Prognostic Nomograms Stratify Survival of Patients with Hepatocellular Carcinoma Without Portal Vein Tumor Thrombosis After Curative Resection

Abstract

Background: The prognosis of patients with hepatocellular carcinoma (HCC) without portal vein tumor thrombosis (PVTT) after curative resection is at variance. We identified the risk factors of poor postoperative prognosis and consequently developed prognostic nomograms generating individual risk of death and recurrence for this subgroup of patients with HCC.

Methods: The risk factors were identified and nomograms were developed based on a retrospective study of 734 patients in the primary cohort who underwent curative resection for HCC from 2010 to 2012. The predictive accuracy and discriminative ability of the nomograms were determined by concordance index (C-index) and calibration curve and compared with traditional staging systems of HCC. The results were validated in an independent cohort of 349 patients operated at the same institution in 2007.

Results: All of the independent factors for survival in multivariate analysis in the primary cohort were selected into the nomograms. The calibration curve for probability of survival showed good agreement between prediction by nomograms and actual observation. The C-indices of the nomograms for predicting overall survival and recurrence-free survival were 0.755 (95% confidence interval [CI], 0.752-0.758) and 0.665 (95% CI, 0.662-0.668), respectively, which were statistically higher than the C-indices of other HCC prognostic models. The results were further confirmed in the validation cohort.

Conclusion: The proposed nomograms resulted in more accurate prognostic prediction for patients with HCC without PVTT after curative resection. The Oncologist 2017;22:561-569 IMPLICATIONS FOR PRACTICE: Hepatocellular carcinoma (HCC) poses a great therapeutic challenge due to the poor prognosis in patients underwent surgical resection. The portal vein tumor thrombosis (PVTT) as a robust risk factor for survival has been routinely integrated to staging systems. Nonetheless, the prognosis stratification for patients without PVTT was neglected to some extent. Herein, independent risk factors of OS and RFS in HCC patients without PVTT were reconfirmed. A predictive nomogram was constructed on these risk factors and was demonstrated to be a more accurate predictive model in HCC patients without PVTT, compared with the traditional staging systems.

Keywords: Hepatocellular carcinoma; Nomogram; Portal vein tumor thrombosis; Prognosis; Resection.

Figure 1.

Hepatocellular carcinoma OS (A) and RFS (B) nomograms. (To use the nomogram, the value of an individual patient is located on each variable axis, and a line is drawn upward to determine the number of points received for each variable value. The sum of these numbers is located on the total point axis, and a line is drawn downward to the survival axes to determine the likelihood of 2‐ or 3‐year survival). Abbreviations: AFP, α‐fetoprotein; GGT, γ‐glutamyl transferase; MVI, microscopic vascular invasion; OS, overall survival; RFS, recurrence‐free survival.

Figure 2.

The calibration curve for predicting OS of patients at 2 years (A) and 3 years (B), RFS at 2 years (C) and 3 (D) years in the training cohort; predicting patient OS at 2 years (E) and 3 years (F) and predicting patient RFS at 2 years (G) and 3 years (H) in the validation cohort. Nomogram‐predicted probability of survival is plotted on the x‐axis; actual survival is plotted on the y‐axis. Abbreviations: OS, overall survival; RFS, recurrence‐free survival.

Figure 3.

DCA. DCAs depict the clinical net benefit in pairwise comparisons between integrated nomogram, BCLC stage, and CLIP score. Nomograms are compared against the BCLC stage and CLIP score in terms of 2‐ and 3‐year OS (A, B) and 2‐ and 3‐year RFS (C, D). Dashed lines indicate the net benefit of nomogram in each of the curves across a range of threshold probabilities. The horizontal solid black line represents the assumption that no patients will experience the event, and the solid gray line represents the assumption that all patients will die or relapse. On DCA, nomogram showed superior net benefit compared to BCLC stage and CLIP score across a range of threshold probabilities. Abbreviations: BCLC, Barcelona Clinic Liver Cancer; CLIP, Cancer of the Liver Italian Program; DCA, decision curve analysis; RFS, recurrence‐free survival; OS, overall survival.