Introduction

_x000D_ Gold standard treatment for muscle invasive bladder cancer (MIBC) is radical cystectomy (RC) with neoadjuvant chemotherapy (NAC). However, the survival benefit of NAC in unselected patients is considered modest (5-15%). Recently genomic studies identified intrinsic basal, p53-like, and luminal molecular subtypes of MIBC which identify the genetic heterogeneity of bladder cancer. We hypothesized that tumor intrinsic subtype at the time of staging transurethral resection (TURBT) could be associated with clinical benefit from NAC.

Methods

_x000D_ We identified patients with MIBC who underwent RC with or without NAC between 2000 and 2010 at three different institutions. Whole-genome analysis was performed on TURBT specimens and were classified into basal, luminal or p53-like subtypes. Primary outcome is overall survival (OS). Secondary outcome is response is tumor downstaging (

Results

_x000D_ 273 TURBT specimens were analyzed. There were no significant differences in the subtypes between age, sex and stage (P<0.05). 87 (32%) were basal, 95 (35%) were p53-like, and 91 (33%) were luminal. 127 (46%) did not get NAC, and 146 (54%) received NAC. _x000D_ _x000D_ Downstaging occurred in 69 of 273 patients (26%), 2% (2/127) did not receive NAC and 47% (69/146) received NAC (p<0.001). Of patients that received NAC, 51% (25/49) of basal, 33% (16/48) p53-like, and 57% (28/49) of luminal tumors were downstaged (p=0.033)._x000D_ _x000D_ Median OS for patients who did not receive NAC was 33 mo. vs. 102 mo. for those who did (p<0.0001). OS was improved for patients who did vs. those who did not get NAC in basal subtypes (17 mo. vs. 271 mo., p<0.001). However, there was no significant difference in OS for p53-like (58 mo. vs. 70 mo., p=0.3137), and for luminal (43 mo. vs. 85 mo., p=0.0629). For patients that did get NAC, patients with basal tumors had a significant increase in OS over to the other subtypes (p=0.0239) (Figure 1). _x000D_

Conclusions

_x000D_ Basal tumors in the absence of NAC are high risk, but they have a favorable response to NAC which results in an increased OS. Luminal tumors have a favorable downstage rate at RC, but this does not translate into increased OS. P53-like tumors have a poor prognosis regardless of use of NAC. We demonstrate that the intrinsic molecular subtypes of MIBC identified at TURBT have variable response to NAC with significant implications on OS.

Funding

National Cancer Institute SPORE & VF Foundation