Overdiagnosis of gastric cancer by endoscopic screening

Abstract

Gastric cancer screening using endoscopy has recently spread in Eastern Asian countries showing increasing evidence of its effectiveness. However, despite the benefits of endoscopic screening for gastric cancer, its major harms include infection, complications, false-negative results, false-positive results, and overdiagnosis. The most serious harm of endoscopic screening is overdiagnosis and this can occur in any cancer screening programs. Overdiagnosis is defined as the detection of cancers that would never have been found if there is no cancer screening. Overdiagnosis has been estimated from randomized controlled trials, observational studies, and modeling. It can be calculated on the basis of a comparison of the incidence of cancer between screened and unscreened individuals after the follow-up. Although the estimation method for overdiagnosis has not yet been standardized, estimation of overdiagnosis is needed in endoscopic screening for gastric cancer. To minimize overdiagnosis, the target age group and screening interval should be appropriately defined. Moreover, the balance of benefits and harms must be carefully considered to effectively introduce endoscopic screening in communities. Further research regarding overdiagnosis is warranted when evaluating the effectiveness of endoscopic screening.

Keywords: Cancer screening; Gastric cancer; Harm; Overdiagnosis; Upper gastrointestinal endoscopy.

Figure 1

Trends of breast cancer incidence before and after mammographic screenings in the United States. A: Use of mammographic screening and incidence of stage-specific breast cancer among women 40 years of age and older; B: Incidence of stage-specific breast cancer among women younger than 40 years of age[12].

Figure 2

Screen detection capability based on tumor biology and growth rates[13]. The growth rates of cancer vary and are divided into 4 categories: Rapid, slow, very slow, and non-progressive. Periodic screening detects slow-growing (Tumor B) and non-progressive (Tumor A) cancers early, and finds some progressive cancer (Tumor C) early. Tumor A remains undetectable and causes no morbidity during the patients’ lifetime without screening. However, rapid-growing cancer (Tumor D) which is a fatal tumor is not screened earlier and can cause death even with treatment.

Figure 3

Estimation of frequency of overdiagnosis on the basis of the results of Malmö and Canadian studies. The frequency of overdiagnosis was calculated on the basis of 2 randomized controlled trials for mammographic screening using 4 methods with different denominators as follows: A: Excess cancers as the frequency of cancers diagnosed over the whole follow-up period in unscreened women; B: Excess cancers as the frequency of cancers diagnosed over the whole follow-up period in women invited for screening; C: Excess cancers as the frequency of cancers diagnosed during the screening period in women invited for screening; D: Excess cancers as the frequency of cancers detected at screening in women invited for screening[16].

Figure 4

A value framework for cancer screening. The value of cancer screening strategies is linked to the screening intensity (population screened, frequency, and sensitivity of the test used) and is determined by the balance among benefits (e.g., cancer mortality reduction), harms (e.g., anxiety from false-positive test results, harms of diagnostic procedures, labeling, and overdiagnosis leading to overtreatment), and costs. The value of cancer screening is determined by a trade-off between benefits vs harms and costs. As the intensity increases, the benefits of screening rapidly increase. However, as the intensity increases beyond an optimal level, the increase in benefits slows down whereas harms and costs increase rapidly, and the value decreases[14].