Estimating the clinical benefit of metastases resection in liver-limited metastatic colorectal cancer: an IPD-based pooled analysis of nine randomized trials
In brief
Liver surgery halves time patients spend on chemotherapy in metastatic colorectal cancer
In a pooled analysis of 855 patients with liver-limited metastatic colorectal cancer, those who underwent liver resection spent only 26% of their follow-up on systemic therapy versus 47% for unresected patients, regardless of disease-free interval. Surgery also showed a trend toward longer overall survival in patients with high baseline tumor burden, suggesting a selective benefit.
- Journal
- ESMO open (Q1)
- Published
- 2 November 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- M M Germani, A Taravella, D Rossini, L Weiss, F Morano, F Bergamo, et al.
- PMID
- 42970859
- DOI
- 10.1016/j.esmoop.2026.108616
Why clinicians should know about it
- Picked for Surgical Oncology (paper of the day, 4 November 2026): Pooled analysis of liver‑limited metastatic colorectal cancer resection
- Picked for Surgery (paper of the day, 3 November 2026): Directly addresses selection and outcomes for colorectal liver metastasis resection
Abstract
BACKGROUND: In resected liver-limited metastatic colorectal cancer (LL-mCRC), disease-free survival (DFS) and postsurgical overall survival (psOS) have been found to be weakly related in heterogeneous retrospective series, challenging the role of DFS as a surrogate biomarker of psOS. Additionally, it remains unclear whether early relapses (DFS <6 months) are associated with overall survival (OS) benefit. PATIENTS AND METHODS: We analyzed individual data of patients with LL-mCRC enrolled in nine randomized trials of first-line chemotherapy plus biologics. Correlation and surrogacy between DFS and psOS were calculated with ρ and R2. psOS of resected patients with DFS <6 months was compared with time from minimum disease load (post-min OS) of unresected patients, with stratification according to baseline tumor burden score (TBS). Time on systemic therapy was also evaluated. RESULTS: Eight hundred fifty-five patients with LL-mCRC were included and 357 (42%) were radically resected. DFS and psOS were highly correlated (ρ = 0.73), with R2 at the patient and trial levels for surrogacy of 0.70 and 0.32, respectively. psOS and post-min OS in resected patients with early relapse (n= 115) and unresected patients (n = 498) were comparable [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.70-1.11, P = 0.29]. However, a benefit from surgery was detected in patients with high baseline TBS (HR 0.69, 95% CI 0.45-1.05, P = 0.09) but not in patients with low/medium baseline TBS (HR 1.12, 95% CI 0.74-1.69, P = 0.59) (p interaction = 0.10). Resection was associated with a lower percentage of time on systemic therapy (26%) regardless of DFS (47% if <6 months, 26% if ≥6 months) (P < 0.001). CONCLUSIONS: In LL-mCRC resected after first-line chemotherapy plus biologics, DFS is highly correlated with psOS, with high patient-level surrogacy. In high-burden patients, liver surgery seems associated with a trend toward long-term benefit, also after early relapse (<6 months), whereas time on systemic therapy is reduced.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.