Body Composition as an Independent Predictive and Prognostic Biomarker in Advanced Urothelial Carcinoma Patients Treated with Immune Checkpoint Inhibitors.

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 ß 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 < .001), progression-free survival (HR, 5.82; p < .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.

Modified Glasgow Prognostic Score associated with survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors.

BACKGROUND: The modified Glasgow Prognostic Score (mGPS) is a composite biomarker that uses albumin and C reactive protein (CRP). There are multiple immune checkpoint inhibitor (ICI)-based combinations approved for metastatic renal cell carcinoma (mRCC). We investigated the ability of mGPS to predict outcomes in patients with mRCC receiving ICI. METHODS: We retrospectively reviewed patients with mRCC treated with ICI as monotherapy or in combination at Winship Cancer Institute between 2015 and 2020. Overall survival (OS) and progression-free survival (PFS) were measured from the start date of ICI until death or clinical/radiographical progression, respectively. The baseline mGPS was defined as a summary score based on pre-ICI values with one point given for CRP>10 mg/L and/or albumin<3.5 g/dL, resulting in possible scores of 0, 1 and 2. If only albumin was low with a normal CRP, no points were awarded. Univariate analysis (UVA) and multivariate analysis (MVA) were carried out using Cox proportional hazard model. Outcomes were also assessed by Kaplan-Meier analysis. RESULTS: 156 patients were included with a median follow-up 24.2 months. The median age was 64 years and 78% had clear cell histology. Baseline mGPS was 0 in 36%, 1 in 40% and 2 in 24% of patients. In UVA, a baseline mGPS of 2 was associated with shorter OS (HR 4.29, 95% CI 2.24 to 8.24, p<0.001) and PFS (HR 1.90, 95% CI 1.20 to 3.01, p=0.006) relative to a score of 0; this disparity in outcome based on baseline mGPS persisted in MVA. The respective median OS of patients with baseline mGPS of 0, 1 and 2 was 44.5 (95% CI 27.3 to not evaluable), 15.3 (95% CI 11.0 to 24.2) and 10 (95% CI 4.6 to 17.5) months (p<0.0001). The median PFS of these three cohorts was 6.7 (95% CI 3.6 to 13.1), 4.2 (95% CI 2.9 to 6.2) and 2.6 (95% CI 2.0 to 5.6), respectively (p=0.0216). The discrimination power of baseline mGPS to predict survival outcomes was comparable to the IMDC risk score based on Uno's c-statistic (OS: 0.6312 vs 0.6102, PFS: 0.5752 vs 0.5533). CONCLUSION: The mGPS is prognostic in this cohort of patients with mRCC treated with ICI as monotherapy or in combination. These results warrant external and prospective validation.

Bladder preserving chemoradiotherapy compared to surgery for variants of urothelial carcinoma and other tumors types involving the bladder: An analysis of the National Cancer Database.

PURPOSE: For muscle-invasive bladder cancer, bladder preserving chemoradiotherapy (BPCRT) has shown to be a viable alternative for patients with urothelial carcinoma (UCa). Traditionally bladder cancer with variant histology UCa or other tumors types involving the bladder have worse outcomes and BPCRT has been contraindicated. However, there is limited high level evidence for this recommendation. MATERIALS/METHODS: The National Cancer Database (NCDB) was queried for all patients with Bladder cancer treated from 2004 to 2015 restricted to clinical stage T2-4, N0, M0 who had variants of UCa or other tumors types involving the bladder (e.g. adenocarcinoma and squamous cell carcinoma). Only patients treated with definitive intent with either radical cystectomy or BPCRT after maximal transurethral tumor resection were analyzed. Propensity-score matching was used. RESULTS: 356 patients had BPCRT and 2093 patients had definitive surgery for muscle-invasive bladder cancer limited to variants of UCa and other tumors types involving the bladder. On multivariable analysis worse prognosis was associated with age >65 years old (HR 1.24, p = 0.004) and T4 disease (HR 1.90, p < 0.001). In propensity score weighted sample, there was no statistical significant difference in OS for patients with BPCRT as compared to cystectomy (p = 0.387) and for neuroendocrine, micropapillary or not otherwise specified histology subgroups there was no significant difference. Patients with adenocarcinoma (HR 1.75) or squamous cell carcinoma (HR 1.49) had worse OS associated with BPCRT compared to surgery. CONCLUSION: From 2004 to 2015, BPCRT in muscle-invasive bladder cancer was associated with similar overall survival compared to cystectomy in patients with selected variant histology but with worse OS for adenocarcinoma or squamous cell carcinoma specifically. As our study has inherent limitations, these hypotheses require validation in a prospective setting and/or with a larger sample size.