O9-1 Updated analysis of circulating tumor DNA in advanced genitourinary cancers: SCRUM-Japan MONSTAR SCREEN Project

Circulating tumor DNA (ctDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we precisely determined mutational status of plasma ctDNA in patients with genitourinary (GU) cancers. SCRUM-Japan consortium of Nationwide Cancer Genome Screening Project has started MONSTAR-SCREEN project which evaluates ctDNA for patients with advanced solid tumors since Apr 2019 in Japan. We collected plasma and tumor samples in patients with prostate cancer (PC), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Plasma ctDNA and tumor genomic DNA were analyzed by a NGS-based ctDNA assay, Foundation One ® Liquid (F1L) and tissue-based panel, Foundation One ® CDx (F1CDx), respectively. As of May 2021, we enrolled 1206patients with advanced solid tumors in MONSTAR-SCREEN. Among them, we analyzed 226 ctDNA samples of advanced GU cancers (95 PC, 73 UC, and 58 RCC) and compared the feature in GU cancers with that in non-GU cancers. The level of ctDNA in GU cancers was similar to that in non-GU cancers (median 1.92% vs. 3.80%, P = 0.229). Although UC possessed the highest median blood tumor mutation burden (bTMB) in all cancers (4.39), there was no significant bTMB difference between GU cancers and non-GU cancers (2.63 vs. 2.63, P = 0.995). Interestingly, the mutation rate in genes related to DNA damage response pathway tended to be higher in GU cancers compared to that in non-GU cancers (24.3 % vs. 19.1%, P = 0.08). When we focus on other major oncogenic signaling pathways such as PI3K, MAPK and Wnt-signal pathway, we found that related genes in these pathways were less frequently altered in GU cancer versus non-GU cancers (P = 9.3E-4, P = 1.3E-10 and P = 2.6E-6, respectively). We performed comprehensive genomic profiling of ctDNA in GU cancers and found some evidences related to distinguishing profile in GU cancers, which lead to conduct clinical trials.