Distal cholangiocarcinoma mimicking pancreatic ductal adenocarcinoma successfully converted to resection following PD-1/CTLA-4 bispecific immunotherapy (cadonilimab) combined with nab-paclitaxel–based chemotherapy: a case report providing preliminary real-world insight

Vollständiger Abstract

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Background Distal cholangiocarcinoma (dCCA) and pancreatic ductal adenocarcinoma (PDAC) share highly overlapping clinical presentations and radiological features, often leading to preoperative misdiagnosis. Therapeutic strategies for these malignancies differ substantially. While PDAC is commonly treated with gemcitabine plus nab-paclitaxel (AG regimen) or FOLFIRINOX as neoadjuvant or conversion therapy, first-line treatment for cholangiocarcinoma (CCA) typically consists of gemcitabine plus cisplatin (GC regimen), with or without immunotherapy. In recent years, increasing attention has been paid to immunotherapy-based combination strategies in biliary tract cancers, although their role in conversion therapy remains to be fully elucidated. Case presentation A 70-year-old male presented with upper abdominal discomfort. Imaging findings and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) suggested moderately differentiated ductal adenocarcinoma. Based on the tumor location in the pancreatic uncinate process and associated vascular involvement, the lesion was initially considered borderline resectable PDAC. The patient received neoadjuvant therapy consisting of a programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) bispecific antibody (cadonilimab) combined with the AG regimen for seven cycles. Post-treatment imaging demonstrated marked tumor regression and reduced vascular involvement. The patient subsequently underwent pancreaticoduodenectomy, with partial resection and reconstruction of the superior mesenteric vein (SMV), as well as arterial divestment of the superior mesenteric artery (SMA), achieving R0 resection. However, postoperative pathological evaluation revealed that the tumor originated from the distal bile duct, confirming a final diagnosis of dCCA. Conclusion This case highlights the limitations of EUS-FNA in accurately determining the primary tumor origin in periampullary and pancreatobiliary junction malignancies, while immunohistochemistry lacks sufficient specificity in this setting. Importantly, it demonstrates that the AG regimen combined with PD-1/CTLA-4 bispecific immunotherapy, commonly used in PDAC, may exert significant antitumor activity in dCCA, providing a novel perspective for conversion therapy in biliary tract cancers. This report offers a preliminary real-world therapeutic insight from a single case, suggesting that dual immune checkpoint blockade combined with chemotherapy may enable conversion surgery in selected patients with CCA. Further studies are warranted to elucidate the underlying immunological mechanisms.