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We assessed survival dependent on pathological response after neoadjuvant chemotherapy in a large multicenter patient cohort, with a particular focus on the difference between the absence of residual cancer (pT0) and the presence of only nonmuscle invasive residual cancer (pTa, pTis, pT1).We retrospectively reviewed records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent radical cystectomy at 19 contributing institutions from 2000 to 2013. Patients with cT2-4aN0M0 and eventual pN0 disease were selected for this analysis. Estimated overall survival was compared between patients with pT0 and pTa/Tis/T1 disease. A multivariable Cox proportional hazards regression model for overall survival was generated to evaluate hazard ratios for variables of interest.Of 1,543 patients treated with neoadjuvant chemotherapy and radical cystectomy during the study period 257 had pT0N0 and 207 had pTa/Tis/T1N0 disease. The Kaplan-Meier mean estimates of overall survival for pT0 and pTa/Tis/T1 cases were 186.7 months (95% CI 145.9-227.6, median 241.1) and 138 months (95% CI 118.2-157.8, median 187.4), respectively (p=0.58). In the Cox proportional hazards regression model for overall survival pTa/Tis/T1N0 status (HR 0.36, 95% CI 0.23-0.67) and pT0N0 status (HR 0.28, 95% CI 0.17-0.47) compared to pT2N0 pathology, positive surgical margin (HR 1.75, 95% CI 1.07-2.86), and receiving a methotrexate, vinblastine, doxorubicin and cisplatin regimen compared to an "other" regimen (HR 0.45, 95% CI 0.27-0.76) were predictors of overall survival.pTa/Tis/T1N0 and pT0N0 stage on the final cystectomy specimen are strong predictors of survival in patients treated with neoadjuvant chemotherapy and radical cystectomy. We did not discern a statistically significant difference in overall survival when comparing these 2 end points.

INTRODUCTION AND OBJECTIVES: Following radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder cancer, a proportion of clinically node negative patients will be diagnosed with metastasis in the regional lymph nodes (pNþ). A number of clinical factors such as local stage and lymphovascular invasion (LVI) have been identified as potential predictors for pNþ status; however, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). Our objective is to assess clinical and therapeutic factors predicting pNþ in clinically node negative patients treated with NAC and RC. METHODS: Patients from four North American institutions with cT2-4N0M0 UC who received three or four cycles of NAC followed by RC were included. A logistic regression model was formulated for predicting pNþ status. The variables included were age, gender, clinical T-stage, transurethral resection (TUR) histology (UC or UC variant) and LVI, number of cycles of NAC, the regimen administered and the extent of pelvic node dissection. RESULTS: The analysis was conducted on 238 patients. Median age was 64 years (IQR: 58-71) and 79% of patients were male. The clinical stage was cT2 in 143 (60.1%), cT3 in 76 (39.1%) and cT4 in 19 (8%) cases. MVAC was used in 26.9% and GC in the remainder of the patients. 60.9% of the MVAC group received four cycles of NAC compared to 42.5% of the GC group (p1⁄40.013). Pathological Nþ was seen in 45 (19.5%) patients. In the logistic regression analysis, cT4 stage (OR: 3.32, [95% CI: 1.15-9.56]) and the fewer cycles of NAC (3 vs. 4 cycles OR: 2.10, [95% CI: 1.03-4.29]) were significant predictors of pNþ status. LVI was not significant in this cohort of patients (OR: 1.15, [95%CI 0.50-2.63]). The observed advantage of the additional cycle of NAC was persistent in subanalysis of the GC patients (OR: 2.67, [CI: 1.11-6.41]) but not MVAC patients (OR: 1.11, [CI: 0.25-4.92]). CONCLUSIONS: Patients with locally advanced disease are at higher risk of harboring lymph node metastasis at the time of RC following NAC. LVI in the TUR specimen was not a significant predictor of nodal metastasis in these patients. Potential advantage of an additional cycle of NAC in GC patients requires further confirmation.