Screening for cancer: future potential

Much progress has been made in cancer screening over the past decade, but a great deal more needs to be done if screening is to make a major impact on worldwide cancer mortality. Where fully implemented, cytological screening for cervical precursor lesions has had a major impact on mortality. However, the cost and required infrastructure levels are high, and new approaches are needed if screening is to be effective in the developing world. Testing for the human papillomavirus and automated liquid based cytology offer great promise to improve quality, reduce overall cost and make screening more viable generally. Breast screening has been less successful, although useful mortality benefits have been achieved in women aged over 50 years. Full implementation in countries that can afford it will save lives, but radical new approaches will be needed to conquer breast cancer. Colorectal cancer screening offers the best hope of a major reduction in cancer mortality over the next decade. Less certainty exists about screening for other major cancers such as lung, prostate and ovary, but a range of potential approaches merit investigation. ©     

Breast cancer screening and cost-effectiveness; policy alternatives, quality of life considerations and the possible impact of uncertain factors

Mammographic screening for women aged 50-70 is effective in reducing breast cancer mortality, but the impact on quality of life and the attainable mortality reduction remain to be discussed. The consequences of expanding screening programmes to include women in other age groups are uncertain. We have predicted the effects and costs for 5 popular screening variants, differing in age group and screening interval, on the basis of our analysis of the Dutch screening trials and of the reported mortality reductions in other trials. We have also investigated the influence of a large number of uncertain factors. Screening for women aged 50 and over with a 2- or 3-year interval is very cost-effective and will result in reductions of respectively 16% or 10% in breast cancer mortality in a real population. Variation of most variables keeps the cost-effectiveness (CE) ratio limited to the range of US $3,000 to 5,000 per life-year gained. A 2- to 3-fold change in CE ratio would only occur if the extreme estimates of mortality reduction in the Swedish screening trials were applied. The impact on quality of life (QoL) is limited: for the 2-yearly screening policy for women aged 50-70, the cost per Quality-Adjusted Life-Year (QALY) gained is 4,050, whereas the cost per life-year gained is US $3,825. The CE ratio for 2-yearly screening of women aged 40-70 is 5,400, but the additional cost per additional life-year gained is US $35,000. It would be preferable by far to extend the screening programme to women over the age of 70 or to shorten the screening interval for women aged 50-70. Screening performances, the demand for mammograms outside screening and the possibility of a survival improvement irrespective of screening have a strong impact on QoL and CE.     

Role of early diagnosis and screening; biomarkers

Currently there is evidence to support the inclusion of screening for breast and cervix cancer in programs for cancer control. Breast cancer programs have an important impact in women over the age of 50, but increasingly there are suggestions that, at least in the early years, there are no benefits for women age 40 to 49, and even that mortality from breast cancer may be increased. Cervix cancer programs can have a major impact if appropriately organized. There is no justification at present to recommend screening for colorectal cancer. Screening can be expected to have only a minor influence on reduction in cancer mortality by the year 2000. Biomarkers may be of value as indicators of risk or indicators of disease. Some have been proposed for the former, such as mammographic parenchymal patterns and breast cancer risk. There are good theoretical reasons for not incorporating them in screening programs, as the program sensitivity will decrease, even if the program specificity increases. Biomarkers as indicators of disease may be valuable when the marker is linked to the etiologic agent for the disease, providing that valid screening tests can be developed for the marker, or could be a biological indicator of the presence of disease, such as a monoclonal antibody, specific to the cancer. Examples include markers for hepatitis B virus (HBV) infection and liver cancer screening, and potentially in the future, markers for human papillomavirus (HPV) infection and cervix cancer screening. Specific monoclonal antibodies to cancer utilizable in screening are being sought, but are not yet available for use. One example under evaluation is the CA 125 monoclonal for ovarian cancer.     

The role of screening in the management of skin cancer

The incidence of skin cancer has been rising at an alarming rate for the past several years. This poses a significant public health problem in the United States. Detection and treatment of melanoma early in its course is critical for improved outcome. Of the approaches to cancer control that can reduce mortality from melanoma and nonmelanoma skin cancer, screening holds the greatest promise for a rapid and major impact. Prevention and early detection are crucial in reducing morbidity and mortality from skin cancer. For a number of reasons, however, the full effect of screening for both melanoma and nonmelanoma skin cancers has not been achieved. Controversy exists regarding who should perform screening, who should be screened, and whether screening should be performed at all. It is clear that melanoma and nonmelanoma skin cancer control programs combining primary prevention, education, and screening are in developmental stages. This review will discuss the advantages and disadvantages of screening for skin cancer.     

