Gemcitabine-cisplatin (GC) plus radical cystectomy-pelvic lymph node dissection (RC-PLND) for patients (pts) with muscle-invasive bladder cancer (MIBC): Assessing impacts of neoadjuvant chemotherapy (NAC) and the PLND.

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355 Background: NAC and RC-PLND improves survival in MIBC and GC is a standard NAC option. However, little is known about GC efficacy endpoints and the individual contribution of NAC and surgery. Methods: Pts with clinical T2-T4aN0M0 MIBC treated from 1/2000 to 10/2012 with a planned 4 cycles of GC plus RC-PLND within 90 days (D) of NAC were evaluated retrospectively for the number (#) of cycles, dose delivered, D from end of NAC to RC-PLND, margin status, LN status and # of LN identified. Post-NAC pathologic endpoints included complete response (pT0), residual Non-MIBC disease (pTa/Tis/T1;N0) and ≥MIBC disease (≥pT2N0). Associations with overall survival (OS) and disease-free survival were analyzed using Cox regression; non-linear associations with # of resected LN used linear and quadratic terms. Results: 154 pts met inclusion criteria. 5-year (yr) OS was 61% (95% CI 53-71%). Post-NAC pT0 was achieved in 21% (32/154) and Non-MIBC in 25% (39/154 - pTa (2), pTis (25), pT1 (12)). Post-NAC pT0 and Non-MIBC had similar 5-yr OS (85% and 89%, respectively) and combined (<pT2) pts differed significantly from pts with ≥pT2, (87% (95% CI 78, 98%) and 38% (95% CI 27, 53%), respectively; p<0.001). Median D from NAC to RC-PLND was 34 and median # of resected LN was 19. On univariate analysis, # of cycles (4 vs <4), GC dose intensity and total dose, clinical stage (cT2 vs cT3/cT4), # of resected LN, positive (+) LN and + margins were significant for OS. In multivariate analysis, post-NAC pathology ≥pT2 (HR 6.7; 95% CI 2.6-17.4; p<0.001), + LN (HR 3.21; 95% CI 1.6-6.4; p=0.001) and + margins (HR 3.2; 95% CI 1.4-7.5; p=0.007) were significant for increased risk of death. Using a model with these 3 predictors to estimate the benefit of PLND, the hazard ratio decreased with each LN resected until 25 and then plateaued beyond 25 (p=0.016). Conclusions: NAC with GC has excellent drug delivery, permits rapid RC-PLND and achieves meaningful pathologic responses. Survival is similar with <pT2N0 and pT0N0 post NAC pathology. Pts with post NAC ≥pT2, + margins, and + LN do poorly. Increasing LN yield on PLND contributes to OS.