Li Zhihao, Chen Itsuko Chih-Yi, Centonze Leonardo, Magyar Christian T J, Choi Woo Jin, Shah Sachin, O'Kane Grainne M, Vogel Arndt, De Carlis Luciano, Lerut Jan, Lai Quirino, Mehta Neil, Chen Chao-Long, Sapisochin Gonzalo
HBP & Multi-Organ Transplant Program, Department of Surgery, University Health Network, Toronto, Ontario, Canada.
Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Liver Transpl. 2025 Apr 1;31(4):450-463. doi: 10.1097/LVT.0000000000000501. Epub 2024 Oct 3.
Posttransplant HCC recurrence significantly impacts survival, yet its management is challenging due to limited evidence. With recent advancements in HCC treatment, updated data on managing recurrent diseases are needed. In this retrospective study across 6 centers (2000-2022), we employed Cox proportional-hazards regression and log-rank tests to assess survival differences. A prognostic score model was developed to categorize patient survival. The efficacy of tyrosine kinase inhibitors was evaluated through propensity score matching. In our study, 431 of 3349 (14%) patients with HCC who underwent transplantation developed recurrence within a median interval of 18 (IQR: 9-32) months. One hundred forty-seven (34%) underwent curative-intent treatments, 207 (48%) received palliative treatments, and 77 (18%) were given best-supportive care. Patients undergoing curative-intent treatments had better survival from the time of recurrence with a median survival of 45 (95% CI: 36-63) months and 1/3/5-year survival of 90%/56%/43% compared to those receiving noncurative treatments (median: 11 [95% CI: 10-13] mo, 1/3/5-y survival of 46%/10%/7%, log-rank p < 0.001). Patients with recurrence diagnosed in the era 2018-2022 showed improved survival over the previous era (HR 0.64 [95% CI: 0.47-0.86]). Multivariable analysis identified 5 prognostic factors: ineligibility for curative-intent treatment (HR: 3.5 [95% CI: 2.7-4.6]), recurrence within 1 year (HR: 1.7 [95% CI: 1.3-2.1]), poor tumor differentiation (HR: 1.5 [95% CI: 1.1-1.9]), RETREAT score ≥3 (HR: 1.4 [95% CI: 1.1-1.8]), and alpha-fetoprotein at recurrence ≥400 ng/mL (HR: 1.4 [95% CI: 1.1-1.9]). These factors contributed to a prognostic scoring system (0-9) that stratified patients into 3 prognosis groups. Both propensity score-matched analysis and multivariable regression indicated that lenvatinib was not statistically superior to sorafenib in terms of efficacy. Curative-intent treatments should be advocated for patients with posttransplant recurrence whenever possible. Prognostic factors linked to aggressive tumor biology significantly influence survival. Advancements in HCC management have improved survival outcomes over the past 5 years.
肝移植后肝癌复发对生存有显著影响,但由于证据有限,其管理具有挑战性。随着肝癌治疗的最新进展,需要有关复发性疾病管理的最新数据。在这项跨越6个中心(2000 - 2022年)的回顾性研究中,我们采用Cox比例风险回归和对数秩检验来评估生存差异。开发了一种预后评分模型来对患者生存进行分类。通过倾向得分匹配评估酪氨酸激酶抑制剂的疗效。在我们的研究中,3349例接受移植的肝癌患者中有431例(14%)在中位间隔18个月(IQR:9 - 32)内出现复发。147例(34%)接受了根治性治疗,207例(48%)接受了姑息性治疗,77例(18%)接受了最佳支持治疗。与接受非根治性治疗的患者相比,接受根治性治疗的患者从复发时起的生存期更好,中位生存期为45个月(95% CI:36 - 63),1/3/5年生存率分别为90%/56%/43%(非根治性治疗患者的中位生存期为11个月[95% CI:10 - 13],1/3/5年生存率分别为46%/10%/7%,对数秩检验p < 0.001)。在2018 - 2022年期间诊断为复发的患者的生存期较前一个时期有所改善(HR 0.64 [95% CI:0.47 - 0.86])。多变量分析确定了5个预后因素:不符合根治性治疗条件(HR:3.5 [95% CI:2.7 - 4.6])、1年内复发(HR:1.7 [95% CI:1.3 - 2.1])、肿瘤分化差(HR:1.5 [95% CI:1.1 - 1.9])、RETREAT评分≥3(HR:1.4 [95% CI:1.1 - 1.8])以及复发时甲胎蛋白≥400 ng/mL(HR:1.4 [95% CI:1.1 - 1.9])。这些因素促成了一个预后评分系统(0 - 9),该系统将患者分为3个预后组。倾向得分匹配分析和多变量回归均表明,在疗效方面,乐伐替尼在统计学上并不优于索拉非尼。对于肝移植后复发的患者,应尽可能提倡根治性治疗。与侵袭性肿瘤生物学相关的预后因素显著影响生存。在过去5年中,肝癌管理的进展改善了生存结果。