Pathological Complete Response after Conversion Surgery for Distal Cholangiocarcinoma with High Tumor Mutational...

Pathological complete response (pCR) following conversion resection after chemotherapy for initially unresectable distal cholangiocarcinoma (DCC) is rare. The efficacy of the immune checkpoint inhibitors (ICIs) pembrolizumab and durvalumab for treating unresectable biliary tract cancer (BTC) has been reported in randomized trials, and they are used as first-line therapies, regardless of specific genetic mutations. High tumor mutation burden (TMB-High) has gained attention as a biomarker for predicting treatment response to ICI; however, it has been reported to be rare in BTC.

A 78-year-old man was referred to our hospital after mild liver dysfunction was detected during a routine medical checkup. Contrast-enhanced CT revealed wall thickening with contrast enhancement of the distal bile duct. Endoscopic ultrasonography revealed an irregular hypoechoic mass in the distal bile duct. Endoscopic retrograde cholangiopancreatography confirmed a distal bile duct stricture, and biopsy of the stricture site confirmed adenocarcinoma. Further evaluation revealed DCC with para-aortic lymph node (PALN) metastasis. The tumor was initially considered unresectable. Comprehensive cancer genomic profiling using tissue samples revealed TMB-High. The patient underwent 8 cycles of systemic chemotherapy consisting of gemcitabine, cisplatin, and durvalumab, followed by durvalumab monotherapy. After more than 1 year of chemotherapy, improvement in the bile duct stricture was confirmed, and complete disappearance of fluorodeoxyglucose uptake in the primary lesion and PALNs was observed. Based on these findings, conversion surgery was considered feasible, and subtotal stomach-preserving pancreaticoduodenectomy was performed. Histopathological examination revealed no residual tumor in the distal bile duct or PALNs. The therapeutic effect was grade 4, indicating pCR. The patient remains alive without recurrence 6 months after surgery.

We encountered a case of TMB-High DCC in which conversion resection became feasible after systemic chemotherapy including the ICI durvalumab, resulting in pCR.