Long-term yield of pancreatic cancer surveillance in high-risk individuals

Abstract

ObjectiveWe aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.DesignFrom 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.Results366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1–32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001).ConclusionThe diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

Recommendations for a More Organized and Effective Approach to the Early Detection of Pancreatic Cancer From the PRECEDE (Pancreatic Cancer Early Detection) Consortium

“…This is relevant in light of a 2021 study that found a cumulative incidence of pancreatic cancer of 3.1% at 5 years and 4.7% at 10 years, with all cases occurring in PGV carriers. 7 This study also found that 4 of 8 incident pancreatic cancers were resectable. This shift toward detection of earlier stage, resectable disease is encouraging, but larger studies with longer follow-up will be needed to exclude the possibility of lead-time bias.…”

“…However, for patients with familial pancreatic cancer and those with pathogenic germline variants that increase risk for pancreatic cancer, cross-sectional and endoscopic imaging will likely remain the cornerstone of surveillance for a period of time. Consortiums like PRECEDE (Pancreatic Cancer Early Detection), 32 CAPS (Cancer of the Pancreas Screening), 33 the Dutch Familial Pancreatic Cancer Surveillance study, 7 and EUROPAC (European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer) 34 are well positioned to collect these data and, given the relatively low event rate in surveillance cohorts, these large, multiinstitutional studies will be critical in defining the natural history and predictors of progression. However, given the expected volume of screening procedures, it is essential that standardization is broadly practiced even outside of these registries and that we define and develop resources to achieve a common standard irrespective of the practice setting.…”

“…However, these studies have been limited by relatively small sample sizes, short follow-up, heterogeneity of inclusion criteria, and variability in screening techniques. 7 A meta-analysis of 16 studies published between 2004 and 2016, which included 1550 participants, found nearly 2% of HRIs had pancreatic cancer or a high-grade precursor lesion identified. 8 A 2018 study of 350 HRIs found that 9 of 10 incident pancreatic cancers discovered during a median follow-up time of 5.6 years were surgically resectable, 9 with a resulting 5-year survival rate of 60% in the surgically treated group.…”

CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606

“…Pancreatic cancer is one of digestive cancers with the highest mortality rate [ 14 ]. Most cases of pancreatic cancer are generally diagnosed in advanced stages, with poor treatment outcomes and poor prognosis [ 15 ]. Emerging evidence has confirmed that circRNAs participated in irreplaceable regulatory functions involved in multiple biological processes, especially in the occurrence, development and metastasis of cancers [ 16 ].…”

Endoscopy to Diagnose and Prevent Digestive Cancers in Lynch Syndrome

“…Screening for pancreatic cancer is recommended in these cases through annual pancreatic magnetic resonance imaging (MRI) and endoscopic ultrasonography in alternation, beginning at 45 years old or 10 years before the youngest case in the family. There is still limited evidence to support these guidelines and each context must be discussed with the patient [ 90 , 91 ].…”