KEY POINTS
- The systematic review and meta-analysis included 28 retrospective cohorts and 2,438 patients eligible for quantitative synthesis. Women comprised 83.3%, angiosarcoma accounted for 58%, and breast cancer was the preceding malignancy in 68%, limiting representation of other post-radiation sarcoma phenotypes.
- Reported latency from radiotherapy to sarcoma ranged from 0.5 to 74 years, with approximately seven years the most commonly reported median. Median age at diagnosis was generally 65–70 years.
- Older age was associated with worse overall survival (HR 1.85, 95% CI 1.28–2.69), while larger tumors were associated with worse overall survival (HR 1.54, 1.02–2.35) and disease-specific survival (HR 2.06, 1.34–3.18).
- High histological grade remained strongly prognostic despite post-radiation sarcomas often being regarded as uniformly aggressive. Higher grade was associated with worse overall survival (HR 2.38, 95% CI 1.86–3.04; I² = 0%) and distant recurrence-free survival (HR 2.60, 1.65–4.09).
- Positive or incomplete margins were the most consistent adverse factor: overall survival HR 2.22 (95% CI 1.75–2.80), disease-specific survival HR 2.13 (1.45–3.13), local recurrence-free survival HR 4.19 (1.66–10.62), and distant recurrence-free survival HR 1.94 (1.31–2.85).
- Radical surgery was associated with better disease-specific survival (HR 0.53, 95% CI 0.30–0.94) and local recurrence-free survival (HR 0.43, 0.19–0.94). Observational cohorts also favored management in specialist sarcoma centres, supporting early referral before definitive surgery.
- Additional radiotherapy was not associated with improved overall survival (HR 1.37, 95% CI 0.94–1.98), and chemotherapy showed no overall survival benefit (HR 0.82, 0.60–1.12). A possible disease-specific survival benefit from neoadjuvant chemotherapy (HR 0.41, 0.19–0.90) came from limited observational evidence and may reflect selection at expert centres.
CLINICAL TAKEAWAY
Post-radiation sarcomas retain the same fundamental prognostic architecture as sporadic sarcomas: size, grade, age, and above all margin status matter. The most actionable message is early referral to a sarcoma centre and planning for complete en bloc resection; evidence for chemotherapy or re-irradiation remains insufficient and highly confounded.