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Addressing overuse and overdiagnosis in colorectal cancer screening for average-risk individuals Montse Garcia*
Practice points ●●
Minimal research has examined overuse and overdiagnosis in colorectal cancer (CRC) screening and the studies addressing these issues have been conducted only in opportunistic screening settings.
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Postpolypectomy surveillance is one of the biggest challenges of CRC screening at present because of the high volume of affected individuals.
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There appears to be significant discordance between current recommendations for CRC sceening and actual
practice. There is a substantial overutilization of surveillance colonoscopy among subjects with low-risk adenomas, and underutilization among subjects with advanced adenoma. ●●
There is likely little overdiagnosis in CRC. In a recent study, the probability of overdiagnosis was approximately 6–9% among the screen-diagnosed cases.
SUMMARY Inappropriate screening harms healthy individuals and squanders precious resources. The purpose of this review is to address harms of colorectal cancer screening derived from overuse and overdiagnosis in average-risk individuals. Overuse is associated with shorter than recommended repeat screening and surveillance intervals, and screening in individuals who would not derive benefit because of advanced age or significant comorbidity. Overuse can unnecessarily increase patient harm from overdiagnosis or colonoscopy complications as well as gastroenterologist workload and healthcare costs. There is no evidence to suggest that overdiagnosis is an issue for colorectal cancer screening. However, targeting on cancer prevention (detection of adenomatous polyps) rather than early detection will lead to overdiagnosis as only a small minority of polyps develop into cancer.
Colorectal cancer (CRC) is the third most common cancer and the fourth common cause of cancer death in the world. Approximately 1.36 million people are diagnosed annually with CRC, and approximately 694,000 die from CRC annually [1] . Approximately 54% of CRC cases are diagnosed in developed countries, and Europe represents one of the regions with the highest rates both in incidence and mortality. Screening for CRC provides a simple and effective public health intervention to prevent and minimize the impact of CRC on the community. The rationale behind cancer screening programs is that early detection of cancer (before symptoms arise) will reduce cause-specific mortality [2] .
KEYWORDS
• colorectal cancer screening • harms • overdiagnosis • overuse
*Cancer Prevention & Control Program, Catalan Institute of Oncology, IDIBELL, Av. Gran Via 199–203, 08908, L’Hospitalet de Llobregat, Barcelona, Spain; Tel.: +34 932 607 186; Fax: +34 932 607 956;
[email protected]
10.2217/CRC.15.4 © 2015 Future Medicine Ltd
Colorect. Cancer (2015) 4(1), 27–35
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Review Garcia The lifetime risk of CRC (0–74 years) in developed countries is approximately 4% [1] . This means that 96% of individuals will never suffer from CRC, irrespective of screening or other preventive measures. Screening can only address the 4% of the population who will be diagnosed with CRC and reduce their risk, whilst the remaining 96% will have no personal gain from screening. The absolute risk reductions shown for different screening modalities for CRC are larger than those recently reported for breast cancer screening and thus may be considered as clinically significant [3] . However, it is not possible to find out who will develop the disease and who will not. We have to be aware of the ‘prevention paradox’. An individual’s decision to get screened regularly may only have a small impact on that individual’s risk of disease in the near future even though the consequence will be of significant benefit to the population as a whole [4] . Many individuals have to get screened in order for a much smaller number to benefit. Reductions in mortality seen in randomized trials can only be reproduced in the wider population if participation is adequate [5] . Moreover, screening has also the potential to harm. Thus, it is paramount that health professionals provide balanced, unbiased, quantified, understandable and evidence-based information about all the risks and benefits of screening and help individuals to make an informed choice to attend or no to attend CRC screening [6] . Information on cancer screening is often biased, incomplete and persuasive. Some leaflets mention the possibility of harms however do not quantify them [7] . The potential harms of CRC screening with reference to screening colonoscopy and fecal occult blood test (FOBT) are the following: risks of inaccurate test results, including falsepositive results (that may lead to complications of follow-up, emotional distress and lost work days) and false-negative results (that miss disease and thus cause a delay in treatment); harms of the screening test including those due to preparation, sedation or the procedure itself (pain, bleeding, infection, perforations or death); harms of overdiagnosis from true-positive identification of CRC or precancerous abnormalities that would not have been harmful and led to death [8,9] . The benefit in cancer screening is defined as the extent to which screening reduces mortality but it can also be defined as the reduction in incidence of the disease when the screen identifies preinvasive lesions. If an incident cancer is
