Background: With very low survival rates, pancreatic cancer (PC) remains a disease in need of diagnostic and therapeutic innovation and novel biomarkers to guide and optimize treatment decisions are urgently needed. Analysis of circulating tumor DNA (ctDNA) has been shown to be a highly accurate method for determining treatment efficacy and detecting molecular residual disease (MRD) in patients (pts) with various cancer types as compared to tumor markers and imaging modalities. However, it has been reported that the ctDNA detection rate in PC using existing tumor-agnostic ctDNA assays was lower than those in other cancer types because of the high stromal and low cellular features of PC, which prevents the shedding of ctDNA into blood circulation. Even in advanced cancers, the sensitivity of ctDNA utilizing tumor-agnostic mutation panels is much lower as compared to that in tumor tissue specimens. The Invitae Personalized Cancer MonitoringTM test is a novel and highly sensitive, tumor-informed MRD detection assay. MRD assessment as well as recurrence and treatment response monitoring using this novel assay could lead to the development of improved treatment algorithms for pts with PC. The ARTEMIS-PC study (UMIN000043561) aims to evaluate the clinical utility of the Invitae Personalized Cancer Monitoring test in pts with resectable and unresectable PC. Methods: This is a multi-site, prospective, observational trial in Japan of 150 pts with resectable (50) and unresectable (100) PC. The main eligibility criteria are histopathologically diagnosed as adenocarcinoma, no prior treatment for PC, scheduled to undergo surgery for resectable PC or receive systemic therapy for unresectable PC. In resectable PC cohort, blood samples will be collected before surgery and at 1, 3, 6, 9, 12, 18, and 24 months after surgery, and imaging study will be performed before surgery, and at 3, 6, 9, 12, 18, and 24 months after surgery. In the unresectable PC cohort, blood samples will be collected before treatment and at 4, 8, 12, 16, 24, 32, 40, and 48 weeks on treatment, and imaging study will be performed before treatment and every 8 weeks on treatment until 48 weeks. Primary endpoint in the resectable PC cohort is success rate of creating personalized panel using tumor tissue obtained by EUS-FNA/FNB, and that in unresectable PC cohort is rate of concordance of KRAS mutations between tumor tissue and blood samples. Key secondary endpoints in resectable PC cohort are rate of ctDNA positivity for each cancer stage before neoadjuvant chemotherapy and 4 weeks after surgery, and that in unresectable PC cohort is pretreatment ctDNA detection rate for each disease stage. Active enrollment started in December, 2022 and 21 pts with resectable PC and 64 pts with unresectable have been enrolled as of September 2023. Clinical trial information: NCT06043921.