Opportunistic and organized screening
When asymptomatic persons, at the individual scale, are the target of early detection of cancer, screening is called opportunistic; in this situation endoscopy, the primary procedure of detection, is included in an individual health contract between patient and doctor. When screening for cancer is adopted as a population based national policy, by the heath authorities of a country, the intervention is called organized or mass screening; then endoscopy is performed only in those persons positive to a relatively simple filter selection test. Actually there is no clear cut distinction between indications of endoscopy in organized or in opportunistic screening. Opportunistic screening by primary endoscopy, with free examination at regular intervals, may be offered by an industrial company, or by health care insurances or hospitals to their employees of affiliated persons. In this situation the screening is organized, but not population based. In the near future cancer screening should undergo a strategic revolution with the development of new selection tests prior to endoscopy. Stool and blood DNA tests based on epigenetics and nanotechnology, will be more easy to collect and have a larger spectrum, with enough sensitivity and specificity.
For squamous cell esophageal cancer early detection in opportunistic screening is based on upper gastrointestinal (GI) endoscopy in asymptomatic persons smoking and drinking alcohol. Organized screening trials are proposed to high risk populations in some areas of China exposed to a high risk and in Southern Brazil. The selection test is a balloon or sponge scrapping for cytology followed by upper GI endoscopy in positive cases.
For esophageal adenocarcinoma in columnar lined esophagus, the risk is too low to justify opportunistic or organized screening in asymptomatic persons, in the absence of reflux symptoms.
For stomach cancer, opportunistic screening with endoscopy is of current practice in persons asymptomatic or complaining from dyspepsia in regions of the world exposed to a high risk, particularly in Asia; Population based screening trials are occurring since 1963 in Japan[8
]; the selection test is photofluorography with 7 small films, or the measure of the Pepsinogen I/II ratio in the blood[32
]. The filter test is followed by upper GI endoscopy in positive cases. The prolonged policy of organized and opportunistic screening in this country resulted in a higher proportion of early gastric cancer and an increased 5-year survival.
For colorectal cancer, opportunistic endoscopic screening with flexible sigmoidoscopy or colonoscopy in asymptomatic persons from age 50-year, is of current practice in regions of Western countries exposed to a high risk. Organized and population based screening protocols are also proposed in in Europe, North America and in Japan. The fecal occult blood test (FOBT) is still the current selection test, either as a Guaiac FOBT or as a immunochemical test, like in Japan; this test requires only one stool sample and no specific diet. Various randomized trials on the efficacy of the FOBT test have been conducted[35
]: (1) the American Minnesota trial, conducted in volunteers, with an annual rehydrated guaiac test, achieves a reduction in mortality in the screened group of 33%[37
]. However the rate of positive tests is very high as well as the proportion of screened persons submitted to colonoscopy; and (2) the 2 European population based trials (Nottingham trial, Funen trial) based on a biennial non rehydrated test show a lower reduction is mortality in the screened group (15%-18%) but are more cost/effective because the proportion of colonoscopies is much lower[35
]. The sensitivity of the FOBT trials to the detection of premalignant colorectal lesions is fairly low; therefore there is no impact on the incidence of cancer.
Evaluation of screening for cancer
Evaluation is not applicable to opportunistic screening at the individual scale. In contrast, evaluation of benefits, drawbacks, and cost/effectiveness, including follow-up of the results, is required for organized population based screening. The intervention is launched by the health authorities of a country in age classes exposed to the risk, from the age 50-year. Priority in evaluation of the benefit is given to the prevalence of the concerned cancer, screening is worthwhile only if there is a sizable impact on the health of the population. Aging persons are exposed to multiple concurrent causes of mortality. A life saved from digestive cancer is not saved from other diseases. Screening trials in age classes prone to cancer have an excessively high cost and a negligible impact on the global mortality of the population.
The benefit of a screening intervention with early detection of premalignant and malignant lesions is shown by the impact on the 5-year survival and mortality from the targeted tumor site. This impact is analyzed on death statistics and, in reference to stage and treatment, in cancer registries.
The harms and drawbacks of screening are as follows: (1) the intervention has an impact on morbidity with the potential complications of endoscopy; and (2) the number of cases detected and their mortality is artificially increased as compared to data in cancer registries because some of the detected cases would not be the final cause of death. This factor is well acknowledged for the screening of prostate cancer with the PSA antigen.
Multiple interfering bias must be accounted for, in the evaluation: (1) the lead time bias applies to cancer detected at an early preclinical stage, then the length of the survival is prolonged by definition; (2) the selection bias applies to cases detected during the first years of the intervention; these cases usually have a slow evolution and better prognosis; and (3) the stage migration bias refers to progress in early detection of cancer occurring along the years and independently from the screening intervention. Similarly the progress in treatment improves the results and increases artificially the impact of the intervention on mortality and 5-year survival, this is why randomized trials are required.