Profesionales médicos

Jan. 07, 2026

Perihilar cholangiocarcinoma (pCCA) is one of the most challenging cancers to treat, especially in patients whose tumors are unresectable. Neoadjuvant chemoradiation therapy (CRT) followed by liver transplantation (LT) has emerged as a potentially curative option, yet nearly 1 out of 3 patients with pCCA experiences recurrence after transplant that significantly impacts survival.

Researchers have identified several risk factors associated with post-transplant recurrence. However, the management of patients with pCCA is hindered by the lack of an accurate risk stratification tool to help guide surveillance strategy and facilitate the development of adjuvant therapy.

In an article published in the Annals of Surgery in 2025, researchers from Mayo Clinic William J. von Liebig Center for Transplantation and Clinical Regeneration describe their efforts to develop and validate a risk score. The novel risk prediction model uses readily available clinical and pathological factors to predict post-transplant pCCA recurrence.

Methods

The researchers conducted a retrospective, multicenter study that included 399 patients with unresectable de novo or primary sclerosing cholangitis (PSC)-associated pCCA who underwent neoadjuvant CRT followed by LT at Mayo Clinic from 1993 to 2024. Of the 399 patients, 301 were in the development cohort and 98 were in the validation cohort.

Using multivariable Cox regression with a Least Absolute Shrinkage and Selection Operator (LASSO) variable selection, the researchers identified several predictors of post-transplant recurrence and created the Perihilar Cholangiocarcinoma Risk Estimation of Tumor Recurrence After Transplant (PRETREAT) risk score by assigning points from model coefficients. The researchers then evaluated the PRETREAT score performance by discrimination (c-statistic), internally validating it with tenfold cross-validation and externally validating it in a separate cohort.

Patients were stratified into three different risk groups based on their PRETREAT scores: low risk (0 to 7), moderate risk (8 to 15) and high risk (16 to 22). The researchers also compared survival outcomes achieved by the combined study population (development and validation cohorts) during two time periods — 1993 to 2014 and 2015 to 2024. This stratification was performed to help researchers determine whether significant outcome improvements occurred in the most recent decade and to create comparably sized groups.

Results and conclusions

"Until now, clinicians have lacked a reliable way to identify which patients are most at risk of recurrence after transplant, making post-transplant management largely uniform rather than tailored to individual risk," explains first author Zhihao Li, M.D., an abdominal transplant surgery fellow at Mayo Clinic in Rochester, Minnesota. "The PRETREAT score provides, for the first time, a validated framework to estimate recurrence risk based on readily available clinical and pathological factors."

Overall, the five-year cumulative incidence of post-transplant recurrence was 29.7% in the development cohort and 27.6% in the validation cohort. Specific research findings demonstrating the performance of the PRETREAT score include the following:

• Multivariable analysis identified four independent predictors of pCCA recurrence: macroscopic residual tumor on explant, vascular encasement, lymphovascular invasion and radial tumor diameter.
• The PRETREAT score achieved a C-index of 0.849 and demonstrated excellent performance in both internal validation (C-index of 0.83) and external validation (C-index of 0.85).
• Patients in the low-risk group achieved a significantly higher five-year recurrence-free survival rate (89.0%) than patients in the moderate-risk (38.3%) and high-risk (15.4%) groups.
• In comparing the five-year overall survival rates achieved during the two time periods studied, only patients in the moderate-risk group experienced a statistically significant improvement. Results showed 46.9% in the 1993 to 2014 era versus 70.4% in the 2015 to 2024 era.

The co-authors explain that this risk stratification model has direct implications for clinical practice. "This tool will allow clinicians to tailor surveillance intensity, focusing closer monitoring and earlier imaging on patients at highest risk, while avoiding unnecessary testing in patients with low risk," says Dr. Li. "It may also help guide discussions around prognosis and long-term expectations with patients and families in a more informed and individualized way. Moreover, the score establishes a foundation for designing future clinical trials by identifying the subgroup of patients most likely to benefit from additional therapy or modified immunosuppression strategies."

Next steps

The research team plans to prospectively validate the PRETREAT score in routine clinical practice and to develop risk-stratified clinical trials. These efforts could include conducting studies evaluating adjuvant systemic therapy or alternative immunosuppression approaches in patients who are at high risk of pCCA recurrence. The researchers also plan to examine the integration of molecular biomarkers such as circulating tumor DNA and tumor genomic signatures, which may enhance predictive accuracy and offer insight into potential therapeutic targets.

"Ultimately, the goal is not simply to predict recurrence, but to intervene in ways that improve long-term survival for individuals who currently face the highest risk," says Dr. Li.

For more information

Li Z, et al. Development of the Perihilar Cholangiocarcinoma Risk Estimation of Tumor Recurrence After Transplant (PRETREAT) score. Annals of Surgery. 2025;282:503.

Refer a patient to Mayo Clinic.