Abstract 3335: DNA methylation markers for the surveillance of non-muscle invasive bladder cancer: Results from a prospective pilot study

Abstract Objectives: Bladder cancer (BC) is a common urinary tract cancer with a variable clinical course. With recurrence as high as 70%, cystoscopy and urine cytology are routinely employed during follow-up of patients with a history of non-muscle invasive bladder cancer (NMIBC). Although multiple FDA approved urine-based tests for BC detection and surveillance exist, diagnostic accuracy of these urine-based assays is still suboptimal. Here, we evaluate the diagnostic value of a newly developed non-invasive DNA methylation-based test for surveillance of NMIBC. Methods: We included patients undergoing blue-light surveillance cystoscopy for NMIBC between February 2019 and September 2021. Urine samples were collected at each surveillance cystoscopy prior any genitourinary manipulation. Samples were analyzed with Bladder CARE, a urine-based test that measures the methylation level of 3 bladder cancer specific biomarkers (TRNA-Cys, SIM2, and NKX1-1) and two internal control loci using methylation-sensitive restriction enzymes coupled with qPCR. Results are reported as Bladder CARE Index (BCI) score and categorized as “positive” (BCI > 5), “high risk” (2.5 < BCI ≤ 5) or “negative” (BCI ≤ 2.5). Association between BCI score and category, cytology and cystoscopy findings were assessed. Results: A total of 503 samples were collected from 159 patients (median age of 73, 77% male). 103 biopsies were performed during surveillance cystoscopies, of which 26 (25%) showed evidence of cancer recurrence.Bladder CARE was positive (22) or high-risk (4) in all the positive biopsies, while cytology was atypical only in 7 and highly suspicious in 2. Among 77 negative biopsies, Bladder CARE was positive in 27 collected from 20 patients, 8 of whom developed recurrence detected during subsequent follow ups. Cytology was atypical in 2 of these 8 recurrence patients. 3 patients with positive Bladder CARE results and normal cystoscopies developed upper tract urothelial carcinoma later. Bladder CARE test was able to predict the recurrence within a median of 7 months prior cystoscopy. The Receiver Operating Characteristic (ROC) curve using the BCI values demonstrated the sensitivity, specificity, positive predictive values, and negative predictive value of 93%, 65%, 73.5%, and 89.5%, respectively (Table 1). Conclusions: Urine cytology had low sensitivity and PPV for urothelial carcinoma in this cohort. Our findings demonstrated the necessity of more accurate urine biomarkers in the surveillance of NMIBC patients. Our preliminary results showed that Bladder CARE test has high sensitivity and can potentially predict future recurrence. Citation Format: Paolo Piatti, Sanam Ladi-Seyedian, Sidney Roberts, Farshad Sheybaee Moghadam, Alireza Ghoreifi, Jeffrey Bhasin, Benjamin Jara, Lucy Sanossian, Yap Ching Chew, Sumeet Bhanvadia, Hooman Djaladat, Anne Schuckman, Gangning Liang, Siamak Daneshmand. DNA methylation markers for the surveillance of non-muscle invasive bladder cancer: Results from a prospective pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3335.