Optimal Endoscopic Screening Interval for Early Detection of Gastric Cancer: a Single-Center Study

The incidence rate of gastric cancer (GC) is known to be high, with more than 1 million new patients affected in 2012. Although its incidence rate is declining, GC is still the second most common cancer-related cause of death worldwide.1, 2 GC is most prevalent in East Asia, including Korea and Japan by region.3 The prognosis of patients with GC is highly correlated with the stage of cancer diagnosis. The 5-year survival rate of patients with early gastric cancer (EGC) is known to be over 90%.4 This suggests that early detection and treatment, especially endoscopic resection, can decrease the morbidity and mortality rates of patients with GC.5

In Korea, the National Cancer Screening Program recommends a GC screening interval of 2 years for men and women aged over 40 years.6 The optimal interval of endoscopic screening for the early detection of GC has been investigated in many studies. A previous study has shown that a barium meal study and subsequent endoscopic examinations at 1.5-year intervals were beneficial for the early detection of GC.7 Since then, an interval of 2 or 3 years was regarded as optimal in many reports.8, 9, 10, 11 There were also several studies conducted on the optimal interval for high-risk groups, and one study in Korea has reported that a 1-year interval is beneficial for patients with severe intestinal metaplasia.5 However, only few studies exist, and such studies report variable results.

Therefore, to clarify the optimal interval of endoscopic examination for the early detection of GC, we analyzed the clinicopathological characteristics according to the type of GC and endoscopic interval. We also confirmed the detection rate of EGC and the stage of GC according to the extent of endoscopic examination interval.

GC is still one of the most common malignancies worldwide. In 2012, nearly half of all GC cases developed in Eastern Asia.17 The prognosis of GC is related to the stage at the time of diagnosis.10, 18 The 5-year survival rate of patients with EGC exceeds 90%.19 The mortality rate of patients with GC in Korea has been steadily declining for the past 30 years, probably owing to the early detection and treatment of the disease after screening was introduced.20 We compared EGC- and AGC-diagnosed patients using a univariate analysis. The proportions of < 2 cm-size tumors, more differentiated histology, curative management, and < 3-year endoscopic interval were significantly higher in the EGC group than those in the AGC group.

Several studies on the optimal interval of endoscopic examination have been conducted. The study on Chinese populations did not show a decrease in mortality with endoscopic screening every 5 years.21 However, previous studies in Japan suggested that intervals of < 1.5 or 2 years are appropriate for the early diagnosis and curative resection of GC.7, 8 In Korea, several studies showed that the effective interval to detect EGC is < 3 years.22, 23 Other studies have suggested that biennial endoscopic screening can increase the rate of early detection of EGC and reduce the number of cases of progression to AGC.10, 24 In one cross-sectional study of these reports, the authors analyzed GC patients except the group of endoscopic resection as a treatment of GC. As a result, the 5-year GC-specific survival rates of < 2 years interval group were significantly higher than > 2 years interval group and the risk of AGC decreased in < 2 years interval group.24 In addition, a 1-year GC screening interval is beneficial for patients with severe intestinal metaplasia in another study.5 As mentioned above, our study showed that both endoscopic intervals of < 2 years and 3 years are appropriate for EGC detection.

Meanwhile, one study showed significant results when a family history of GC, one of the important risk factors of GC, was present. In this study, the interval of < 3 years was effective for the group of patients who had a positive family history of GC (odds ratio [OR], 1.62; 95% CI, 1.10–2.37; P = 0.014).11 Conversely, when the relationship between family history of GC and endoscopic interval was analyzed in our study, no statistically significant results were obtained. We think that further research and evaluation are needed on this subject.

In addition, a study from Korea reported that 1-year intervals of GC screening would be effective for patients with severe intestinal metaplasia.5 Another study showed that a shorter endoscopic screening interval improves the optimal detection of EGC and survival.23 However, we believe that a considerable portion of the GCs with < 1-year intervals are likely to be missing cancers. One meta-analysis reported that missing cancers occur in one out of ten GCs (9.4%; 95% CI, 5.7–13.1).25 Another previous meta-analysis showed 11.3% of GCs were missing cancers within 3 years before upper gastrointestinal cancer diagnosis.26 Based on these findings, we excluded patients diagnosed with GC with a 1-year interval in our study.

In our study, we performed both univariate and multivariable analyses using logistic regression by dividing the patients into two groups according to the intervals of 2 years and 3 years. In the univariate analysis, the proportions of EGC (< 2-cm size, stage I) and endoscopic resection were significantly higher in both < 2-year and < 3-year intervals. Further, the OR for the detection of EGC or early stage of GC in the multivariable analysis was significantly higher in both the < 2-year and < 3-year interval groups. The P value between the two ORs in both cases was less than 1. In other words, although the OR was higher in the < 3-year interval group than in the < 2-year interval group, it is difficult to conclude that the 3-year interval was better than the 2-year interval for EGC detection. Moreover, there was no statistically significant difference between the two groups. One study mentioned that the OR for AGC detection did not increase in the 2-year (19–30 months) (OR, 1.11) and 3-year (31–42 months) interval groups (OR, 1.21), but increased in the 4-year (43–54 months) (OR, 2.53) and 5-year (55–66 months) interval groups (OR, 2.16). Thus, such a study reported that an endoscopic examination interval of ≤ 3 years was associated with an earlier stage of GC; therefore, changing the interval of GC screening to 3 years should be considered.11 Another report suggested that 3-year intervals were adequate for endoscopic treatment, but did not yield significant results in reducing the rate found in AGC.10 Our findings are also consistent with such results in part. When taken together, we suggest that 3-year examination intervals are as efficient as 2-year intervals for the early detection of EGC, with a high probability of curative treatment.

Our study has several limitations. First, this study was performed in a single center; thus, we cannot conclude that the enrolled patients can represent all patients with GC. However, the total number of enrolled patients was up to 1,000, and we think that this complements such a limitation. Second, although we enrolled the patients prospectively using a questionnaire, we relied on each patient's memory in several parts, such as the date of penultimate endoscopy and family history of GC, which can lead to a recall bias. Third, we did not include patients diagnosed with gastric adenoma. In the hypothesis of gastric carcinogenesis called Correa's cascade, chronic inflammation can develop into atrophic gastritis, which in turn can progress to intestinal metaplasia, gastric adenoma and gastric adenocarcinoma.27 Because gastric adenoma is a premalignant lesion, early detection and appropriate treatment will help prevent GC, particularly EGC.28, 29 In addition, a study has been conducted on the optimal endoscopic interval including gastric adenoma.10 Fourth, Helicobacter pylori infection, one of the major risk factors for GC, was not analyzed because not all patients were tested for infection with this pathogen, and this could affect the outcome of the analysis. Fifth, this study was conducted in areas with high prevalence rate of GC; therefore, our results may not be suitable for use in areas with low prevalence rates, including Western regions. Finally, we did not analyze the survival rate. In another study, the cutoff interval to increase the risk of AGC and detect EGC was 3 years; this screening interval had a similar effect on the disease-free survival rate.23 But survival rate of GC is well correlated to the tumor stage and we analyzed the stage of the GC to replace the survival rate. If we could add a direct analysis of the survival rate, it would largely support our opinion.

In conclusion, triennial endoscopic screening might be as effective as biennial screening in increasing the detection rate of EGC and rate of curative endoscopic management and in sequentially reducing the number of lesions that could progress to AGC.