Inadequate Evidence of Benefit Associated With Screening
Several screening techniques, including barium-meal photofluorography, gastric endoscopy, and serum pepsinogen, have been proposed as screening methods for the early detection of gastric cancer. No randomized trials evaluating the impact of screening on mortality from gastric cancer have been reported.[1,2] Even in very high-risk areas, the positive predictive value (PPV) of the screening tests may be very low. In a screening program of 17,647 men aged 40 to 60 years in Wakayama City, Japan, the PPV of combined serum pepsinogen and barium meal with digital radiography over the 7-year period was 0.85%.[3] The positive test rates were 19.5% for serum pepsinogen and 22.5% for radiography, with a cancer detection rate of 0.28%. Over the 7-year period, there was no reduction in gastric cancer mortality compared with an age-matched surrounding population.
Barium-Meal Gastric Photofluorography
A national program of population-based screening for gastric cancer using barium-meal photofluorography has been ongoing since the 1960s in Japan. Participation rates have been in the range of only 10% to 20%.[1,3] Although there has been a coincident decrease in mortality from gastric cancer in Japan, mortality rates have been decreasing in many developed countries without screening programs. Case-control studies from Japan show decreases in gastric mortality in people who have undergone screening, but results from prospective studies were not consistent.[1,2]
A pilot study of community-based photofluorography was conducted in Costa Rica using the same techniques as those used in Japan's national program (with consultation from Japanese experts).[4] People were invited by letter from a population registry to attend two rounds of screening, and a total of 6,200 eligible screened participants (of a planned 12,000) were analyzed. Their gastric cancer mortality from 2 to 7 years after screening was compared with four control groups that had not been invited to be screened, and the relative risk was about 0.5 (no P value reported). The study was, however, prone to strong biases, including selection bias, and likely differential exclusion of people with previously diagnosed gastric cancer favoring the screened population. In addition, unlike the community controls, patients diagnosed with gastric cancer through the screening program were treated at a single referral center. The PPV of a suspicious fluorograph was 3%; the specificity in the two rounds was 67% and 80%; and the positivity rates were 34% and 20%. Despite the authors' belief that their results provided substantial evidence that routine screening would decrease gastric cancer mortality, they concluded that the costs of screening with photofluorography would be far too high in their country.
A screening study was begun in Venezuela in 1980, using radiographic fluorography.[5] The efficacy of this program in reducing mortality from gastric cancer was evaluated by means of a case-control study. The study showed no detectable reduction in mortality from gastric cancer.
Gastric Endoscopy
Endoscopy appears to be more sensitive than photofluorography for the detection of gastric cancer.[6]
A meta-analysis of gastric cancer endoscopic screening studies in Asia identified ten relevant studies, all nonrandomized.[7] These studies were conducted between 1989 and 2014 in South Korea, China, and Japan. Of the ten studies, a never-screened group was the comparator in six studies, a radiographic-screening group was the comparator in one study, and expected deaths based on population rates was the comparator in three studies. In some of the studies, the endoscopic screening was performed as part of a national screening program. The meta-analysis pooled risk ratio (RR) estimate of gastric cancer mortality associated with endoscopic screening was 0.60 (95% confidence interval [CI], 0.49–0.73), with all but one study showing an individual RR of 0.72 or lower. There was significant heterogeneity across studies (P = .001), which was because of the one study with an RR greater than 1 (1.01); removing that study resulted in no significant heterogeneity (P = .14). Pooled estimates for the four nested case-control studies and six cohort studies were 0.60 (95% CI, 0.47–0.76) and 0.57 (95% CI, 0.39–0.83), respectively. The pooled estimate for the six studies with the never-screened comparator group was 0.58 (95% CI, 0.48–0.70).
