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Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective?
Arab Journal of Gastroenterology xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Review article
Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective? Mostafa Ahmed Arafa, Karim Hamda Farhat ⇑ College of Medicine, King Saud University, Riyadh, Saudi Arabia
a r t i c l e
i n f o
Article history: Received 19 January 2017 Accepted 27 May 2017 Available online xxxx Keywords: Colorectal cancer Cost-effectiveness Diagnostic procedures Screening
a b s t r a c t Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. Reduction in mortality rates in some countries worldwide are most likely ascribed to CRC screening and/or improved treatments. We reviewed the most relevant articles which discuss the costeffectiveness of colorectal cancer screening procedures, in particular, the recent ones through the last eight years. The effectiveness of screening estimated by discounted life years gained (LYGs) compared to no screening, differed considerably between the studies. Despite these differences, all studies consistently emphasized that screening for CRC was cost-effective compared with no screening for each of the recognized screening strategies. Newer technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon are less invasive and accurate, however, they are not cost-effective, as their cost was higher than all other established screening strategies. When compliance and adherence to such new techniques are increased more than the established strategies they would be more cost-effective particularly CTC. Ó 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Colorectal cancer (CRC) is one of the main causes of morbidity and mortality throughout the world. It accounts for more than 9% of all cancer incidence and it is the third most common incident cancer worldwide and the fourth most common cause of death. The highest increases in the colorectal cancer incidence are in Asia (Japan, Kuwait) and Eastern Europe (Czech Republic, Slovakia, and Slovenia) [1]. In fact, rates amongst males in the Czech Republic, Slovakia, and Japan have not only surpassed the peak rates witnessed in long-lasting developed countries such as the United States, Canada, and Australia but they continue to increase [2]. The decrease in colorectal cancer incidence in the USA partially mirrors the improvement in discovery and removal of precancerous lesions; whilst the increase in many Asian and Eastern EuroAbbreviations: AAA, abdominal aortic aneurism; CTC, colonography; CS, colonoscopy; CRC, colorectal cancer; CEA, cost-effective analysis; CER, costeffectiveness ratios; FAP, familial polyposis; FOBT, faecal-occult-blood tests; GDP, gross-domestic product; HNPCC, hereditary non-polyposis colon cancer; ICER, incremental cost-effectiveness ratio; LYS, life-year saved; NHS, National health System; OC, optical-colonoscopy; USPSTF, United States Preventive Services Task Force; WTP, willingness to pay. ⇑ Corresponding author at: College of Medicine, King Saud University, P.O Box 76047, Riyadh 11922, Saudi Arabia. E-mail address: [email protected] (K.H. Farhat).
pean countries may reflect variations in risk factors for colorectal cancer that are associated with westernization such as raised obesity and smoking prevalence. In contrast to incidence trends, decreasing CRC mortality rates which have been detected in USA in the last years is most likely ascribed to CRC screening and/or improved treatments [2]. However, mortality rates are still increasing in countries that have more limited resources, including Mexico and Brazil, Romania and Russia in Eastern Europe [1–4]. The incidence of colorectal cancer can be abridged with growing efforts focused on a mass screening of average-risk individuals, 50 years and older [5]. The study conducted by researchers who simulated the 1980 through 2030 US adult population aged 50 years and over using micro simulation modelling, indicated that Increasing CRC screening rates to 80% by 2018 would reduce CRC mortality rates by 19% and incidence rates by 17% during shortterm follow-up and by 22% and 33%, respectively, during extended follow-up [6]. The aim of this study was to review the most relevant articles that discuss the cost-effectiveness of colorectal cancer screening procedures, in particular, the recent ones through the last eight years.
https://doi.org/10.1016/j.ajg.2017.05.011 1687-1979/Ó 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Arafa MA, Farhat KH. Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective? Arab J Gastroenterol (2017), https://doi.org/10.1016/j.ajg.2017.05.011
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M.A. Arafa, K.H. Farhat / Arab Journal of Gastroenterology xxx (2017) xxx–xxx
Who are at increased risk of CRC?
Methods
Many risk factors have been incriminated in the occurrence and increased risk of colorectal cancer, amongst them; physical inactivity, obesity, smoking, a diet that is high in red meats (beef, pork, lamb, or liver) and processed meats (some luncheon meats and hot dogs), heavy alcohol consumption, inflammatory bowel syndrome in addition to family history of CRC. The risk is almost two-folds in those with only one affected first-degree relative and it is even higher if there are more than one relative is affected or if that relative was diagnosed with CRC cancer when they were younger than 45 years [7–10]. American Cancer Society, CDC and U.S preventive services recommended to start screening for both men and women at average risk of developing colorectal cancer at the age of 50, however for people at an increased risk, for example, history of colorectal cancer and/or adenomatous polyp, history of inflammatory bowel syndrome, a family history of a hereditary CRC syndrome such as familial polyposis (FAP), hereditary non-polyposis colon cancer (HNPCC), they should start their screening at the age of 45 or less [11–13].
