Liver transplantation is not currently considered a standard therapeutic option for patients with unresectable, liver-limited intrahepatic cholangiocarcinoma (iCCA) because of historically poor outcomes. However, recent studies have suggested that transplantation may have a role in highly selected patients who achieve sustained disease control following neoadjuvant treatment.
In July 2026, JHEP Reports published the study titled “Liver transplantation in unresectable intrahepatic cholangiocarcinoma following neoadjuvant chemotherapy and SIRT.”
Authors: Baptiste Giguet, Florent Artru, Heithem Jeddou, Pauline Houssel-Debry, Marc-Antoine Jegonday, Valentin Coirier, Caroline Jezequel, Alexandre Chebaro, Fabien Robin, Karim Boudjema, Yan Rolland, Etienne Garin, Luc Beuzit, Bruno Turlin, Edouard Bardou-Jacquet, Julien Edeline, and Thomas Uguen.
Selecting Patients for Liver Transplantation
This retrospective single-center study included patients who underwent liver transplantation at Rennes University Hospital for locally advanced, unresectable intrahepatic cholangiocarcinoma following neoadjuvant treatment combining chemotherapy and selective internal radiation therapy, or SIRT.
Patients considered for transplantation had to be younger than 70 years, have histologically confirmed mass-forming measurable iCCA, and have disease considered unresectable because of tumor location or the severity of underlying liver disease. Patients with lymphatic or extrahepatic tumor spread, macrovascular invasion, uncontrolled disease, or contraindications to liver transplantation were not eligible.
Multifocal iCCA with diffuse liver involvement was also an exclusion criterion.
Importantly, placement on the transplant waiting list was considered only in patients with controlled disease, defined as at least 6 months of response or stable disease during treatment, while the tumor remained unresectable. Cases were reviewed repeatedly in multidisciplinary meetings involving oncologists, hepatologists, radiologists, and surgeons.
Between January 2010 and December 2023, 147 patients underwent SIRT for unresectable liver-limited iCCA at the center. Among patients younger than 70 years, 44 achieved stable disease or a response lasting longer than 6 months. Nineteen of these patients subsequently underwent secondary liver resection. Six of the remaining 25 patients were listed for liver transplantation. Two additional patients referred from another center specifically for SIRT and transplant evaluation were also listed.
Overall, eight patients were listed, and six ultimately underwent liver transplantation. The median time from iCCA diagnosis to listing was 351 days, while the median time from listing to transplantation was 114 days.
Neoadjuvant Chemotherapy Plus SIRT
All six transplanted patients received SIRT. Four patients received gemcitabine plus cisplatin, one received gemcitabine plus cisplatin together with durvalumab, and one received LV5FU2 plus cisplatin.
The median age of the transplanted patients was 50.7 years, and three of the six patients were women. The median total tumor size at baseline was 100 mm, with a median of one tumor nodule. At the time of listing, the median total tumor size was 80 mm.
Patients underwent restaging with CT and MRI every 2 to 3 months before and after listing, while FDG-PET was performed during the pre-transplant evaluation.
Before listing, lymph node sampling was performed in five of the six patients. All five had negative lymph node results.
Five-Year Overall Survival Reached 100%
After a median follow-up of 4.9 years, 5-year overall survival among the six transplanted patients was 100%. Five-year progression-free survival was 44.4%, with a 95% confidence interval of 8.9% to 88.0%. Three patients experienced iCCA recurrence at 573, 577, and 1,180 days after liver transplantation.
All recurrences were extrahepatic. Two patients developed pulmonary recurrence and underwent surgical treatment, with no subsequent recurrence reported at the time of analysis.
One patient developed isolated lymph node recurrence and was treated with gemcitabine plus cisplatin, with a minor response at the last evaluation. Stereotactic body radiation therapy was subsequently completed.
No patient had died from tumor progression at the time of the study analysis. Pathological examination of the explanted livers showed residual tumor in all six patients, with no complete tumor responses. The median tumor size on explant was 70 mm. No lymphatic invasion was identified, while microvascular invasion was present in two patients and perineural invasion in one.
Post-Transplant Outcomes
The median length of hospitalization following liver transplantation was 12 days. According to the Dindo-Clavien classification, one patient experienced grade 1 complications, four experienced grade 2 complications, and one developed a grade 3b complication.
Arterial complications occurred in three patients, while biliary complications were reported in four patients.
Three patients developed ischemic cholangitis. One required retransplantation, another died from recurrent cholangitis and septic shock 6.4 years after transplantation, and the third remained alive and was undergoing endoscopic management at the time of reporting. One additional patient developed a bilio-biliary anastomotic stricture. No cases of primary non-function were observed.
How Did Outcomes Compare With Other Patients?
The investigators also evaluated 5-year overall survival among 44 patients after excluding patients considered non-transplantable because of age or early disease progression. Five-year overall survival was 45.3% among 19 patients who underwent secondary liver resection, 25.9% among 19 patients who underwent neither resection nor transplantation, and 100% among the six patients who ultimately underwent liver transplantation.
The difference between the three groups was statistically significant, with a p value of 0.03. However, the transplanted patients represented a highly selected subgroup. They had liver-only disease that remained unresectable despite treatment and demonstrated prolonged response or stable disease before transplantation.
A “Test-of-Time” Approach
The investigators emphasized the importance of selecting patients according to their response to neoadjuvant treatment.
In this series, patients were observed for approximately 1 year after diagnosis before transplantation. The authors described this as a “test-of-time” strategy intended to avoid transplantation in patients with rapid disease progression after first-line treatment.
The transplanted patients had relatively large tumors. Median total tumor size was 100 mm at baseline and 70 mm on explant. According to the authors, these findings suggest that response to treatment and prolonged disease stability may be more important than tumor size alone when identifying potential candidates for transplantation in this setting.
Despite the selection of patients with favorable disease control before transplantation, all six patients had residual tumor in their explanted liver. The authors noted that all observed recurrences were oligometastatic and extrahepatic, suggesting that transplantation may have contributed to local disease control in these selected patients.
What Do the Findings Mean?
This study represents one of the first series of patients with unresectable iCCA treated with neoadjuvant chemotherapy and SIRT, with highly selected patients subsequently undergoing liver transplantation. Among the six transplanted patients, 5-year overall survival was 100% and 5-year progression-free survival was 44.4%.
However, the transplanted patients represented a highly selected subgroup. Only six patients underwent transplantation over approximately 15 years, and the authors emphasized that this approach cannot currently be proposed to the majority of patients with unresectable iCCA.
The study was retrospective, conducted at a single center, and included a very small number of transplanted patients. The findings support further evaluation of a response-based selection strategy in patients with liver-limited, persistently unresectable iCCA who achieve prolonged response or stable disease following neoadjuvant systemic therapy and SIRT.
The authors concluded that prolonged response or stability under treatment may help identify appropriate candidates for liver transplantation. They emphasized the need for prospective trials evaluating SIRT combined with systemic therapy before transplantation to validate and expand these findings and determine whether iCCA could become a viable indication for liver transplantation in a carefully selected subgroup of patients.
The full article is available in JHEP Reports.
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