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.

Automated summary

This systematic review identifies prognostic factors for early recurrence and 24-month disease-free survival after curative-intent resection of intrahepatic cholangiocarcinoma (iCCA). Multiple tumors, microvascular invasion, macrovascular invasion, lymph node metastasis, and R1 resection were associated with increased risk for early recurrence or reduced 24-month disease-free survival. Receipt of adjuvant chemo/radiation therapy was associated with improved outcomes. Cirrhosis, sex, and HBV status were not associated with early recurrence or 24-month disease-free survival.