Pancreatic cancer surveillance: Risk stratification of individuals with a germline CDKN2A pathogenic variant

Abstract

Background: Individuals carrying a germline CDKN2A pathogenic variant (PV) are at a high risk of developing pancreatic ductal adenocarcinoma. Risk stratification could allow tailored surveillance.

Objective: To develop a Fine-Gray prediction model for the risk of PDAC in carriers of a CDKN2A PV.

Methods: Data from two large Dutch pancreatic cancer surveillance programs were used. A limited set of predictor variables were selected bsased on previous literature and the clinical expertise of the study group.

Results: A total of 506 CDKN2A PV carriers were included, among whom we showed a substantial lifetime risk of PDAC (23%). The model identifies having a first-degree relative with PDAC (B = 0.7256) and a history of smoking (B = 0.4776) as significant risk factors. However, the model shows limited discrimination (c-statistic 0.64) and calibration.

Conclusion: Our study highlights the high lifetime risk of PDAC in carriers of a CDKN2A PV. While identifying significant risk factors such as family history of PDAC and smoking, our prediction model shows limited precision, highlighting the need for additional factors such as biomarkers to improve its clinical utility for tailored surveillance of high-risk individuals.

Keywords: PDAC; biomarkers; diagnosis; familial history; genes; genetics; predictors; screening; smoking; tailored.

FIGURE 1

Cumulative incidence of pancreatic ductal adenocarcinoma (PDAC; red) or death from other causes (blue).

FIGURE 2

Calibration plot depicting the predicted versus actual probabilities of developing pancreatic ductal adenocarcinoma 20 years after enrollment in surveillance.