Introduction

There is evidence supporting the use of neoadjuvant (NAC) or adjuvant chemotherapy (AC) in combination with radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). However, no study has been devised to compare upfront RC followed - performance status and absence of surgical contraindications permitting - by the selective delivery of AC in patients with adverse pathological features, while watching those with organ-confined disease (selAC-based strategy) vs. the systematic delivery of NAC in all eligible individuals followed by surgery if amenable (sysNAC-based strategy). We hypothesized that a selAC-based strategy is associated with an overall survival (OS) benefit when performing an "intention-to-treat" analysis._x000D_

Methods

Within the National Cancer Data Base (2003-2011), we identified 10,056 patients who received selAC- vs. sysNAC-based strategy for cT2-T4N0M0 UCB. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox regression analyses with time-varying covariate were used to compare OS of patients who received selAC- vs. sysNAC-based strategy. Exploratory analyses according to baseline characteristics were additionally performed.

Results

Overall, 8,312 (82.7%) vs. 1,744 (17.3%) patients underwent selAC- vs. sysNAC-based strategy, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer in the selAC- vs. sysNAC-based strategy group (42.0 [95%CI, 39.5-44.6] vs. 33.7 [95%CI, 29.4-38.1] months; P=0.001). The 5-year IPTW-adjusted rates of OS for selAC- vs. sysNAC-based strategy were 42.98% [95%CI, 41.8-44.2] vs. 37.45% [95%CI, 34.8-40.1], respectively. In IPTW-adjusted Cox regression analyses with time-varying covariate, selAC-based strategy was associated with a significant OS benefit after 17 months of follow-up (HR=0.79; 95%CI=[0.70-0.90]; P<0.001). In exploratory analyses, this benefit was significant in cT2 patients (HR=0.78; 95%CI=[0.67-0.88]; P<0.001) while there was no difference between treatment groups in >=cT3 patients (HR=1.18; 95%CI=[0.95-1.47]; P=0.129).

Conclusions

We report an OS benefit for individuals treated with a selAC- vs. sysNAC-based strategy for muscle-invasive UCB - especially cT2 disease. Our findings warrant further consideration in randomized controlled trials to explore this hypothesis.

Funding

none