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

Abstract

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.Intrahepatic cholangiocarcinoma (iCCA) is the second most common type of primary liver cancer, with an incidence of 0.85 per 100,000 annually. 1,2 Although iCCA is a rare and complex disease, its incidence in in North America has increased almost five-fold, and the reasons for this increase are not clear. 3,4 Surgery remains the mainstay therapy for curative intent, but only about 20% of iCCAs are surgically resectable at the time of diagnosis. In addition, the recurrence rates after liver resection (LR) are exceedingly high, reaching 50-70% and leaving limited treatment options. [5][6][7] In fact, most of the recurrence occurs relatively early, about 25% within 6 months and 50% within 2 years after surgery. 8

Adequate lymph node dissection is essential for accurate nodal staging in intrahepatic cholangiocarcinoma: A population‐based study

“…In general, the presence of regional LNM often portends a poor prognosis. 12 , 26 , 27 , 28 A growing number of studies have shown that the number of metastatic LNs has an impact on prognosis in many cancers. 29 , 30 However, there remains insufficient data regarding their association in ICC.…”

Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival

“…In a systematic review and meta-analysis by Choi et al the authors identified four series describing early intrahepatic recurrence (defined as either 6, 12, or 24 months after resection) and noted a 49.6% 24-month intrahepatic recurrence rate, similar to our finding of 41%. 18 Unfortunately, the majority of patients will expereince liver recurrence, with most reports describing >50% isolated liver or simultaneous liver and extrahepatic Note: Data are n (%) unless noted.…”

Apparent Diffusion Coefficient MRI Shows Association With Early Progression of Unresectable Intrahepatic Cholangiocarcinoma With Combined Targeted‐Immunotherapy

“…This research also identified the role of multiple tumors and lymphatic metastasis in the prediction of EP, in line with a recently published systematic review. 31 An increase in the number of tumors and the presence of lymphatic metastasis indicates higher tumor burden in a more advanced stage, representing an essential prognostic factor for poor survival of ICC. 22 Besides, EP was more common in ICCs with ill-defined margin and APE.…”