Pancreatic Cancer Screening of High-Risk Individuals Leads to Early-Stage Diagnosis

Pancreatic cancer screening is recommended for high-risk individuals to reduce mortality through early detection. To further evaluate the effectiveness of this approach, investigators conducted the prospective, multicenter, Cancer of Pancreas Screening-5 (CAPS5) study, which employed imaging surveillance (MRI and endoscopic ultrasound) from 2014–2021 for 1461 individuals (mean age, 60; 65% women) at high risk for developing pancreatic cancer. Individuals were considered high risk if they had a hereditary syndrome, germline variant, or at least one first- and second-degree relative with pancreatic cancer.

Half of the cohort (49%) had a pathogenic germline variant, including 23% with BRCA1 or BRCA2 mutation, 6% with ATM mutation, 4% with Lynch syndrome, and 4% with PALB2 mutation. All had one or more first- or second-degree relatives with pancreatic cancer; 5% had familial atypical multiple mole melanoma syndrome (CDKN2A mutation), and 1% had Peutz-Jeghers syndrome (STK11 mutation). The other half of the cohort, without known pathogenic germline mutations, had either two or more first-degree relatives or one first-degree relative and one or more second-degree relatives with pancreatic cancer. Nearly a third of all patients (31%) had a history of prior cancer.

Among 9 patients who developed pancreatic cancer, 7 had stage I disease and 8 had resectable tumors; 7 were alive after a median 2.6 years (median overall survival, 3.84 years). Cancers were detected in high-risk individuals with or without a pathogenic germline variant. Of 8 patients who underwent resection of cystic lesions, 3 had high-grade dysplasia and 5 had low-grade dysplasia.

In a pool of 1731 patients from CAPS5 and prior CAPS trials (Gastroenterology 2018; 155:740), 26 pancreatic cancers were detected during a greater than 20-year period. Of these, 19 were detected during surveillance, and most (58%) were stage I, whereas 6 of the 7 cancers (86%) diagnosed outside of surveillance were stage IV. Median overall survival was significantly longer for patients diagnosed during surveillance versus outside of surveillance (9.8 vs. 1.5 years; hazard ratio, 0.13; P=0.003).