Body composition and immunotherapy outcomes in patients with advanced urothelial carcinoma.

Abstract

762 Background: Abnormalities in body composition, including sarcopenia and myosteatosis, have been identified as prognostic factors in patients (pts) receiving cytotoxic chemotherapy. However, data regarding the impact of these factors in patients undergoing immune checkpoint inhibitors (ICI) therapy, particularly in those with advanced urothelial carcinoma (aUC), remain limited. This study aimed to evaluate the prognostic significance of body compositions obtained from abdomen-pelvis computed tomography (APCT) in pts with aUC. Methods: This retrospective study included pts with aUC who received ICI (atezolizumab or pembrolizumab) between Jan 2019 and Dec 2022 at Asan Medical Center, Seoul, Korea. Body composition was evaluated using selected axial images at the L3 lumbar vertebrae level from APCT, through an artificial intelligence-driven imaging analysis platform. T-score ≤-2 (-2 SD from the mean reference value in Korean population) was used as cutoff points for sarcopenia and myosteatosis. Visceral obesity (VO) was defined as visceral fat area ≥ 100cm 2 and subcutaneous obesity (SFO) as subcutaneous fat area / height 2 ≥ 50cm 2 /m 2 in males and 42cm 2 /m 2 in females. The associations between body composition parameters with overall survival (OS) and progression-free survival (PFS) were analyzed. Results: A total of 212 pts were included. Median age was 68 (range, 31-86) and 53 pts (25%) were females. ICIs were primarily administered as second-line treatment following failure to platinum-based treatment (N=207, 98%), with 5 pts (2%) receiving ICI as first-line treatment in a metastatic setting. Atezolizumab was given to 174 pts (82%) and pembrolizumab to 38 pts (18%). The prevalence of sarcopenia prior to treatment was 22% (45/212), while myosteatosis was observed in 52% of pts (110/212). VO and SFO were present in 62% and 43% of pts, respectively, with 37% classified as overweight (body mass index (BMI) ≥25kg/m 2 ). Myosteatosis at baseline was associated with an increased risk of mortality (HR 1.58, 95% CI: 1.11–2.23), while sarcopenia, VO, SFO, and BMI did not show significant associations with OS. PFS was not affected by any body composition parameters. Multivariate Cox regression analysis demonstrated that liver metastasis (HR 2.78, 95% CI: 1.94–4.00), hemoglobin (HR 0.52, 95% CI 0.35-0.77), and myosteatosis (HR 1.57, 95% CI 1.12-2.19) were independently associated with OS after adjusting for age and sex. Conclusions: In pts with aUC treated with ICI, myosteatosis showed poorer OS, while sarcopenia, VO, SFO, and BMI did not demonstrate a significant impact. Myosteatosis was significantly associated with OS after adjusting for other clinical factors, which suggests a possibility of a novel prognostic marker in pts with aUC receiving ICI.