Medline was searched for articles which discuss the different aspects of CRC screening cost-effectiveness. The search was limited to the last eight years. Most of the studies were conducted in North America, European countries and few in Asia and Australia. The current review was carried out to review the most relevant articles, published in MEDLINE database, and science direct that discuss the cost-effectiveness of colorectal cancer screening procedures, in particular, the recent ones.
Cost-effectiveness analysis Cost-effectiveness analysis is a tool for assessing the gains in health relative to the costs of multiple health interventions. It helps identify neglected chances and opportunities by highlighting interventions that are moderately inexpensive, yet have the potential to decrease the disease burden significantly. It identifies ways to redirect resources and to reveal not only the utility of allotting resources from ineffective to effective interventions, but also the utility of allotting resources from less to more cost-effective interventions [14]. WHO defined a ‘‘cost-effective intervention” as cost per quality adjusted life years (QALY) gained or saved as a result of the intervention which is lower than or equal to three times the per-capita gross-domestic product (GDP) (personal income) in a given country or setting [15]. Model-based cost-effective analysis (CEA) is a tool which can be used to consider the probable impacts of various policy options and medical interventions on forthcoming program welfares and costs. CEA permits estimation of costs per outcome measured in natural units such as life-year saved (LYS) compared to the local willingness to pay (WTP) threshold. It addresses the following questions: How much the intervention costs? What are the costs compared to alternatives? Is it worth the cost? [16,17]
Cost-effectiveness ratios (CER) Two types of CER ratios are described; CER comparing each intervention strategy with the no intervention scenario or the standard of care, and incremental cost-effectiveness ratio (ICER) comparing each strategy with the most effective substitute which may or may not be a ‘‘no intervention” scenario. ICERs are then calculated for strategies which are effective or economically rational, which denotes that no further strategy or a combination of strategies offers more life-years for the same or lower costs [16].
Deciding the balance between costs and benefits Screening may be applied if there is a good balance between costs and benefits, such good balance has no universal definition but when an intervention provides an additional year of life at an incremental cost of $50,000 or less, it is considered acceptable in many industrialized countries [16,17].
Cost-effectiveness of new CRC diagnostic and screening strategies It has been established that CRC screening is cost-effective in comparison with no screening for each of the recognized screening strategies, where CRC screening could save 18,800 lives per year [18,19]. In several studies, almost all screening strategies, except stool DNA showed incremental cost-effectiveness ratios (ICERs) below $20,000/LYG when a comparison is made with no screening [20–27]. There is developing evidence on recent technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon or capsule endoscopy. They are less invasive and accurate, however, several issues should be discussed before applying these procedures for population-based screening programs. The most important is the cost-effectiveness of such procedures, particularly after they have been deemed acceptable by United States Preventive Services Task Force (USPSTF) [13] as an option for CRC screening in 2002 (but not capsule endoscopy). In the last decades, CTC or virtual colonoscopy has emerged as an alternative to conventional colonoscopy for colorectal carcinoma screening, and has recently been adopted by several medical societies [28]. Given the fact that CTC technique is standardized, easy to perform and less invasive than colonoscopy (CS) [20,29], yet, the existing data on the cost-effectiveness of CTC for screening based on mathematical models are conflicting. The current review addressed the results of the recent studies discussing the costeffectiveness of CTC, within the time range used in this review, where different screening strategies were compared: faecaloccult-blood tests (FOBT), CTC, optical-colonoscopy (OC) and flexible sigmoidoscopy. Some models evaluated 5-yearly CTC and others evaluated 10-yearly and 15-yearly CTC. All studies [20,29,30–38] established that CTC is cost-effective compared with no screening. Contradicting results have emerged from two different studies which used ten-year simulation modelling to assess asymptomatic, average-risk population 50–74 years old; the first one was in UK [30] which found that CTC has the potential to bear a cost-effective choice for CRC screening in the UK, National health System (NHS) and may be cost saving compared with the existing program of biennial FOBT depending on the