Elevated serum bilirubin levels are associated with improved survival in patients with curatively resected non-small-cell lung cancer

Abstract

Background: Bilirubin levels have been associated with risk of several malignancies. The association between pretreatment serum bilirubin levels and survival of curatively resected non-small-cell lung cancer (NSCLC) is unclear.

Methods: This analysis was performed retrospectively in a cohort of 1617 consecutive patients with bilirubin levels within the range considered normal, who received curative resection for NSCLC. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off points. The significance of pretreatment serum total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels in the prognosis of patients with curatively resected NSCLC was investigated.

Results: The cutoff points of serum TBIL, DBIL and IBIL were 9.50μmol/L, 3.45μmol/L and 6.95μmol/L, respectively. High TBIL was observed in 65.2% of entire patient population, high DBIL 50%, and high IBIL 56.8%. The high-TBIL group had significantly lengthened overall survival (OS; hazard ratio [HR], 0.73; 95% confidence interval [CI] 0.63-0.84; P<0.001), disease-free survival (DFS; HR, 0.72; 95% CI 0.64-0.82; P<0.001) and distant metastasis-free survival (DMFS; HR, 0.74; 95% CI 0.60-0.91; P=0.004). Similarly, high-DBIL and high-IBIL levels were associated with longer OS, DFS, and DMFS with significant differences. In multivariable analysis, IBIL level was identified as an independent significant prognostic factor.

Conclusions: Moderately elevated pretreatment bilirubin levels are associated with longer OS, DFS, and DMFS for patients with curatively resected NSCLC. IBIL is an independent prognostic factor in curative resected NSCLC.

Keywords: Bilirubin; Lung cancer; Prognosis; Survival.