Total Tumor Volume Is a Better Marker of Tumor Burden in Hepatocellular Carcinoma Defined by the Milan Criteria

The Milan criteria are used to define small hepatocellular carcinoma (HCC) and to select patients for curative treatments. Total tumor volume (TTV) is an alternative parameter for tumor burden. We aimed to evaluate whether TTV is a feasible prognostic marker in HCC patients with upper boundary TTV of 65.5 cm(3), which is equivalent to a single 5 cm tumor nodule defined by the Milan criteria. A total of 774 HCC patients with TTV < 65.5 cm(3) receiving surgical resection, liver transplantation, or radiofrequency ablation (RFA) as the primary treatment were retrospectively analyzed. Of these patients, 50 (6.5 %) did not fulfill the Milan criteria. Patients beyond the Milan criteria more often had larger tumor size and TTV, as well as more tumor nodules (p values all < 0.01). There was no significant survival difference between patients within and beyond the Milan criteria (p = 0.205). Patients with TTV > 15 cm(3) had a significantly poorer survival than patients with TTV < 15 cm(3) (p = 0.007). There was no survival difference between patients receiving surgical treatments versus RFA (p = 0.932). In the Cox proportional hazards model, TTV > 15 cm(3) [risk ratio (RR): 1.474, p = 0.005], serum bilirubin a parts per thousand yen1.5 mg/dL (RR: 1.663, p = 0.003), serum sodium < 135 mmol/L (RR: 2.016, p = 0.01), and alpha-fetoprotein (AFP) a parts per thousand yen100 ng/mL (RR: 1.37, p = 0.033) were independent predictors of poor prognosis. Total tumor volume, is an independent and better prognostic marker than the Milan criteria to indicate tumor burden in HCC patients who had tumor volume defined by the Milan criteria and underwent curative therapies.