Risk of Neoplastic Progression in Individuals at High Risk for Pancreatic Cancer Undergoing Long-term Surveillance

Abstract

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.

Keywords: Early Detection; Familial Pancreatic Cancer; IPMN; PanIN-3.

Conflict of interest statement

Disclosures: MG, APK and RHH have received royalties for the licensing of PALB2 as a pancreatic cancer susceptibility gene. All other authors have no relevant financial, personal, or professional conflicts.

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Cumulative risk (hazard) for neoplastic progression (PDAC, IPMN-HGD, or PanIN-3) for high risk individuals after baseline screening. Overall neoplastic progression rate was 1.6% per year.

Figure 2

Risk for neoplastic progression was significantly increased in HRI with worrisome features (radiologic progression) (p 60 (2B).

Figure 2

Risk for neoplastic progression was significantly increased in HRI with worrisome features (radiologic progression) (p 60 (2B).

Figure 3

Incident asymptomatic 7 mm pancreatic cancer detected after 10 years of surveillance, shown by arrows in endoscopic ultrasound (EUS) image (A) and gross pathology section of the pancreatic body (B). Final pathologic diagnosis was stage T1N0 moderately differentiated adenocarcinoma with negative margins (cytology smear from EUS-guided fine needle aspiration) C; hematoxylin and eosin stain, venous and perineural invasion were not identified (D).

Figure 4

Kaplan-Meier curves for overall survival for high risk individuals diagnosed with pancreatic neoplasms diagnosed by surgery or endoscopic ultrasound guided fine needle aspiration. The group “Others” includes pathologically-proven lower grade pancreatic neoplasms that were not PDAC, IPMN-HGD, or PanIN-3 (IPMN with LGD or MGD, PanIN-2, PanNET, serous cystadenoma, pseudocyst).