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

Abstract

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 Clínic 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.

Keywords: CDKN2A; hereditary; pancreatic cancer; surveillance.

Figure 1

Flow chart—patients included in the study. HRC, high-risk clinic.

Figure 2

Surveillance findings. IPMN, intraductal papillary mucinous neoplasm.

Figure 3

(A) Endoscopic ultrasound picture of the detected pancreatic cancer (24.1 × 14.1 mm). (B) Fine needle puncture in this operable tumor was performed and the cytology was positive for malignancy (adenocarcinoma). The final size was 28 × 16 mm (in the surgically removed piece).