Extrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive cancer with poor prognosis. ECCA can be further subcategorised in perihilar and distal cholangiocarcinoma (pCCA and dCCA). Surgical resection is the only potential cure, but only one-third of patients are eligible. Even among those deemed resectable, a significant portion (≈30%) experience disease progression before surgery, while another 30% are found unresectable during exploration. High recurrence rates and postoperative complications further limit survival, with 5-year overall survival ranging from 13% (R1 resection) to 40% (R0 resection). Given the long preoperative work-up period and lack of treatment during this phase, a neoadjuvant approach may improve outcomes by increasing R0 resections, reducing recurrence, and optimizing patient selection.
This multicenter, randomized phase 2B/3 trial aims to assess whether neoadjuvant gemcitabine and cisplatin plus perioperative pembrolizumab improves event-free survival in patients with resectable and borderline resectable pCCA and dCCA.
Histologically or cytologically confirmed resectable or borderline resectable pCCA and dCCA. These are all the patients considered candidates for upfront surgical exploration, with intent to resect, as confirmed by local MDT and the study expert panel also taking into consideration endoscopic and radiological findings. In cases where drainage is not required, patients with a disease highly suspicious for extrahepatic cholangiocarcinoma, as determined by the expert MDT, may be included without histological proof to prevent unnecessary post-ERCP complications.
Successful drainage, in case of clinical significant bile duct obstruction.
MidCCA inclusion in the NEODISCO-trial will be permitted and will be included according to the proposed type of resection.
Male/female participants who are at least 18 years of age on the day of signing informed consent.
Upfront "clearly" unresectable pCCA: circumferential unreconstructable vascular involvement of the FLR and/or insufficient FLR for potential radical resection. Insufficient FLR is defined as <30% residual volume or a function <2.7 min/m2. Patients considered borderline resectable but, by the discretion of the MDT, not a candidate for upfront exploration/resection, are considered ineligible for NEODISCO.
Upfront clearly unresectable dCCA (following DPCG criteria).
Patients with proven N2 lymph nodes (according to the AJCC 8th edition).
PCCA eligible for liver transplantation.
Amsterdam UMC, location VUmc
Lead sponsor
Maastricht University Medical Center
Collaborator
UMC Utrecht
Collaborator
University Medical Center Groningen
Collaborator
Erasmus Medical Center
Collaborator