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prevented by screening, then also the death from this cancer will be prevented [10] . In average-risk individuals, CRC mostly arises from adenomatous polyps and the time span for the transition process is estimated to nearly 10 years on average [11] . Given the slow progression of colorectal adenomas into invasive adenocarcinoma, early detection and endoscopic resection of these precancerous lesions have been claimed to be also effective in decreasing incidence rate of CRC as well as disease-specific mortality. Several screening methods are effective in reducing mortality from CRC. Compelling and consistent evidence either from randomized controlled trials or observational studies shows that FOBT, flexible sigmoidoscopy and screening colonoscopy reduce mortality from CRC [12–19] . However, a debate exists as to which approach to use. Benefits should be weighted against the costs, discomfort, complications rates, capacities needed and possible differences in compliance. Screening with FOBT intends to detect earlystage cancer. The goal of FOBT is to reduce cancer-site specific mortality due to early disease detection whereas preventive screening by structural exam of the colon, like colonoscopy or flexible sigmoidoscopy, aims at the disease before it gets malignant by detecting and removing precursor lesions [20] . This approach fails to consider other important factors in the risk-benefit equation such as overdiagnosis and overtreatment, and the relative harms of screening and diagnostic follow-up associated with a particular test [21] . The aim of this review is to address harms of CRC screening for average-risk individuals derived from overuse and overdiagnosis. Prior, we will provide an overview regarding which factors are associated with a balance of benefit to harm and the current status of screening for CRC in Europe. Quality of screening Muir Gray stated that evidence of a favorable balance of benefit to harm in a research setting does not guarantee that a similar balance will be reproduced in practice, so screening programs need to be introduced in a way that allows their quality to be measured and continuously improved [22] . The quality of the screening program and, therefore, the magnitude of the beneficial and adverse effects, is of central importance in determining the shape of both the cost benefit curve and the gradient of the straight line relationship between resources invested and
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Overuse & overdiagnosis in colorectal cancer screening adverse effects [23] . Thus, screening has to be carefully organized for maximum effectiveness. Guidelines and recommendations on how best to deliver screening in a population are diverse [24–26] . In Europe the approach is to implement organized cancer screening programs [27] . In the USA, general recommendations are given to the population and screening practice is dependent on the medical insurance of individuals [27] . Tests can be offered during contact between individuals and their physician in primary health care or in other healthcare settings [28] . It is worthwhile to notice that when quality assurance is introduced, quality problems are revealed. A quality assurance screening program gets more negative publicity than a screening program with no quality assurance structure in which no one can be below standard. As a result of this, those involved in screening may find themselves criticized [23] . There is steadily growing criticism from parts of the scientific community about cancer screening programs. The controversy concerns the relevance and magnitude of various harms and benefits of being screened. Unlike a diagnostic test, a screening test is done in apparently healthy and asymptomatic people, not interested in risk exposure to obtain confirmation of being healthy. The situation is quite different for patients worried about symptoms [29,30] . CRC incidence [31,32] and mortality [33–35] have been decreasing in recent years, particularly in countries where CRC is actively recommended. The reasons for this positive trend have been attributed to detection at a more favorable tumor stage as well as the removal of polyps. However, in a recently published study conducted under opportunistic screening in Luxembourg, although a decline of CRC incidence was observed there was no significant variation concerning the advanced tumor stage. This may be due to the fact that a significant proportion of persons at risk were not sufficiently aware of screening (under use) [36] . Opportunistic screening is less efficient and more costly both in terms of resources and harms, and thus it is not recommended as an alternative to organized screening [8] . CRC screening programs In a survey conducted by the Joint Research Center to the European State Members in 2012, 14 countries reported they have ongoing screening programs for CRC (Austria, Belgium, Cyprus, Czech Republic, Spain, France, Croatia,
