Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance
Open accessAbstract
Background & aims Screening of individuals who have a high risk of pancreatic ductal adenocarcinoma (PDAC), because of genetic factors, frequently leads to identification of pancreatic lesions. We investigated the incidence of PDAC and risk factors for neoplastic progression in individuals at high risk for PDAC enrolled in a long-term screening study.Methods We analyzed data from 354 individuals at high risk for PDAC (based on genetic factors of family history), enrolled in Cancer of the Pancreas Screening cohort studies at tertiary care academic centers from 1998 through 2014 (median follow-up time, 5.6 years). All subjects were evaluated at study entry (baseline) by endoscopic ultrasonography and underwent surveillance with endoscopic ultrasonography, magnetic resonance imaging, and/or computed tomography. The primary endpoint was the cumulative incidence of PDAC, pancreatic intraepithelial neoplasia grade 3, or intraductal papillary mucinous neoplasm with high-grade dysplasia (HGD) after baseline. We performed multivariate Cox regression and Kaplan-Meier analyses.Results During the follow-up period, pancreatic lesions with worrisome features (solid mass, multiple cysts, cyst size > 3 cm, thickened/enhancing walls, mural nodule, dilated main pancreatic duct > 5 mm, or abrupt change in duct caliber) or rapid cyst growth (>4 mm/year) were detected in 68 patients (19%). Overall, 24 of 354 patients (7%) had neoplastic progression (14 PDACs and 10 HGDs) over a 16-year period; the rate of progression was 1.6%/year, and 93% had detectable lesions with worrisome features before diagnosis of the PDAC or HGD. Nine of the 10 PDACs detected during routine surveillance were resectable; a significantly higher proportion of patients with resectable PDACs survived 3 years (85%) compared with the 4 subjects with symptomatic, unresectable PDACs (25%), which developed outside surveillance (log rank P < .0001). Neoplastic progression occurred at a median age of 67 years; the median time from baseline screening until PDAC diagnosis was 4.8 years (interquartile range, 1.6-6.9 years).Conclusions In a long-term (16-year) follow-up study of individuals at high-risk for PDAC, we found most PDACs detected during surveillance (9/10) to be resectable, and 85% of these patients survived for 3 years. We identified radiologic features associated with neoplastic progression.
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The median time to progression from baseline was 4.8 years.
“The median time to progression from baseline was 4.8 years.”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [76]
The Results section (Rates of Progression and Time to Radiologic and Neoplastic Progression) reports a median of 4.8 years from baseline screening to neoplastic progression, but specifically for the 14 high-risk individuals who developed invasive pancreatic cancer after baseline. The citing sentence omits that restriction and could be read as applying to progression generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn a highly selected cohort of 354 HRIs undergoing long-term surveillance (>16 years) at one institution, EUS and MRI surveillance can lead to detection of early PDAC and high-grade precursor IPMNs and PanINs.
“In a highly selected cohort of 354 HRIs undergoing long-term surveillance (>16 years) at one institution, EUS and MRI surveillance can lead to detection of early PDAC and high-grade precursor IPMNs and PanINs, with most (90%) resected screen-detected PDACs found to be resectable, at an earlier stage than symptomatic PDAC.76”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [76]
The Results (Cumulative Incidence and Outcomes of Surveillance and Treatment) report 354 high-risk individuals, detection of PDAC and high-grade IPMN/PanIN lesions, and resectability in 9 of 10 PDACs detected during routine surveillance, compared with 1 of 4 in patients presenting with symptoms. The Discussion says the EUS/MRI program identified high-grade precursors and notes that the cohort was followed at a single institution. The duration is overstated: the Results describe a 16-year study period, not more than 16 years of surveillance for the cohort; median individual follow-up was 5.6 years. (LLM, conf=0.87)
Experimental — accuracy not yet measuredRecent evidence indicates that pancreas surveillance can downstage pancreatic cancers diagnosed in high-risk individuals, though based on few studies.
