Li Zhihao, Taner Timucin, Eaton John E, Smith Byron H, Ilyas Sumera I, Hallemeier Chris L, Tran Nguyen H, Diwan Tayyab S, Mathur Amit K, Lizaola-Mayo Blanca C, Perry Dana K, Yang Liu, Gores Gregory J, Heimbach Julie K
Division of Transplant Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN.
Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN.
Ann Surg. 2025 Sep 1;282(3):503-514. doi: 10.1097/SLA.0000000000006815. Epub 2025 Jun 23.
To develop and validate a risk score for predicting post-transplant recurrence in perihilar cholangiocarcinoma (pCCA) patients.
pCCA is an aggressive malignancy with a poor prognosis. Although neoadjuvant chemoradiation (CRT) followed by liver transplantation (LT) offers a potential cure for patients with unresectable, early-stage de novo or primary sclerosing cholangitis (PSC)-associated pCCA, post-transplant recurrence negatively impacts survival. Currently, no risk stratification tools exist.
This retrospective study included consecutive patients with unresectable de novo or PSC-associated pCCA who underwent neoadjuvant CRT followed by LT at Mayo Clinic (1993-2024). Predictors of post-transplant recurrence were identified using multivariable Cox regression with LASSO variable selection. The Perihilar Cholangiocarcinoma Risk Estimation of Tumor Recurrence after Transplant (PRETREAT) risk score was created by assigning points from model coefficients. Score performance was evaluated by discrimination (c-statistic), internally validated with 10-fold cross-validation, and externally validated in a separate cohort. Survival outcomes were compared across 3 PRETREAT risk groups and between 2 time periods.
This study included 399 patients (development: 301; validation: 98). The 5-year cumulative incidence of post-transplant recurrence was 29.7% in the development cohort and 27.6% in the validation cohort. Multivariable analysis identified 4 independent predictors: macroscopic residual tumor on explant [hazard ratio (HR): 12.4], vascular encasement (HR: 2.18), lymphovascular invasion (HR: 2.04), and radial tumor diameter (HR: 1.02/mm). The PRETREAT score (0-22), based on these factors, demonstrated excellent performance in both internal and external validation (C-index 0.83 and 0.85, respectively). Patients were stratified into low-risk (0-7), moderate-risk (8-15), and high-risk (16-22) groups. The 5-year recurrence-free survival rates significantly differed across low-risk, moderate-risk, and high-risk groups (89.0%, 38.3%, and 15.4%, respectively; P <0.001). Over the last decade, overall survival improved significantly only in moderate-risk patients (70.4% vs 46.9%, P =0.024), without significant improvement in recurrence-free survival.
The PRETREAT score provides a valuable tool for guiding post-transplant management of pCCA, enabling risk-stratified surveillance, and laying the foundation for future clinical trials.
开发并验证一种用于预测肝门部胆管癌（pCCA）患者移植后复发的风险评分。
pCCA是一种侵袭性恶性肿瘤，预后较差。尽管新辅助放化疗（CRT）后行肝移植（LT）为不可切除的早期原发性或原发性硬化性胆管炎（PSC）相关pCCA患者提供了潜在的治愈方法，但移植后复发对生存率有负面影响。目前，尚无风险分层工具。
这项回顾性研究纳入了在梅奥诊所（1993 - 2024年）接受新辅助CRT后行LT的连续不可切除原发性或PSC相关pCCA患者。使用多变量Cox回归和LASSO变量选择确定移植后复发的预测因素。通过从模型系数中分配分数创建肝门部胆管癌移植后肿瘤复发风险评估（PRETREAT）风险评分。通过辨别力（c统计量）评估评分性能，采用10倍交叉验证进行内部验证，并在一个单独队列中进行外部验证。比较3个PRETREAT风险组和2个时间段的生存结果。
本研究纳入399例患者（开发队列：301例；验证队列：98例）。开发队列中移植后复发的5年累积发生率为29.7%，验证队列中为27.6%。多变量分析确定了4个独立预测因素：切除标本上的宏观残留肿瘤[风险比（HR）：12.4]、血管包绕（HR：2.18）、淋巴管浸润（HR：2.04）和肿瘤径向直径（HR：1.02/mm）。基于这些因素的PRETREAT评分（0 - 22分）在内部和外部验证中均表现出色（C指数分别为0.83和0.85）。患者被分为低风险（0 - 7分）、中度风险（8 - 15分）和高风险（16 - 22分）组。低风险、中度风险和高风险组的5年无复发生存率有显著差异（分别为89.0%、38.3%和15.4%；P <0.001）。在过去十年中，仅中度风险患者的总生存率有显著提高（70.4%对46.9%，P =0.024），无复发生存率无显著改善。
PRETREAT评分提供了一个有价值的工具，用于指导pCCA移植后的管理，实现风险分层监测，并为未来的临床试验奠定基础。
