Multiplication of Tumor Volume by Two Tumor Markers Is a Post-Resection Prognostic Predictor for Solitary Hepatocellular Carcinoma

Abstract

Background: We hypothesized that microvascular invasion (MVI) and post-resection prognosis in patients with solitary hepatocellular carcinoma (HCC) could be predicted using blood tumor markers and tumor volume (TV). We intended to identify a simple surrogate marker of HCC via a combination of clinical variables.

Methods: This retrospective study used the strictly selected development cohort (n = 1176) and validation cohort (n = 551) containing patients who underwent curative resection of solitary HCC.

Results: In the development cohort study, the median values were 13.7 mL for TV, 24.2 ng/mL for α-fetoprotein (AFP), and 75 mAU/mL for des-γ-carboxy prothrombin (DCP); there was no correlation among these three factors (r ² ≤ 0.237, p < 0.001). The 1-, 3-, and 5-year rates were 22.4, 41.7, and 46.8 % for tumor recurrence and 93.6, 84.0, and 78.2 % for patient survival, respectively. Independent risk factors for both tumor recurrence and patient survival were tumor diameter >5 cm or TV >50 mL, MVI, satellite nodules, and high DCP. Multiplication of AFP, DCP, and TV (ADV score) resulted in prediction of MVI at a cutoff of 5log with sensitivity of 73.9 % and specificity of 66.7 %. Patient stratifications according to ADV score with cutoffs of 5log alone, 6log and 9log, and its combination with MVI showed significant prognostic differences (all p < 0.001). These prognostic significances were reliably reproduced in the validation cohort study (all p < 0.001).

Conclusions: We suggest that ADV score is an integrated surrogate marker of HCC prognosis. We believe that it can be used to predict MVI and post-resection prognosis for solitary HCC.

Keywords: Hepatocellular carcinoma; Microvascular invasion; Recurrence; Resection; Tumor marker.