Prognostic Factors and Outcomes for Post-Radiation Sarcoma—A Systematic Review and Meta-Analysis

Background/Objectives: Post-radiation sarcomas (PRS) are secondary malignancies occurring years after radiotherapy. Due to low incidence, evidence on prognostic factors and management is limited. Methods: MEDLINE, Embase, and the Cochrane Library were searched from January 1960 to January 2026. Eligible studies included observational cohorts reporting outcomes of histologically confirmed PRS. We excluded case reports, case series with fewer than ten patients, reviews, editorials, and studies without survival or recurrence outcomes. Two authors independently screened studies, extracted data, and assessed risk of bias. Hazard ratios (HRs) and 95% confidence intervals were extracted or calculated. The primary outcome was overall survival. Heterogeneity was assessed using the I2 statistic. This study was registered with PROSPERO (CRD42023457401). Results: The search identified 4222 records, of which 28 studies comprising 2438 patients were eligible for analysis. Most patients were female (2008, 83.3%), reflecting a predominance of breast radiation-associated angiosarcoma. Older age, larger tumor size, higher histological grade, and positive surgical margins were consistently associated with worse overall survival. Complete (R0) resection was associated with improved survival (pooled HR < 1.0), as was treatment in specialized sarcoma centers. Chemotherapy and additional radiotherapy were not associated with improved overall survival. Substantial heterogeneity was observed (I2 > 50% for several analyses). Overall risk of bias was moderate. Conclusions: PRS share key prognostic determinants with sporadic sarcomas. Complete surgical resection and management in specialized sarcoma centers are the most important factors associated with improved outcomes. These findings support centralized care and highlight the need for prospective research to improve risk stratification and management of PRS.