Does adjuvant therapy improve survival in patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma? A systematic review, meta-analysis and meta-regression

The role of adjuvant therapy (AT) after pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DC) remains controversial. This systematic review and meta-analysis aimed to evaluate the impact of AT on overall survival (OS) and disease-free survival (DFS) in patients with resected DC. A systematic review was conducted following PRISMA guidelines (PROSPERO: CRD42024561780). PubMed, Scopus, Web of Science, and Cochrane databases were searched for studies published between January 2000 and August 2023. Eligible studies included patients who underwent PD for DC, comparing AT to follow-up (FUP) alone. Primary endpoints were OS and DFS, analyzed using hazard ratios (HR) with 95% confidence intervals (CI). Meta-regression explored potential sources of heterogeneity. The analysis included 22 studies with 7078 patients (3860 FUP group, 3218 AT group): of the studies, only 3 (13.6%) were RCTs (even if none of them was specifically designed for DC). AT significantly improved OS (HR 0.80; 95% CI 0.73-0.89; p < 0.001) and DFS (HR 0.84; 95% CI 0.74-0.96; p = 0.023) compared to FUP. Subgroup analysis showed a greater benefit for chemo-radiotherapy (OS HR 0.81; 95% CI 0.72-0.91) over chemotherapy alone (OS HR 0.78; 95% CI 0.64-0.94). High heterogeneity (I-2 = 98%) was identified among the included studies. This meta-analysis demonstrates that AT is associated with improved survival outcomes in patients undergoing PD for DC. However, the significant limitations of the existing literature, particularly the lack of RCTs designed specifically for DC, necessitate caution, especially on which type of chemotherapy should be adopted.