Update on PSA testing

The use of prostate-specific antigen (PSA) testing for prostate cancer screening has increased dramatically over the past decade. Determining the most efficient way to use PSA testing and how to interpret total PSA levels and changes in PSA values over time remain challenging. Guidelines for early detection of prostate cancer have a direct impact on the number of unnecessary tests performed and are critical for developing a successful screening approach for prostate cancer. The age at which PSA screening should begin, PSA testing intervals, and the importance of understanding fluctuations in PSA values over time are discussed in the framework of recent discoveries in the field. Results from ongoing randomized trials will confirm whether prostate cancer screening is an effective method for reducing deaths from prostate cancer and what approaches will provide the most cost-effective screening strategies.     

Breast cancer screening: the evolving evidence

Breast cancer is a leading cause of cancer and death from cancer among women in the developed and developing world. Detecting and treating breast cancer earlier in its natural history improve prognosis and result in a reduction in breast cancer mortality. There have been eight population-based randomized controlled trials (RCTs) of mammography screening, which individually and collectively provide strong support for the efficacy of breast cancer screening. The evaluation of modern service screening also has shown that modern breast cancer screening is contributing to reductions in breast cancer mortality at a rate as good as or better than that observed in the RCTs. In the last decade, different interpretations of the evidence from the RCTs and observational studies have resulted in different screening guidelines and contentious academic debates over the balance of benefits and potential harms from breast cancer screening. In this paper, the historic and recent evidence supporting the value of breast cancer screening will be described, along with the underpinnings of the current debate over the relative and absolute benefit of regular mammography screening.     

Screening for gastric cancer in China: Advances,challenges and visions

Gastric cancer (GC) is one of the major cancers in China and all over the world. Most GCs are diagnosed at an advanced stage with unfavorable prognosis. Along with some other countries, China has developed the government-funded national screening programs for GC and other major cancers. GC screening has been shown to effectively decrease the incidence of and mortality from GC in countries adopting nationwide screening programs (Japan and Korea) and in studies based on selected Chinese populations. The screening of GC relies mostly on gastroendoscopy, the accuracy, reliability and safety of which have been indicated by previous studies. However, considering its invasive screening approach, requirements on skilled endoscopists and pathologists, and a high cost, developing noninvasive methods to amend endoscopic screening would be highly needed. Numerous studies have examined biomarkers for GC screening and the combination of biomarkers involving pepsinogen, gastrin, and Helicobacter pylori antibodies has been proposed for risk stratification, seeking to narrow down the high-risk populations for further endoscopy. Despite all the achievements of endoscopic screening, evidence on appropriate screening age, intervals for repeated screening, novel biomarkers promoting precision prevention, and health economics need to be accumulated to inform policymakers on endoscopic screening in China. With the guide of Health China 2030 Planning Outline, we have golden opportunities to promote prevention and control of GC. In this review, we summarize the characteristics of screening programs in China and other East Asian countries and introduce the past and current approaches and strategies for GC screening, aiming for featuring the latest advances and key challenges, and illustrating future visions of GC screening.     

Surveillance and early diagnosis of colorectal cancer

Colorectal cancer is a major health problem in western countries such as the United States. The annual incidence of more than 130,000 new cases, and the annual mortality of more than 60,000 people justifies a consideration of efforts for its control. New concepts of risk, better understanding of the adenoma-adenocarcinoma natural history, and new screening and diagnostic technology have provided a basis for possible preventive approaches. Trials are in progress evaluating the fecal occult blood test and sigmoidoscopy screening tests, and colonoscopy as a diagnostic and surveillance test. Evaluation of data from the trials requires many considerations regarding bias and validity. Although the data from screening trials appear to be promising, they are still preliminary. In the interim, guidelines have been proposed for screening strategies related to average risk and high risk groups. Considerably more work will be required in order to provide the scientific basis for the control of large bowel cancer. In addition, efforts will have to be directed toward the effective communication of new concepts, data and techniques to the majority of physicians who interact with the at-risk population. Efforts will also have to be directed to the public at large to enhance their compliance with the approaches to increase their awareness of colorectal cancer as an important disease and to eliminate their misconceptions. Finally the cost effectiveness of various screening strategies will have to be examined once data indicates a benefit of such approaches.     

