Association of immunohistochemical markers of tumor subtype with response to neoadjuvant chemotherapy and survival in patients with muscle-invasive bladder cancer

PURPOSE: A readily accessible biomarker to identify which patients with bladder cancer are more likely to respond to neoadjuvant chemotherapy (NAC) could help clinicians avoid unnecessary chemotherapy and prevent its subsequent complications in some patients. The primary objective of this study was to investigate the association of immunohistochemical markers of tumor subtype with response to NAC and survival of patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: MIBC patients treated with NAC were retrospectively included. The tissue microarrays were assembled from transurethral resection of bladder tumor (TURBT) specimens and immunohistochemistry (IHC) was performed. The association of independent variables, including IHC markers, and clinical covariates with clinical complete response to NAC and with overall survival was assessed by using logistic regression and Cox proportional hazard regression analysis, respectively. Kaplan-Meier curves were plotted for different IHC-based tumor subtypes. RESULTS: Data from 140 MIBC patients treated with NAC were retrospectively reviewed. A total of 63 patients with available TURBT specimens were eligible to be included in the analysis. Our results showed that the IHC signature of KRT5/6(+)/KRT20(−), as a combined marker of basal subtype, was the only covariate significantly associated with complete response to NAC (p=0.037). Moreover, we found no statistically significant differences in overall survival between different IHC-based subtypes (p=0.721). CONCLUSIONS: The IHC expression of KRT5/6 and KRT20, as a readily accessible combined marker, may help us to identify the patients most likely to benefit from chemotherapy. The clinical utility of this marker needs to be established in larger prospective studies.