Pancreatic Cancer Surveillance in Carriers of a Germline CDKN2A Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up
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PURPOSE: Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in CDKN2A. METHODS: Prospectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound. RESULTS: Three hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia. CONCLUSION: This long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in CDKN2A. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival.
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Germline CDKN2A mutation is associated with an increased risk of melanoma and pancreatic cancer.
“Germline CDKN2A mutation is associated with an increased risk of melanoma and pancreatic cancer, and somatic CDKN2A loss is common in pancreatic cancer49–51.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [51]
Somatic CDKN2A loss is common in pancreatic cancer.
“Germline CDKN2A mutation is associated with an increased risk of melanoma and pancreatic cancer, and somatic CDKN2A loss is common in pancreatic cancer49–51.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [51]
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- Authors
- Klatte, D. C. F., Boekestijn, B., Wasser, M. N. J. M., Feshtali Shahbazi, S., Ibrahim, I. S., Mieog, J. S. D., Luelmo, S. A. C., Morreau, H., Potjer, T. P., Inderson, A., Boonstra, J. J., Dekker, F. W., Vasen, H. F. A., van Hooft, J. E., Bonsing, B. A., & van Leerdam, M. E.
- Affiliations
- Leiden University Medical Center (NL)
- Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
- Corresponding author
- Klatte, Derk C.F.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2022-10-01
- Volume
- 40
- Issue
- 28
- Pages
- 3267-3277
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W4281612084
- Cited by
- 102
- References
- 33
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 34 · 2023: 23 · 2022: 6
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
- Keywords
- pancreatic cancer surveillance, CDKN2A, germline pathogenic variants, pancreatic ductal adenocarcinoma, high-risk individuals, early-stage cancer detection, resectability, survival, magnetic resonance cholangiopancreatography, endoscopic ultrasound, cancer susceptibility
- MeSH terms
- Aged, Follow-Up Studies, Germ Cells, Humans, Middle Aged, Pancreatic Neoplasms, Prospective Studies, Cyclin-Dependent Kinase Inhibitor p16, Carcinoma, Pancreatic Ductal, Early Detection of Cancer
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