Identifying key factors for the effectiveness of pancreatic cancer screening: A model-based analysis

Abstract

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high-risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5-yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery-related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: -57% for "Progressive-only" vs -41% for "Indolent Included"). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high-risk individuals.

Keywords: microsimulation model; pancreatic cancer; screening.

FIGURE 1

Estimated age‐specific prevalence of different disease stages in high‐risk individuals when modeling only progressive lesions (panel A), or modeling both indolent and faster progressive lesions (panel B), in the absence of screening

FIGURE 2

Screening strategy evaluated in the MISCAN‐pancreas model. Transition 1 (“continue screening”) is the effect of a (false‐) negative test result. Values in table are for the base case situation. *1‐ or 5‐year interval. **In case of cancer Stage III/IV, patients only receive palliative care (no resection) [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

The effect on NNS of the sensitivity analyses for screening from ages 50 to 75, with a 1 year interval for both the Progressive‐only and the Indolent Included pathway. NNS is the number of screening tests needed to prevent one cancer death. Vertical line: base case result. Light grey bars: PC risk doubled, test sensitivity for each disease stage increased with 10% (110% of base case value), test specificity decreased to 85%. Dark grey bars: PC risk halved, mortality rate increased from 3% to 5%, test sensitivity decreased with 10% (to 90% of base case value), test specificity increased to 95%