Long-term validation of a molecular progression-associated gene classifier for prediction of muscle invasion in primary non-muscle-invasive bladder cancer.

Our previous study reported a clinically applicable prognostic gene classifier for primary non-muscle-invasive bladder cancer (NMIBC). The present study aimed to perform long-term validation of this classifier in the prediction of muscle-invasive disease. Previously published gene expression profiles were used from 176 patients with NMIBC with extended follow-up. Progression was defined as development of muscle invasion or metastasis, and the progression risk score was calculated using the previously developed eight-gene progression classifier. During median follow-up of 72.8 (interquartile range, 37.0-118.7) months, 26 (14.8%) patients progressed to muscle-invasive bladder cancer. The molecular progression risk score was significantly associated with clinicopathological variables, including tumor number, stage, grade and multivariate risk assessment tools (P<0.05 in each case). Multivariate Cox regression analysis revealed that molecular progression risk score was an independent predictor of development of invasive tumor, either as a continuous variable [hazard ratio (HR), 1.489; 95% confidence interval (CI), 1.216-1.823; P<0.001] or as a categorical variable (HR, 5.026; 95% CI, 1.619-15.608; P=0.005). In conclusion, the present results confirmed the clinical utility of the progression-associated gene classifier for prediction of development of muscle invasion in NMIBC. The molecular progression risk score may aid in selecting patients who could benefit from more aggressive therapeutic intervention.