Molecular classification of patients with NMIBC predicts the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine-immunohistochemistry-based classification.

Abstract

To investigate the relationships between non-muscle invasive bladder cancer molecular subtypes and predict the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine. A total of 160 patients with T1 stage non-muscle invasive bladder cancer were enrolled in this study. Fifty-three patients underwent anthracycline (Pirarubicin and Pharmorubicin) therapy and 107 patients accepted gemcitabine therapy. Uroplakin II and CK20 were categorized as immunohistochemistry (IHC) markers for luminal subtype, whereas CK5/6 and CD44 were categorized as immunohistochemistry markers for basal subtype. The cluster results with immunohistochemical score indicated that non-muscle invasive bladder cancer can be subgrouped into three major classes. Class 2 showed the luminal-like characteristics, whereas class 3 showed the basal-like characteristics. Class 1 showed no high expression of luminal or basal-associated immunohistochemistry markers. The molecular subtype is an independent risk factor for recurrence-free survival (P=0.030) and progression-free survival (P=0.006) in patients with T1 stage non-muscle invasive bladder cancer. In class 1 and class 2 (luminal-like) subtypes, gemcitabine and anthracycline show no difference in recurrence-free survival and progression-free survival. Gemcitabine was associated with reduced recurrence compared with anthracycline (P=0.039) in class 3 (basal-like) subtypes and show no difference in decreasing progression. The molecular classification based on immunohistochemical results is an independent risk factor for the prognosis of non-muscle invasive bladder cancer with T1 stage. Different therapeutic methods should be selected according to different molecular subtypes.