Endosc Int Open 2014; 02(02): E96-E104
DOI: 10.1055/s-0034-1377182
Original article
© Georg Thieme Verlag KG Stuttgart · New York

Cost-effectiveness of colorectal cancer screening in Germany: current endoscopic and fecal testing strategies versus plasma methylated Septin 9 DNA[1]

Uri Ladabaum
1   Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
,
Lourdes Alvarez-Osorio
2   Boston Healthcare Associates International GmbH, Berlin, Germany
,
Thomas Rösch
3   Charité Medical University of Berlin, Virchow Clinic Campus, Berlin, Germany
,
Bernd Brueggenjuergen
2   Boston Healthcare Associates International GmbH, Berlin, Germany
4   Steinbeis University, Berlin, Germany
› Author Affiliations
Further Information

Publication History

submitted 28 February 2014

accepted 17 March 2014

Publication Date:
06 June 2014 (online)

Background and study aims: Colorectal cancer (CRC) screening strategies in Germany include guaiac-based fecal occult blood testing (gFOBT) starting at age 50 and a switch to colonoscopy at age 55 or continued gFOBT testing, but screening utilization is limited. Blood-based biomarkers, such as methylated Septin 9 DNA ( m SEPT9), may improve screening rates. We performed a cost-effectiveness analysis of current and emerging CRC screening strategies in Germany.

Methods: Using a validated Markov model, we compared annual gFOBT for ages 50 through 54 followed by biennial testing until age 75 (FOBT) or by colonoscopy at ages 55 and 65 (FOBT/COLO 55,65), substitution of fecal immunochemical testing (FIT) for gFOBT (FIT, FIT/COLO 55,65), and annual or biennial plasma m SEPT9 testing. We also considered persons who utilize only colonoscopy and varied age at colonoscopy utilization.

Results: The current strategies were more effective and less costly than no screening. FIT was more effective and less costly than m SEPT9 testing. FIT/COLO 55,65 cost €12 200 per quality-adjusted life-years gained in comparison with FIT. m SEPT9-based screening was cost-effective in comparison with no screening but was dominated by other cost-saving strategies. Differential screening utilization and adherence greatly affected incremental results between strategies. In probabilistic analyses, FIT was preferred in 49 % and FIT/COLO 55,65 in 47 % of iterations.

Conclusion: Currently available CRC screening strategies in Germany, including hybrid fecal testing/colonoscopy, are likely to be cost-saving. Current strategies appear superior to m SEPT9-based screening. The impact of blood-based biomarkers is likely to depend on utilization and adherence as much as on test performance characteristics and cost.

1 Contributorship: conception and design, U. L.; analysis and interpretation of data, U. L., L. A., B. B.; drafting the article or revising it critically for important intellectual content, U. L., L. A., T. R., B. B.; final approval of the version to be published, U. L., L. A., T. R., B. B.
Funding sources: unrestricted research grant from Abbott Molecular, Des Plaines, IL, USA. The sponsor had no role in the conduct of this study. No future research funding by the sponsor is pending for any author.


