Body Composition as an Independent Predictive and Prognostic Biomarker in Advanced Urothelial Carcinoma Patients Treated with Immune Checkpoint Inhibitors
Authors: Martini Dylan J. , Shabto Julie M. , Goyal Subir , Liu Yuan , Olsen T. Anders , Evans Sean T. , Magod Benjamin L. , Ravindranathan Deepak , Brown Jacqueline T. , Yantorni Lauren , Russler Greta Anne , Caulfield Sarah , Goldman Jamie M. , Nazha Bassel , Joshi Shreyas Subhash , Kissick Haydn T. , Ogan Kenneth E. , Harris Wayne B. , Kucuk Omer , Carthon Bradley C. , Master Viraj A. , Bilen Mehmet Asim 
Published: August 2021

Abstract

Background
Several immune checkpoint inhibitors (ICIs) are approved for the treatment of advanced urothelial carcinoma (UC). There are limited biomarkers for ICI-treated patients with UC. We investigated the association between body composition and clinical outcomes in ICI-treated UC patients.

Materials and Methods
We conducted a retrospective analysis of 70 ICI-treated patients with advanced UC at Winship Cancer Institute from 2015 to 2020. Baseline computed tomography images within 2 months of ICI initiation were collected at mid-L3 and muscle and fat compartments (subcutaneous, intermuscular, and visceral) were segmented using SliceOMatic v5.0 (TomoVision, Magog, Canada). A prognostic body composition risk score (high: 0–1, intermediate: 2–3, or low-risk: 4) was created based on the β coefficient from the multivariate Cox model (MVA) following best-subset variable selection. Our body composition risk score was skeletal muscle index (SMI) + 2 × attenuated skeletal muscle (SM) mean + visceral fat index (VFI). Concordance statistics (C-statistics) were used to quantify the discriminatory magnitude of the predictive model.

Results
Most patients (70%) were men and the majority received ICIs in the second- (46%) or third-line (21%) setting. High-risk patients had significantly shorter overall survival (OS; hazard ratio [HR], 6.72; p &lt; .001), progression-free survival (HR, 5.82; p &lt; .001), and lower chance of clinical benefit (odds ratio [OR], 0.02; p = .003) compared with the low-risk group in MVA. The C-statistics for our body composition risk group and myosteatosis analyses were higher than body mass index for all clinical outcomes.

Conclusion
Body composition variables such as SMI, SM mean, and VFI may be prognostic and predictive of clinical outcomes in ICI-treated patients with UC. Larger, prospective studies are warranted to validate this hypothesis-generating data.

Implications for Practice
This study developed a prognostic body composition risk scoring system using radiographic biomarkers for patients with bladder cancer treated with immunotherapy. The study found that the high-risk patients had significantly worse clinical outcomes. Notably, the study's model was better at predicting outcomes than body mass index. Importantly, these results suggest that radiographic measures of body composition should be considered for inclusion in updated prognostic models for patients with urothelial carcinoma treated with immunotherapy. These findings are useful for practicing oncologists in the academic or community setting, particularly given that baseline imaging is routine for patients starting on treatment with immunotherapy.