Recurrence beyond the Milan criteria after curative-intent resection of hepatocellular carcinoma: a novel tumor-burden based prediction model

Background: Accurate prediction of recurrence patterns of hepatocellular carcinoma (HCC) may allow for prioritization of patients for resection or transplantation as well as guide post-resection surveillance strategies. Methods: Patients who underwent curative-intent R0 resection for HCC between 2000 and 2017 were identified using a multi-institutional database. A prognostic model that incorporated HCC tumor burden score (TBS) to predict recurrence beyond the Milan criteria (MC) was developed and validated. Results: Among 718 patients who underwent R0 resection for HCC, 185 (25.8%) recurred within and 110 (15.3%) beyond the MC. On multivariable analysis, AFP more than 400 ng/mL (hazard ratio [HR] = 2.26; 95% confidence interval [CI]: 1.27-4.02), lymphovascular invasion (HR = 2.00; 95% CI: 1.14-3.50), and TBS (HR = 1.08; 95% CI: 1.03-1.12) were associated with recurrence beyond the MC. A weighted TBS-based score was constructed: [0.074*TBS + 0.692*lymphovascular invasion (yes: 1, no: 0) + 0.816*AFP > 400 (yes:1, no:0)]. Patients with a low, medium, and high TBS-based risk score had a 5-year incidence of recurring beyond the MC of 16.2%, 28.6%, and 47.2%, respectively (P <.001). The predictive accuracy of the model was very good in the training (C-index: 0.761) and validation (C-index: 0.706) datasets and outperformed the previously reported clinical risk score (CRS; C-index: 0.680). Conclusion: A TBS-based model accurately predicted recurrence beyond MC after curative-intent resection of HCC and outperformed the CRS. Incorporating TBS allows for better risk stratification and identifies patients in need of closer surveillance.