Screening of individuals at high risk of pancreatic cancer facilitates early diagnosis

Screening of individuals at high risk of pancreatic cancer is currently recommended with the aim of reducing mortality
through early detection of the disease.
To further evaluate the effectiveness of this approach, the investigators conducted a prospective, multicenter CAPS5 (Cancer of Pancreas Screening-5) study that used 1,461 individuals at high risk of developing pancreatic cancer (mean age, 60 years; 65% were women) in imaging monitoring (MRI and endoscopic ultrasound)
from 2014 to 2021.
High-risk individuals are judged by having a genetic syndrome, carrying germline variants, or having a first- or second-degree relative with pancreatic cancer
.

Half of the cohort (49%) had pathogenic germline variants, including 23% with BRCA1 or BRCA2 mutations, 6% with ATM mutations, 4% with Lynch syndrome, and 4% with PALB2 mutations
.
All people have one or more first- or second-degree relatives with pancreatic cancer; 5% had familial atypical multiple nevus melanoma syndrome (CDKN2A mutation) and 1% had Peutz-Jeghers syndrome (STK11 mutation).

The other half of the cohort without germline mutations known to cause pathogenic germline mutations had pancreatic cancer in two or more first-degree relatives, or one first-degree relative and one or more second-degree relatives
.
Nearly 1/3 of patients (31%) have a history of
cancer.

Among the 9 patients with pancreatic cancer, 7 had stage I.
, and 8 had resectable tumors; Seven cases survived after a median of 2.
6 years (median overall survival, 3.
84 years).

Cancer is detected in high-risk individuals with or without pathogenic germline variants
.
Of the 8 patients who underwent cystic resection, 3 had high-grade dysplasia and 5 had low-grade dysplasia
.

In previous CAPS trials from CAPS5 and previous CAPS (Gastroenterology 2018; 155:740), 26 cases of pancreatic cancer
were detected over a 20-year period.
Of these, 19 were detected during surveillance, most (58%) were stage I, and of the 7 cancers diagnosed outside the surveillance period, 6 (86%) were stage
IV.
Median overall survival among patients diagnosed during the surveillance period was significantly higher than that of patients diagnosed outside the surveillance period (9.
8 years vs.
1.
5 years; Risk ratio, 0.
13; P=0.
003).

Results from CAPS5 and combined CAPS1–5 analyses suggest that despite the low detection rate of pancreatic cancer, resectable early disease has a high incidence and longer survival
.
Improving the selection and screening methods of the screening population through new biomarkers is currently a research area
.

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