The role of age in pancreatic intraductal papillary mucinous neoplasms of the pancreas: Same risk of death but different implications for management

Abstract

Background

Current guidelines do not address the role of age in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.

Aim

To evaluate whether clinical features and risk for malignancy are affected by patient’s age at diagnosis.

Methods

In total, 2189 IPMNs, both surgically resected or surveilled, were dichotomized according to a 50-year-old cutoff and compared in terms of pathological features, cumulative risk of developing high-risk stigmata (HRS), overall survival (OS) and disease-specific survival (DSS).

Results

Patients <50 years had more frequent abdominal pain (38.5 vs. 22.4%; p < 0.01) and acute pancreatitis (20.4 vs. 9.3%; p < 0.01) at presentation. Patients ≥50 years old had more multifocal IPMNs (50 vs. 36.9%; p < 0.01), HRS (8.5% vs. 4.3%; p = 0.04) and invasive IPMNs (26.6% vs. 17.3%; p = 0.03) when resected. Moreover, patients ≥50 years old had a significantly higher cumulative risk of developing HRS over time, and a significantly lower OS, but similar DSS when compared with those <50 years old.

Conclusions

IPMNs diagnosed in older patients are more likely to progress to HRS despite the fact that cancer-related death is not affected by age. The follow-up schedule should not be adjusted according to age, but one should take into account that IPMNs in younger individuals have more time to progress toward malignancy.

Introduction

Due to the extensive use of cross-sectional imaging, Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are frequently discovered in otherwise asymptomatic patients. Large studies have estimated that at least 2.6% of the population has an undefined pancreatic cystic neoplasm that in most of the cases presents radiological features of an IPMN [1], [2]. The prevalence of IPMNs at cross-sectional imaging increases with age and may reach 13% in older patients [3], [4]. IPMNs have a well-known malignant potential [5], [6] as they follow the typical adenoma-to-carcinoma sequence. For this reason, time could play a major role in the possible progression of the disease. As a matter of fact, malignant IPMNs, intended as IPMNs harboring either high-grade dysplasia (HGD) or invasive carcinoma (iCa), are more commonly found in older patients, regardless of the site of duct involvement [7], [8], [9], [10]. For these reasons, the majority of available evidence comes from series of individuals in their sixth decade of life. These data have been eventually condensed into guidelines [11], [12], [13], [14], [15] aimed to outline a risk profile in terms of potential malignant progression. On the basis of clinical and radiological features, patients can be either referred to surgery or maintained under surveillance. Of note, patient’s age is never considered as a main determinant in the decision making and guidelines are limited in suggesting surgery in younger individuals.

The diagnosis of a presumed IPMN in a young individual raises several concerns. Those features recognized as predictors of malignant potential may have a different weight in determining the risk, the time needed by a high-risk lesion to become cancer could vary, the follow-up schedule could be inadequate, and its cost-effectiveness based on available guidelines could improperly tip the scale toward an expensive life-long follow-up or a high-risk surgical procedure.

The aim of the present study was to describe the clinical, radiological, and pathological features of a large cohort of overall IPMNs, both observed and resected, stratified by age of diagnosis. We sought to evaluate whether patient’s age at diagnosis could affect the risk of harboring malignancy in resected IPMN and the risk of malignant progression over time for followed-up cases.