Neoadjuvant Gemcitabine-Cisplatin Plus Radical Cystectomy-Pelvic Lymph Node Dissection for Muscle-invasive Bladder Cancer: A 12-year Experience

We sought to define the efficacy and tolerability of the commonly used regimen of neoadjuvant gemcitabine and cisplatin (GC) followed by surgery at a single center. Retrospective analysis of 154 patients who received neoadjuvant GC revealed a pathologic downstaging rate of 46% and a 5-year overall survival of 87% with any degree of downstaging from muscle invasion. No significant delay to surgery or surgical complication rates were observed following GC administration, and no difference in response rates were observed when cisplatin was split over days 1 and 8. These data support the use of GC as an effective, tolerable regimen in the management of muscle-invasive bladder cancer. Introduction: The aim of this study was to determine drug delivery/toxicity, and pathologic/surgical outcomes of patients with muscle-invasive bladder cancer (MIBC) receiving neoadjuvant gemcitabine-cisplatin (GC) plus radical cystectomypelvic lymph node dissection (RC-PLND). Patients and Methods: Chemotherapy and surgical/pathologic outcomes were retrospectively analyzed with 5-year survival follow-up at a referral center. Post-neoadjuvant chemotherapy (NAC) pathologic endpoints included complete response (pT0N0), residual non-MIBC (pTa/Tis/T1N0), and >= MIBC (>= pT2 and/or N ). Associations of pathologic/surgical findings with overall survival (OS), disease-free survival (DFS), and surgical management with RC-PLND were analyzed (Cox regression). Results: Clinical T2a-T4aN0M0 MIBC patients (n = 154) from January 2000-October 2012 received GC plus RC-PLND. Patients (n = 117; 76%) received GC x 4 and 136 (88%) GC x 3. Five-year OS was 61% (95% confidence interval [CI], 53-71). Median number of resected lymph nodes (LNs) was 19. Down-staging was observed as follows: pT0N0: 21%; pTa/Tis/T1N0: 25%, with similar 5-year OS (85% and 89%, respectively). Five-year OS for < pT2 versus >= pT2 residual disease was 87% (95% CI, 78%-98%) versus 38% (95% CI, 27%-53%); P < .001. Post-NAC stage >= pT2 (HR, 6.79; 95% CI, 2.63-17.53; P < .001), positive LN (HR, 3.64; 95% CI, 1.84-7.19; P < .001), and positive margins (HR, 4.15; 95% CI, 1.68-10.25; P - .002) were associated with increased risk of all-cause death (multivariable analysis). An HR of 0.97 (95% CI, 0.94-1.00) was observed for each additional node removed, but this effect was not statistically significant (P = .056). Conclusions: Neoadjuvant GC achieves meaningful pathologic responses. Patients with >= pT2 residual disease, positive margins, or positive LN post-chemotherapy have inferior survival. (C) 2020 Elsevier Inc. All rights reserved.