adherence rate and also yielded better health benefits in terms of QALYs and lifeyears. The second study was in France and concluded that CTC is the most effective but not the most cost-effective in contrary to FOB which is the least effective but the most cost-effective [31]. For USA Medicare population, CTC would likely be cost-effective and highly efficacious and decreasing the Medicare expenditure [20,32], where three strategies were found to be highly costeffective compared with no screening, with an incremental costeffectiveness ratio (ICER) of $6088, $1251, and $1104 per lifeyear gained for 5-year CTC, 10-year CTC, and 10-year optical colonoscopy strategies, respectively [20]. Lansdorp-Vogelaar I et al. [38] estimated the threshold costs for which CTC screening would be a cost-effective substitute to colo-
Please cite this article in press as: Arafa MA, Farhat KH. Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective? Arab J Gastroenterol (2017), https://doi.org/10.1016/j.ajg.2017.05.011
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noscopy for CRC screening in the general population. With equal costs ($662), optical colonoscopy dominated CTC screening, for CTC to achieve comparable life-years as colonoscopy screening every 10 years, it should be offered every five years with referral of polyps > or = 6 mm and to be cost-effective as colonoscopy screening, the costs must not surpass $285 or 43% of colonoscopy costs. Whilst, the results of most recent SIGGAR Trials [33] showed no difference between CTC and colonoscopy with regards to detection rate of large polyps and cancers and also their cost; CTC with nonreporting of diminutive lesions was reported to be the most costeffective and safest screening tool evaluated, because of its ability to concurrently screen for both CRC and abdominal aortic aneurism (AAA), providing a high adherence rate [20,34]. Bowel preparation is reported to be one of the main barriers to the uptake of CRC screening [39,40]. A systematic review of patient preference for COL versus CTC displayed that patients preferred CTC, as it needs limited bowel preparations [41]. The Dutch Randomized controlled trial comparing CTC and COL showed that involvement in screening with CTC was significantly better than with COL [42]. Participants in the study of the diagnostic accuracy of laxative-free CTC indicated that such procedure is more comfortable and easier to prepare for, and it was the favourite screening method for 62% of respondents [43]. Referring to such results, CTC was sensitive and accurate in identifying adenomas 10 mm or larger but less for smaller lesions, which suggest a potential role for laxative-free CTC as a substitute screening method. In the same context, the results of the Brazilian study concluded that, patients prefer CTC to colonoscopy and it may be considered as an alternative to diagnostic colonoscopy, in addition there was no statistical relationship between colon distention, quality of bowel preparation (residual fluid) and the patient’s preference or degree of discomfort [44]. The randomized controlled trial of Pickhardt [45] showed that, there was 55% improvement in screening participation with CTC over COL (22% for COL vs 34% for CTC), on the other hand, Schwartz [46] reported that the successful initiation of CTC program didn’t result in a decrease in the number of screening colonoscopies. The USPSTF suggested that CTC could be an important alternative choice in CRC screening for patients who accepted this test and would have otherwise refused other CRC choices [47]. In general, cost-effectiveness of CTC is influenced by the CTC threshold-based reporting of polyps (6 mm threshold for polypectomy is associated with cost reduction), cost, CTC sensitivity for large polyps, natural history of adenoma transition to cancer, abdominal aortic aneurism (AAA) parameters and importantly, adherence [20,33,36–38]. The cost-effectiveness of capsule endoscopy was compared to traditional colonoscopy in one study, which revealed that colonoscopy was more cost-effective when equal adherence was simulated using Markov process, however, when compliance to capsule endoscopy was increased by 30% better than endoscopy or when the strategy of 6 mm threshold of post-capsule polypectomy was taken into account, the cost of capsule endoscopy became less and the effectiveness became more [48]. Yet, colonoscopy is preferred by patients because of its high sensitivity, so no second tests are needed [49]. Though, Colon capsule endoscopy could rise CRC screening adherence rates amongst those who decline screening colonoscopy [49]. Capsule endoscopy was compared to CTC to evaluate the cost-effectiveness and impact on Ontario health budget, where it was found that the additional cost of unnecessary colonoscopies due to false-positive results of capsule endoscopy and additional cost of life years lost for patients with false-negative results would result in additional cost of $26,750 per life-year gained for capsule endoscopy versus CTC [50].
