Benchmarking the real-world transplant benefit in unresectable colorectal liver metastases: A preliminary external validity assessment of the TransMet trial

Liver transplantation (LT) for unresectable colorectal liver metastases (CRLM) has regained interest after the TransMet trial, which reported 5-year survival exceeding 70%. However, estimates of transplant benefit (TB) are lacking. This study provides a first external validity assessment of the TransMet criteria and estimates the 5-year TB using a real-world international cohort. A retrospective multicenter study included 61 TransMet-eligible patients with unresectable CRLM who underwent LT between 2006 and 2020 across seven centers. Matching-adjusted indirect comparisons were used to improve comparability, with sensitivity analyses on effective sample size. Survival was analyzed using Kaplan-Meier curves and restricted mean survival time up to 5 years. Weighted multivariable Cox regressions were employed to assess prognostic factors after transplantation. The 5-year restricted mean survival time was identical in the weighted cohort (effective sample size=19) and the TransMet LT arm (51.0 mo). Sensitivity analysis yielded a 5-year restricted mean survival time consistent with residual imbalance (48.2 mo, ESS=35). KRAS mutation (HR: 5.90, 95% CI: 1.89-18.4), right-sided primary tumor (HR: 4.17, 95% CI: 1.40-12.4), and female sex (HR: 5.73, 95% CI: 1.04-31.6) were associated with poorer survival; CEA≥80 ng/mL emerged as a potential prognostic factor (HR: 6.3, 95% CI: 1.73-22.6) across alternative specifications. The estimated 5-year TB of LT versus chemotherapy was 22.5 months (95% CI: 15.5-29.6). The findings of this first real-world assessment of the TransMet trial criteria and 5-year TB estimation in unresectable CRLM point to reasonable prognostic candidates and support evaluating the inclusion of CRLM in LT allocation models. We advocate expanded multicenter data to reach sufficient prognostic stratification through well-calibrated, highly discriminative studies.