Abstract I19: Early detection of pancreatic cancer: Challenges and opportunities

Research in early detection of pancreatic cancer is considered one of the highest priority areas by the National Cancer Institute (NCI) in its updated Roadmap for Progress in Pancreatic Ductal Adenocarcinoma (2019). However, current United States Screening and Prevention Task Force (USPSTF) guidelines recommend against screening for pancreatic cancer in the general population, due to the lack of credentialed biomarkers and the considerable potential for overdiagnosis. On the contrary, individuals at high-risk for pancreatic cancer represent an opportunity for cancer interception, including the conduct of imaging and biomarker validation studies in prospective cohorts. High-risk cohorts ripe for surveillance include individuals harboring germline deleterious mutations, those with pancreatic mucinous cystic lesions, and patients with new onset diabetes. Approximately 10% of pancreatic cancer patients carry germline mutations in genes such as BRCA1/2, ATM, PALB2, CDKN2A, and mismatch repair genes, amongst others. In the past year, the National Comprehensive Cancer Network (NCCN) guideline for germline testing has evolved towards a recommendation of “universal testing” in all index cases, which has been facilitated through the availability of relatively cheap CLIA multi-gene panels. “Cascade testing” of unaffected family members can identify asymptomatic individuals who might benefit from surveillance. Notably, the risk of harboring or developing pancreatic cancer varies widely between carrier mutations, and the guidelines for screening modality and interval are still evolving. A second high-risk group includes individuals with mucinous pancreatic cysts. It is important to reiterate that the overwhelming majority of patients with mucinous cysts will not progress to cancer, and routinely used clinical and imaging criteria can lead to overtreatment in a significant minority of patients. Thus, algorithms that improve the management of cystic lesions using the confluence of clinical, radiological, biochemical and molecular parameters are under active development. Pancreatic cancer is a “diabetogenic” neoplasm, with over three quarters of patients developing some measure of paraneoplastic aberration in glucose homeostasis. While 25-40% of pancreatic cancer patients present with frank new onset or worsening diabetes (classified as Type 3c diabetes) less than 1% of patients with new onset diabetes harbor an asymptomatic cancer. Thus, while adult new onset diabetes represents a high-risk population, significant enrichment of this population is needed in order to enable a clinically feasible early detection program. Algorithms such as “Enriching New Onset Diabetes for Pancreatic Cancer” (ENDPAC) that leverage structured data within electronic medical records (EMR) will enable the selection of individuals with the highest probability of subclinical disease. Following the discussion on high risk cohorts, we will pivot to some of the current challenges underlying biomarker development in the context of early detection, and why CA19-9 remains the only FDA approved biomarker for this disease despite 1000s of publications on this subject. Finally, we will briefly allude to how imaging modalities might be utilized in the context of localizing subclinical disease, including recent data on extra-pancreatic alterations induced by systemic metabolic alterations by the developing neoplasm that can be detected using standard of care imaging assays. Early detection of pancreatic cancer continues to be a challenging conundrum, but sustained investment and team science efforts facilitated by the National Cancer Institute and foundations, including the Lustgarten Foundation, Pancreatic Cancer Action Network and Cancer Research UK, are making tangible advances within this space. Citation Format: Anirban Maitra. Early detection of pancreatic cancer: Challenges and opportunities [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I19.