The effect of hysterectomies and screening on mortality from cancer of the uterus in canada

The trends in mortality from cancer of the uterine cervix, cancer of the endometrium and all uterus in Canada and the ten Canadian Provinces from 1951-53 to 1974-76 at ages 30-64 have been re-evaluated in relation to screening for cancer of the cervix in 1966 and 1971 and hysterectomies for non-malignant conditions from 1969 to 1976. By means of a series of mathematical models, the effect of different prior extrapolations of the numbers of hysterectomies performed by age and province has enabled the potential impact of hysterectomies on the trends of mortality from uterine cancer to be evaluated by relating deaths to ?uteri at risk’? rather than ?women at risk’? irrespective of the presence of an intact uterus. It has been found that the numbers of hysterectomies performed have little impact on the fall in mortality certified to cancer of the cervix or to all uterine cancer, but in the decade 1964-66 to 1974-66 they convert an apparent fall in mortality from cancer of the endometrium to stability. Re-evaluation of the fall in mortality from 1960-62 to 1970-72 in relation to the intensity of screening shows little impact of the hysterectomies performed on the significant correlation reported previously. However, after extension of the analysis to 1974-76 the correlation disappears. This finding may indicate a more limited potential for the application of screening, as practised in Canada, to reduce mortality from cancer of the cervix, than has been anticipated previously.     

Trends in cervical cancer and carcinoma in situ in Great Britain

Doubts have frequently been expressed about the effectiveness of the screening programme for cervical cancer in Britain. These doubts have been reinforced as a result of recent increases in mortality from this disease among younger women. In this paper we discuss trends in registration and mortality data, relate these to the level of screening, and conclude that screening may in fact have had a considerable impact on mortality rates. There is good evidence that in some age groups there has been a large increase in the incidence of carcinoma in situ of the cervix; it seems likely that the potential increase in cervical cancer incidence and mortality may have been partially prevented as a result of the screening programme. The extent of this effect cannot be quantified precisely because of uncertainties concerning the natural history of cervical cancer, differences in risk for different cohorts, and the possible effects of other factors. It is likely that incidence rates will continue to change, and it will be necessary to monitor these and the screening programme with some care in order to make the best use of the resources available for cervical cytology.     

Economic decision analysis model of screening for lung cancer

The objective of this study was to evaluate the potential clinical and economic implications of an annual lung cancer screening programme based on helical computed tomography (CT). A decision analysis model was created using combined data from the Surveillance, Epidemiology and End Results (SEER) registry public-use database and published results from the Early Lung Cancer Action Project (ELCAP). We found that under optimal conditions in a high risk cohort of patients between 60 and 74 years of age, annual lung cancer screening over a period of 5 years appears to be cost effective at approximately $19 000 per life year saved. A sensitivity analysis of the model to account for a 1-year decrease in survival benefit and changes in assumptions for incidence rate and costs generated cost effectiveness estimates ranging from approximately $10 800 to $62 000 per life year saved. Based on the assumptions embedded in this model, annual screening of high risk elderly patients for lung cancer may be cost effective under optimal conditions, but longer term data are needed to confirm if this will be borne out in practice.     

Current noninvasive tests for colorectal cancer screening: An overview of colorectal cancer screening tests

Colorectal cancer (CRC) has become the third most common cancer in the world. Screening has been shown to be an effective way to identify early CRC and precancerous lesions, and to reduce its morbidity and mortality. Several types of noninvasive tests have been developed for CRC screening, including the fecal occult blood test (FOBT), the fecal immunochemical test (FIT), the fecal-based DNA test and the blood-based DNA test (the SEPT9 assay). FIT has replaced FOBT and become the major screening test due to high sensitivity, specificity and low costs. The fecal DNA test exhibited higher sensitivity than FIT but its current cost is high for a screening assay. The SEPT9 assay showed good compliance while its performance in screening needs further improvements. These tests exhibited distinct sensitivity and specificity in screening for CRC and adenoma. This article will focus on the performance of the current noninvasive in vitro diagnostic tests that have been used for CRC screening. The merits and drawbacks for these screening methods will also be compared regarding the techniques, usage and costs. We hope this review can provide suggestions for both the public and clinicians in choosing the appropriate method for CRC screening.     

