Abstracts from the New England Section of the AUA 2021

NE-AUA 2021 Abstracts Concurrent Poster Session II Comparison of Signal Intensity in Bladder Urothelial Carcinomas Using pHLIP® Molecular Probes Borivoj Golijanin, BS 1 , Ali Amin, MD 1 , Michael DuPont, BS 2 , Anna Moshnikova, PhD 2 , Ohad Kott, MD 3 , Yana K. Reshetnyak, PhD 2 , Oleg A. Andreev, PhD 2 , Dragan J. Golijanin, MD 3 1 Department of Pathology & Laboratory Medicine, The Miriam Hospital; The Warren Alpert Medical School of Brown University, Providence, RI, USA; 2 Physics Department, University of Rhode Island, Kingston, RI, USA; 3 The Minimally Invasive Urology Institute, The MiriamHospital; The Warren Alpert Medical School of Brown University, Providence, RI, USA Introduction: Urothelial carcinomas (UC) are a heterogeneous malignancy with an acidic microenvironment. pH low insertion peptides (pHLIPs) are a class of pH specific transmembrane peptides that target the acidic microenvironment of cancer cells. pHLIP variant-3 (Var3-pHLIP) was conjugated to a near infrared fluorescent (NIRF) dye to evaluate specificity and sensitivity as a tumor targeting molecular imaging probe. Materials & Methods: After incubation for 15 minutes with Var3-pHLIP conjugated to indocyanine green (ICG) or IRDye® 800CW, 38 ex-vivo bladder specimens from patients undergoing robotic assisted laparoscopic radical cystectomy for bladder cancer were placed under NIRF capable laser to excite the fluorophore. Peak signal intensity and the corrected mean intensity of malignant and nonmalignant cases were analyzed and compared using paired samples t-test. The number of lesions visible under NIRF was compared with the number identified under white light using paired samples t-test. Expression of NIRF signal and identification of lesions under white light by urologic oncology pathologist were compared to histopathology for specificity and sensitivity calculations. Results: Of 58 lesions processed for histopathological evaluation, 47 (81%) were seen under white light and 57 (98.3%) were seen with Var3=pHLIP, representing an improved diagnosis by 17.3% (p=0.003). InNIRF, Var3-pHLIP demonstrated an average peak signal intensity of 116.4 relative fluorescent units (RFU) in malignant cases, and nonmalignant cases had average peak of 44.3 RFU (p<0.001). Corrected average signal intensity of malignant cases demonstrated an average of 52.9 RFU/µm 2 and nonmalignant cases showed an average of 25 RFU/µm 2 (p<0.001). Var3-pHLIP demonstrated 98% sensitivity and 100% specificity in identification of UC. Conclusions: Var3-pHLIP NIRF enhanced visualization and improved diagnosis of UC. Categorizing into broader categories of malignant and nonmalignant, the unique Var3-pHLIP NIRF signal can be used to differentiate between the two groups based on both peak signal intensity and mean intensity per unit area of lesion. NIRF Var3-pHLIP identified UC irrespective of subtype, previous treatment, and stage. All CIS cases missed by white light cystoscopy were diagnosed using Var3-pHLIP NIRF imaging. Additional work into digital, automated analysis of Var3-pHLIPNIRF signal and development of a fluorescent signal analysis capable cystoscope can lead to diagnosis of bladder cancer at the time of cystoscopy. P30 Candidate Urine microRNA Biomarkers Differentially Expressed in Preoperative Urine Specimens fromPatientsWith pT0 Compared toMuscle Invasive Urothelial Carcinoma at Time of Cystectomy Amanda Sherman, MD , Travis Sullivan, MS, Kimberly Rieger-Christ, PhD Lahey Hospital and Medical Center, Burlington, MA, USA Introduction: Radical cystectomy with urinary diversion is crucial in managing muscle invasive bladder cancer (MIBC). Despite the increasing adoption of minimally invasive techniques to perform the operation, it remains a morbid procedure with a relatively high rate of accepted post-operative complications. A small, but significant number of patients undergoing the procedure have T0 disease on pathologic examination. This study aims to identify these pT0 patients using microRNA (miRNA) profiles from preoperative urine specimens. Materials &Methods: Total RNAwas isolated from cell-free urine of patients undergoing cystectomy for a history of muscle-invasive cancer. Each sample was profiled for 376 unique miRNA using a novel qPCR based detection system (MIRXES). Statistical evaluations were performed to determine the potential of miRNA to distinguish these cohorts using receiver operator characteristic curves. Results: Urine samples from twenty four patients were analyzed: twelve from patients with subsequently confirmed muscle invasive bladder cancer and twelve patients with pathology of pT0. Clinical characteristics were similar between the groups. 144 miRNAwere detected in each of the samples from pT0 patients while 215 were detected in each of the samples from the muscle invasive cohort. Nine miRNA were significantly differentially expressed between the cohorts (P<0.05). Seven of these achieved an AUC>0.75 for distinguishing MIBC. Conclusions: This novel qPCR analysis of preoperative urine specimens was successful in identifying candidate miRNA to be further evaluated as a noninvasive test to detect eradication of MIBC prior to cystectomy. Of 9 total miRNAs that are differentially expressed in urine between pT0 and MIBC specimens, 7 exhibit anAUC > 0.75, strengthening their candidacy as markers. Validation with further samples is planned, and once complete, inquiry will shift towards optimizing a urine assay for use in clinical surveillance, intended to detect patients in whom cystectomy can be safely delayed or deferred. Subgroup analysis comparing differential expression based on type of neoadjuvant treatment is another planned direction for expansion of investigation. P29 51