Neoadjuvant chemotherapy (NAC) with dose-dense gemcitabine/cisplatin (DDGC) in localized muscle-invasive bladder cancer (MIBC).

e16527 Background: NAC prior to radical cystectomy (RC) with MVAC or GC represents a standard for non-metastatic MIBC. DDGC has shown similar efficacy and favorable toxicity to DDMVAC in metastatic disease. Neoadjuvant DDGC has shown encouraging efficacy but concerns due to increased incidence of serious vascular events have been raised. For this reason, we analyzed our experience of DDGC as NAC in MIBC. Methods: Patients (pts) with non-metastatic MIBC (cT2-T4a) received NAC with 4 Cycles of DDGC (2500mg/m2, 70mg/m2) and G-CSF support every 2 weeks. Efficacy and safety were the primary end-points of the analysis. Clinical lymph-node involvement (cN+) was assessed radiologically. In pts eventually not undergoing RC, response to NAC was assessed with TURB-T, urine cytology and CT scan of chest, abdomen and pelvis. Results: 44 pts received NAC from 19/01/2012 to 2/10/2017: median age 68 (37-82); cT1: 1 (2.3%), cT2 39 (88.6%), cT3 2 (4.5%), cT4a 1 (2.3%), no muscle included 2 (4.5%); hydronephrosis 10 (23%); pure TCC 42 (96%); cN+ 8 (18%). 41 pts (93%) received all 4 cycles of NAC. Post-chemotherapy management included: RC in 29 (66 %) pts, Radiotherapy in 7 (16%) and non-surgery/non-RT in 8 (18%). Median time from NAC completion to cystectomy was 5.8 weeks. Following RC, pT0 was found in 5/28 (18%) and ≤pT1 in 11/28 (39%) pts. Complete response (CR) rate for pts not undergoing RC was 39%. Among 5 pts with cN+ who underwent RC, 2 achieved pN0. Median follow-up was 18 months (95% CI: 10-41). 1, 2 and 3 year disease-free survival rates were 81% (95% CI: 56-92), 67% (95% CI: 39-84) and 67% (95% CI: 39-84), respectively. Grade ≥3 toxicities were reported in 5 (11%) pts: thrombocytopenia (2 pts), non-neutropenic sepsis, GI hemorrhage, electrolyte abnormalities. No vascular events were reported during follow-up. Conclusions: Our analysis did not confirm excessive vascular toxicity by NAC DDGC. NAC achieved pN0 in 2 among 5 pts with cN+ disease. pCR rate was modest, probably due to the inclusion of cN+ disease and the selection of patients with best response to NAC for bladder preservation. Shortening the time to cystectomy from the end of NAC represents an important target.