MULTIPLEX BIOMARKER SERUM ASSAY DETECTS EARLY PANCREATIC ADENOCARCINOMA IN HIGH-RISK PATIENTS

Background:
Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed after reaching an advanced stage. High-risk patients with genetic predisposition (ie. BRCA2, CHEK-2 mutations), family history of pancreatic cancer (FPC), or high-risk intraductal papillary mucinous neoplasm (IPMN) could benefit from additional screening. However, optimal screening for high-risk patients has not been established. Biomarker assays have been validated on patients with known PDAC and healthy controls but not for primary screening. Our study investigates the potential of a multiplex biomarker serum assay to screen high-risk patients for PDAC.
Methods:
High-risk patients prospectively screened in a pancreatic cancer and cyst early detection center were tested with a multiplex biomarker immunoassay between July 2022 and May 2023. Electronic medical records of patients were reviewed.
Results:
Blood samples were collected from 40 patients to be screened using the assay. These included patients with BRCA2 mutations (n=20), IPMN (n=14), IPMN with FPC (n=3), CHEK2 mutation with FPC (n=1), and FPC alone (n=2). High risk signatures were found in six patients with mean CA 19-9 of 112.8 U/mL (SD 169, range 19.3-421.4). Five patients had borderline-risk signatures with mean CA 19-9 levels of 26.1 (SD 12.3, range 18.6-48) and 28 patients had low risk signatures with mean CA 19-9 levels of 10.8 (SD 6.4, range 4.1-29.5). One patient was a CA 19-9 non-producer thus the full assay was not completed per test guidelines. Twelve patients underwent surgery: three with high-risk signature and nine with low-risk signature. From the high-risk signature group, the subsequent surgical pathology found the following: one patient with pancreatic intraepithelial neoplasia 1A (who had a CA 19-9 of 116 and a pancreatic duct stricture) and two patients with stage I PDAC. The first PDAC patient had a CA 19-9 of 367, a biopsy with high-grade dysplasia, and on surgical pathology had a PDAC arising from an IPMN. The second PDAC patient had a CA 19-9 of 421, a biopsy with no dysplasia, and on surgical pathology had a PDAC and a separate invasive IPMN. The other three patients with a high-risk signature had no identifiable abnormality of the pancreas and are undergoing high-intensity surveillance. From the low-risk signature group, two patients had high grade IPMN and seven had low grade IPMN with one having an incidental 3 mm pancreatic neuroendocrine tumor on surgical pathology.
Conclusions:
Among high-risk patients who underwent resection, a multiplex biomarker assay was 100% sensitive and 90% specific for detecting PDAC. The test may identify early cancers not otherwise detected in selected high-risk patients. Further studies and follow-up of high-risk signature patients are needed to validate this use of a multiplex biomarker test as a screening tool.