Risk factors and patterns of postoperative recurrence in distal cholangiocarcinoma: A systematic review and
Si-Qi Yang1, Fei Liu1, Pei-Yan Sun1
1Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Background:
Distal cholangiocarcinoma (dCCA) is characterized by an unfavorable prognosis and high recurrence rates even after curative-intent resection. This study aimed to evaluate clinicopathological factors associated with postoperative recurrence.
Methods:
This systematic review and meta-analysis followed PRISMA guidelines. Electronic databases including MEDLINE, Embase, the Cochrane Library, and Web of Science were searched through February 10, 2026. When both adjusted and unadjusted estimates were available, multivariable-adjusted estimates were preferentially extracted. Meta-analyses restricted to adjusted estimates were performed, alongside complementary analyses incorporating all available estimates.
Results:
Among 2043 identified publications, 41 studies involving 7836 patients met eligibility criteria. Adjusted-only analyses showed significant associations between postoperative recurrence and female sex, elevated CA19-9 and CEA levels, larger tumor size, advanced T stage, lymph node metastasis (LNM), lymph node ratio, poor differentiation, lymphovascular invasion (LVI), microvascular invasion (MVI), perineural invasion (PNI), portal vein invasion, vascular resection, R1 resection and adjuvant therapy. Regarding specific recurrence patterns, CA19-9, poor tumor differentiation, LNM, LVI, MVI, PNI, vascular resection and R1 resection were significantly associated with an increased risk of early recurrence. For local recurrence, LNM, poor tumor differentiation and R1 resection were significantly associated with local recurrence.
Conclusion:
Fifteen factors remained associated with postoperative recurrence after restriction to adjusted estimates. However, heterogeneous adjustment strategies, correlated prognostic variables, and predominantly retrospective evidence limit causal or fully independent interpretation. Prospective studies using standardized definitions and harmonized adjustment strategies are needed.