3
Simulation models were used to measure the cost-effectiveness of 3 and 5-yearly Stool DNA screening in comparison to other recommended strategies. In terms of life-years gained, the screening benefit of DNA stool test was lower that of annual hemoccult II testing compared with no screening and the cost was higher than all other established screening strategies, assuming reimbursement at $350 per test. To be cost-effective, DNA stool test would need to cost between $34 and $51 when implemented every 5 years, or between $40 and $60 when implemented every 3 years. If the adherence with 3-yearly stool DNA test reached to 50% better than all other recommended strategies, it would be cost-effective at the current test costs [23]. One of the important limitation of simulation studies, which discuss all relevant cost-effectiveness data, that they assume 100% adherence of using each screening policy, which does not reflect the real clinical adherence rate. In addition, differences in the model structure (e.g. micro-simulation versus Markov analysis) or outcomes considered (e.g. models which examine and compare the effects of 5 years, 10 years and 20 years of screening, respectively) can make comparisons across models difficult. Conclusion A more expensive treatment does not always translate to better health outcomes. There is an agreement between studies that the newly developed screening procedures are not yet cost–effective compared with the established screening options. The studies indicated that adherence to a strategy of screening is a crucial component of saving life years. Although the evidence on costeffectiveness of CTC screening is heterogeneous, the USPSTF recommended CTC as an alternative tool for CRC screening and diagnosis for patients who refuse other established screening tests. It is vital to remember that cost-effective analysis has not accounted for certain costs that should, at least, be considered when appraising a screening program; in particular, the costs of an individual’s time and the costs needed to set up, and sustain a screening program in practice. The new CRC strategies are accurate and less invasive, however when considering such procedures for CRC screening and/or diagnosis, certain important issues should be addressed: The cost, the patients’ preference and the aim of the screening program (detection of adenomas vs. advanced neoplasia). When the cost is decreased, the patients would prefer an easier and less invasive procedures. Funding The project was fully financially supported by King Saud University – Saudi Arabia, through Vice Deanship of Research Chairs. Conflict of interest The authors declare no conflict of interest. Acknowledgement The authors would like to express their thanks and gratitude to King Saud University, Vice Deanship of Research Chairs. References [1] Dušek L, Muzˇík J, Malúšková D, Šnajdrová L. Epidemiology of colorectal cancer: international comparison. Fourth European colorectal cancer days. Berno 2015 – prevention and screening. Available from: [accessed on 01/07/2016].
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[27] Sharaf RN, Ladabaum U. Comparative effectiveness and cost-effectiveness of screening colonoscopy vs. sigmoidoscopy and alternative strategies. Am J Gastroenterol 2013;108(1):120–32. [28] Cummings LC, Cooper GS. Colorectal cancer screening: update for 2011. Semin Oncol 2011;2011(38):483–90. [29] Zauber AG, Knudsen AB, Rutter CM, Lansdorp-Vogelaar I, Savarino JE, van Ballegooijen M, et al. Cost-effectiveness of CT colonography to screen for colorectal cancer. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009. [30] Lee D, Muston D, Sweet A, Cunningham C, Slater A, Lock K. Cost effectiveness of CT colonography for UK NHS colorectal cancer screening of asymptomatic adults aged 60–69 years. Health Econ Health Policy 2010;8(3):141–54. [31] Lucidarme O, Cadi M, Berger G, Taieb J, Poynard T, Grenier P, et al. Costeffectiveness modeling of colorectal cancer: computed tomography colonography vs colonoscopy or fecal occult blood tests. Eur J Radiol 2012;81(7):1413–9. [32] Pyenson B, Pickhardt PJ, Sawhney TG, Berrios M. Medicare cost of colorectal cancer screening: CT colonography vs. optical colonoscopy. Abdom Imaging 2015;40(8):2966–76. [33] Halligan S, Dadswell E, Wooldrage K, Wardle J, von Wagner C, Lilford R, et al. Computed tomographic colonography compared with colonoscopy or barium enema for diagnosis of colorectal cancer in older symptomatic patients: two multicenter randomized trials with economic evaluation (the SIGGAR trials). Health Technol Assess 2015;19(54):1–134. [34] Pickhardt PJ, Hassan C, Laghi A, Zullo A, Kim DH, Morini S. Cost-effectiveness of colorectal cancer screening with computed tomography colonography: the impact of not reporting diminutive lesions. Cancer 2007;109(11):2213–21. [35] Hassan C, Pickhardt PJ. Cost-effectiveness of CT colonography. Radiol Clin North Am 2013;51(1):89–97. [36] Kriza C, Emmert M, Wahlster P, Niederländer C, Kolominsky-Rabas P. An international review of the main cost-effectiveness drivers of virtual colonography versus conventional colonoscopy for colorectal cancer screening: is the tide changing due to adherence? Eur J Radiol 2013;82(11): e629–36. [37] Heresbach D, Chauvin P, Hess-Migliorretti A, Riou F, Grolier J, Josselin JM. Costeffectiveness of colorectal cancer screening with computed tomography colonography according to a polyp size threshold for polypectomy. Eur J Gastroenterol Hepatol 2010;22(6):716–23. [38] Lansdorp-Vogelaar I, van Ballegooijen M, Zauber AG, Boer