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 onetime workup of a "heurisk" (hyou-risk) leads to earlier detection of cancer. A heurisk is an early warning sign with three defining characteristics: i) indicates higher-than-threshold-probability of having prevalent invasive cancer, ii) is associated with a meaningful lead time to diagnosis, and iii) 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 proportion of patients with advanced disease, and maximize treatment options leading to increases in lead time-adjusted 1-, 3- and eventually 5- year survival. A specific example of a heurisk for pancreatic cancer is glycemically defined new onset diabetes (GNOD) and the Early Detection Initiative (NCT04662879) an example of GNOD-based heuriskance. As heuriskance has no precedent, we provide i) a tiered risk stratification approach (Define-Enrich-Find), ii) metrics for choosing a heurisk, iii) success metrics for strategy and iv) 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. The concept of heuriskance is applied to pancreatic cancer but could be extended to other cancer types.