Serum Pepsinogen
There are no studies evaluating the effect of screening with serum pepsinogen on gastric cancer mortality, and there are important limitations to its use as a screening test. Low serum pepsinogen levels indicate the presence of atrophic gastritis and are therefore applicable to the detection of presumed precursors for intestinal-type gastric cancer rather than the diffuse type.[3] In addition, there are no standard cut-off values of abnormality.[1,8] Finally, eradication of H. pylori and use of proton pump inhibitors for the management of indigestion change pepsinogen levels, making interpretation of results difficult in the setting of widespread use of these interventions.[1,3]
In Japan, one study measured serum pepsinogen levels I and II (PGI and PGII) in 5,113 patients who were also screened by endoscopy (13 gastric cancers detected). This study used cut-off points for identifying risk of gastric cancer, which were less than 70 ng/mL for PGI and less than 3 ng/mL for the PGI:PGII ratio. This combination provided a sensitivity of 84.6%, a specificity of 73.5%, a PPV of 0.81%, and a negative predictive value of 99.6%.[9]
Clinical Considerations for High-Risk Groups
There may be justification for screening some populations of Americans at higher risk, although there is considerable discussion about how much incidence would make the examination worthwhile. Potential subgroups might include older patients with atrophic gastritis or pernicious anemia; patients with partial gastrectomy;[10] patients with the diagnosis of sporadic adenomas,[11] familial adenomatous polyposis,[12] or hereditary nonpolyposis colon cancer;[13] and immigrant ethnic populations from countries with high rates of gastric carcinoma.[14,15]
References:
- Leung WK, Wu MS, Kakugawa Y, et al.: Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol 9 (3): 279-87, 2008.
- Hamashima C, Shibuya D, Yamazaki H, et al.: The Japanese guidelines for gastric cancer screening. Jpn J Clin Oncol 38 (4): 259-67, 2008.
- Ohata H, Oka M, Yanaoka K, et al.: Gastric cancer screening of a high-risk population in Japan using serum pepsinogen and barium digital radiography. Cancer Sci 96 (10): 713-20, 2005.
- Rosero-Bixby L, Sierra R: X-ray screening seems to reduce gastric cancer mortality by half in a community-controlled trial in Costa Rica. Br J Cancer 97 (7): 837-43, 2007.
- Pisani P, Oliver WE, Parkin DM, et al.: Case-control study of gastric cancer screening in Venezuela. Br J Cancer 69 (6): 1102-5, 1994.
- Tashiro A, Sano M, Kinameri K, et al.: Comparing mass screening techniques for gastric cancer in Japan. World J Gastroenterol 12 (30): 4873-4, 2006.
- Zhang X, Li M, Chen S, et al.: Endoscopic Screening in Asian Countries Is Associated With Reduced Gastric Cancer Mortality: A Meta-analysis and Systematic Review. Gastroenterology 155 (2): 347-354.e9, 2018.
- Yanaoka K, Oka M, Mukoubayashi C, et al.: Cancer high-risk subjects identified by serum pepsinogen tests: outcomes after 10-year follow-up in asymptomatic middle-aged males. Cancer Epidemiol Biomarkers Prev 17 (4): 838-45, 2008.
- Kitahara F, Kobayashi K, Sato T, et al.: Accuracy of screening for gastric cancer using serum pepsinogen concentrations. Gut 44 (5): 693-7, 1999.
- Staël von Holstein C, Eriksson S, Huldt B, et al.: Endoscopic screening during 17 years for gastric stump carcinoma. A prospective clinical trial. Scand J Gastroenterol 26 (10): 1020-6, 1991.
- MING SC, GOLDMAN H: Gastric polyps: a histogenetic classification and its relation to carcinoma. Cancer 18: 721-6, 1965.
- Utsunomiya J, Maki T, Iwama T, et al.: Gastric lesion of familial polyposis coli. Cancer 34 (3): 745-54, 1974.
- Aarnio M, Salovaara R, Aaltonen LA, et al.: Features of gastric cancer in hereditary non-polyposis colorectal cancer syndrome. Int J Cancer 74 (5): 551-5, 1997.
- Kurtz RC, Sherlock P: The diagnosis of gastric cancer. Semin Oncol 12 (1): 11-8, 1985.
- Boeing H: Epidemiological research in stomach cancer: progress over the last ten years. J Cancer Res Clin Oncol 117 (2): 133-43, 1991.