Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant-negative familial pancreatic cancer families

• Published in: United European gastroenterology journal
• Main Authors: Maurer, Elisabeth, Lehman, Bettina, Matthäi, Elvira, Denzer, Ulrike, Figiel, Jens, Jesinghaus, Moritz, Slater, Emily P, Stefenelli, Ulrich, Gress, Thomas M, Bartsch, Detlef K
• Format: Journal Article
• Language: English
• Published: England 19-07-2024
• Subjects: genetic; high; PDAC; increased; intraepithelial; adenocarcinoma; diagnosis; IPMN; familiar; neoplasia
• ISSN: 2050-6406; 2050-6414; 2050-6414
• DOI: 10.1002/ueg2.12631

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).
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, high-grade pancreatic-intraepithelial-neoplasia (PanIN3) and intraductal-papillary-mucinous-neoplasia (IPMN) with high-grade dysplasia. Screening results were compared between carriers of pathogenic variants and variant-negative IAR.
337 IAR, including 74 (22%) variant-carriers and 263 IAR of variant-negative FPC families (mean age 49; standard deviation [SD] + 8.9) were followed 64 (SD + 55) months. IAR underwent 5.1 (SD + 3.9) screening visits with 1733 MRI (5.1,SD + 3.9 per IAR) and 728 EUS (2.2,SD + 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%).
The diagnostic yield seems to justify PDAC screening in IAR of FPC-families with pathogenic germline variants in PDAC predisposing genes, not in IAR of variant-negative families.