Systematic Review and Meta-Analysis of Prognostic Factors for Early Recurrence in Intrahepatic Cholangiocarcinoma After Curative-Intent Resection

Background: Recurrence rates of intrahepatic cholangiocarcinoma (iCCA) after curative hepatectomy are as high as 50% to 70%, and about half of these recurrences occur within 2 years. This systematic review aims to define prognostic factors (PFs) for early recurrence (ER, within 24 months) and 24-month disease-free survival (DFS) after curative-intent iCCA resections. Methods: Systematic searching was performed from database inception to 14 January 2021. Duplicate independent review and data extraction were performed. Data on 13 predefined PFs were collected. Meta-analysis was performed on PFs for ER and summarized using forest plots. The Quality in Prognostic Factor Studies tool was used for risk-of-bias assessment. Results: The study enrolled 10 studies comprising 4158 patients during an accrual period ranging from 1990 to 2016. In the risk-of-bias assessment of patients who experienced ER after curative-intent iCCA resection, six studies were rated as low risk and four as moderate risk (49.6%; 95% confidence interval [CI], 49.2–50.0). Nine studies were pooled for meta-analysis. Of the postoperative PFs, multiple tumors, microvascular invasion, macrovascular invasion, lymph node metastasis, and R1 resection were associated with an increased hazard for ER or a reduced 24-month DFS, and the opposite was observed for receipt of adjuvant chemo/radiation therapy. Of the preoperative factors, cirrhosis, sex, HBV status were not associated with ER or 24-month DFS. Conclusion: The findings from this systematic review could allow for improved surveillance, prognostication, and treatment decision-making for patients with resectable iCCAs. Further well-designed prospective studies are needed to explore prognostic factors for iCCA ER with a focus on preoperative variables.