Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma Considering Alternative Treatment Approaches

Importance Although surgery offers the best chance of a potential cure for patients with localized, resectable intrahepatic cholangiocarcinoma (ICC), prognosis of patients remains dismal largely because of a high incidence of recurrence. Objective To predict very early recurrence (VER) (ie, recurrence within 6 months after surgery) following resection for ICC in the pre- and postoperative setting. Design, Setting, and Participants Patients who underwent curative-intent resection for ICC between May 1990 and July 2016 were identified from an international multi-institutional database. The study was conducted at The Ohio State University in collaboration with all other participating institutions. The data were analyzed in December 2019. Main Outcomes and Measures Two logistic regression models were constructed to predict VER based on pre- and postoperative variables. The final models were used to develop an online calculator to predict VER and the tool was internally and externally validated. Results Among 880 patients (median age, 59 years [interquartile range, 51-68 years]; 388 women [44.1%]; 428 [50.2%] white; 377 [44.3%] Asian; 27 [3.2%] black]), 196 (22.3%) developed VER. The 5-year overall survival among patients with and without VER was 8.9% vs 49.8%, respectively (P < .001). A preoperative model was able to stratify patients relative to the risk for VER: low risk (6-month recurrence-free survival [RFS], 87.7%), intermediate risk (6-month RFS, 72.3%), and high risk (6-month RFS, 49.5%) (log-rank P < .001). The postoperative model similarly identified discrete cohorts of patients based on probability for VER: low risk (6-month RFS, 90.0%), intermediate risk (6-month RFS, 73.1%), and high risk (6-month RFS, 48.5%) (log-rank, P < .001). The calibration and predictive accuracy of the pre- and postoperative models were good in the training (C index: preoperative, 0.710; postoperative, 0.722) as well as the internal (C index: preoperative, 0.715; postoperative, 0.728; bootstrapping resamples, n = 5000) and external (C index: postoperative, 0.672) validation data sets. Conclusion and Relevance An easy-to-use online calculator was developed to help clinicians predict the chance of VER after curative-intent resection for ICC. The tool performed well on internal and external validation. This tool may help clinicians in the preoperative selection of patients for neoadjuvant therapy as well as during the postoperative period to inform surveillance strategies. Question Which patients will develop very early recurrence (VER) (ie, recurrence within 6 months) after resection for intrahepatic cholangiocarcinoma and are the best candidates for neoadjuvant chemotherapy? Findings In this multi-institutional cohort study, 196 patients (22.3%) developed VER following resection with a detrimental association with overall survival (5-year overall survival, 8.9%). Two predictive models were developed to identify high-risk patients for VER in the pre- and postoperative setting with a good predictive accuracy in the training as well as the internal and external validation data sets. Meaning These data emphasize that VER is common after intrahepatic cholangiocarcinoma resection and highlight the need for an alternative treatment approach (ie, neoadjuvant chemotherapy) for high-risk patients. This cohort study examines very early recurrence following resection for intrahepatic cholangiocarcinoma in the preoperative and postoperative setting.