Abstract 1159: Circulating cell-free DNA (cfDNA) levels and fragmentation patterns discriminate muscle invasive from non-muscle invasive urothelial cancer of the bladder
Authors: Shinjini Ganguly, Jaleh Fallah, Hong Li, Wei Wei, Aysegul Balyimez, Claudia Marcela Diaz, Pat Rayman, Marcelo Lamenza, Priscilla Dann, Donna Company, Rahul Tendulkar, Jacob Scott, Mohamed Abazeed, Jorge A. Garcia, Moshe C. Ornstein, Brian R. Rini, Byron Lee, Petros Grivas, Omar Mian
Journal: Cancer Research (2020)

Abstract Purpose: There is risk of clinical under-staging of muscle invasive bladder cancer (MIBC) by trans-urethral resection (TURBT) alone. Circulating biomarkers may improve the staging and pre-treatment risk stratification of patients with bladder cancer by discriminating non-muscle invasive (NMIBC) and MIBC. Methods: Peripheral blood from 74pts with BC (30NMIBC, 15 MIBC and 29 Met BC was collected in Streck BCT tubes and processed to obtain cfDNA. Total cfDNA quantity (ng/mlof plasma) was assessed by fluorimetry. cfDNA fragment size was measured by Bioanalyzer DNA analysis. Wilcoxon rank sum test, Cochran-armitage trend test, Fisher's exact t-test were used to compare cfDNA quantity and fragmentation pattern (small fragments are indicative of circulating tumor DNA) among pts with NMIBC, MIBC, met BC to predict invasiveness of BC. Results: There was no significant difference in cfDNA concentration between MIBC and met BC, however, cfDNA levels were significantly lower in pts with NMIBC vs MIBC and met BC. The difference was even more pronounced in case of cfDNA fragment (100-400bp) conc. Total cfDNA (ng/ml) was a good predictor in bladder cancer invasiveness, AUC 0.8 (95% CI 0.7-0.9). The risk of invasion was significantly lower inpatients with total cfDNA &amp;lt 1.5 ng/ml and significantly higher in patients with cfDNA &amp;gt 7.0ng/ml. In 18 pts with cfDNA&amp;lt1.5ng/ml, only 1 pt (5.6%) had invasive cancer (at 1.2). The percent risk of invasive disease was 70.6% for cfDNA concentrations between 1.5-7.0ng/ml and 79.0% for cfDNA &amp;gt 7.0. No invasion was observed among 13 pts with total cfDNA less than 1. This exploratory study suggests that cfDNA levels may correlate with BC stage and hence can be used in juxtaposition with TURBT, exam under anesthesia and CT to better predict clinical staging. Conclusions: Circulating cfDNA may be a dynamic, low-cost and minimally invasive biomarker that can be used in conjunction with TURBT to predict tumor invasiveness, reduce under-staging, and risk stratify patients for appropriate curative intent therapy. cfDNA variation with BC stagingcfDNA parametersTotalNMIBCMIBCMET BCp-value(N=74)(N=30)(N=15)(N=29)cfDNA_ng/ml of plasma7.3[2.9,12.5]1.3[0.48,7.4]9.7[4.0,13.3]8.7[6.1,14.4]&amp;lt;0.001bcfDNA fragment (100to400bp)_pg/ml of plasma76.9[0.00,5591.2]0.00[0.00,59.4]3322.7[0.00,8405.2]3344.7[53.8,21930.3]&amp;lt;0.001b Citation Format: Shinjini Ganguly, Jaleh Fallah, Hong Li, Wei Wei, Aysegul Balyimez, Claudia Marcela Diaz, Pat Rayman, Marcelo Lamenza, Priscilla Dann, Donna Company, Rahul Tendulkar, Jacob Scott, Mohamed Abazeed, Jorge A. Garcia, Moshe C. Ornstein, Brian R. Rini, Byron Lee, Petros Grivas, Omar Mian. Circulating cell-free DNA (cfDNA) levels and fragmentation patterns discriminate muscle invasive from non-muscle invasive urothelial cancer of the bladder [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1159.