Temporal trends in the 3 countries during the 1975–95 period
One objective of examining these 3 data sets is to investigate the effects of the relative contributions of unplanned prevention and early detection through screening have been on mortality, by studying time trends in both incidence and mortality in Japan (a country with a high incidence and a screening policy) and in 2 other countries with no screening program (the USA, with a low incidence, and Slovenia, with an intermediate incidence). Overall, there is a decline in incidence in all 3 countries, over the whole period in all age groups. The linear drift of the regression models implies that the observed trends are uniform and that the contributions of birth cohort effects and the period-specific risk cannot be distinguished; they also imply that the existing trends may be continued in the future. The decline in incidence is greater in Japan than in the other 2 countries and concerns all age groups, except for those over 80 years. Japan is the only country where a significant cohort effect was observed: the highest risk occurred for men and women born around 1900 and then decreased in successive birth cohorts throughout the 20th century. The birth cohort-specific decline in incidence (which is reflected in mortality) is evident in Japan because, unlike the other countries, there was an increase in risk in cohorts born before 1900. It suggests that the declines in incidence were the result of lifestyle change (probably dietary). On the other hand, the changes in localized disease are clearly due to screening and are discernible as a period effect.
In our study, temporal trends of age-adjusted incidence by stage suggest that, despite the increasing role of endoscopic exploration, no progress in the detection of cases at earlier stages has occurred in Slovenia and the USA: the ratio of the tumors staged as localized versus advanced (regional or distant) was stable during the period. In Japan the incidence of regional cancer has declined while the rate for distant cancer has remained stable, and the proportion of localized tumors almost doubled between 1976–80 and 1991–95 (Table III). These trends suggest that diagnostic methods have changed over the period. Two factors have to be considered in interpreting the results:
- 1The high proportion of unstaged tumors in the data from Osaka in the early years. In the first 5-year interval of the study (1976–80) the age-adjusted incidence of the unstaged tumors for men was 42.6% of the total rate for men and decreased to 29.6% in the last interval (1991–95). The proportions in women were 42.8% and 28.8%, respectively. The distribution of cases of known stage must be interpreted accordingly.
- 2In Japan, the localized cancer group included intramucosal tumors and therefore, according to the Japanese classification, cases with no invasion of the lamina propria. Such cases would not be included as gastric cancers in Western countries. This bias may interfere with the proportion of localized cancer, and of course with survival.
However, the extent of the change in stage distribution in Japan is too large to be explained by variations in proportions of unstaged tumors. The increasing incidence of localized cancer occurs in all age groups, up to those aged 70–79 years. The increasing incidence of localized cancer is period-specific, suggesting that it relates to a specific intervention, presumably the Japanese mass screening program.
A decline in mortality is evident in all 3 countries, except for men aged 80 years or more in Japan. Declines in mortality are period-specific in Slovenia and the USA, whereas in Japan (as for incidence) the decline involves successive birth cohorts since 1900. The higher survival from stomach cancer reported in Japan compared with the USA has been a matter of debate. A low M/I ratio is considered an indication of good survival; however, the M/I ratio is in the same range for both countries. Factors such as the completeness of case registration may explain the discrepancy. In Japan, the decline in mortality is greater than for incidence; the persisting trend throughout the period suggests that this is not an artifact and that survival from stomach cancer is improving
Respective roles of lifestyle and screening
The generalized decline in incidence of stomach cancer, evident in most developed countries (“unplanned prevention”), relates to changes in lifestyle, particularly with respect to diet and food storage.15 Such influences have certainly been important in the decline in risk in Japan.24, 25 The role of H. pylori in increasing the risk of gastric cancer through the promotion of chronic atrophic gastritis is also clearly established.26, 27 The prevalence of H. pylori infection in Japan has been declining in successive birth cohorts.28–30 A recent study suggests that the declines in gastric cancer incidence in young subjects in Japan involves the intestinal (rather than the diffuse) type of carcinomas,31 which would be consistent with the greater risk for this subtype conferred by H. pylori infection.26, 32 These changes are often attributed to the generalization of a western style of life in Japan just after World War II in Japan, under American influence. Most studies focus on changing environmental factors during this period. Actually, although the full impact of the declining trend occurred in the post-World War II period, the causes were active at least 30 years earlier. Helicobacter pylori infection is just one factor among others in gastric carcinogenesis, and etiologic factors should be examined in perspective since the early 20th century. Japan entered the industrial arena and behaved as a world power much earlier, under the influence of Emperor Meiji, in the period just after the Sino-Japanese war (1894–95) and the Russo-Japanese war (1904–05), ending with the Port Arthur surrender to the Japanese. Changing environmental factors occurring in the infancy of persons born in the cohort 1910 and after must play a major role.
