Impact of Immunohistochemistry-Based Subtypes in Muscle-Invasive Bladder Cancer on Response to Chemoradiation Therapy

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A bladder-sparing strategy is a useful option for patients with muscle-invasive bladder cancer (MIBC), in which the response to chemoradiation therapy (CRT) is primarily important in achieving favorable oncologic outcomes. Our objective is to evaluate the impact of immunohistochemistry (IHC)-based subtyping in MIBC on prediction of CRT response. Treatment protocol consisted of induction CRT followed by partial or radical cystectomy as consolidative surgery; 118 eligible patients with nonmetastatic MIBC were retrospectively analyzed. Of these patients, 92 eventually underwent partial or radical cystectomy after CRT. We applied the IHC-based subtyping model developed by Lund University, which classifies patients into urobasal (Uro), genomically unstable (GU), and squamous cell cancer-like (SCCL) subtypes. GU and SCCL cancers are supposed to be highly aggressive and to have worse prognoses than Uro. Correlations of subtypes with CRT response were analyzed clinically in all patients and pathologically in 92 cystectomized patients. The impact of each subtype on cancer-specific mortality (CSM) was also analyzed. Of all patients, 26 (22%), 61 (52%), and 31 (26%) were classified into Uro, GU, and SCCL subtypes, respectively. Clinical complete response (CR) was achieved in 42% of patients overall after CRT, with a significantly higher proportion in GU patients (52%) and SCCL patients (45%) than in Uro patients (15%; P<.001 and P=.01, respectively). On multivariate analysis, the GU/SCCL subtype was a significant predictor of clinical CR, as was absence of hydronephrosis or concomitant carcinoma in situ. Analyses for pathologic CR in the cystectomized patients revealed analogous findings. Five-year CSM of Uro, GU, and SCCL patients was 16%, 23%, and 28% overall, respectively, and 19%, 22%, and 23% in cystectomized patients, respectively, with no significant difference among the subtypes. CR status after CRT was significantly and independently correlated with low CSM in both clinical and pathologic evaluations. GU and SCCL cancers showed significantly more favorable CRT response than did Uro cancers. IHC-based subtyping may improve clinical decisions about the indication of CRT for MIBC patients.