Tumor Factors Associated With Poorer Overall Survival in Patients With Intrahepatic Cholangiocarcinoma Undergoing Curative Intent Surgery


Key Points

  • Tumor factors consisting of larger tumor size, presence of multiple tumors, lymph node metastasis, vascular invasion, and poor tumor differentiation were associated with poorer overall survival after curative intent surgery.
  • Earlier diagnosis and effective adjuvant therapies are needed.

There are limited data on outcomes after surgery for intrahepatic cholangiocarcinoma. In a systematic review and meta-analysis reported in JAMA Surgery, Mavros et al found that tumor characteristics are the primary predictors of survival after curative intent surgery, indicating the need for earlier diagnosis and effective adjuvant therapy.

Study Details

Investigators searched for studies published on or after January 1, 2000, that reported on prognostic factors in patients undergoing curative intent surgical treatment for intrahepatic cholangiocarcinoma. Studies published in English, French, German, Italian, or Greek were considered eligible. A total of 57 studies involving 4,756 patients were included in the analysis.

Patients had a median age range of 49 to 67 years and 57% were male. Most patients had a solitary (69%), large (median 4.5–8.0 cm) tumor of the mass-forming type (86%); 34% of patients had lymph node metastasis and 38%, 29%, and 29% had vascular, perineural, and biliary invasion. Overall, 82% of patients had a major hepatectomy, along with lymphadenectomy in 67% and extrahepatic bile duct resection in 23%.

Poor Overall Survival and Associated Factors

Median and 5-year overall survival generally were approximately 28 months (range = 9–53 months) and 30% (range = 5%–56%) in the included studies.

Factors that predicted shorter overall survival on univariate analysis in the studies included age (older in 3 vs younger in 1 of 32 studies), sex (males in 4 vs females in 1 of 32 studies), larger tumor size (15 of 35 studies), multiple tumors (13 of 23 studies), satellite nodules (5 of 7 studies), any vascular invasion (13 of 19 studies), microvascular invasion (4 of 7 studies), perineural invasion (7 of 12 studies), lymph node metastases (29 of 34 studies), positive surgical margin (R1/R2 vs R0 in 21 of 31 studies), poor tumor differentiation (12 of 22 studies), major liver resection (1 of 7 studies), concomitant resection of extrahepatic bile ducts (2 of 6 studies), cirrhosis (1 of 5 studies), concurrent chronic hepatitis B (1 of 10 studies), multiple blood transfusions (2 of 6 studies), postoperative morbidity (1 of 2 studies), and preoperative or postoperative chemotherapy (1 of 1 study). Postoperative adjuvant chemotherapy/radiotherapy was associated with longer overall survival in 3 of 10 studies. Concurrent chronic hepatitis C infection was not associated with overall survival in 3 studies.

Predictive Factors on Multivariate Analysis

Seven studies including 2,132 patients provided data for the meta-analysis. Factors associated with shorter overall survival included older age (pooled hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.03–1.17), larger tumor size (HR = 1.09, 95% CI = 1.02–1.16), presence of multiple tumors (HR = 1.70, 95% CI = 1.43–2.02), lymph node metastasis (HR = 2.09, 95% CI = 1.80–2.43), vascular invasion (HR = 1.87, 95% CI = 1.44–2.42), and poor tumor differentiation (HR = 1.41, 95% CI = 1.17–1.71). Male sex (HR = 1.11, 95% CI = 0.97–1.26) and positive surgical margin (HR = 1.06, 95% CI = 0.49–2.32) were not associated with overall survival.

The investigators concluded: “The prognosis of [intrahepatic cholangiocarcinoma] remains grave, with less than one-third of the patients who undergo curative-intent surgical treatment surviving beyond 5 years after resection. Prognosis is dictated primarily by tumor factors, such as tumor size, lymph node invasion, and vascular invasion, which underlines the necessity for earlier diagnosis. Furthermore, the high incidence of recurrence and its association with certain tumor-specific factors highlight the need for more effective adjuvant therapies. Future research should therefore target the identification of novel agents with more activity toward [intrahepatic cholangiocarcinoma] so as to increase the goal of prolonging survival among this challenging group of patients.”

Timothy M. Pawlik, MD, MPH, PhD, of Johns Hopkins University School of Medicine, is the corresponding author for the JAMA Surgery article.

The authors reported no potential conflicts of interest. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.