Changes in body composition during neoadjuvant platinum-based chemotherapy associations prior to radical cystectomy: Implications for chemotherapy-associated adverse events and oncologic outcomes.

Abstract

476 Background: Low skeletal muscle index (SMI) is associated with an increased risk of mortality in muscle-invasive bladder cancer (MIBC) and chemotherapy-related adverse events (AE) across numerous other malignancies. Small case series suggest neoadjuvant chemotherapy (NAC) is associated with a significant decline in SMI in patients with MIBC. However, limited data exists regarding changes in fat mass during NAC. Herein, we examine changes in SMI, visceral fat index (VFI), and subcutaneous fat index (SFI) in patients receiving NAC for MIBC before radical cystectomy (RC). We describe associations between body composition changes and NAC-associated AE and all-cause mortality (ACM) in patients with MIBC. Methods: Retrospective review of patients with MIBC (≥pT2 N0/x/1 M0) who received NAC (2006-2019). Patients with digitized abdominal computed tomography scans (CT) within 75 days prior (T1) and 75 days following completion (T2) of NAC were included. We segmented and calculated the indices (cm2/m2) for SMI, VFI, and SFI at the third lumbar vertebra level at T1 and T2 using validated methodology. Associations with AE during NAC and ACM were evaluated with multivariate logistic regression and Cox proportional hazards models. Results: Included 170 patients, median age 63 years receiving a median of 4 (IQR 3-5) cycles of Gemcitabine/Cisplatin (52%), MVAC (28%), or other NAC (20%). Absolute and relative changes in SMI, VFI, and SFI over a median of 112 days (IQR 94-146) between measurements are presented in the Table. 117 (69%) patients experienced grade ≥3 chemotherapy-related AE. No associations between baseline body composition or change in body composition during NAC with chemotherapy-related AE. T1 SMI (HR: 0.98; 0.97-0.99, p = 0.008), as well as T2 SMI (HR: 0.98; 0.96-0.99, p = 0.003), T2 VFI (HR: 0.99; 0.99-1.0, p = 0.05) and T2 SFI (HR: 0.99; 0.98-1.0, P = 0.03) were associated with ACM after adjusting for age, clinical T and N stage, and performance status. Conclusions: Patients undergoing NAC prior to RC experienced a 6.4% decrease in SMI and a 5.2% decrease in VFI during an average of 112 days. Chemotherapy-related AE were not associated with a change in body composition. Baseline SMI and T2 SMI, SFI, and VFI were associated with ACM on multivariable analysis. Future work is needed to understand the mechanisms underpinning such changes and the extent to which potentially detrimental changes in body composition may be mitigated before surgery.[Table: see text]