Nakayama Toshihiro, Sasaki Kazunari, Margonis Georgios Antonios
Stanford Transplant Outcomes Research Center (STORC), Division of Abdominal Transplantation, Stanford University Medical Center, Stanford, CA, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Sloan School of Management and Operations Research Center, Massachusetts Institute of Technology, Boston, MA, USA.
Chin Clin Oncol. 2025 Aug;14(4):44. doi: 10.21037/cco-25-46.
Liver transplantation (LT) for unresectable colorectal liver metastases (uCRLM) initially showed no clear survival advantage in early attempts, leading to waning enthusiasm. Interest was revived in 2013 following the prospective, non-randomized Norwegian Secondary Cancer (SECA) I study, which reported a 5-year overall survival (OS) of 60%-far surpassing outcomes with systemic therapy alone. More recently, the TransMet randomized controlled trial demonstrated a 5-year OS of 73% in the LT-plus-chemotherapy arm vs. 9% with chemotherapy alone, a result comparable to outcomes for established LT indications. This review aims to summarize recent advances and discuss key considerations for implementing LT for uCRLM in clinical practice-particularly patient selection and standardization of protocols.
In this narrative review of currently available reports on the outcomes of LT for uCRLM, we identified eight studies [2017-2025] from European and North American centers.
Four were prospective (including one randomized trial) and three were multicenter. Their protocols varied considerably, especially regarding donor sources (living vs. deceased) and inclusion criteria for factors such as primary tumor laterality, kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status, and metabolic tumor volume. Overall, 3-year OS ranged from 62% to 100%. Recurrence-free survival (RFS) also showed wide variability, with 3-year RFS between 38% and 68.6%. Centers that employed consistent selection protocols typically reported better survival outcomes, underscoring the importance of standardization. Donor availability emerged as a key factor, with living donor LT offering an alternative in regions where deceased donor access is limited-such as North America and parts of Asia. Extended observation periods and stratification by KRAS status or tumor location (right- vs. left-sided) might help refine patient selection.
Although LT for uCRLM is no longer considered purely exploratory, questions remain about the best use of adjuvant chemotherapy. Moving forward, multicenter collaborations, standardized protocols, incorporation of tumor biology insights from resectable CRLM literature, and decision-support strategies (including artificial intelligence) may help optimize patient selection and improve outcomes in this advancing field.
不可切除的结直肠癌肝转移（uCRLM）患者的肝移植（LT）在早期尝试中最初未显示出明显的生存优势，导致人们的热情逐渐消退。2013年，前瞻性、非随机的挪威继发性癌症（SECA）I研究报告了60%的5年总生存率（OS），远超单纯全身治疗的结果，这使得人们重新燃起了兴趣。最近，转移性结直肠癌肝转移（TransMet）随机对照试验表明，肝移植联合化疗组的5年总生存率为73%，而单纯化疗组为9%，这一结果与既定肝移植适应证的结果相当。本综述旨在总结近期进展，并讨论在临床实践中对uCRLM实施肝移植的关键考虑因素，特别是患者选择和方案标准化。
在对目前关于uCRLM肝移植结果的现有报告进行的叙述性综述中，我们从欧洲和北美中心确定了八项研究[2017 - 2025年]。
四项为前瞻性研究（包括一项随机试验），三项为多中心研究。它们的方案差异很大，特别是在供体来源（活体与尸体）以及原发性肿瘤侧别、 Kirsten大鼠肉瘤病毒癌基因同源物（KRAS）突变状态和代谢肿瘤体积等因素的纳入标准方面。总体而言，3年总生存率在62%至100%之间。无复发生存率（RFS）也显示出很大差异，3年无复发生存率在38%至68.6%之间。采用一致选择方案的中心通常报告了更好的生存结果，强调了标准化的重要性。供体可用性成为一个关键因素，在尸体供体获取有限的地区，如北美和亚洲部分地区，活体供体肝移植提供了一种替代方案。延长观察期以及按KRAS状态或肿瘤位置（右侧与左侧）进行分层可能有助于优化患者选择。
尽管uCRLM的肝移植不再被视为纯粹的探索性治疗，但关于辅助化疗的最佳使用仍存在问题。展望未来，多中心合作、标准化方案、纳入可切除CRLM文献中的肿瘤生物学见解以及决策支持策略（包括人工智能）可能有助于优化患者选择并改善这一不断发展领域的治疗结果。
