Pancreatic Cancer Surveillance in CDKN2A and Other High Risk Mutation Carriers

Rationale: Pancreatic cancer (PC) surveillance programs for high risk individuals, such as CDKN2A mutation carriers, require continuous evaluation and improvement.
Objective: The primary objective is to study if PC surveillance in individuals with a CDKN2A or other high risk mutations leads to an increase of 5-year survival rate, as compared to PC in the general population. Secondary objectives are: (1) to study long-term survival; (2) to identify additional risk factors that predict neoplastic progression in order to improve risk stratification; (3) to evaluate the accuracy of MRI/MRCP and EUS for detecting neoplastic lesions; (4) to investigate the role of ct-DNA as a diagnostic and prognostic marker; (5) to investigate the molecular characteristics of CDKN2A PDAC; (6) to study the cost-effectiveness of pancreatic surveillance; and (7) to explore the psychological aspects of genetic testing and surveillance.
Study design: This study is a registry of CDKN2A and other high risk mutation carriers enrolled in the Leiden University Medical Center PC surveillance program.
Study population: All individuals ≥ 40 and ≤ 75 years of age with a proven CDKN2A mutation and other high risk mutation carriers.
Main study endpoint: The main study endpoint is the 5-year survival rate of patients with a CDKN2A mutation undergoing surveillance who develop PC.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The majority of the data that will be collected in this study is part of routine care. As a study procedure, we will collect two extra blood samples during annual blood sampling, which is part of routine care. In addition, with subset of participants (30 individuals) we will conduct a focus-group study (in-depth interview), which will last a maximum of 2 hours. We feel that the risks and burden in this study are neglectable. We expect that the study outcomes may be directly beneficial for (future) individuals participating in our surveillance program, and individuals participating in surveillance programs in other expert centers.

Our hypothesis is that surveillance for pancreatic cancer in CDKN2A and other high risk mutation carriers leads to increased short and long term survival, as compared to pancreatic cancer diagnosed in the general population.

The primary outcome (survival rate) will be evaluated in 2021.

Annual magnetic resonance imaging (MRI) with or without endoscopic ultrasound (EUS)