R, Wilschut J, Habbema JD. At what costs will screening with CT colonography be competitive? A cost-effectiveness approach. Int J Cancer 2009;124(5):1161–8. [39] Beebe TJ, Johnson CD, Stoner SM, Anderson KJ, Limburg PJ. Assessing attitudes toward laxative preparation in colorectal cancer screening and effects on future testing: potential receptivity to computed tomographic colonography. Mayo Cli Proc Mayo Clin 2007;82(6):666–71. [40] Jones RM, Devers KJ, Kuzel AJ, Woolf SH. Patient-reported barriers to colorectal cancer screening: a mixed-methods analysis. Am J Prev Med 2010;38 (5):508–16. [41] Lin OS, Kozarek RA, Gluck M, Jiranek GC, Koch J, Kowdley KV, et al. Preference for colonoscopy versus computerized tomographic colonography: a systematic review and meta-analysis of observational studies. J Gen Intern Med 2012;27 (10):1349–60. [42] Stoop EM, de Haan MC, de Wijkerslooth TR, Bossuyt PM, van Ballegooijen M, Nio CY, et al. Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: a randomised controlled trial. Lancet Oncol 2012;13(1):55–64. [43] Zalis ME, Blake MA, Cai W, Hahn PF, Halpern EF, Kazam IG, et al. Diagnostic accuracy of laxative-free computed tomographic colonography for detection of adenomatous polyps in asymptomatic adults: a prospective evaluation. Ann Intern Med 2012;156(10):692–702. [44] Soares Maia MVA, von Atzingen AC, Tiferes DA, Saad SS, Deak E, Matos D, et al. Patient preferences toward colon cancer screening: a comparison between computed tomography colonography and conventional colonoscopy. Radiol Bras 2012;45(1):24–8. [45] Pickhardt PJ. Randomized controlled trial evaluating participation and yield of colonoscopy versus CT colonography screening. Expert Rev Med Devices 2012;9(2):107–10. [46] Schwartz DC, Dasher KJ, Said A, Gopal DV, Reichelderfer M, Kim DH, et al. Impact of CT colonography screening program on endoscopic colonoscopy in clinical practice. Am J Gastroentol 2008;103(2):346–51. [47] U.S. Preventive Services Task Force. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008;149(9):627–37. [48] Hassan C, Zullo A, Winn S, Morini S. Cost-effectiveness of capsule endoscopy in screening for colorectal cancer. Endoscopy 2008;40(5):414–21. [49] Imaeda A, Bender D, Fraenkel L. 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Please cite this article in press as: Arafa MA, Farhat KH. Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective? Arab J Gastroenterol (2017), https://doi.org/10.1016/j.ajg.2017.05.011
Contents lists available at ScienceDirect
Arab Journal of Gastroenterology journal homepage: www.elsevier.com/locate/ajg
Review article
Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective? Mostafa Ahmed Arafa, Karim Hamda Farhat ⇑ College of Medicine, King Saud University, Riyadh, Saudi Arabia
a r t i c l e
i n f o
Article history: Received 19 January 2017 Accepted 27 May 2017 Available online xxxx Keywords: Colorectal cancer Cost-effectiveness Diagnostic procedures Screening
a b s t r a c t Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. Reduction in mortality rates in some countries worldwide are most likely ascribed to CRC screening and/or improved treatments. We reviewed the most relevant articles which discuss the costeffectiveness of colorectal cancer screening procedures, in particular, the recent ones through the last eight years. The effectiveness of screening estimated by discounted life years gained (LYGs) compared to no screening, differed considerably between the studies. Despite these differences, all studies consistently emphasized that screening for CRC was cost-effective compared with no screening for each of the recognized screening strategies. Newer technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon are less invasive and accurate, however, they are not cost-effective, as their cost was higher than all other established screening strategies. When compliance and adherence to such new techniques are increased more than the established strategies they would be more cost-effective particularly CTC. Ó 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Introduction Colorectal cancer (CRC) is one of the main causes of morbidity and mortality throughout the world. It accounts for more than 9% of all cancer incidence and it is the third most common incident cancer worldwide and the fourth most common cause of death. The highest increases in the colorectal cancer incidence are in Asia (Japan, Kuwait) and Eastern Europe (Czech Republic, Slovakia, and Slovenia) [1]. In fact, rates amongst males in the Czech Republic, Slovakia, and Japan have not only surpassed the peak rates witnessed in long-lasting developed countries such as the United States, Canada, and Australia but they continue to increase [2]. The decrease in colorectal cancer incidence in the USA partially mirrors the improvement in discovery and removal of precancerous lesions; whilst the increase in many Asian and Eastern EuroAbbreviations: AAA, abdominal aortic aneurism; CTC, colonography; CS, colonoscopy; CRC, colorectal cancer; CEA, cost-effective analysis; CER, costeffectiveness ratios; FAP, familial polyposis; FOBT, faecal-occult-blood tests; GDP, gross-domestic product; HNPCC, hereditary non-polyposis colon cancer; ICER, incremental cost-effectiveness ratio; LYS, life-year saved; NHS, National health System; OC, optical-colonoscopy; USPSTF, United States Preventive Services Task Force; WTP, willingness to pay. ⇑ Corresponding author at: College of Medicine, King Saud University, P.O Box 76047, Riyadh 11922, Saudi Arabia. E-mail address: [email protected] (K.H. Farhat).
