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.     

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.     

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.     

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.     

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.     

Precision medicine for gastrointestinal cancer: Recent progress and future perspective

Gastrointestinal (GI) cancer has a high tumor incidence and mortality rate worldwide. Despite significant improvements in radiotherapy, chemotherapy, and targeted therapy for GI cancer over the last decade, GI cancer is characterized by high recurrence rates and a dismal prognosis. There is an urgent need for new diagnostic and therapeutic approaches. Recent technological advances and the accumulation of clinical data are moving toward the use of precision medicine in GI cancer. Here we review the application and status of precision medicine in GI cancer. Analyses of liquid biopsy specimens provide comprehensive real-time data of the tumor-associated changes in an individual GI cancer patient with malignancy. With the introduction of gene panels including next-generation sequencing, it has become possible to identify a variety of mutations and genetic biomarkers in GI cancer. Although the genomic aberration of GI cancer is apparently less actionable compared to other solid tumors, novel informative analyses derived from comprehensive gene profiling may lead to the discovery of precise molecular targeted drugs. These progressions will make it feasible to incorporate clinical, genome-based, and phenotype-based diagnostic and therapeutic approaches and apply them to individual GI cancer patients for precision medicine.     

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.     

Mammographic screening before age 50 years in the UK: comparison of the radiation risks with the mortality benefits

Mammographic screening before age 50 years is less effective than at older ages and the associated radiation risks are higher. We estimated how many breast cancer deaths could be caused and how many could be prevented by a decade of annual two-view mammographic screening starting at ages 20, 30 and 40 years, respectively, in the UK; for all women, and for women with first-degree relatives affected with breast cancer. We extrapolated from a radiation risk model to estimate the number of radiation-induced breast cancer deaths, and used results from randomised trials, which suggest a reduction in breast cancer mortality of 10-20% in women invited to screening before age 50 years, to estimate the number of deaths that could be prevented. The net change in breast cancer deaths was defined as the number of radiation-induced deaths minus the number of prevented deaths. For all women, assuming a reduction in mortality from screening of 20%, a decade of annual screening was estimated to induce more deaths than it prevents if started at age 20 years and at age 30 years (net increase = 0.86 and 0.37 breast cancer deaths, respectively, per 1000 women screened). The corresponding estimate for screening starting at age 40 years was a net decrease of 0.46 deaths/1000 women screened and a zero net change assuming a 10% mortality reduction. Results for women with first-degree relatives with breast cancer were generally in the same direction but, because their background incidence rates are higher, the net increases or decreases were greater. In conclusion, our estimates suggest that a decade of annual two-view mammographic screening before age 40 years would result in a net increase in breast cancer deaths, and that starting at age 40 years could result in a material net decrease only if breast cancer mortality is reduced by about 20% or more in women screened. Although these calculations were based on a number of uncertain parameters, in general, the conclusions were not altered when these parameters were varied within a feasible range.     

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.     

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.     

Eurogin 2016 Roadmap: how HPV knowledge is changing screening practice

Human papillomaviruses (HPVs) are the necessary cause of most cervical cancers, a large proportion of other anogenital cancers, and a subset of oropharyngeal cancers. The knowledge about HPV has led to development of novel HPV‐based prevention strategies with important impact on clinical and public health practice. Two complementary reviews have been prepared following the 2015 Eurogin Conference to evaluate how knowledge about HPV is changing practice in HPV infection and disease control through vaccination and screening. This review focuses on screening for cervical and anal cancers in increasingly vaccinated populations. The introduction of HPV vaccines a decade ago has led to reductions in HPV infections and early cancer precursors in countries with wide vaccination coverage. Despite the high efficacy of HPV vaccines, cervical cancer screening will remain important for many decades. Many healthcare systems are considering switching to primary HPV screening, which has higher sensitivity for cervical precancers and allows extending screening intervals. We describe different approaches to implementing HPV‐based screening efforts in different healthcare systems with a focus in high‐income countries. While the population prevalence for other anogenital cancers is too low for population‐based screening, anal cancer incidence is very high in HIV‐infected men who have sex with men, warranting consideration of early detection approaches. We summarize the current evidence on HPV‐based prevention of anal cancers and highlight important evidence gaps.     

Colorectal cancer screening: Systematic review of screen-related morbidity and mortality

BackgroundImplementation of mass colorectal cancer screening, using faecal occult blood test or colonoscopy, is recommended by the European Union in order to increase cancer-specific survival by diagnosing disease in an earlier stage. Post-colonoscopy complications have been addressed by previous systematic reviews, but morbidity of colorectal cancer screening on multiple levels has never been evaluated before.AimTo evaluate potential harm as a result of mass colorectal cancer screening in terms of complications after colonoscopy, morbidity and mortality following surgery, psychological distress and inappropriate use of the screening test.MethodsA systematic review of all literature on morbidity and mortality attributed to colorectal cancer screening, using faecal occult blood test or colonoscopy, from each databases’ inception to August 2016 was performed. A meta-analysis was conducted to examine the pooled incidence of major complications of colonoscopy (major bleedings and perforations).ResultsSixty studies were included. Five out of seven included prospective studies on psychological morbidity reported an association between participation in a colorectal screening program and psychological distress. Serious morbidity from colonoscopy in asymptomatic patients included major bleedings (0.8/1000 procedures, 95% CI 0.18–1.63) and perforations (0.07/1000 procedures, 95% CI 0.006–0.17).ConclusionsParticipation in a colorectal cancer screening program is associated with psychological distress and can cause serious adverse events. Nevertheless, the short duration of psychological impact as well as the low colonoscopy complication rate seems reassuring. Because of limited literature on harms other than perforation and bleeding, future research on this topic is greatly needed to contribute to future screening recommendations.     

