Bladder-sparing strategy is a useful option for patients with muscle-invasive bladder cancer (MIBC), in which the response to chemoradiotherapy (CRT) is primarily important in achieving favorable oncological 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/radical cystectomy as consolidative surgery; 118 eligible patients with non-metastatic MIBC were retrospectively analyzed. Of these, 92 patients eventually underwent partial/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 (52%)/SCCL (45%) than in Uro (15%; p<0.001/=0.01, respectively). On multivariate analysis, GU/SCCL subtype was a significant predictor of clinical CR, as was absence of hydronephrosis or concomitant carcinoma in situ. Analyses for pathological CR in the cystectomized patients revealed analogous findings. Five-year CSM of Uro/GU/SCCL patients were 16%/23%/28% overall and 19%/22%/23% in cystectomized patients, respectively, showing no significant difference among the subtypes. CR status after CRT was significantly and independently correlated with low CSM in both clinical and pathological evaluations.
GU and SCCL cancers showed significantly more favorable CRT-response than Uro. IHC-based subtyping may improve clinical decisions about the indication of CRT for MIBC patients.