The period studied (1975–95) coincides with the full-scale introduction of a mass screening program for gastric cancer in Japan, organized either in municipalities or through private companies.4–10, 33–41 The results of the screening examinations are given in the annual reports on mass screening for digestive cancer throughout the country The latest report, for 1997,34 confirms that of 5,151 stomach cancers detected by mass screening, superficial tumors staged T1 (m or m+sm) represent 67.8%, whereas advanced cancer accounts for only 32% of cases. The proportion of intramucosal cancers (m) was 40% (2058 cases). However, even in Japan, the proportion of the population examined in this organized program is not so large; in 1983 the coverage of the screening was 9.6% of the target population.5 According to the report of the Ministry of Health and Welfare of Japan, the proportion covered by the program of the health services mandated by law was 13.3% of the target population in 1998. As a further illustration, it may recalled that the estimated number of incident cases of stomach cancer in Japan in 2000 is 115,294 according to the IARC data base Globocan 2000.42 However, in addition to the organized screening program, there have been an increasing number of opportunistic tests, carried out in various settings. According to the survey of the Osaka Prefecture in 1997, the proportion of those people who had stomach cancer screening tests and/or stomach x-rays during the previous year was 39.4% (A. Oshima, personal communication) Extensive early detection explains why the proportion of localized cancer doubled during the study period in the Osaka Registry, whereas it was stable in the USA. On the other hand, the decline in the proportion of localized cancer in Slovenia during the period is largely attributable to the progression in staging procedures and the higher resectability rate in the country since 1982.43
Among the cases detected in Japan at the stage of intramucosal neoplasia, many would be classified high-grade dysplasia in the Western world21 and not recorded as “cancer.” This is a major cause of the different prognosis of stomach cancer in Japan and in the West. The potential for progression from early to advanced cancer is uncertain, and early gastric cancer has even been called a pseudo-cancer. However, a study conducted in Japan confirms that lesions fulfilling the endoscopic criteria for early gastric cancer in Japan usually progress to advanced cancer, the 5-year risk for progression being 63%.39, 40 Thus, despite staging based on endoscopy alone, the malignant potential of intramucosal neoplasia can be accepted. The higher survival from stomach cancer in Japan has also been attributed to different strategies in surgical treatment, mainly the routine use of the D2 resection, which involves a radical extended regional lymphadenectomy. However, the improvement in results obtained with that operation in Japan have not been confirmed in Western countries.44, 45
The evidence for the efficacy of gastric cancer screening in Japan in preventing advanced disease as well as death from gastric cancer rests on the results of observational studies, so the contribution of selection bias to any favorable effect (low-risk individuals choosing to be screened) is hard to evaluate. Only one randomized trial has been reported,33 and, although no results were available at the time, it is highly unlikely that, given the small difference in screening experience between intervention and control groups, any benefit could emerge later. Three case control studies, of prevention of cancer deaths6, 35 or of advanced disease,36 all suggested a beneficial effect of screening, as did 2 prospective cohort studies comparing mortality rates in individuals participating or not in the mass screening program.37, 38 The study in Osaka37 showed a rather higher than expected incidence of gastric cancer in individuals undergoing screening, implying possible overdiagnosis (detection of nonprogressive “cancer”) in this group.10 On a population level, a previous study of incidence and mortality in Miyagi prefecture between 1960 and 198533 showed that, after the introduction of screening (around 1970), mortality fell more rapidly than incidence, particularly in the age groups targeted for mass screening (50–79 years). Similar data were observed in Osaka.39