Pancreatic Cancer Surveillance in Carriers of a Germline Pathogenic Variant in CDKN2A

Simple Summary Pancreatic cancer surveillance in high-risk individuals is not well-defined, and recommendations in this regard have recently changed. Specifically, in carriers of a germline pathogenic variant in CDKN2A, the risk of pancreatic ductal adenocarcinoma seems to be higher than previously reported. We present a cohort with a large number of CDKN2A heterozygotes under surveillance, in which an early pancreatic cancer was detected and a curative treatment was offered. Our data support the latest surveillance recommendations in these individuals. Three percent of patients with pancreatic ductal adenocarcinoma (PDAC) present a germline pathogenic variant (GPV) associated with an increased risk of this tumor, CDKN2A being one of the genes associated with the highest risk. There is no clear consensus on the recommendations for surveillance in CDKN2A GPV carriers, although the latest guidelines from the International Cancer of the Pancreas Screening Consortium recommend annual endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI) regardless of family history. Our aim is to describe the findings of the PDAC surveillance program in a cohort of healthy CDKN2A GPV heterozygotes. This is an observational analysis of prospectively collected data from all CDKN2A carriers who underwent screening for PDAC at the high-risk digestive cancer clinic of the Hospital Clinic de Barcelona between 2013 and 2021. A total of 78 subjects were included. EUS or MRI was performed annually with a median follow-up of 66 months. Up to 17 pancreatic findings were described in 16 (20.5%) individuals under surveillance, although most of them were benign. No significant precursor lesions were identified, but an early PDAC was detected and treated. While better preventive strategies are developed, we believe that annual surveillance with EUS and/or MRI in CDKN2A GPV heterozygotes may be beneficial.

Automated summary

Surveillance methods for pancreatic cancer in high-risk individuals are unclear and have recently changed. A study found that the risk of pancreatic ductal adenocarcinoma is higher in carriers of a germline pathogenic variant in CDKN2A than previously reported. The findings support the latest surveillance recommendations for these individuals.