Pathologic down-staging and complete pathologic response with gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder.

Abstract

307 Background: Neoadjuvant chemotherapy (NC) with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) improves survival in muscle invasive urothelial cancer (MI−UC) with patients who achieve pathologic complete response (PCR) following radical cystectomy (RC). Gemcitabine/cisplatin (GC) NC is increasingly employed due to lower toxicity, however, its effectiveness as neoadjuvant therapy is controversial and multiple studies have reported poor utilization of this therapy, despite recent recommendations advocating for broader use. We describe pathologic and clinical outcomes following NC and RC. Methods: We retrospectively evaluated patients with MI−UC who received NC between 2003 and 2011 (n=38). Those who were treated with neoadjuvant radiation therapy (n= 15) were excluded. We compared initial clinical stage at surgery to final pathological stage and assessed overall−median progression free−survival. Mean follow−up was 25 months (SD 21.6, range 3 –76 months). Results: Twenty-three patients who received NC were included. Nineteen patients (82.6%) were treated with GC, 3 (13.0%) with MVAC, and 1 (4.3%) with gemcitabine/paclitaxel. The median time from start of NC to RC was 119 days (IQR 98.5−146). 10/19 (52.6%) patients treated with GC achieved PCR (pT0) from clinical stage T2 (n=5), cT3 (n=2) and cT4 (n=3), and 6 (31.2%) were downstaged to pT1 and pTIS from cT2. Two patients treated with MVAC were downstaged to pT1 and one achieved PCR. Median recurrence-free survival was 13 months (IQR 6−19 months) with 8 patients developing recurrent or metastatic UC following RC. At median follow-up of 19 months (IQR 8−31.2 months, Range 1−71 months), 15/23 (65.2%) patients were disease free, all of whom had received GC NC prior to cystectomy. Conclusions: Neoadjuvant GC for MI−UC was associated with a 52.6% PCR rate at RC and was well tolerated. These data compare favorably with published data on GC and MVAC as NC, and warrant further study.