pean countries may reflect variations in risk factors for colorectal cancer that are associated with westernization such as raised obesity and smoking prevalence. In contrast to incidence trends, decreasing CRC mortality rates which have been detected in USA in the last years is most likely ascribed to CRC screening and/or improved treatments [2]. However, mortality rates are still increasing in countries that have more limited resources, including Mexico and Brazil, Romania and Russia in Eastern Europe [1–4]. The incidence of colorectal cancer can be abridged with growing efforts focused on a mass screening of average-risk individuals, 50 years and older [5]. The study conducted by researchers who simulated the 1980 through 2030 US adult population aged 50 years and over using micro simulation modelling, indicated that Increasing CRC screening rates to 80% by 2018 would reduce CRC mortality rates by 19% and incidence rates by 17% during shortterm follow-up and by 22% and 33%, respectively, during extended follow-up [6]. The aim of this study was to review the most relevant articles that discuss the cost-effectiveness of colorectal cancer screening procedures, in particular, the recent ones through the last eight years.
https://doi.org/10.1016/j.ajg.2017.05.011 1687-1979/Ó 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Arafa MA, Farhat KH. Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective? Arab J Gastroenterol (2017), https://doi.org/10.1016/j.ajg.2017.05.011
2
M.A. Arafa, K.H. Farhat / Arab Journal of Gastroenterology xxx (2017) xxx–xxx
Who are at increased risk of CRC?
Methods
Many risk factors have been incriminated in the occurrence and increased risk of colorectal cancer, amongst them; physical inactivity, obesity, smoking, a diet that is high in red meats (beef, pork, lamb, or liver) and processed meats (some luncheon meats and hot dogs), heavy alcohol consumption, inflammatory bowel syndrome in addition to family history of CRC. The risk is almost two-folds in those with only one affected first-degree relative and it is even higher if there are more than one relative is affected or if that relative was diagnosed with CRC cancer when they were younger than 45 years [7–10]. American Cancer Society, CDC and U.S preventive services recommended to start screening for both men and women at average risk of developing colorectal cancer at the age of 50, however for people at an increased risk, for example, history of colorectal cancer and/or adenomatous polyp, history of inflammatory bowel syndrome, a family history of a hereditary CRC syndrome such as familial polyposis (FAP), hereditary non-polyposis colon cancer (HNPCC), they should start their screening at the age of 45 or less [11–13].
Medline was searched for articles which discuss the different aspects of CRC screening cost-effectiveness. The search was limited to the last eight years. Most of the studies were conducted in North America, European countries and few in Asia and Australia. The current review was carried out to review the most relevant articles, published in MEDLINE database, and science direct that discuss the cost-effectiveness of colorectal cancer screening procedures, in particular, the recent ones.
Cost-effectiveness analysis Cost-effectiveness analysis is a tool for assessing the gains in health relative to the costs of multiple health interventions. It helps identify neglected chances and opportunities by highlighting interventions that are moderately inexpensive, yet have the potential to decrease the disease burden significantly. It identifies ways to redirect resources and to reveal not only the utility of allotting resources from ineffective to effective interventions, but also the utility of allotting resources from less to more cost-effective interventions [14]. WHO defined a ‘‘cost-effective intervention” as cost per quality adjusted life years (QALY) gained or saved as a result of the intervention which is lower than or equal to three times the per-capita gross-domestic product (GDP) (personal income) in a given country or setting [15]. Model-based cost-effective analysis (CEA) is a tool which can be used to consider the probable impacts of various policy options and medical interventions on forthcoming program welfares and costs. CEA permits estimation of costs per outcome measured in natural units such as life-year saved (LYS) compared to the local willingness to pay (WTP) threshold. It addresses the following questions: How much the intervention costs? What are the costs compared to alternatives? Is it worth the cost? [16,17]
Cost-effectiveness ratios (CER) Two types of CER ratios are described; CER comparing each intervention strategy with the no intervention scenario or the standard of care, and incremental cost-effectiveness ratio (ICER) comparing each strategy with the most effective substitute which may or may not be a ‘‘no intervention” scenario. ICERs are then calculated for strategies which are effective or economically rational, which denotes that no further strategy or a combination of strategies offers more life-years for the same or lower costs [16].
