Introduction:

Introduction: Neoadjuvant chemotherapy has been shown to improve overall survival in patients who undergo cystectomy for muscle invasive bladder cancer (MIBC). To date, it is unclear whether select patients with high-risk non-muscle invasive bladder cancer (HR NMIBC) could benefit from NAC. In this study, we analyze recurrence and survival post-cystectomy outcomes for HR NMIBC, MIBC responsive to NAC, and MIBC responsive to TURBT. We additionally analyze risk factors for recurrence in patients with HR NMIBC.

Methods:

Methods: We performed a retrospective review of our institution’s cystectomy database from database inception in February 2000 to August 2019 to identify patients with pN0 and pT0, pTa, pT1, or pTis urothelial carcinoma on cystectomy pathology. Comparisons were made between patients with HR NMIBC, MIBC that downstaged with NAC, and MIBC that downstaged with TURBT without NAC. Kruskal Wallis and Chi-Squared tests were used to compare continuous and categorical variables respectively. Log Rank and Cox Regression tests were used to analyze recurrence-free and overall survival outcomes for all three groups.

Results:

Results: We identified 512 patients with pN0 and pT0, pTa, pT1, or pTis urothelial cell carcinoma on cystectomy pathology. 249 patients had clinical HR NMIBC that remained pathologic NMIBC on cystectomy, 190 patients had MIBC that downstaged with NAC, and 73 patients had MIBC that downstaged with TURBT and without NAC. Patients with HR NMIBC, MIBC downstaged with NAC, and MIBC downstaged with TURBT without NAC had significantly different times to cystectomy (685.25 months, 297.18, 283.72, p<0.001), rates of intravesical therapy (73.39%, 15.26%, 18.06, p<0.001), rates of pathologic T stage pT0 (15.26%, 45.79%, 45.21%, p<0.001), rates of carcinoma in situ (CIS) (67.07%, 45.79%, 49.32%, p<0.001), and rates of tumor size > 2 cm (62.65%, 36.84%, 36.99%, p<0.001). Location of recurrence was not significantly different between groups (p=0.834). Kaplan-Meier curves comparing overall survival and recurrence-free survival for each patient group are shown in Figure 1. Of note, HR NMIBC patients had significantly different recurrence-free survivals compared with MIBC downstaged with NAC and MIBC downstaged with TURBT respectively (p=0.004, p=0.014 respectively), but did not have significantly different overall survival (p=0.078, p=0.386 respectively). The MIBC groups were not significantly different in terms of recurrence-free and overall survival (p=0.576 and p=0.752 respectively). The results of Cox Regression analysis for patients with HR NMIBC are depicted in Table 1. Of note, age at cystectomy (HR=1.0351,p=0.032), time to cystectomy (HR=1.0005,p=0.003), and lack of intravesical therapy (HR=2.308,p=0.017) predicted recurrence while age at cystectomy (HR=1.0460,p=0.004) and smoking (HR=1.2713,p=0.019) predicted death.

Conclusion:

Conclusions: Patients from our cohort with HR NMIBC had worse post-cystectomy outcomes relative to MIBC downstaged with NAC or with TURBT without NAC in terms of recurrence-free survival but did not have significantly different overall survival. Patients with NAC responsive and TURBT responsive MIBC had similar recurrence-free and overall survival outcomes. Further work is needed to determine why certain patients with HR NMIBC recur more frequently than downstaged MIBC patients and whether NAC can be useful in certain settings for patients with HR NMIBC.

Funding: N/A