Implications of CA19-9 elevation for survival, staging, and treatment sequencing in intrahepatic cholangiocarcinoma: A national cohort analysis

Abstract

Background Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 remains undefined. We hypothesized CA19-9 elevation above normal indicates aggressive biology and that inclusion of CA19-9 would improve staging discrimination. Methods The National Cancer Data Base (NCDB-2010-2012) was reviewed for patients with ICCA and reported CA19-9. Patients were stratified by CA19-9 above/below normal reference range. Unadjusted Kaplan–Meier and adjusted Cox-proportional-hazards analysis of overall survival (OS) were performed. Results A total of 2,816 patients were included: 938 (33.3%) normal; 1,878 (66.7%) elevated CA19-9 levels. Demographic/pathologic and chemotherapy/radiation were similar between groups, but patients with elevated CA19-9 had more nodal metastases and less likely to undergo resection. Among elevated-CA19-9 patients, stage-specific survival was decreased in all stages. Resected patients with CA19-9 elevation had similar peri-operative outcomes but decreased long-term survival. In adjusted analysis, CA19-9 elevation independently predicted increased mortality with impact similar to node-positivity, positive-margin resection, and non-receipt of chemotherapy. Proposed staging system including CA19-9 improved survival discrimination over AJCC 7th edition. Conclusion Elevated CA19-9 is an independent risk factor for mortality in ICCA similar in impact to nodal metastases and positive resection margins. Inclusion of CA19-9 in a proposed staging system increases discrimination. Multi-disciplinary therapy should be considered in patients with ICCA and CA19-9 elevation.

Impact of serum carbohydrate antigen 19‐9 level on prognosis and prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma

“…Bergquist et al . performed a large‐scale retrospective analysis of s‐CA19‐9 in patients with ICC, and a significant association between s‐CA19‐9 and regional lymph node status was identified . Shen et al .…”

“…Bergquist et al performed a large-scale retrospective analysis of s-CA19-9 in patients with ICC, and a significant association between s-CA19-9 and regional lymph node status was identified. 26 Shen et al also reported a significant relationship between elevation of s-CA19-9 and pN1 according to logistic regression analysis. 27 However, the cut-off value for s-CA19-9 of 37 U/mL was set based solely on the upper limit of the normal range in those institutions, and the detailed strategies of regional lymph node dissection were not described.…”

“…Bergquist et al . also focused on the impact of s‐CA19‐9 for survival and management of ICC patients and proposed a new staging system including s‐CA19‐9 level to stratify overall survival . In the present study, the prognosis of ICC patients with a high s‐CA19‐9 level ≥ 100 U/mL was significantly poor even in the absence of regional lymph node metastasis (pN0).…”

“…in 1979 and is widely known as a useful biomarker in the diagnosis of several adenocarcinomas, including cholangiocarcinoma . In addition, some reports have identified preoperative serum CA19‐9 (s‐CA19‐9) level as an independent prognostic factor in ICC patients . However, no previous studies have examined in detail the role of s‐CA19‐9 for the preoperative prediction of lymph node metastasis in ICC patients.…”

“…[22][23][24][25] In addition, some reports have identified preoperative serum CA19-9 (s-CA19-9) level as an independent prognostic factor in ICC patients. [5][6][7][8][9]15,[26][27][28] However, no previous studies have examined in detail the role of s-CA19-9 for the preoperative prediction of lymph node metastasis in ICC patients. One reason might be that the criteria for the operability of ICC have differed among institutions.…”