Deciding the balance between costs and benefits Screening may be applied if there is a good balance between costs and benefits, such good balance has no universal definition but when an intervention provides an additional year of life at an incremental cost of $50,000 or less, it is considered acceptable in many industrialized countries [16,17].
Cost-effectiveness of new CRC diagnostic and screening strategies It has been established that CRC screening is cost-effective in comparison with no screening for each of the recognized screening strategies, where CRC screening could save 18,800 lives per year [18,19]. In several studies, almost all screening strategies, except stool DNA showed incremental cost-effectiveness ratios (ICERs) below $20,000/LYG when a comparison is made with no screening [20–27]. There is developing evidence on recent technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon or capsule endoscopy. They are less invasive and accurate, however, several issues should be discussed before applying these procedures for population-based screening programs. The most important is the cost-effectiveness of such procedures, particularly after they have been deemed acceptable by United States Preventive Services Task Force (USPSTF) [13] as an option for CRC screening in 2002 (but not capsule endoscopy). In the last decades, CTC or virtual colonoscopy has emerged as an alternative to conventional colonoscopy for colorectal carcinoma screening, and has recently been adopted by several medical societies [28]. Given the fact that CTC technique is standardized, easy to perform and less invasive than colonoscopy (CS) [20,29], yet, the existing data on the cost-effectiveness of CTC for screening based on mathematical models are conflicting. The current review addressed the results of the recent studies discussing the costeffectiveness of CTC, within the time range used in this review, where different screening strategies were compared: faecaloccult-blood tests (FOBT), CTC, optical-colonoscopy (OC) and flexible sigmoidoscopy. Some models evaluated 5-yearly CTC and others evaluated 10-yearly and 15-yearly CTC. All studies [20,29,30–38] established that CTC is cost-effective compared with no screening. Contradicting results have emerged from two different studies which used ten-year simulation modelling to assess asymptomatic, average-risk population 50–74 years old; the first one was in UK [30] which found that CTC has the potential to bear a cost-effective choice for CRC screening in the UK, National health System (NHS) and may be cost saving compared with the existing program of biennial FOBT depending on the adherence rate and also yielded better health benefits in terms of QALYs and lifeyears. The second study was in France and concluded that CTC is the most effective but not the most cost-effective in contrary to FOB which is the least effective but the most cost-effective [31]. For USA Medicare population, CTC would likely be cost-effective and highly efficacious and decreasing the Medicare expenditure [20,32], where three strategies were found to be highly costeffective compared with no screening, with an incremental costeffectiveness ratio (ICER) of $6088, $1251, and $1104 per lifeyear gained for 5-year CTC, 10-year CTC, and 10-year optical colonoscopy strategies, respectively [20]. Lansdorp-Vogelaar I et al. [38] estimated the threshold costs for which CTC screening would be a cost-effective substitute to colo-
Please cite this article in press as: Arafa MA, Farhat KH. Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective? Arab J Gastroenterol (2017), https://doi.org/10.1016/j.ajg.2017.05.011
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noscopy for CRC screening in the general population. With equal costs ($662), optical colonoscopy dominated CTC screening, for CTC to achieve comparable life-years as colonoscopy screening every 10 years, it should be offered every five years with referral of polyps > or = 6 mm and to be cost-effective as colonoscopy screening, the costs must not surpass $285 or 43% of colonoscopy costs. Whilst, the results of most recent SIGGAR Trials [33] showed no difference between CTC and colonoscopy with regards to detection rate of large polyps and cancers and also their cost; CTC with nonreporting of diminutive lesions was reported to be the most costeffective and safest screening tool evaluated, because of its ability to concurrently screen for both CRC and abdominal aortic aneurism (AAA), providing a high adherence rate [20,34]. Bowel preparation is reported to be one of the main barriers to the uptake of CRC screening [39,40]. A systematic review of patient preference for COL versus CTC displayed that patients preferred CTC, as it needs limited bowel preparations [41]. The Dutch Randomized controlled trial comparing CTC and COL showed that involvement in screening with CTC was significantly better than with COL [42]. Participants in the study of the diagnostic accuracy of laxative-free CTC indicated that such procedure is more comfortable and easier to prepare for, and it was the favourite screening method for 62% of respondents [43]. Referring to such results, CTC was sensitive and accurate in identifying adenomas 10 mm or larger but less for smaller lesions, which suggest a potential role for laxative-free CTC as a substitute screening method. In the same context, the results of the Brazilian study concluded that, patients prefer CTC to colonoscopy and it may be considered as an alternative to diagnostic colonoscopy, in addition there was no statistical