Long-term survival and prognostic factors after repeated metastasectomies in metastatic colorectal cancer: a 15-years retrospective study

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BACKGROUND: Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality. While metastasectomy could improve survival in selected patients, the role of repeated resections in oligorecurrent disease is less defined. METHODS: We retrospectively analyzed patients with mCRC treated at Fondazione Policlinico Universitario Agostino Gemelli-IRCCS (Rome, Italy) between 2010 and 2024. Eligible patients underwent ≥2 resections of metastatic lesions. Disease-free survival after second metastasectomy (DFS2) and overall survival (OS) were the coprimary end points. Prognostic factors were tested with Cox regression, and a composite risk score (Fondazione Policlinico Gemelli Risk Score [FPGRiskScore]) was developed. RESULTS: Among 1586 patients with mCRC, 396 (24.9%) received at least one metastatic surgery and 143 (9%) underwent ≥2 metastasectomies. Median DFS2 was 8.2 months (95% confidence interval [CI]: 7.3-13.1), and 5-years OS rate was 73.1% (95% CI: 64.5-83.0); after a median follow-up from the last metastasectomy of 34.3 months, 49/143 patients (34.2%) were relapse-free and median DFS after the second surgery of the metastases from the last surgery was 13.1 months (95% CI: 9.1-17.5). Patients stratified by FPGRiskScore (disease-free interval [DFI] from the first metastasectomy ≤ vs. >12 months, metastatic burden ≤ vs >5 cm, RAS/BRAF status, and Eastern Cooperative Oncology Group Performance Status [ECOG PS] scale 0 vs. ≥1) showed distinct outcomes: low-risk patients achieved a median DFS2 of 18.4 months and 5-years OS of 87.6%, compared with 7.8 months/72.0% in intermediate-risk and 4.9 months/55.3% in high-risk group. CONCLUSIONS: Repeated metastasectomy offers substantial survival benefit in selected patients with oligorecurrent mCRC, with long-term disease control achievable in a subset. Prognostic stratification incorporating clinical and molecular features (FPGRiskScore) may refine patient selection and guide multidisciplinary management.

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