Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes.

Abstract

336 Background: To evaluate gemcitabine-cisplatin (GC) neoadjuvant chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) and identify clinical parameters associated with pR. Methods: We studied 150 consecutive cases of MIBC that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index (JHH-DI) to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results: No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (p=0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, p<0.01) and decreased nodal positivity rates (0% vs. 41.3%, p<0.01) compared to non-responders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic non-responders (pNR) compared to the entire RC-only treated cohort. A lower pNR rate was seen in patients tolerating sufficient dosing of NAC as stratified by the JHH-DI (p=0.049), congruent with NCCN guidelines. A multivariate decision tree model demonstrated age ≤60 years and clinical stage cT2 as significant of NAC response (p<0.05). Conclusions: Pathologic non-responders fare worse than patients proceeding directly to RC alone. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients most likely to benefit from GC NAC.