Advertisement
You are prohibited from using or uploading content you accessed through this website into external applications, bots, software, or websites, including those using artificial intelligence technologies and infrastructure, including deep learning, machine learning and large language models and generative AI.
You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (MP17)1 Apr 2020

MP17-16 A URINE-BASED DNA METHYLATION TEST TO MONITOR RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN BLADDER CANCER

    View All Author Information

    INTRODUCTION AND OBJECTIVE:

    Neoadjuvant chemotherapy provides a survival benefit compared to cystectomy alone in muscle invasive bladder cancer (MIBC), but only in those who respond at least partially to the treatment. There have been extensive efforts to develop tools to predict response to chemotherapy. Herein, we explore the feasibility of a urine based epigenetic assay to monitor neoadjuvant therapy (NAT) response.

    METHODS:

    Urine samples were collected from MIBC patients undergoing NAT (chemotherapy or immunotherapy) under an IRB approved protocol at baseline and with each therapy cycle. Samples were analyzed with Bladder CARE (Pangea Laboratory), a urine-based assay that measures methylation levels 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”, “high-risk”, or “negative”, which are proportional to the concentration of cancer cells in the sample. Changes in BCI score and surgical pathology were reviewed to determine association.

    RESULTS:

    Of the 21 enrolled patients, 10 completed NAT and underwent cystectomy. 7/10 patients received gemcitabine/cisplatin (GemCis) (Table 1). Histology included urothelial carcinoma without/with differentiation in 9/10 patients. 7/10 (70%) patients showed decrease in BCI. 6/7 (85%) patients with decrease in BCI showed at least partial response to NAT including 5/6 (83%) patients with pure urothelial histology who received GemCis. One patient with complete response on final pathology had a negative BCI at baseline and throughout NAT (#7). Of the 4 patients with weak or no change in BCI (#3, 11,12,14), 2 had variant histology (#3,12) and 2 received NAT asides from GemCis (#12, 14).

    CONCLUSIONS:

    We present a novel urine based epigenetic assay that may have utility in monitoring response to NAT in patients with MIBC. Further studies are underway to evaluate the utility of this test.

    Source of Funding:

    Zymo Research Corp, Pangea Laboratory

    Advertisement