Management of Gastric Cancer in the Asia-Pacific Region — Necessity Drives Differences
Victoria P.Y. Tan, MD
Clinical Assistant Professor, Department of Medicine, University of Hong Kong
Benjamin C.Y. Wong, MD
Honorary Clinical Professor, Department of Medicine, University of Hong Kong
Gastric cancer is the fourth most common cancer worldwide, but the second leading cause of cancer deaths.1 Gastric cancer is a major public health burden in the Asia-Pacific region, but this burden varies due to the heterogeneity of the ethnic populations that form the backbone of this region. The risk of gastric cancer varies from high-risk areas in East Asia, including China, Japan and Korea, where the age-standardized incidence rate (ASR) is greater than 20 per 100,000, to low-risk areas such as Australia, India and Thailand where the ASR is just half of that. In Malaysia, Singapore and Taiwan, the risk of gastric cancer is intermediate between the highest- and lowest-risk areas.2 This pattern of risk explains the divergence in allocation of resources. In western populations, where the risk of gastric cancer tends to fall into the low-risk category, gastric cancer management has very much been focused on the management of advanced gastric cancer; this statement does not hold true for the highest-risk areas in the Asia-Pacific region where resources have focused on preventive strategies and management of early gastric cancer.
It is widely accepted that gastric cancer, like colonic cancers, progresses through a cancer cascade.3 However, why certain individuals and families have a greater propensity to move along the cascade towards gastric cancer is most certainly a multi-factorial process, and arises from complex interactions between host factors, Helicobacter pylori (H. pylori) infection and environmental factors. These factors have long been considered targets for preventive programs to reduce the burden of gastric cancer development.
Diets high in salt and nitrates seem to confer the highest risks, with salt in particular demonstrating an ability to augment the effects of gastric carcinogens. A diet rich in fresh fruits and vegetables is associated with a reduced risk of gastric cancer. However, augmentation of the diet with ascorbic acid or use of multivitamins does not appear to confer the same protection.2, 4, 5 Despite these observations, sustained measurable alterations in diet sufficient to affect gastric cancer prevalence would be difficult to assess in a study population, particularly over the long lead times gastric cancer studies require.
However, H. pylori infection has proven to be a more interesting target in this region. Multiple studies have indicated that H. pylori infection is a necessary, but not a sufficient causal factor in the development of gastric cancer.2 This has led to gastric cancer prevention strategies focused on H. pylori eradication in the Asia-Pacific region, which sees some of the highest rates of H. pylori infection (between 31 to 92 percent in developed and developing countries, respectively) and gastric cancer prevalence rates.4 Unfortunately, despite four randomized placebo-controlled trials evaluating H. pylori screening and eradication on gastric cancer prevalence, all four did not show a significant reduction in gastric cancer development; however, there was a nonsignificant trend towards risk reduction for gastric cancer with H. pylori eradication.6 The strategy of population screening and treatment of H. pylori infection appears to be the strategy of choice in high gastric cancer risk populations, particularly in light of the suggestive population-based studies mentioned. However, unresolved issues include the optimal age of intervention, ethical considerations — including the induction of antibiotic resistance — and the costs to individual countries incurred by population-based screening programs.
Management of early gastric cancers
Countries such as Japan and Korea are trailblazers in terms of the management of early gastric cancer, and this has primarily been driven by need. Given that these countries have some of the highest gastric cancer ASRs, Japan, Korea and Matsu Island in Taiwan have established population screening programs for early gastric cancer. Screening is done through barium meal (Japan), gastroscopy (Japan and Korea) and serum pepsinogen/gastroscopy (Taiwan).7-9 Studies from the Asia-Pacific region examining the techniques of endoscopic mucosal resection and endoscopic submucosal dissection have proven that with improving technical expertise, the outcome for patients with early gastric cancer is excellent — as high as 100 percent survival at five years in carefully selected patients.10 However, the detection of early gastric cancer is difficult and only systematic population screening has been shown to increase early detection and confer a survival advantage.11, 12 Health economics modeling indicates that population endoscopic screening for early gastric cancer is cost effective in moderate- to high-risk populations,13 hence it may not be applicable to other countries.
