Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer
Authors: Paiella Salvatore , Capurso Gabriele , Carrara Silvia , Secchettin Erica , Casciani Fabio , Frigerio Isabella , Zerbi Alessandro , Archibugi Livia , Bonifacio Cristiana , Malleo Giuseppe , Cavestro Giulia Martina , Barile Monica , Larghi Alberto , Assisi Daniela , Fantin Alberto , Milanetto Anna Caterina , Fabbri Carlo , Casadei Riccardo , Donato Giulio , Sassatelli Romano , De Marchi Giulia , Di Matteo Francesco Maria , Arcangeli Valentina , Panzuto Francesco , Puzzono Marta , Dal Buono Arianna , Pezzilli Raffaele , Salvia Roberto , Rizzatti Gianenrico , Casadio Marco , Franco Monica , Butturini Giovanni , Pasquali Claudio , Coluccio Chiara , Ricci Claudio , Cicchese Noemi , Sereni Giuliana , de Pretis Nicolò , Stigliano Serena , Rudnas Britt , Marasco Matteo , Lionetto Gabriella , Arcidiacono Paolo Giorgio , Terrin Maria , Crovetto Anna , Mannucci Alessandro , Laghi Luigi , Bassi Claudio , Falconi Massimo 
Published: October 2023

INTRODUCTION:
Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before.

METHODS:
HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195).

RESULTS:
During the study period (June 2015–September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported.

DISCUSSION:
PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time.