International Pancreatic Cancer Screening Program Displays Practicality

George Zogopoulos, MD, PhD

An early detection and prevention program for pancreatic cancer proved to be feasible on an international scale, according to findings from the observational Pancreatic Cancer Early Detection Consortium (PRECEDE) study (NCT04970056)published in the Journal of the National Comprehensive Cancer Network.¹

At the April 1, 2023, data cutoff, findings from an interim enrollment analysis of PRECEDE demonstrated that patients enrolled in cohort 1 of the study (n = 1759) completed baseline imaging at a rate of 79.6%. Individuals in cohort 1 were further divided into 3 subgroups: individuals with family history of pancreatic cancer (FPC; n = 839); individuals with a pathogenic germline variant (PGV) and a FPC (n = 138); and individuals with a PGV without a FPC (n = 782). Pancreatic cysts were detected in the 3 subgroups at rates of 41.2%, 30.4%, and 29.4%, respectively (P <.001). Twenty-three patients in cohort 1 were found to have solid lesions on baseline imaging; 10 patients were found to have a pancreatic neuroendocrine tumor and another 9 patients had benign of nondiagnostic solid lesions.

“Our work demonstrates the potential of a large international integrated clinical and research program developed to detect and intercept precancerous and cancerous changes in the pancreas,” George Zogopoulos, MD, PhD, the co-lead author of the study and an associate professor in the Departments of Oncology and Surgery of the Research Institute at McGill University Health Centre (RI-MUHC) and the Rosalind and Morris Goodman Cancer Institute at McGill University in Montreal, Canada, said in a press release.

“This surveillance program may lead to improved outcomes in a disease that currently has low survival rates. Individuals who are concerned they are at risk for pancreatic cancer can participate in PRECEDE and obtain an assessment from one the PRECEDE sites in North America and Europe. If the individual is assessed to be at increased risk for pancreatic cancer, they will have the opportunity to undergo clinical surveillance for pancreatic cancer, according to the clinical surveillance services available in their area,” Zogopoulos added.²

The multicenter, prospective PRECEDE study enrolled patients aged 18 to 90 years who presented for pancreatic cancer risk assessment and assigned them to 1 of 7 cohorts based on family history and carrier status of PGVs in predisposition genes for pancreatic cancer. Investigators obtained a 3-generation family cancer pedigree at enrollment and updated it during subsequent clinical visits. Cohort 1 was the highest-risk cohort and required patients to undergo PGV testing in genes associated with pancreatic cancer disposition. Annual surveillance via MRI/MR-cholangiopancreatography or endoscopic ultrasound was mandated in cohort 1.¹

The other 6 cohorts served to support the growth of cohort 1 or provide controls. Individuals in cohorts 2 (n = 508), 3 (n = 269), and 4 (n = 699) did not meet the criteria for cohort 1 but were permitted to cross over to cohort 1. Cohort 5 (n = 32) was a control cohort of individuals who did not meet other cohort criteria and included nonmutation carriers harboring a PGV. Cohort 6 (n = 62) included patients with pancreatic cancer at enrollment and predisposition based on family history, PGV carrier status, or onset at an early age.

Additional findings from cohort 1 showed that 86.3% of patients in the FPC subgroup of cohort 1 underwent germline testing. Pancreatic cysts were reported at a rate of 35.1% in cohort 1, including 2 patients with cysts harboring worrisome features. Study authors noted that the higher prevalence of pancreatic cysts in the FPC population was an unexpected finding, so they performed a univariable logistic regression analysis to identify clinical features that could be associated with their presence. Results from the analysis revealed that increasing age (OR, 1.06; 95% CI, 1.04-1.07; P < .001), presence of diabetes (OR, 1.60; 95% CI, 1.09-2.33; P =.01), and assignment to the FPC group relative to the PGV-positive/FPC-negative group (OR, 1.70; 95% CI, 1.35-2.16; P < .001) were significantly associated with the presence of a pancreatic cyst. On multivariable logistic regression, increasing age (OR, 1.05; 95% CI, 1.04-1.07; P <.001) and FPC group assignment (OR, 1.57; 95% CI, 1.23-1.99; P <.001) were independent predictors of harboring a pancreatic cyst, after adjusting for covariates.

“The presence of cysts may identify individuals that are at increased risk of developing pancreatic cancer over time because of cyst changes or because the presence of cysts signals that the pancreas has an intrinsic aberration making it more susceptible to cyst progression or other precancerous growths,” Diana M. Simeone, MD, director of the UC San Diego Moores Cancer Center, stated in a press release. “Longer follow-up time is needed to determine if familial pancreatic cancer signifies a higher risk for developing pancreatic cancer compared with PGV status in a pancreatic cancer predisposition gene.”³

In terms of safety, no adverse effects were reported following surveillance examinations or invasive diagnostic procedures. Fourteen endoscopic ultrasoundfine-needle biopsies (n = 11) or fine-needle aspirations (n = 3) were performed to evaluate solid tumors, as well as 1 fine-needle aspiration to examine a cystic lesion greater than 3 cm in diameter. Patients who underwent surgical resection (n = 2) did not experience significant postoperative complications.¹

“This research highlights that—although barriers have prevented the wide-spread implementation of pancreatic cancer screening programs for high-risk individuals—a multicenter international consortium and longitudinal study is feasible; early imaging findings from this study show the need for further pancreatic cancer early detection research,” Cassadie Moravek, senior director of Clinical Trial Portfolio and Program Management, Pancreatic Cancer Action Network, added in the press release.³

References

1. Zogopoulos G, Haimi I, Sanoba SA, et al. The Pancreatic Cancer Early Detection (PRECEDE) study is a global effort to drive early detection: baseline imaging findings in high-risk individuals. J Natl Compr Canc Netw. 2024;22(3):158-166. doi:10.6004/jnccn.2023.7097
2. New findings illustrate pathway for screening high-risk individuals for pancreatic cancer. News release. McGill University Health Centre. April 17, 2024. Accessed April 22, 2024. https://muhc.ca/news-and-patient-stories/research/new-findings-illustrate-pathway-screening-high-risk-pancreatic
3. New findings in JNCCN illustrate pathway for screening high-risk individuals for pancreatic cancer in PRECEDE study. News release. National Comprehensive Cancer Network. April 16, 2024. Accessed April 22, 2024. https://www.prnewswire.com/news-releases/new-findings-in-jnccn-illustrate-pathway-for-screening-high-risk-individuals-for-pancreatic-cancer-in-precede-study-302118643.html