Management of advanced gastric cancer
In the management of advanced gastric cancer, the majority of the studies have been carried out in the West, as primarily, some 80 to 90 percent of gastric cancer in the West present late.14 The backbone of the management of advanced gastric cancer is chemotherapy, and despite little evolution over the last 15 years in chemotherapy regimes, we are entering an exciting age with the introduction of biological agents.15 In Asia, the first-line treatment of advanced gastric cancer remains doublet chemotherapy, with preferred regimens including a platinum compound, usually cis-platinum in combination with 5-fluoro-uracil, capecitabine or S-1. Fluoro-pyrimidines show less toxicity in Asian populations, possibly owing to polymorphisms in genes encoding drug-metabolizing enzymes, translating into more options for advanced gastric cancer treatments in Asian populations.16 Unfortunately, in the Asia-Pacific region, access to oral fluoro-pyrimidines, including capecitabine and S-1 or the biologic agents is not routinely funded by the government. This severely limits the choices available to patients in this region of higher gastric cancer prevalence and where a majority of patients still present with advanced gastric cancer.
The Asia-Pacific region is somewhat heterogeneous in its gastric cancer risk, and the unique specialization developed to manage gastric cancer reflects this. Due to the region’s relatively higher rates of gastric cancer, proportionately more interest and resources have been allocated to population screening and treatment for H. pylori, and towards the development and refinement of advanced endoscopic techniques for early gastric cancer. This, along with the availability of new biologics ushers in an exciting next phase in the management of gastric cancer in the Asia Pacific.
Dr. Tan had no conflicts to disclose.
Dr. Wong received honoraria for lectures organized or co-sponsored by AstraZeneca, Eisai, Sanofi and Takeda.
1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.
2. Fock KM, Katelaris P, Sugano K, et al. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol 2009;24:1587-600.
3. Correa P, Piazuelo MB, Camargo MC. The future of gastric cancer prevention. Gastric Cancer 2004;7:9-16.
4. Goh KL, Cheah PL, Md N, Quek KF, Parasakthi N. Ethnicity and H. pylori as risk factors for gastric cancer in Malaysia: A prospective case control study. Am J Gastroenterol 2007;102:40-5.
5. Tatematsu M, Takahashi M, Fukushima S, Hananouchi M, Shirai T. Effects in rats of sodium chloride on experimental gastric cancers induced by N-methyl-N-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide. J Natl Cancer Inst 1975;55:101-6.
6. Wong BC, Lam SK, Wong WM et al. Helicobacter pylori eradication to prevent gastric cancer in a high risk region of China: a randomized controlled trial. JAMA 2004;291:187-94.
7. Kim YS, Park HA, Kim BS, Yook JH, Lee MS. Efficacy of screening for gastric cancer in a Korean adult population: a case-control study. J Korean Med Sci 2000;15:510-5.
8. Tsubono Y, Hisamichi S. Screening for gastric cancer in Japan. Gastric Cancer 2000;3:9-18.
9. Liu CY, Wu CY, Lin JT, Lee YC, Yen AM, Chen TH. Multistate and multifactorial progression of gastric cancer: results from community-based mass screening for gastric cancer. J Med Screen 2006;13 Suppl 1:S2-5.
10. Isomoto H, Ohnita K, Yamaguchi N, et al. Clinical outcomes of endoscopic submucosal dissection in elderly patients with early gastric cancer. Eur J Gastroenterol Hepatol;22:311-7.
11. Whiting JL, Sigurdsson A, Rowlands DC, Hallissey MT, Fielding JW. The long term results of endoscopic surveillance of premalignant gastric lesions. Gut 2002;50:378-81.
12. Kubota H, Kotoh T, Masunaga R, et al. Impact of screening survey of gastric cancer on clinicopathological features and survival: retrospective study at a single institution. Surgery 2000;128:41-7.
13. Dan YY, So JB, Yeoh KG. Endoscopic screening for gastric cancer. Clin Gastroenterol Hepatol 2006;4:709-16.
14. Wagner AD, Unverzagt S, Grothe W, et al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev;17:CD004064.
15. Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet;376:687-97.
16. Ma BB, Hui EP, Mok TS. Population-based differences in treatment outcome following anticancer drug therapies. Lancet Oncol;11:75-84.