Sex-based differences in survival after liver transplantation for colorectal cancer liver metastases: A multivariable analysis

IF 7.5 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

JHEP Reports Pub Date : 2025-06-27 DOI:10.1016/j.jhepr.2025.101505

Alessandro Vitale , Jacopo Lanari , Umberto Cillo , Ilaria Billato , Alessandro Rovetta , Mohammad Ali Mansournia , Matteo Cescon , Matteo Serenari , Federico Aucejo , Bassam Estfan , Laurent Coubeau , Samuele Iesari , Vincenzo Mazzaferro , Carlo Sposito , Roberto Hernandez-Alejandro , Koji Tomiyama , Morten Hagness , Svein Dueland , Pål Dag Line

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引用次数: 0

Abstract

Background & aims

Liver transplantation (LT) for colorectal liver metastases (CRLMs) is attracting increasing interest, especially after publication of the TransMet trial. However, multivariable survival analyses are lacking. Here, we performed such an analysis in a multicentre cohort.

Methods

We conducted a retrospective multicentre study of 82 patients with CRLMs undergoing LT (from 2006 to 2020) across seven US and European centres, using multivariable Cox, competing-risk models, and extensive sensitivity analyses.

Results

Overall survival rates after 1, 3, and 5 years were 93.7%, 73.4%, and 54.9%, respectively. The findings align with an association between higher risk and the female sex (estimated hazard ratio (HR) 4.1, 95% CI: 1.8–9.2), and the following variables: carcinoembryonic antigen >80 μg/L, right-located colorectal cancer (CRC), largest diameter >5.5 cm, KRAS mutation, and absence of previous liver therapy. Other possible associations with higher uncertainty were pN2-positive CRC and the number of nodules (>10). Variables such as progressive disease after pretransplant chemotherapy and time from primary CRC surgery to LT of ≤24 months, exhibited weaker, less consistent associations.

Conclusions

This first multivariable survival analysis of LT for CRLM suggests that female sex is associated with worse outcomes, whereas the prognostic strength of the model currently used in clinical practice is not confirmed. Our findings challenge current selection criteria, highlighting the need for improved prognostic models with better discrimination and calibration.

Impact and implications

This multicentre retrospective study analysed survival outcomes in 82 patients undergoing liver transplantation for colorectal liver metastases across seven US and European centres. Several factors, including female sex, high carcinoembryonic antigen levels, right-sided colorectal cancer, larger tumours, KRAS mutation, pN2-positive CRC, number of nodules, and no prior liver therapy, were linked to poorer outcomes. The study questions current prognostic models and selection criteria, emphasizing the need for more accurate tools to guide decision-making in patients with colorectal liver metastases.

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结直肠癌肝转移患者肝移植术后生存率的性别差异：一项多变量分析

背景：银移植（LT）治疗结直肠癌肝转移（crlm）正引起越来越多的兴趣，特别是在TransMet试验发表后。然而，缺乏多变量生存分析。在这里，我们在一个多中心队列中进行了这样的分析。方法：我们对美国和欧洲7个中心的82例接受肝移植的crlm患者（2006年至2020年）进行了回顾性多中心研究，使用多变量Cox、竞争风险模型和广泛的敏感性分析。结果1年、3年、5年总生存率分别为93.7%、73.4%、54.9%。研究结果表明，高风险与女性相关（估计风险比（HR） 4.1, 95% CI: 1.8-9.2），以及以下变量：癌胚抗原80 μg/L，右位结直肠癌（CRC），最大直径5.5 cm， KRAS突变，既往未接受肝脏治疗。其他具有较高不确定性的可能关联是pn2阳性CRC和结节数量（>10）。诸如移植前化疗后疾病进展和从原发性结直肠癌手术到肝移植≤24个月的时间等变量表现出较弱且不一致的相关性。这是首个针对CRLM患者的多变量生存分析，表明女性与较差的预后相关，而目前临床实践中使用的模型的预后强度尚未得到证实。我们的研究结果挑战了当前的选择标准，强调需要改进预后模型，使其具有更好的辨别和校准能力。影响和意义这项多中心回顾性研究分析了美国和欧洲7个中心的82例结肠直肠癌肝转移患者接受肝移植的生存结果。包括女性、高癌胚抗原水平、右侧结直肠癌、较大肿瘤、KRAS突变、pn2阳性结直肠癌、结节数量以及先前未接受肝脏治疗在内的几个因素与较差的预后有关。该研究质疑了目前的预后模型和选择标准，强调需要更准确的工具来指导结直肠肝转移患者的决策。

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来源期刊

JHEP Reports GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

12.40

自引率

2.40%

发文量

161

审稿时长

36 days

期刊介绍： JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology. The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies. In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.