Increasing use of neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC): Prognostic impact of non-standard of care (SOC) regimens.

Abstract

4532 Background: Cisplatin-based NAC can prolong overall survival (OS) in patients (pts) with MIBC. Utilization of NAC has increased to about 20% of pts with MIBC over the last decade. We evaluated NAC utilization with and without SOC cisplatin-based combination regimens and oncologic outcomes using registry data. Methods: This is a population-based analysis of linked SEER-Medicare data (2004-2011). We identified 4534 pts with MIBC (cT2-4N0-1) undergoing radical cystectomy (RC). Based on pharmacy records data, pts were stratified into 3 groups: SOC, non-SOC, and immediate cystectomy (IC). We used descriptive statistics to compare groups, and multivariate logistic regression to define factors associated with receiving SOC NAC. Competing risk bladder cancer-specific mortality (BCSM) incidence curves were generated and KM analysis was used to assess OS from time of RC. The impact of NAC on OS was evaluated with Cox regression analysis. Results: 694 (15.3%) pts received NAC, increasing from 11% in 2004 to 24.8% in 2011, with 345 (50%) receiving non-SOC, e.g. gemcitabine/carboplatin (49.3%), gemcitabine alone (21.2%), carboplatin alone (14.8%), cisplatin alone (8.4%), and methotrexate/vinblastine/ adriamycin/carboplatin (0.8%). On logistic regression, increasing age (OR 0.91, 95%CI 0.88 – 0.94, p < 0.0001), Hispanic/Latin ethnicity (OR 0.49, 95%CI 0.22 – 1.10, p = 0.08), and ≥moderate renal dysfunction (OR 0.20, 95%CI 0.08 – 0.51, p < 0.001) were associated with lower odds of SOC NAC. Non-SOC NAC was associated with higher BCSM (competing risk) and lower OS (KM) vs. IC and SOC NAC. On multivariable analysis, non-SOC NAC was associated with higher risk of BCSM (HR 1.35, 95%CI 1.06 – 1.72, p = 0.01) and lower OS (HR 1.38, 95%CI 1.11 – 1.70, p = 0.003) vs. SOC NAC. Conclusions: About 50% of pts receiving NAC were not treated with SOC regimens. Non-SOC NAC was associated with higher bladder cancer death risk. This stresses the role of SOC NAC ideally in a multidisciplinary expert setting, as well as the need for timely RC and neoadjuvant clinical trials, including cisplatin-ineligible pts.