions to obtain PSMA PET, to determine the pre-PDRT systemic-management plan, and to consider comprehensive PDRT are made independently of registry participation. The registry comprises three calendar-defined data-origin cohorts: (1) a retrospective classical-burden cohort treated before June 26, 2026, with 1-5 qualifying progressing metastatic lesions; (2) a prospective pre-amendment classical-burden cohort enrolled from June 26, 2026, until the amendment becomes effective at each site, with 1-5 qualifying progressing metastatic lesions; and (3) a post-amendment prospective cohort with 1-10 qualifying progressing metastatic lesions. Within the post-amendment cohort, burden is prespecified as 1-5 versus 6-10 metastatic lesions. Six to ten lesions constitute an exploratory expanded-burden limited-progression stratum and are not presented as an established consensus definition of oligoprogression. Baseline PSMA PET/CT or PSMA PET/MRI is mandatory for every included episode. For post-amendment prospective enrollment, the qualifying PSMA PET must be performed within 60 days before enrollment, and index PDRT must be planned to begin within 60 days after the scan. Repeat staging or documented multidisciplinary reconfirmation is required if this interval is exceeded or if an intervening clinical event or systemic-treatment change could alter metastatic burden. The eligibility ceiling and burden stratum are based only on qualifying progressing metastatic lesions. Intraprostatic and prostate-bed progressing foci are recorded separately, do not count toward the metastatic ceiling, and must also be included in the comprehensive PDRT plan. Otherwise eligible patients with zero progressing metastases and isolated local or prostate-bed progression form a separate descriptive stratum and do not contribute to the metastatic-burden comparison or metastatic-threshold progression endpoints. Before prospective analytic-cohort enrollment, all qualifying metastatic and local progressing sites must be judged technically amenable to definitive-intent PDRT. Candidates deemed feasible are enrolled before the first PDRT fraction. Prospectively enrolled participants who do not start or do not complete all planned PDRT remain in the enrolled and implementation denominators. Only participants receiving at least one PDRT fraction enter the prospective safety set and the treatment-start clinical-outcome sets. PDRT 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 treatment, according to institutional standards. Every qualifying metastatic and local progressing site must be included in a predefined index treatment strategy. For post-amendment prospective participants, PDRT initiation is assessed within 60 days after enrollment, and comprehensive implementation requires definitive-intent treatment of every locked baseline site within 60 days after the first index fraction. The primary endpoint is time to next systemic therapy (TTNS) in treatment-start participants whose pre-PDRT management plan was continuation of the same systemic regimen and who had not initiated a new systemic therapy line before the first PDRT fraction. Participants with a documented pre-PDRT plan to change or escalate systemic therapy are excluded from the primary TTNS estimand but remain eligible for other analyses. The broad TTNS definition used in the first posted registry version is retained as a supportive analysis for all treatment-start participants. The common expanded-state progression endpoint is time to widespread or non-PDRT-amenable progression (TWNP-10), defined by more than 10 new or unequivocally regrowing metastatic lesions, diffuse or non-enumerable progression, or a documented determination that all active progressing sites can no longer be safely treated with comprehensive definitive-intent local therapy. A supportive classical endpoint, TTPP-5, is restricted to participants with 1-5 metastatic lesions at baseline and retains the threshold of more than five progressing metastatic lesions or loss of comprehensive PDRT eligibility. Other outcomes include radiographic progression-free survival, lesion-level local control, overall survival, repeat limited progression, subsequent lesion-directed therapy, PDRT initiation and comprehensive implementation, disease trajectory, and acute and late treatment-related adverse events graded according to CTCAE version 5.0. The primary 1-5 versus 6-10 metastatic-burden comparison is limited to concurrent post-amendment prospective participants and uses endpoint-specific denominators. All comparisons are exploratory and estimate associations rather than causal treatment effects. The coordinating center uses a controlled data dictionary and prespecified edit checks for date order, metastatic-count consistency, cohort assignment, lesion-to-treatment linkage, dose and fraction plausibility, endpoint derivation, and duplicate records. Data queries are sent to participating sites for correction or documented resolution. Selected post-amendment records, enriched for 6-10 metastases and discordant disease, may undergo source-data, imaging, and treatment-completeness review. Missingness is reported by data-origin cohort and burden stratum, and time-to-event observations without an event are censored at the last adequate assessment. The statistical analysis plan will be finalized before the comparative post-amendment data lock.
Study Type
OBSERVATIONAL
Enrollment
1,000
Observed 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.
Affidea Nu-Med Cancer Diagnostics and Therapy Center
Zamość, Lublin Voivodeship, Poland
RECRUITINGTime 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.
Time frame: From first index PDRT fraction to a new systemic therapy line, death, last adequate assessment, or study data cutoff, up to 5 years
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.
Time frame: From first index PDRT fraction to the event, death, last adequate assessment, or study data cutoff, up to 5 years
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.
Time frame: From first index PDRT fraction to radiographic progression, death, last adequate assessment, or study data cutoff, up to 5 years
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.
Time frame: From first index PDRT fraction to death, last known follow-up, or study data cutoff, up to 5 years
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.
Time frame: From completion of PDRT for each lesion to local failure, death, last adequate assessment, or study data cutoff, up to 5 years
Acute and Late Treatment-Related Adverse Events
Number and proportion of prospectively enrolled participants who receive at least one index PDRT fraction and experience treatment-related adverse events graded by CTCAE version 5.0. Acute events occur through day 90 after treatment initiation and late events occur after day 90. Maximum grade, serious events, grade 2 or higher events, grade 3 or higher events, and selected site-specific toxicities are summarized. Retrospectively ascertained toxicity is reported separately when adequate.
Time frame: From first index PDRT fraction through day 90 for acute events and from day 91 through study data cutoff, up to 5 years, for late events
Time to First Repeat Limited-Progression Episode
Time from the first index PDRT fraction to the first subsequent limited-progression episode with no more than 10 new or unequivocally regrowing qualifying metastatic lesions at one assessment and with every active progressing metastatic and local site judged technically amenable to comprehensive PDRT. Death before repeat limited progression is treated as a competing event; otherwise participants are censored at the last adequate assessment.
Time frame: From first index PDRT fraction to repeat limited progression, death, last adequate assessment, or study data cutoff, up to 5 years
Time to Next Systemic Therapy in All Treatment-Start Participants
Supportive analysis of time from the first fraction of index PDRT to initiation of the first new systemic anticancer therapy line among all participants who receive at least one PDRT fraction, regardless of the pre-PDRT intended systemic-management strategy. This outcome preserves the population scope of the first posted registry version. Death before a new line is treated as a competing event; otherwise participants are censored at the last adequate assessment.
Time frame: From first index PDRT fraction to a new systemic therapy line, death, last adequate assessment, or study data cutoff, up to 5 years
Time to Widespread or Non-PDRT-Amenable Progression (TWNP-10)
Time to the earliest of more than 10 new or unequivocally regrowing qualifying metastatic lesions at one assessment; diffuse, confluent, or otherwise non-enumerable progression; or a documented multidisciplinary determination that all active progressing sites can no longer be safely treated with comprehensive definitive-intent local therapy. Death without this progression state is treated as a competing event.
Time frame: From first index PDRT fraction to the event, death, last adequate assessment, or study data cutoff, up to 5 years
Time to First Subsequent Lesion-Directed Therapy
Time from the first index PDRT fraction to initiation of the first subsequent local treatment course for repeat limited progression. Participants without subsequent lesion-directed therapy are censored at the last adequate assessment.
Time frame: From first index PDRT fraction to subsequent lesion-directed therapy, last adequate assessment, or study data cutoff, up to 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.