Application of Hazard Function to Investigate Recurrence of Intrahepatic Cholangiocarcinoma After Curative-Intent Liver Resection: A Novel Approach to Characterize Recurrence

Purpose To investigate recurrence patterns after surgery for intrahepatic cholangiocarcinoma (ICC) relative to lymph node status, tumor extension, tumor burden score (TBS), and adjuvant chemotherapy. Methods Patients who underwent curative-intent resection for ICC from 1990 to 2020 were enrolled from a multi-institutional database. The hazard function was applied to plot the hazard rates over time, with further stratification by T and N AJCC 8th edition categories, TBS, and adjuvant chemotherapy. Results A total of 1192 patients underwent curative-intent resection for ICC and 59.9% experienced recurrence. Overall, the peak of recurrence occurred at 6.6 months. Among patients with negative lymph nodes, the T4-category had a higher peak rate of recurrence (0.1199 at 10.2 months) compared with other T-categories, while high TBS had an earlier peak of recurrence (4.2 months) compared with lower TBS. Among patients with N1 disease, T2-T4 categories had multipeak patterns of recurrence with higher hazard rates during the first 3 years after surgery in comparison with T1-category, while patients with high TBS had an earlier (4.0 months) and higher hazard peak rate compared with lower TBS groups. The administration of adjuvant chemotherapy was associated with delayed hazard rates of recurrence for N1 (4 months) and NX (6 months) categories. Discussion The novel application of the hazard function to assess hazard rates and timing patterns of recurrence following resection for ICC demonstrated that recurrence varied based on T- and N-categories, as well as TBS. Hazard function-based recurrence data may be helpful to tailor counseling, surveillance, and adjuvant therapy recommendations.

Automated summary

This study aimed to investigate the patterns of recurrence after surgery for intrahepatic cholangiocarcinoma (ICC) in relation to lymph node status, tumor extension, tumor burden score (TBS), and adjuvant chemotherapy. The results showed that the peak of recurrence typically occurred at 6.6 months after surgery. Among patients with negative lymph nodes, T4-category had a higher peak rate of recurrence compared to other T-categories, while high TBS was associated with an earlier peak of recurrence. Among patients with positive lymph nodes, T2-T4 categories had multiple peaks of recurrence with higher hazard rates during the first 3 years after surgery compared to the T1-category, and high TBS groups had an earlier and higher peak rate of recurrence. The administration of adjuvant chemotherapy was associated with delayed hazard rates of recurrence.