Time-varying hazards of recurrence patterns among patients with colorectal liver metastases undergoing liver resection and the role of the modified tumor burden score

Background: Hepatectomy remains the standard treatment for colorectal liver metastases (CRLM), yet over half of patients recur within two years. Optimizing postoperative surveillance is important for timely detection and improved survival. The objective of the current study was to characterize recurrence patterns following CRLM hepatectomy, identify peak time of recurrence based on these patterns, assess the predictive role of the modified Tumor Burden Score (mTBS), and analyze post-recurrence survival by pattern to inform more personalized follow-up. Materials and methods: Patients undergoing curative-intent CRLM resection (2000-2023) were identified from a multi-institutional database. Outcomes included recurrence-free survival and recurrence hazard functions for isolated liver, isolated lung, isolated non-liver/lung, intra-/extrahepatic multi-site, and extrahepatic multi-site recurrences. Analyses used flexible parametric modeling, Kaplan-Meier curves, and Cox regression. Results: Among 962 patients, median age was 63.0 years (IQR 55.0-69.0) and most individuals had ASA class>2 (n = 622, 64.7 %). Bilateral disease was associated with a higher incidence of R1 resection (20.9 % vs. 14.4 %) and higher mTBS (8.1, IQR 5.9-11.5 vs. 3.4, IQR 2.2-5.1) than unilateral CRLM. Among 511 patients who recurred, isolated liver recurrence was most common (49.7 %), followed by intra-/extrahepatic multi-site (21.7 %), isolated non-liver/lung (11.7 %), isolated lung (11.0 %), and extrahepatic multi-site (5.9 %). Peak recurrence hazards were observed for isolated liver at 5 months (0.025) and intra-/extrahepatic multi-site at 8 months (0.012); smaller, earlier peaks were observed for other patterns of recurrence. Isolated lung recurrence peaked at 14 months. mTBS influenced hazard magnitude, particularly for hepatic recurrences, but not the timing. Conclusion: Distinct time-varying recurrence hazards following CRLM resection highlight the need for early, tailored surveillance, particularly in high burden, bilateral, and liver-involved disease.