Challenging the Limits: Liver Transplantation vs. Liver Resection for CRLM, a Multicenter Study

Colorectal liver metastases (CRLM) represent one of the main prognostic determinants in patients with colorectal cancer. Liver resection (LR) currently represents the standard treatment for resectable patients; however, its long-term oncological benefit may be limited in cases characterized by high tumor burden, bilobar disease, risk of radiological understaging, and unfavorable tumor biology. In this context, liver transplantation (LT) has emerged as a potential therapeutic strategy in selected patients with CRLM, aiming to overcome some intrinsic limitations of resection, including the persistence of occult micrometastases and the phenomenon of hepatic field cancerization. This multicenter study compared the oncological outcomes of patients undergoing liver resection and liver transplantation for CRLM. To reduce confounding by indication, the main comparison was performed between the LT group and a subcohort of resected patients harmonized according to SECA-I criteria, defined as LR-SECA-I. The primary endpoint was overall survival, while secondary endpoints included disease-free survival, survival after recurrence, and recurrence patterns. Tumor burden was assessed using the Tumor Burden Score, with TBS ≥ 9 considered as high tumor burden; transplant-favorable biology was primarily defined by the coexistence of maximum tumor diameter < 5.5 cm and CEA < 80 µg/L, both of which are components of the Oslo score. The descriptive cohort included 507 LR-SECA-I patients and 84 LT patients; survival analyses were conducted on 502 LR-SECA-I and 83 LT patients. At baseline, transplanted patients had a significantly higher tumor burden, with a median number of lesions of 10.0 compared with 3.0 in resected patients, and a median TBS of 11.0 compared with 5.2. Despite this unfavorable imbalance, the LT group showed superior overall survival in the more selected comparisons: 5-year OS was 56.5% after LT compared with 30.4% in the LR-SECA-I group. This difference was even more pronounced among patients with TBS ≥ 9, in whom 5-year OS was 56.3% after LT compared with 6.8% after LR-SECA-I. Sensitivity analyses confirmed the robustness of these findings, showing a transplantation benefit particularly among patients with high tumor burden and a low Oslo score. In the overall comparison with resected SECA-I patients, recurrence free survival did not differ significantly between LT and LR (log-rank p = 0.931), whereas it was significantly better after LT among patients in TBS zone 3 (log-rank p = 0.035). Therefore, the transplantation benefit did not appear to depend on a substantial reduction in the overall frequency of recurrence, but rather on a shift toward recurrence patterns with a more favorable prognosis. Pulmonary recurrences were more represented in the LT arm and were associated with the best survival after recurrence; in the LT group, 5-year SAR was 60.4% after pulmonary recurrence compared with 25.6% after intrahepatic recurrence. In conclusion, the results of this study support the potential role of liver transplantation as a therapeutic option in selected subgroups of patients with CRLM, particularly in the presence of high tumor burden and favorable biological criteria. Liver resection remains the standard treatment for low-risk resectable patients, whereas in patients at high oncological risk, technical resectability alone may not translate into a meaningful long-term benefit. Further prospective multicenter studies are required to validate these findings and to define shared criteria for transplant selection.