Abstract LB327: DNA methylation biomarkers for early bladder cancer detection and treatment response monitoring
Authors: Piatti Paolo , Daneshmand Sia , Seyedian Sanam Ladi , Ghodossipour Saum , Ahmadi Hamed , Roberts Suzanne , Ghoreifi Alireza , Basin Michael , Hajian Simin , Chew Yap Ching , Bhasin Jeffrey , Jara Benjamin , Sanossian Lucy , Djaladat Hooman , Shuckman Anne , Bhavandia Sumeet , Liang Gangning 
Published: April 2024

Abstract
Objectives: Bladder cancer (BC) stands as the 5th most prevalent cancer in the USA, with over 83,000 new cases diagnosed in 2023. The absence of non-invasive diagnostic tools for sensitive early BC detection and treatment response monitoring poses a significant challenge. This study evaluates the clinical potential of the Bladder CARE™ Assay for early BC detection and monitoring treatment response in BC patients.
Methods: Under an institutional review board-approved protocol, voided urine samples were prospectively collected from USC patients with prior BC history under surveillance/anticancer treatment, prior genitourinary manipulation. Enrollment spanned February 2019 to September 2021. Samples underwent analysis using the Bladder CARE™ Assay, a DNA methylation test for quantitative BC and upper tract urothelial carcinoma (UTUC) detection from urine. Results were reported as Bladder CARE Index (BCI) and samples were categorized as “positive” (BCI &gt; 5), “low-positive” (2.5 &lt; BCI &lt; 5), or “negative” (BCI &lt; 2.5). Correlations between BCI value and categories, and clinicopathological findings were assessed.
Results: A total of 110 previously diagnosed BC patients (median age: 74; 86% male) were enrolled in this study. Within 36 months post-TURBT, 24 patients (21.8%) showed evidence of recurrence. Bladder CARE™ Assay detected all recurrences, averagely 7.35 months earlier than cystoscopy. Of 55 patients (50%) undergoing anticancer therapies (45 BCG, 4 MMC, 2 GEM, 1 9UT, 1 GEM/DOCE, 1 MMC/BCG, and 1 BCG, MMC, and GEM), 7 (12.7%) recur (non-responders) and 11 (20%) did not show evidence of recurrence by 18 months post-TURBT (responders); 18-month post-operative data was unavailable for 37 patients (67.3%), which could not be classified in responders or non-responders. Bladder CARE™ detected 85.7% of non-responders, with BCI increasing prior to positive histology (avg. BCI: 86.1). In responders, BCI remained stable in negative/low-positive range post-TURBT (avg. BCI: 2.5). In addition, data from pre- and post-TURBT assessments were available for 20 of the 110 enrolled patients. The Bladder CARE™ Assay demonstrated a decrease in BCI post-TURBT in 19 of these 20 patients (95%).
Conclusions: This prospective pilot study underscores the Bladder CARE™ Assay's capacity to pre-emptively detect BC months ahead of the gold standard. Furthermore, its quantitative nature offers prognostic insight, enabling non-invasive monitoring of patient response to anticancer treatments. A larger-scale study is the next step to validating these promising findings.
Citation Format: Paolo Piatti, Sia Daneshmand, Sanam Ladi Seyedian, Saum Ghodossipour, Hamed Ahmadi, Suzanne Roberts, Alireza Ghoreifi, Michael Basin, Simin Hajian, Yap Ching Chew, Jeffrey Bhasin, Benjamin Jara, Lucy Sanossian, Hooman Djaladat, Anne Shuckman, Sumeet Bhavandia, Gangning Liang. DNA methylation biomarkers for early bladder cancer detection and treatment response monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB327.