Breast cancer screeningA brief historical review

Breast cancer screening by a combination of clinical breast examination (CBE) and mammography is effective in reducing mortality from breast cancer in all age groups for years 40 and above. Mammography is the single most effective method in obtaining the mortality reductions. The CBE should not be omitted, however, in that it does add information not apparent on mammography. The CBE can be done safely by a nonphysician properly trained. Breast self-examination (BSE) is ineffectual in reducing mortality. It is debatable if it has a role in screening for breast cancer at all. This observer believes it should be done, in that its cost is minimal once the training is over.     

Screening for cancer: what's new?

Setting up of screening programmes for cancers has been the result of evaluation studies but even more of the existence (or non existence) of national policies for cancer control. We know for sure that mammographic screening can reduce breast cancer mortality in women from age 50 onwards, smear screening has a favourable impact on cervical cancer mortality and incidence, and faecal blood testing in stools may reduce colon cancer mortality. Other questions, considered for a long time as settled, are coming back, either because new data are available, such as in screening for breast cancer before age 50, or because new screening methods are being proposed, such as for lung cancer. Finally, the recognition of populations at very high genetic risk makes necessary the search for answers for example for familial breast and/or ovarian cancer. Last but not least is the methodological challenge: how can we rapidly provide answers, which implies the need for new approaches, in addition to randomized controlled trials?     

Cancer prevention

The 12 th Oncology Forum discussed the progress and future strategy of cancer prevention in Japan. The National Cancer Center has established a research center for screening focusing on the most common six cancer, stomach, lung, liver, colon, breast and uterus cancer. The program so far had a cumulative detection rate of 3.3%, which is high,and may reflect the selection of subjects. Screening and chemoprevention is also being investigated in prostate cancer, but the issues centre on how to make this widely available. High risk subjects can also be identified for breast cancer. Obesity and family history are especially important. In colorectal cancer studies are evaluating different diets, but general application is not yet possible and the infrastructure to implement any general screening and prevention does not exist. Development of pharmaceutical treatments for prevention is difficult because of the need for very safe treatments, and also because of the length of time needed to carry out studies. Overall, cancer prevention is still in evolution. New approaches are needed, and new infrastructure will be needed at a government level to implement this.     

Preventive and Therapeutic Roles of Ginseng - Focus on Colon Cancer

Colorectal cancer is one of the most prevalent diseases all over the world. Early screening and start ofchemotherapy is effective in decreasing mortality. This type of cancer can be controlled to some extent via a healthydiet rich in fruit and vegetables. Ginseng is a plant which has been consumed as a herbal medicine for thousandsof years in Asian countries. Several in vitro and in vivo studies have shown that this plant not only reduces theincidence of colorectal cancer, but also improves patient’s status by enhancing the effects of chemotherapy drugs.However, further studies are needed to prove this relationship. We briefly review ginseng and its components suchas ginsenosides reported anticancer effects and their mechanisms of action. Understanding these relationshipsmay produce insights into chemical and pharmacological approaches for enhancing the chemo preventive effectsof ginsenosides and for developing novel anticancer agents.     

Systemic treatments for women with breast cancer: outcome with relation to screening for the disease.

Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warranted.     

Colorectal cancer screening and follow-up

Cancer of the colon and rectum is a significant health problem in the United States. Nearly 50% of the 186,000 patients diagnosed annually with colorectal cancer will eventually die of their disease. Because development of a colorectal carcinoma is most frequently preceded by the development of a well-recognized pre-malignant lesion, screening modalities can significantly impact the incidence and mortality rate of this disease. Population screening employing digital rectal examination, fecal occult blood testing and endoscopic examination of the rectum and colon has been demonstrated to reduce the risk of death from colorectal cancer. Screening regimens should be instituted at an earlier age and with increased frequency for patients in the highest risk categories. Patients who have been treated for a cancer of the colon or rectum should undergo surveillance at regular intervals in an attempt to identify recurrences of disease both in the residual colon and rectum and at distant sites. Most physicians and patients believe that intensive follow-up strategies will afford improved survival and quality of life, however few randomized studies examining the utility of intensive follow-up programs have been performed and the quality of cancer-related follow-up literature is generally poor. Good-quality clinical trials are needed to sort out which tests make a difference in the patient's long-term outcome. The algorithm for surveillance for recurrence in the future may be altered as newer testing modalities are developed.