Introduction

While neoadjuvant chemotherapy prior to radical cystectomy (RC) has been demonstrated to improve survival compared to RC alone for urothelial carcinoma of the bladder (UCB), the bulk of this survival benefit has been attributed to patients who achieve ypT0 status at RC. The implications of having residual UCB (rUCB) at RC after preoperative chemotherapy (POC) are less clear. As such, we evaluated survival for patients with and without rUCB at RC after POC compared with pathologic stage-matched RC patients who did not receive POC.

Methods

Patients undergoing RC for UCB between 1980-2010 at Mayo Clinic were identified. All RC pathology was re-reviewed by a single genitourinary pathologist. Patients who received POC for T2-T4 and/or N1-3 M0 UCB were matched 1:2 to patients not exposed to prior chemotherapy based on pT and pN-stage, soft tissue surgical margin status, and year of RC. Kaplan Meier and Cox regression analyses were used to evaluate the associations between POC and cancer-specific (CSS) and overall survival (OS), stratified by presence or absence of rUCB at RC.

Results

We matched 111 patients who underwent POC + RC to 222 RC-alone patients. Median age was 68 yrs (IQR 60,74); 59 (18%) were female. Median follow-up was 7.2 yrs (IQR 6,16), during which time a total of 248 patients died, with 148 dying from UCB. In patients without rUCB at RC, there was no difference in 5-yr CSS (86% vs. 90%, p=0.85) or OS (82% vs. 84%, p=0.46) between patients who did versus did not receive POC. Moreover, on multivariable analysis, chemotherapy exposure was not significantly associated with CSS (HR=1.0; 95%CI 0.3-3.1; p=0.9) or OS (HR=0.9; 95%CI 0.4-1.9; p=0.8) in this subgroup. Conversely, among patients with rUCB at RC, receipt of POC was associated with significantly worse 5-yr CSS (32% vs. 56%, p<0.001) and OS (25% vs. 48%, p<0.001). Moreover, on multivariable analysis, chemotherapy exposure remained independently associated with adverse CSS (HR=2.2; 95%CI 1.6-3.1; p<0.001) and OS (HR=2.0; 95%CI 1.5-2.7; p<0.001) among the patients with rUCB.

Conclusions

While patients who achieve a complete response to POC have excellent survival outcomes, patients with residual UCB at RC after POC have a worse prognosis compared to stage-matched RC patients not exposed to chemotherapy. Such patients should be considered for enrollment in novel adjuvant therapy trials, while continued investigation of which patients are most likely to achieve ypT0 status remains warranted.

Funding

None