e15548 Background: Patients with unresectable colorectal liver metastases (uCRLM) have limited long-term survival with conventional systemic and locoregional therapies. Liver transplantation (LT) has re-emerged as a potential curative strategy in highly selected patients, but comparative evidence remains fragmented. We performed a systematic review and meta-analysis to evaluate survival outcomes of LT compared with best alternative non-transplant therapies (BAT) in uCRLM. Methods: PubMed, Embase, and Cochrane CENTRAL were systematically searched from inception through November 2025 for studies including adults with uCRLM treated with LT. Randomized and non-randomized comparative studies and non-comparative cohorts were eligible. Overall survival (OS) was the primary outcome. Hazard ratios (HRs) were pooled using a random-effects model. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I for non-randomized studies. A leave-one-out sensitivity analysis was performed. Results: Seventeen studies met inclusion criteria, including one randomized controlled trial and sixteen non-randomized studies. Three comparative studies (TransMet 2024, Serenari 2025, Byrne 2024) provided data suitable for meta-analysis. LT was associated with significantly improved OS compared with BAT (pooled HR 0.45, 95% CI 0.28–0.72; P = 0.0009), with low statistical heterogeneity (I² = 3%). Sensitivity analysis identified the TransMet trial as the primary contributor to statistical significance; exclusion of this study attenuated the effect (HR 0.64, 95% CI 0.30–1.35). Non-comparative cohorts consistently reported favorable outcomes, with 1-year OS approaching 100% and 5-year OS ranging from 60% to 83% in biologically selected populations. Despite high overall survival, recurrence remained common, with disease-free survival typically limited to 8–17 months, predominantly involving lung-dominant relapse patterns. Conclusions: In selected patients with uCRLM, liver transplantation is associated with significantly improved overall survival compared with non-transplant strategies. These findings support LT as a viable treatment option in carefully selected patients, while underscoring the importance of biological selection and prospective validation. Comparative Overall Survival Outcomes in Studies Included in the Meta-analysis. Study (Year) Study Design Comparator Patients (LT / Control) Outcome Effect Estimate TransMet (2024) Randomized controlled trial Chemotherapy 45 / 45 Overall survival HR 0.37 (95% CI 0.21–0.65) Serenari (2025) Prospective cohort ALPPS 13 / 21 Overall survival HR 1.40 (95% CI 0.63–3.09) Byrne (2024) Prospective cohort Best alternative therapy 20 / 13 Overall survival HR 0.23 (95% CI 0.02–2.25) Pooled estimate Random-effects model — — Overall survival HR 0.45 (95% CI 0.28–0.72) HR <1 favors liver transplantation.
Valagni et al. (Thu,) studied this question.