Challenges in evaluation of screening for gastric cancer among men based on nonrandomized design

Abstract

Background: Objective was to quantify biases in screening for gastric cancer when comparing attenders to nonattenders using serum pepsinogen I (SPGI) level as primary test. Methods: In mid 1990s, all men aged 51-65 years from two Finnish cities were invited to SPGI screening. Mortality and premature mortality in attenders were compared to nonattenders. Efficacy of screening was studied by 15 years' follow-up of standardized mortality ratio (SMR) and potential years of life lost (PYLL) due to gastric cancer. Bias due to selective attendance was quantified using corrective coefficients based on total cancer incidence and mortality, and gastric cancer-specific incidence and mortality for total population and nonattenders. Results: In 1994-1996, men aged 51-65 years (16,872) were invited to SPGI assay and 12,175 men (72%) attended. SPGI was 25 microg/l or less in 610 (5%) men, indicating severe atrophic gastritis (AG). Post-screening gastroscopy was performed to 435 men with low SPGI. Of these, 168 men were referred for treatment due to abnormal focal lesions. Attributable proportions in reductions of SMR and PYLL from gastric cancer due to screening were 59% and 67%. After correcting for selective participation, attributable proportions were reduced to 23% and 39%. Conclusions: Biomarker screening by low SPGI among middle-aged men followed by upper gastrointestinal endoscopy decreased long-term and premature mortality due to gastric cancer. However, in spite of methodological corrections done, the results do not justify any firm conclusions or recommend general screening programs. Randomized trials are warranted for this purpose.

Risk of gastric cancer in Helicobacter pylori infection in a 15-year follow-up

“…Possible endoscopic, surgical, therapeutic or preventive interventions carried out among the 606 men with AG may decrease the incidence of gastric cancer in the 15-year follow-up. [ 11 ] Therefore, the observed incidences and SIRs of gastric cancer in this subgroup of men are likely underestimations of the real cancer risk. The authors were not able to explore the procedures that were done to these 606 men with AG during the 15-year follow-up period.…”

“…[ 16 ] In addition, the subgroups followed up in the present investigation were derived from the study population that represents the general population of males who were 50–65 years old at the beginning of the follow-up and were living in two cities in southern Finland in 1994–1996. [ 11 ]…”

“…No referral to treatment, clinical surveillance or other actions were carried out by the investigators fpr anyone, and all men were passively followed up by the cancer registry during the 15-year follow-up period from 1994 to 2011. [ 11 ] In addition, the delineation of the men to those with healthy stomach mucosa and to those with nonatrophic H pylori gastritis was done with the HpAb test (from serum samples collected in 1994–1996) only at the end of the follow-up period. However, unknown confounders may still exist that may contribute to estimates of cancer risks in the study subgroups.…”

“…[ 1–5 ] Therefore, all these men were actively referred in 1994–1996 for medical consultation, treatment and clinical surveillance in specialized hospitals or health care centers. [ 11 ]…”

“…In contrast to the mentioned case–control investigations, the risk estimates for gastric cancer in the present study were received from all new cases of gastric cancer that appeared during the follow-up time in all subgroups of men without ongoing H. pylori infection or AG, and those with a verified ongoing H. pylori infection or AG at beginning of the follow-up. [ 11 ]…”