Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant‐negative familial pancreatic cancer families
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Philipps-Universität Marburg
Abstract
Objective: To evaluate the diagnostic yield of pancreatic cancer screening in individuals
at risk (IAR) from familial pancreatic cancer (FPC) families with respect to
the presence or absence of pathogenic germline variants predisposing to pancreatic
adenocarcinoma (PDAC).
Design: In a 20 years period, IAR from FPC families were enrolled in a prospective
screening program of the national case collection for FPC of Germany, including
magnet resonance imaging (MRI) and endoscopic ultrasound (EUS). The diagnostic
yield was analyzed regarding significant pancreatic lesions such as PDAC, highgrade
pancreatic‐intraepithelial‐neoplasia (PanIN3) and intraductal‐papillarymucinous‐
neoplasia (IPMN) with high‐grade dysplasia. Screening results were
compared between carriers of pathogenic variants and variant‐negative IAR.
Results: 337 IAR, including 74 (22%) variant‐carriers and 263 IAR of variantnegative
FPC families (mean age 49; standard deviation [SD] þ 8.9) were followed
64 (SD þ 55) months. IAR underwent 5.1 (SD þ 3.9) screening visits with
1733 MRI (5.1,SD þ 3.9 per IAR) and 728 EUS (2.2,SD þ 1.7 per IAR). In 12 (4%)
cases, significant pancreatic lesions were detected, including 4 PDAC, 3 PanIN3 and
5 high‐grade IPMN. Three of 4 IAR with PDAC died after a mean of 27 months
postoperatively, and one IAR is alive without evidence of disease after 31 months.
The diagnostic yield for significant lesions was 13.5% (10/74) for variant carriers
compared to 0.8% (2/263) for IAR of variant‐negative FPC families (p < 0.001).
Logistic regression analysis revealed that a negative variant status was almost always
accompanied by the absence of a significant lesion over time with a negative
predictive value of 99.2% (95% CI 97.3%–99.9%).
Conclusion: The diagnostic yield seems to justify PDAC screening in IAR of FPCfamilies
with pathogenic germline variants in PDAC predisposing genes, not in
IAR of variant‐negative families.
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