Timeline of development of pancreatic cancer and implications for successful early detection in high-risk individuals.

ABSTRACT Background and aims To successfully implement imaging-based pancreatic cancer (PC) surveillance, it is key to understand the timeline and morphological features of neoplastic progression. We aimed to investigate the progression to neoplasia from serial prediagnostic pancreatic imaging tests in high-risk individuals, and identify factors associated with successful early detection. Methods We retrospectively examined the development of pancreatic abnormalities in high-risk individuals who were diagnosed with PC and/or underwent pancreatic surgery in 16 international surveillance programs. Results Of 2552 high-risk individuals under surveillance, 28 (1%) developed neoplastic progression to PC or high-grade dysplasia during follow-up (median 29 months after baseline, IQR 40). 46% (13/28) presented with a new lesion (median size 15 mm, range 7-57), a median of 11 months (IQR 8, range 3-17) after a prior examination, by which time 77% (10/13) had progressed beyond the pancreas. The other 54% (15/28) had neoplastic progression in a previously detected lesion (12 originally cystic, 2 indeterminate, 1 solid); 11 (73%) had PC progressed beyond the pancreas. The 12 patients with cysts had been followed for 21 months (IQR 15) and had a median growth of 5 mm/year (IQR 8). Successful early detection (as high-grade dysplasia or PC confined to the pancreas) was associated with resection of cystic lesions (versus solid or indeterminate lesions, OR 5.388, 95%CI 1.525-19.029) and small lesions (OR 0.890/mm, 95%CI 0.812-0.976). Conclusion Nearly half of high-risk individuals developing high-grade dysplasia or PC have no prior lesions detected by imaging, yet present at an advanced stage. Progression can occur before the next scheduled annual examination. More sensitive diagnostic tools or a different management strategy for rapidly-growing cysts are needed.