Impact of tumor burden score on timing and patterns of recurrence after curative-intent resection of hepatocellular carcinoma

Background: The ability to predict the incidence, timing, and site of recurrence can be beneficial to select surgical candidates and inform appropriate postoperative surveillance. We sought to identify factors associated with risk and timing of recurrence after resection of hepatocellular carcinoma based on differences in tumor burden score. Methods: Patients who underwent curative-intent liver resection for hepatocellular carcinoma between 2000 and 2020 were identified from an international multi-institutional database. The incidence, timing, and pattern of recurrence was examined relative to traditional clinicopathological factors, as well as tumor burden score using hazard rates and multivariable analysis. Results: Among 1,994 patients (tumor burden score, low: n = 511, 25.6% vs medium: n = 1,286, 64.5% vs high: n = 197, 9.9%), the incidence of recurrence at 5 years was 50.4% (95% confidence interval 47.9-53.0); risk of recurrence varied relative to hepatocellular carcinoma tumor burden score (low: 36.0% vs medium: 54.4% vs high: 62.5%, P < .001). Although intrahepatic recurrence was much more common in low tumor burden score (low: n = 106, 84.1% vs medium: n = 335, 71.7% vs high: n = 48, 56.5%; P < .001), extrahepatic recurrence was more common in high tumor burden score (low: n = 18, 14.3% vs medium: n = 121, 25.9% vs high: n = 37, 43.5%; P < .001). The peak hazard rate for intrahepatic recurrence among patients with a high tumor burden score was almost double the peak hazard noted among patients with a low tumor burden score (low: 0.047, 42.0 months vs medium: 0.051, 6.6 months vs high: 0.094, 15.0 months). Of note, the patients with high tumor burden score were also more likely to recur earlier (≤24 months) (low: n = 227, 44.4% vs medium: n = 686, 53.3% vs high: n = 144, 73.1%) with multiple tumors (low: n = 50, 36.5% vs medium: n = 271, 56.1% vs high: n = 52, 70.3%) and larger lesions (low: 1.8 [interquartile range 1.2-3.0] cm vs medium: 2.0 [interquartile range 1.3-3.0] cm vs high: 2.5 [interquartile range 1.6-4.4] cm) (all P < .001). On multivariable analysis, high tumor burden score remained independently associated with risk of recurrence (referent, low; medium: hazard ratio = 1.49 [95% confidence interval 1.19-1.88], P = .001; high: hazard ratio = 1.95 [95% confidence interval 1.41-2.69]; P < .001]. Conclusion: Tumor burden score was independently associated with higher risk of recurrence. Patients who underwent resection of high tumor burden score lesions were more likely to recur early with multiple tumors and at an extrahepatic site. Tumor burden score is an important tool in assessing risk, timing, and pattern of recurrence after resection of hepatocellular carcinoma.