“Recent evidence indicates that pancreas surveillance can downstage pancreatic cancers diagnosed in high-risk individuals (HRIs), although this is based upon only a few studies,12,14-16 with relatively few PDACs diagnosed, and only a small percentage of which were diagnosed with stage I disease.17”
From The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival (2022) · cites this paper as [14]
The PDAC risk in the familial group appears significant enough to warrant surveillance.
“This observation is consistent with previous reports that the PDAC risk in the familial group appears significant enough to warrant surveillance.9,10,14”
From The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival (2022) · cites this paper as [14]
The five CAPS5 pancreatic resections for worrisome findings that harbored low-grade dysplasia only represent a smaller proportion of resections for low-grade lesions than reported in prior studies, likely due to better selection of patients for surgery.
“it is notable that these five cases represent a smaller proportion of resections for low-grade lesions than has been reported in prior studies14,15,29,30 and likely results from better selection of patients for surgery.”
From The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival (2022) · cites this paper as [14]
Downstaging of pancreatic cancers is associated with better survival compared with historical controls, especially when surveillance detects stage I cancers.
“Such downstaging is associated with better survival compared with historical controls, particularly when surveillance detects stage I cancers.”
Most pancreatic cancers in high-risk individuals with familial risk only under surveillance are diagnosed after age 55.
“To date, most pancreatic cancers in high-risk individuals with familial risk only (ie, no known susceptibility gene mutation) under surveillance are diagnosed after age 55.”
Subcentimetre pancreatic cysts are detected in up to 50% of high-risk individuals, depending on the age of the cohort.
“Subcentimetre pancreatic cysts are detected in up to 50% of high-risk individuals, depending on the age of the cohort.”
The two studies (Vasen et al and the CAPS study) show that pancreatic surveillance of high-risk individuals can lead to downstaging of pancreatic cancers diagnosed.
“These two studies show that pancreatic surveillance of high-risk individuals can lead to downstaging of pancreatic cancers diagnosed.”
High-risk groups for pancreatic ductal adenocarcinoma include people with inherited predisposition, people with pancreatic cystic lesions, and people older than 50 years with newly diagnosed type 2 diabetes.
“Here, we review groups at high risk for pancreatic ductal adenocarcinoma, including individuals with inherited predisposition and patients with pancreatic cystic lesions.”
From Early detection of pancreatic cancer (2020) · cites this paper as [18]
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- Authors
- Canto, M. I., Almario, J. A., Schulick, R. D., Yeo, C. J., Klein, A., Blackford, A., Shin, E. J., Sanyal, A., Yenokyan, G., Lennon, A. M., Kamel, I. R., Fishman, E. K., Wolfgang, C., Weiss, M., Hruban, R. H., & Goggins, M.
- Affiliations
- Johns Hopkins University (US)
- University of Colorado Anschutz (US)
- Thomas Jefferson University (US)
- Corresponding author
- Canto, Marcia Irene
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 155
- Issue
- 3
- Pages
- 740-751.e2
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC6120797
- OpenAlex
- W2803439891
- Cited by
- 414
- References
- 41
- Citations by year
- 2026: 36 · 2025: 33 · 2024: 54 · 2023: 63 · 2022: 73 · 2021: 56 · 2020: 49 · 2019: 40 · 2018: 10
- FWCI
- 14.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA154823, R01CA132829, P50CA062924, R01CA176828, U01CA210170)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK089502)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Keywords
- pancreatic ductal adenocarcinoma, pancreatic cancer screening, high-risk individuals, familial pancreatic cancer, tumor progression, intraductal papillary mucinous neoplasm, high-grade dysplasia, pancreatic cysts, resectable pancreatic cancer, survival after resection
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Pancreas, Pancreatic Neoplasms, Regression Analysis, Risk Factors, Time Factors, Tomography, X-Ray Computed, Incidence, Proportional Hazards Models, Disease Progression, Sentinel Surveillance, Endosonography, Carcinoma, Pancreatic Ductal, Kaplan-Meier Estimate, Early Detection of Cancer
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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