Appendix

 
  • References

  • 1 Benson VS, Patnick J, Davies AK et al. Colorectal cancer screening: a comparison of 35 initiatives in 17 countries. Int J Cancer 2008; 122: 1357-1367
  • 2 Krebs in Deutschland 2005/2006. Berlin: Häufigkeiten und Trends; 2010
  • 3 Mandel JS, Bond JH, Church TR et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328: 1365-1371
  • 4 Mandel JS, Church TR, Bond JH et al. The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 2000; 343: 1603-1607
  • 5 Hardcastle JD, Chamberlain JO, Robinson MH et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348: 1472-1477
  • 6 Kronborg O, Fenger C, Olsen J et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996; 348: 1467-1471
  • 7 Atkin WS, Edwards R, Kralj-Hans I et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 2010; 375: 1624-1633
  • 8 Segnan N, Armaroli P, Bonelli L et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial – SCORE. J Natl Cancer Inst 2011; 103: 1310-1322
  • 9 Schoen RE, Pinsky PF, Weissfeld JL et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 2012; 366: 2345-2357
  • 10 Gatta G, Capocaccia R, Sant M et al. Understanding variations in survival for colorectal cancer in Europe: a EUROCARE high resolution study. Gut 2000; 47: 533-538
  • 11 Becker N. Epidemiological aspects of cancer screening in Germany. J Cancer Res Clin Oncol 2003; 129: 691-702
  • 12 Pox C, Aretz S, Bischoff SC et al. [S3-guideline colorectal cancer version 1.0]. Z Gastroenterol 2013; 51: 753-854
  • 13 German Guideline of Federal Board of Medical Insurances and Representatives of Private Practice and Hospital Physicians. Richtlinie des Gemeinsamen Bundesausschusses über die Früherkennung von Krebserkrankungen. http://www.g-ba.de [Accessed 17 January 2012]
  • 14 Robert Koch Institut. Beiträge zur Gesundheitsberichterstattung. 20 Jahre nach dem Fall der Mauer: Wie hat sich die Gesundheit in Deutschland entwickelt. Kapitel 5. Prävention und Gesundheitsförderung. S 178. November 2009. http://www.gbe-bund.de [Accessed 17 January 2012]
  • 15 Wuppermann D, Wuppermann U, Riemann JF. [Actual state of knowledge of the German population about the early detection of colorectal cancer – a study by the „Stiftung LebensBlicke“ in cooperation with the Institute for Demoscopy in Allensbach]. Z Gastroenterol 2009; 47: 1132-1136
  • 16 Creeden J, Junker F, Vogel-Ziebolz S et al. Serum tests for colorectal cancer screening. Mol Diagn Ther 2011; 15: 129-141
  • 17 deVos T, Tetzner R, Model F et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem 2009; 55: 1337-1346
  • 18 Grutzmann R, Molnar B, Pilarsky C et al. Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay. PloS ONE 2008; 3: e3759
  • 19 Lofton-Day C, Model F, Devos T et al. DNA methylation biomarkers for blood-based colorectal cancer screening. Clin Chem 2008; 54: 414-423
  • 20 Church TR, Wandell M, Lofton-Day C et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectac cancer. Gut 2014; 63: 317-325
  • 21 Ladabaum U, Song K. Projected national impact of colorectal cancer screening on clinical and economic outcomes and health services demand. Gastroenterology 2005; 129: 1151-1162
  • 22 Sharaf RN, Ladabaum U. Comparative effectiveness and cost-effectiveness of screening colonoscopy vs. sigmoidoscopy and alternative strategies. Am J Gastroenterol 2013; 108: 120-132
  • 23 Munich Cancer Registry. http://www.tumorregister-muenchen.de [Accessed 17 January 2012]
  • 24 Statistisches Bundesamt Deutschland. Bevölkerung, Geburten und Sterbefälle, Tabellen. April 2010. http://www.destatis.de/jetspeed/portal/cms/Sites/destatis/Internet/DE/Navigation/Statistiken/Bevoelkerung/GeburtenSterbefaelle/GeburtenSterbefaelle.psml [Accessed 17 January 2012]
  • 25 Glaeske G, Schicktanz C. BARMER GEK Arzneimittel-Report 2010. http://www.barmer-gek.de/barmer/web/Portale/Presseportal/Subportal/Infothek/Studien-und-Reports/Arzneimittelreport-2010/Arzneimittel-Report-lang,property=Data.pdf [Accessed 17 January 2012]
  • 26 Glaeske G, Höffken K, Ludwig WD et al. Sicherstellung einer effizienten Arzneimittelversorgung in der Onkologie. Gutachten im Auftrag des Bundesministeriums für Gesundheit. Bremen: August 2010. http://www.bmg.bund.de/fileadmin/redaktion/pdf_allgemein/Gutachten_Sicherstellung_einer_effizienten_Arzneimittelversorgung_in_der_Onkologie.pdf [Accessed 17 January 2012]
  • 27 Goerner M, Riemer-Hommel P. Economic impact of alternative adjuvant chemotherapy regimens for stage III colon cancer. Onkologie 2009; 32: 647-652
  • 28 EBM: Office-based doctor remuneration. KVB: National Association of Statutory Health Insurance Physicians and the regional Associations of Statutory Health Insurance Physicians (Kassenärtzliche Bundesvereinigung). March 2011. http://www.kbv.de [Accessed 17 January 2012]
  • 29 InEK – Institute for the Hospital Remuneration System (Institut für das Entgeltsystem im Krankenhaus). German DRGs. March 2011. http://www.g-drg.de [Accessed 17 January 2012]
  • 30 Hundt S, Haug U, Brenner H. Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Ann Intern Med 2009; 150: 162-169
  • 31 Whitlock EP, Lin JS, Liles E et al. Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2008; 149: 638-658
  • 32 Zauber AG, Lansdorp-Vogelaar I, Wilschut J et al. Technology Assessment: Cost-Effectiveness of DNA Stool Testing to Screen for Colorectal Cancer. Report to AHRQ and CMS from the Cancer Intervention and Surveillance Modeling Network (CISNET) for MISCAN and SimCRC Models 2007.. http://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id52TA.pdf [Accessed 3 May 2014]
  • 33 Levin B, Lieberman DA, McFarland B et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology 2008; 134: 1570-1595
  • 34 Song K, Fendrick AM, Ladabaum U. Fecal DNA testing compared to conventional colorectal cancer ccreening methods: a decision analysis. Gastroenterology 2004; 126: 1270-1279
  • 35 Siegel JE, Weinstein MC, Russell LB et al. Recommendations for reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in Health and Medicine. JAMA 1996; 276: 1339-1341
  • 36 Weinstein MC, Siegel JE, Gold MR et al. Recommendations of the Panel on Cost-effectiveness in Health and Medicine. JAMA 1996; 276: 1253-1258
  • 37 Lipscomb J, Weinstein MC, Torrance GW. Time preference. In: Gold MR, Siegel JE, Russell LB, et al., eds. Cost-effectiveness in health and medicine. New York, NY: Oxford University Press; 1996: 214-235
  • 38 Briggs A, Claxton K, Sculpher M. Making decision models probabilistic. In: Decision modelling for health economic evaluation. Cambridge, MA: Oxford University Press; 2006: 77-120
  • 39 Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008; 149: 627-637
  • 40 Ladabaum U, Allen J, Wandell M et al. Colorectal cancer screening with blood-based biomarkers: cost-effectiveness of methylated septin 9 DNA versus current strategies. Cancer Epidemiol Biomarkers Prev 2013; 22: 1567-1576
  • 41 van Roon AH, Goede SL, van Ballegooijen M et al. Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening. Gut 2013; 62: 409-415