Introduction

Pancreatic ductal adenocarcinoma (PDAC) surveillance programs are recommended for individuals with a PDAC lifetime-risk ≥5% to improve outcomes.¹ While familial adenomatous polyposis (FAP) is linked to increased PDAC risk, robust data to guide surveillance recommendations is lacking.^2,3 This study evaluates PDAC risk in a large FAP-cohort and cost-effectiveness of PDAC-surveillance in this group.

Aims & Methods

Data were collected from FAP cohorts in the United States (US) and the Netherlands (NL), including individuals (≥18 years) with a confirmed (likely) pathogenic APC variant. To minimize ascertainment bias, individuals whose initial visit or registration was prompted by a PDAC diagnosis were excluded from the analysis. Cumulative PDAC incidence, adjusted for death as competing risk, was calculated for the FAP cohorts and compared with control data from the Netherlands Cancer Registry and Statistics Netherlands. The cost-effectiveness of surveillance was evaluated using our previously developed Markov model.⁴ In comparison to the previous study, the model was modified by setting the inflation rate at 3%, discontinuing surveillance at age 75 and incorporating the relative risk derived from our FAP cohort.

Results

The US-cohort (n=357) and the NL-cohort (n=1000) had a median age at the end of follow-up of 46 years (IQR, 32.0-60.0) and 60 years (IQR, 47.5-72.5), respectively. Female participants comprised 52.9% of the US-cohort and 47.2% of the NL-cohort. Within the US-cohort, three PDAC cases were identified, however, two individuals had been referred to the Mayo Clinic at the time of PDAC diagnosis and were subsequently excluded from the analysis to reduce the risk of ascertainment bias. When combining both FAP-cohorts, the cumulative risk of PDAC by age 70 was 0.7% (95% CI, 0.3-1.8). Detailed cumulative risk estimates, stratified by cohort and age, are presented in Table 1. For comparison, the cumulative incidence of PDAC in the general population at age 70 was 0.32% (95% CI, 0.31-0.33), corresponding to a relative risk of 2.2 (95% CI, 0.9-5.7) for individuals with FAP. The cost-effectiveness analysis estimated that annual magnetic resonance imaging-based PDAC surveillance, starting at age 40, would be considered cost-effective if the relative risk reached at least 4.0, based on a willingness-to-pay threshold of $100 000.

Table 1. Adjusted cumulative incidence of pancreatic ductal adenocarcinoma in individuals with familial adenomatous polyposis

Conclusion

This is the largest cohort study to date to assess PDAC risk in individuals with FAP. Our findings indicate that PDAC risk in FAP patients is not significantly higher than in the general population. Moreover, their surveillance is shown not to be cost-effective.

References

1. Goggins M, Overbeek KA, Brand R, Syngal S, Del Chiaro M, Bartsch DK, et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020;69(1):7-17.
2. Giardiello FM, Offerhaus GJ, Lee DH, Krush AJ, Tersmette AC, Booker SV, et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993;34(10):1394-6.
3. Karstensen JG, Bülow S, Højen H, Jelsig AM, Jespersen N, Andersen KK, et al. Cancer in Patients With Familial Adenomatous Polyposis: A Nationwide Danish Cohort Study With Matched Controls. Gastroenterology. 2023;165(3):573-81.e3.
4. Corral JE, Das A, Bruno MJ, Wallace MB. Cost-effectiveness of Pancreatic Cancer Surveillance in High-Risk Individuals: An Economic Analysis. Pancreas. 2019;48(4):526-36.

Disclosure

None

Introduction

Gastroduodenal neuroendocrine neoplasms (GD-NENs) are being increasingly diagnosed, particularly at stages amenable to endoscopic resection (ER). We aimed to evaluate endoscopic, long-term clinical and oncological outcomes of patients with GD-NENs submitted to ER.

Aims & Methods

Multinational retrospective study (24 centres, 10 Western countries) that analysed all patients who underwent ER of GD-NENs (January 2014-December 2024). Demographic, clinicopathological and long-term oncological data were collected. Curativeness of resection was defined according to the European Neuroendocrine Tumor Society guidelines (2023). Residual disease was defined as histological evidence of neoplastic tissue in the ER scar (local recurrence) or in surgical specimen (parietal residual lesion) and/or as the detection of lymph node metastasis either in the surgical specimen or in the follow-up (distant recurrence).

Results

We evaluated 445 patients: 304 gastric (G-NENs) (74.7% type 1, 19.1% type 3, 5.9% type 2) and 141 duodenal (D-NENs). The median lesion size was 10 mm (IQR 6-12). Endoscopic submucosal dissection (ESD) (32.6%) and conventional endoscopic mucosal resection (C-EMR) (26.5%) were the most performed techniques. G-NENs had significantly higher R0 rates (59.8%; 42.6% D-NENs; p<0.001). Non-curative ER rate was 56.4% (50.3% G-NENs; 69.5% D-NENs; p<0.001).
Median follow-up was 37 months (IQR 14-70). 28 patients (6.3%) needed surgery during follow up (6.3%), with similar rates between G-NENs and D-NENs. Parietal residual lesion was identified in 60.7% of surgical specimens (63.2% G-NENs, 55.6% D-NENs, p = 0.700). Residual disease rate was 16.2% (18.4% vs 11.6%, p = 0.059). Local and distant recurrence rate were 13.2% (14.8% G-NENs; 9.9% D-NENs; p=0.109) and 1.8% (1.3% G-NENs; 2.8% D-NENs; p=0.266), respectively. For type 1 / type 2 G-NENs, a non-curative ER implied significantly higher rates of residual disease (26.8% vs 9.7%, p = 0.005), local recurrence (25.0% vs 9.7%, p = 0.005) and distant recurrence rates (7.1% vs 0.0%, p = 0.014). Type 3 G-NENs also demonstrate higher residual disease rates in the non-curative ER group (26.8% vs 11.8%, p = 0.210). Considering D-NENs, non-curative ER was associated with a non-significant increase in residual disease rate (13.3% vs 7.0%, p = 0.278). There was a single case of NEN related mortality in a D-NEN patient.

Conclusion

In conclusion, our study demonstrates that despite non curative ERs in a significant proportion of patients, the recurrence and tumour-related mortality of GD-NENs remain low. Additionally, up to 40% of the patients submitted to surgery due to non-curative ER had absence of NEN in surgical specimen. These results provide critical insights that may refine clinical decision-making and inform future guidelines for the management of GD-NENs.

References

1. Panzuto, Francesco et al. “European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for gastroduodenal neuroendocrine tumours (NETs) G1-G3.” Journal of neuroendocrinology vol. 35,8 (2023): e13306. doi:10.1111/jne.13306