relationship between colon distention, quality of bowel preparation (residual fluid) and the patient’s preference or degree of discomfort [44]. The randomized controlled trial of Pickhardt [45] showed that, there was 55% improvement in screening participation with CTC over COL (22% for COL vs 34% for CTC), on the other hand, Schwartz [46] reported that the successful initiation of CTC program didn’t result in a decrease in the number of screening colonoscopies. The USPSTF suggested that CTC could be an important alternative choice in CRC screening for patients who accepted this test and would have otherwise refused other CRC choices [47]. In general, cost-effectiveness of CTC is influenced by the CTC threshold-based reporting of polyps (6 mm threshold for polypectomy is associated with cost reduction), cost, CTC sensitivity for large polyps, natural history of adenoma transition to cancer, abdominal aortic aneurism (AAA) parameters and importantly, adherence [20,33,36–38]. The cost-effectiveness of capsule endoscopy was compared to traditional colonoscopy in one study, which revealed that colonoscopy was more cost-effective when equal adherence was simulated using Markov process, however, when compliance to capsule endoscopy was increased by 30% better than endoscopy or when the strategy of 6 mm threshold of post-capsule polypectomy was taken into account, the cost of capsule endoscopy became less and the effectiveness became more [48]. Yet, colonoscopy is preferred by patients because of its high sensitivity, so no second tests are needed [49]. Though, Colon capsule endoscopy could rise CRC screening adherence rates amongst those who decline screening colonoscopy [49]. Capsule endoscopy was compared to CTC to evaluate the cost-effectiveness and impact on Ontario health budget, where it was found that the additional cost of unnecessary colonoscopies due to false-positive results of capsule endoscopy and additional cost of life years lost for patients with false-negative results would result in additional cost of $26,750 per life-year gained for capsule endoscopy versus CTC [50].
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Simulation models were used to measure the cost-effectiveness of 3 and 5-yearly Stool DNA screening in comparison to other recommended strategies. In terms of life-years gained, the screening benefit of DNA stool test was lower that of annual hemoccult II testing compared with no screening and the cost was higher than all other established screening strategies, assuming reimbursement at $350 per test. To be cost-effective, DNA stool test would need to cost between $34 and $51 when implemented every 5 years, or between $40 and $60 when implemented every 3 years. If the adherence with 3-yearly stool DNA test reached to 50% better than all other recommended strategies, it would be cost-effective at the current test costs [23]. One of the important limitation of simulation studies, which discuss all relevant cost-effectiveness data, that they assume 100% adherence of using each screening policy, which does not reflect the real clinical adherence rate. In addition, differences in the model structure (e.g. micro-simulation versus Markov analysis) or outcomes considered (e.g. models which examine and compare the effects of 5 years, 10 years and 20 years of screening, respectively) can make comparisons across models difficult. Conclusion A more expensive treatment does not always translate to better health outcomes. There is an agreement between studies that the newly developed screening procedures are not yet cost–effective compared with the established screening options. The studies indicated that adherence to a strategy of screening is a crucial component of saving life years. Although the evidence on costeffectiveness of CTC screening is heterogeneous, the USPSTF recommended CTC as an alternative tool for CRC screening and diagnosis for patients who refuse other established screening tests. It is vital to remember that cost-effective analysis has not accounted for certain costs that should, at least, be considered when appraising a screening program; in particular, the costs of an individual’s time and the costs needed to set up, and sustain a screening program in practice. The new CRC strategies are accurate and less invasive, however when considering such procedures for CRC screening and/or diagnosis, certain important issues should be addressed: The cost, the patients’ preference and the aim of the screening program (detection of adenomas vs. advanced neoplasia). When the cost is decreased, the patients would prefer an easier and less invasive procedures. Funding The project was fully financially supported by King Saud University – Saudi Arabia, through Vice Deanship of Research Chairs. Conflict of interest The authors declare no conflict of interest. Acknowledgement The authors would like to express their thanks and gratitude to King Saud University, Vice Deanship of Research Chairs. References [1] Dušek L, Muzˇík J, Malúšková D, Šnajdrová L. Epidemiology of colorectal cancer: international comparison. Fourth European colorectal cancer days. Berno 2015 – prevention and screening. Available from:
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[2] Colorectal Cancer Statistics. World cancer research fund International. Available from:
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Please cite this article in press as: Arafa MA, Farhat KH. Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective? Arab J Gastroenterol (2017), https://doi.org/10.1016/j.ajg.2017.05.011