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Hungary, Ireland, Italy, Latvia, Malta, Slovenia and the UK) and another four countries are in transition phase toward and organized program. In fact, Germany is converting its current opportunistic activity into a population-based program, Finland and Norway are currently engaged in a pilot phase, and The Netherlands is starting a program roll-out in 2014 [37] . Organized screening programs require a defined target population, actively invited by the program, the use of homogeneous criteria and quality control activities and the evaluation of results [38] . Compared with organized screening, the opportunistic approach does not systematically invite the whole target population and it is more likely to result in variability in the definition criteria of the individuals invited and in the quality of the screening process, and reduces the possibility of systematically assessing the outcome of the screening activities at the population level [39] . Cancer screening in the USA is predominantly opportunistic [40] . Although some health maintenance organizations have established systems that include many of the dimensions of national systems found elsewhere (e.g., call-recall systems and monitoring of quality), most screening depends upon encounters, upon a patient or a provider recommending cancer screening during a healthcare visit [41] . Although there are several tests recommended for CRC screening in the USA, colonoscopy has become the most commonly used screening test. Among the various implemented programs, there are differences such as the screening intervals or the target population to which they are addressed. The current recommendation for CRC screening in an average-risk population is to begin screening at 50 years old for men and women in most countries. Persons at higher risk should begin screening at a younger age and may need to be tested more frequently. The age group invited to screening is influenced by national guidelines. In Europe, screening typically started at either age 50 or 60 years, with upper age limits typically between ages 66 and 75 years. Screening interval varied by screening modality. Programs using sigmoidoscopy (i.e., Piemonte and Veneto, Italy) screen ‘once only’, whereas programs using Colonoscopy (i.e., Germany, Poland) usually screen every 10 years [42] . For programs using FOBT activities, the interval is annually, biennially and a combination of
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Review Garcia both annually and biennially specified by age for the German program. In most European countries with a population-based CRC screening program, full national coverage has not achieved. The economic crisis, currently affecting Europe makes difficult to increase nationwide coverage of the target population with CRC screening due to budget restrictions. Health and social services budgets have been subjected to large cuts [43] . So it is paramount to monitor every step of the screening pathway in order to improve quality assurance and identify how to reduce healthcare expenditures (i.e., avoiding unnecessary testing). Minimal research has examined overuse and overdiagnosis in CRC cancer screening and as far as we know the studies addressing these issues have been conducted mainly in the USA considering several screening tests (colonoscopy and FOBT). Moreover, research on overdiagnosis is now recognized as part of the future scientific direction of the National Cancer Institute’s division of cancer prevention in the USA [44] . Overuse Inappropriate screening harms healthy individuals and squanders precious resources [29] . One form of overuse is associated with shorter than recommended repeat screening in individuals with a previous negative result. It occurs as well in the follow-up of individuals who had polyp removal (postpolypectomy surveillance) at intervals that are too frequent. It is unclear whether aggressive attempts to remove diminutive polyps that are 5 mm or less in size are warranted or should be also considered overused [45] . Many researchers are of the opinion that removal of diminutive polyps yields little benefit [46–48] and increases the risk for complications. The last type of overuse is screening individuals that because of significant comorbidity or advanced age have consequently little life remaining in which to enjoy the benefits of avoiding a disease that they might have experienced. Several studies show that screening rates in patients with severe comorbidity are similar to rates in those without comorbidity [49–51] . In a simulation study of fecal immunochemical testing the tradeoff between benefits (lifeyears gained) and harms (false-positive test results and CRC overdiagnosed) was concluded that age of cancer screening cessation should be based on comorbid conditions. Approximately
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70% of the current US population aged 74 years has none comorbid conditions to influence life expectancy, this group could continue to be screened until age 76 years and still have the same balance of benefits and harms expected from screening the average-health population until age 74 years. On the contrary, the 13% of the US population aged 65–74 years with severe comorbid conditions should stop screening at age 66 years to have the same balance of benefits and harms as seen among average-health groups having screening from ages 50–74 years [52] . Overuse is important to address, because it can unnecessarily increase: patient harm from overdiagnosis, including colonoscopy complications such as bowel perforation, gastrointestinal bleeding, serious cardiovascular events and death; and gastroenterologist workload, consuming resources that could be used more effectively [53] . Partin et al. estimated levels and correlates of FOBT overuse in a national Veterans Health Administration sample in the USA, 21% of FOBT performed were completed sooner than was considered necessary (
