Heuriskance: a novel paradigm for systematic earlier detection of sporadic pancreatic cancer.

Early detection is key to improving survival and mortality from pancreatic cancer. Traditional periodic screening for cancer in an asymptomatic population is infeasible and not recommended for this low-incidence disease. We describe a novel approach we call "heuriskance" (hyou-ris-kance), wherein a systematic search for and 1-time workup of a "heurisk" (hyou-risk) leads to earlier detection of cancer. A heurisk is an early-warning sign with 3 defining characteristics: (1) the individual has a higher-than-threshold probability of having prevalent invasive cancer, (2) it is associated with a meaningful lead time to diagnosis, and (3) it is identifiable by a systematic and scalable process in the population. Heuriskance aims to systematically detect cancer with clinically meaningful lead time to clinical diagnosis, minimize the proportion of patients with advanced disease, and maximize treatment options, leading to increases in lead time-adjusted 1-, 3-, and 5- year survival. A specific example of a heurisk for pancreatic cancer is glycemically defined new-onset diabetes and the Early Detection Initiative for Pancreatic Cancer (ClinicalTrials.gov identifier NCT04662879) an example of glycemically defined new-onset diabetes-based heuriskance. As heuriskance has no precedent, we provide (1) a tiered risk stratification approach (Define-Enrich-Find), (2) metrics for choosing a heurisk, (3) success metrics for strategy, and (4) phases 1-5 for evaluating the strategy in retrospective and prospective studies. Like all current cancer therapies, heuriskance aims to iteratively improve survival from a fatal disease using a pragmatic, evidence-based, systematic approach to its earlier detection. We apply the concept of heuriskance to pancreatic cancer, but it could be extended to other cancer types.