JMIR Publications

ABSTRACT

Background:

Cholangiocarcinoma (CCA), a bile duct cancer with rising incidence and poor prognosis, is often diagnosed late due to nonspecific symptoms and diagnostic challenges. Surgical resection offers potential cure but is feasible in only 20-35% of cases; recurrence rates remain high. Current guidelines recommend adjuvant chemotherapy but do not endorse neoadjuvant therapy. Emerging immunotherapies and targeted treatments show promise, with ongoing studies exploring their neoadjuvant use. Given limited past research mostly from small, retrospective studies, a systematic review and meta-analysis on neoadjuvant therapy’s safety and efficacy in CCA is warranted to improve treatment strategies and outcomes.

Objective:

This systematic review aims to assess the safety and efficacy of neoadjuvant therapy for patients with bile duct cancer.

Methods:

This systematic review will include randomized controlled trials (RCTs) and non-randomized controlled cohort or observational studies comparing neoadjuvant therapy followed by surgery versus upfront surgery in adult patients (≥18 years) diagnosed with CCA eligible for curative intent surgery, including liver transplantation. Studies lacking a comparator or focusing solely on palliative or biliary drainage treatments will be excluded. Interventions encompass chemotherapy, targeted therapy, immunotherapy, or chemoradiotherapy as neoadjuvant treatments prior to surgery. Primary outcomes include progression-free, event-free, relapse-free, and overall survival, and 12-month progression-free survival. Secondary outcomes cover R0 resection rates, postoperative complications, 30-day readmission, 90-day mortality, and quality of life. Comprehensive searches across multiple databases without language or publication status restrictions will be conducted. Study selection and data extraction will be independently performed by two reviewers, with risk of bias assessed by Cochrane tools. Meta-analyses using random-effects models will pool data when appropriate; otherwise, narrative synthesis will be provided. Subgroup and sensitivity analyses will explore heterogeneity and assess robustness.

Results:

The review follows Cochrane and PRISMA guidelines to ensure rigorous, transparent methodology. Recent systematic reviews show neoadjuvant therapy before surgery may improve survival in cholangiocarcinoma but rely on retrospective studies with clinical heterogeneity.

Conclusions:

To address the mentioned issues, the planned review will analyse pooled biliary tract cancers, then intrahepatic and extrahepatic CCA separately, using a comprehensive, multilingual search to reduce bias. Clinical Trial: Systematic review registration: PROSPERO CRD420251111270 https://www.crd.york.ac.uk/PROSPERO/view/CRD420251111270