The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival

Abstract

Purpose: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies.

Methods: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I v higher-stage). Overall survival was determined using the Kaplan-Meier method.

Results: Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003).

Conclusion: Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.

FIG 1.

Diagram of the CAPS1-5 enrollment periods from 1998 to 2021 summarizing the outcomes of individuals in the CAPS5 study and combined updated outcomes of the CAPS1-5 studies. A summary of the CAPS5 study criteria and surveillance protocol is provided in the boxes and described with more details in the methods section. ^aTwo HRIs from the CAPS1-4 cohort stopped surveillance and then developed PDAC after the last report of that cohort in the study by Canto et al. CAPS, Cancer of Pancreas Screening; EUS, endoscopic ultrasound; FAMMM, familial atypical multiple mole melanoma; HGD, high-grade dysplasia; HRI, high-risk individual; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; PDAC, pancreatic ductal adenocarcinoma.

FIG 2.

PDAC stage and survival in the CAPS5 study cohort. (A) Distribution of stages (eighth edition American Joint Committee on Cancer) of screen-detected PDACs (n = 9) detected during surveillance. (B) Kaplan-Meier curve showing overall survival of all screen-detected PDACs and high-grade neoplasms in the CAPS5 study. CAPS, Cancer of Pancreas Screening; HGD, high-grade dysplasia; PDAC, pancreatic ductal adenocarcinoma.

FIG 3.

Example of a screen-detected stage IA pancreatic cancer (case 2). (A) Surveillance magnetic resonance imaging showing a new 1-cm hypoenhancing lesion in the head of the pancreas (arrow pointing to mass). (B) Confirmatory EUS showing a 1.5-cm hypoechoic lesion in the head of the pancreas without invasion of nearby vessels with cytology (not shown) diagnostic of a moderately differentiated adenocarcinoma. (C) Confirmatory computed tomography of the abdomen showing s 1.5-cm pancreatic head mass without upstream dilation or atrophy. (D) Whole-slide scanned image of a resected 1.4-cm lesion showing at 5× (E) a moderately differentiated invasive ductal adenocarcinoma confined to the pancreas. EUS, endoscopic ultrasound.

FIG 4.

Screen-detected pancreatic cancers in the combined Cancer of Pancreas Screening 1-5 cohorts. (A) Graph showing eighth edition American Joint Committee on Cancer stage distribution of the screen-detected PDACs (n = 19) and (B) PDACs detected outside surveillance (n = 7). (C) Kaplan-Meier curves showing survival of all screen-detected PDACs, PDACs diagnosed outside surveillance, and screen-detected HGD. HGD, high-grade dysplasia; HR, hazard ratio; PDAC, pancreatic ductal adenocarcinoma.