The Cell‐CT 3‐dimensional cell imaging technology platform enables the detection of lung cancer using the noninvasive LuCED sputum test

The war against cancer has yielded important advances in the early diagnosis and treatment of certain cancer types, but the poor detection rate and 5‐year survival rate for lung cancer has changed little over the past 40 years. Early detection through emerging lung cancer screening programs promise the most reliable means of improving mortality. Sputum cytology has been tried without success because sputum contains few malignant cells that are difficult for cytologists to detect. However, research has shown that sputum contains diagnostic malignant cells and could serve as a means of lung cancer detection if those cells could be detected and correctly characterized. Recently, the National Lung Screening Trial reported that screening using 3 consecutive low‐dose x‐ray computed tomography scans provides a 20% reduction in lung cancer mortality compared with chest x‐ray. However, this reduction in mortality comes with an unacceptable false‐positive rate that increases patient risks and the overall cost of lung cancer screening. The LuCED test for detection of early lung cancer is reviewed in the current article. LuCED is based on patient sputum that is enriched for bronchial epithelial cells. The enriched sample is then processed on the Cell‐CT, which images cells in 3 dimensions with submicron resolution. Algorithms are applied to the 3‐dimensional cell images to extract morphometric features that drive a classifier to identify cells that have abnormal characteristics. The final status of these candidate abnormal cells is established by the pathologist's manual review. LuCED promotes accurate cell classification that could enable the cost‐effective detection of lung cancer. Cancer (Cancer Cytopathol) 2015;123:512–523. © 2015 American Cancer Society.     

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.     

Temporal Epidemiological Assessment of Colorectal Cancer Incidence and Mortality in East Kazakhstan, 2004-2013

Colorectal cancer incidence and mortality in Kazakhstan are relatively high but exact statistics have hithertobeen lacking and trends over time are unclear. The present study was therefore undertaken to retrospectively assessdata for East Kazakhstan, accessed from the central registration office, for the period 2004-2013. Approximateage standardized data for incidence and mortality were generated and compared across age groups, gender andyear. It was determined that during the studied period 3,417 new cases of colorectal cancer were registered and2,259 died of this pathology. Average cancer cancer incidence and mortality over the ten years were 24.1/105and 15.9/105 respectively, and the overall ratio of mortality/incidence (M/I) was 0.69:1 (range 0.58-0.73). Bothincidence and mortality tended to remain constant in both males and females. The male to female ratios also didnot significantly vary over time but a trend for improvement of the mortality to incidence ratio was observed,especially for rectum. Whether this might be related to screening remains unclear. These preliminary dataindicate that whereas colorectal cancer continues to be important, change in environmental factors are nothaving a great impact on incidence in East Kazakhstan.     

Advancing Cervical Cancer Prevention in India: Implementation Science Priorities

Cervical cancer is the leading cause of cancer mortality in India, accounting for 17% of all cancer deaths among women aged 30 to 69 years. At current incidence rates, the annual burden of new cases in India is projected to increase to 225,000 by 2025, but there are few large‐scale, organized cervical cancer prevention programs in the country. We conducted a review of the cervical cancer prevention research literature and programmatic experiences in India to summarize the current state of knowledge and practices and recommend research priorities to address the gap in services. We found that research and programs in India have demonstrated the feasibility and acceptability of cervical cancer prevention efforts and that screening strategies requiring minimal additional human resources and laboratory infrastructure can reduce morbidity and mortality. However, additional evidence generated through implementation science research is needed to ensure that cervical cancer prevention efforts have the desired impact and are cost‐effective. Specifically, implementation science research is needed to understand individual‐ and community‐level barriers to screening and diagnostic and treatment services; to improve health care worker performance; to strengthen links among screening, diagnosis, and treatment; and to determine optimal program design, outcomes, and costs. With a quarter of the global burden of cervical cancer in India, there is no better time than now to translate research findings to practice. Implementation science can help ensure that investments in cervical cancer prevention and control result in the greatest impact.     

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency

IntroductionLung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited.MethodsParticipants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk–selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency.ResultsUse of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non–lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention.ConclusionsNon–lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and screening may even offer cost savings if noncurative treatment costs continue to rise.     

An overview of colorectal cancer survival rates and prognosis in Asia

Colorectal cancer is a rapidly rising trend in Asia.The incidence in many Asian countries is on par with the West.Several studies have provided data regarding the survival of patients with colorectal cancer.In Asia,the overall cure rate of colorectal cancer has not improved dramatically in the last decade,5-year survival remaining at approximately 60%.Colorectal cancer survival time has increased in recent years,but mortality rate remains high.Although studies have determined a number of factors that can predict survival of patients after diagnosis,life expectancy has not been increased dramatically.It seems that among the prognostic factors explored so far,the most important are those that relate to early diagnosis of cancer.Primary detection is feasible since efficient screening modalities are available.Colonoscopic surveillance is needed,especially in subjects at higher risk.