Assessment of Serum Pepsinogens with and without Co-Testing with Gastrin-17 in Gastric Cancer Risk Assessment—Results from the GISTAR Pilot Study

Abstract

Introduction––Serum pepsinogen tests for gastric cancer screening have been debated for decades. We assessed the performance of two pepsinogen assays with or without gastrin-17 for the detection of different precancerous lesions alone or as a composite endpoint in a Latvian cohort. Methods––Within the intervention arm of the GISTAR population-based study, participants with abnormal pepsinogen values by ELISA or latex-agglutination tests, or abnormal gastrin-17 by ELISA and a subset of subjects with all normal biomarker values were referred for upper endoscopy with biopsies. Performance of biomarkers, corrected by verification bias, to detect five composite outcomes based on atrophy, intestinal metaplasia, dysplasia or cancer was explored. Results––Data from 1045 subjects were analysed, of those 273 with normal biomarker results. Both pepsinogen assays showed high specificity (>93%) but poor sensitivity (range: 18.4–31.1%) that slightly improved when lesions were restricted to corpus location (40.5%) but decreased when dysplasia and prevalent cancer cases were included (23.8%). Adding gastrin-17 detection, sensitivity reached 33–45% while specificity decreased (range: 61.1–62%) and referral rate for upper endoscopy increased to 38.6%. Conclusions––Low sensitivity of pepsinogen assays is a limiting factor for their use in population-based primary gastric cancer screening, however their high specificity could be useful for triage.

RE.GA.IN.: the Real-world Gastritis Initiative–updating the updates

“…36 The biomarkers serum PgI and II levels, the PgI/II ratio, serum gastrin-17 and H. pylori serology have long been measured and explored, alone or in combination, to detect advanced or late-stage atrophic gastritis. [253][254][255] Low serum PgI and a low PgI/II ratio can provide a non-invasive diagnosis of advanced stage atrophic gastritis, and, importantly when H. pylori serology is also negative, endoscopy is recommended by the MAPS II Guideline Update 2019. 42 An observational study evaluating screening tests in 28 Japanese patients with confirmed histological AIG reported a 78.6% positive predictive value with a serum gastrin >172 pg/mL, or with cut-off values of PgI and PgI/II ratio 14.5 ng/dL and 2.1, respectively.…”

Partial Verification Bias Correction Using Inverse Probability Bootstrap Sampling for Binary Diagnostic Tests

“…By estimating the verification probability, PS demonstrates a clear and direct relationship with the verification problem, in this case, the PVB problem. Recent implementations of PVB correction methods can be seen in studies evaluating MRI and ultrasound in prostate cancer [ 15 ], serum pepsinogens in gastric cancer [ 16 ], and fine needle aspiration cytology in breast cancer [ 17 ], where the studies utilized BG-based and MI methods.…”