Il razionale dello screening del cancro del colon-retto

1. Il razionale dello screening del cancro del colon-retto Prof. Dario Sorrentino Cattedra di Gastroenterologia Università di Udine

2. Caratteristiche fondamentali dello screening per neoplasia nella popolazione generale • Malattia frequente • Preceduta da una lesione preneoplastica asportabile in modo curativo • Che insorge su organo/tessuto “accessibile” Chair of Gastroenterology, University of Udine

3. Caratteristiche fondamentali dello screening per neoplasia nella popolazione generale • Malattia frequente • Preceduta da una lesione preneoplastica asportabile in modo curativo • Che insorge su organo/tessuto “accessibile” Chair of Gastroenterology, University of Udine

4. PESO SOCIO-ECONOMICO DEL CANCRO DEL COLON • Rischio di malattia 6% • Rischio di morte 3% ITALIA 30.000 nuovi casi per anno 15.000 morti per anno USA 152.000 nuovi casi per anno 57.000 morti per anno Chair of Gastroenterology, University of Udine

5. CRC: incidence and mortality worldwide Cases ASR Mortality Males World 498754 19.11 254816 More developed countries 318694 37.30 152178Less developed countries 180059 9.91 102640 Females World 445963 14.44 237595More developed countries 291897 25.37 149470Less developed countries 154064 7.8 88121 (51%) (48%) (56%) (53%) (51%) (57%) Chair of Gastroenterology, University of Udine

6. In Europe, in the 2000’s: CRC cases: 304687 Lung cancer cases: 301090 Increasing incidence since 1970 Unchanged mortality since 1985 In US: Decreasing incidence since 1985 Decreasing mortality since 1974 Chair of Gastroenterology, University of Udine

7. CRC incidence (x100000/year) 2004: males Chair of Gastroenterology, University of Udine

8. Caratteristiche fondamentali dello screening per neoplasia nella popolazione generale • Malattia frequente • Preceduta da una lesione preneoplastica asportabile in modo curativo • Che insorge su organo/tessuto “accessibile” Chair of Gastroenterology, University of Udine

9. TRE TIPI DI CANCRO DEL COLON-RETTO • SPORADICO • CHE INSORGE SU IBD • EREDITARIO Chair of Gastroenterology, University of Udine

10. Il cancro sporadico origina dal polipo adenomatoso Chair of Gastroenterology, University of Udine

11. STORIA NATURALE SEQUENZA ADENOMA-CARCINOMA Chair of Gastroenterology, University of Udine

12. STORIA NATURALE SEQUENZA ADENOMA-CARCINOMA COME LA CONOSCIAMO? Chair of Gastroenterology, University of Udine

13. Epidemiologia della poliposi e del cancro del colon Sleisenger & Fordtran 1986 Chair of Gastroenterology, University of Udine

14. 2006; 355:1912 Fu K, Sano Y Chair of Gastroenterology, University of Udine

15. EVENTI DELLA CARCINOGENESI COLORETTALE MODELLO DI VOGELSTEIN Chair of Gastroenterology, University of Udine

16. Identification of tumorigenic breast cancer cells Al Hajji et al PNAS 2003;100 3983 Chair of Gastroenterology, University of Udine

17. Chair of Gastroenterology, University of Udine

18. Maintenance of normal stem cell: Wnt pathway • Adenomatous polyposis coli: tumor suppressor gene mutated in: • FAP syndrome AND • Vast majority of sporadic colon adenomas and adenocarcinomas Nature 2006 Beachy et al NATURE VOL 432 18 NOVEMBER 2004 Chair of Gastroenterology, University of Udine

19. Wnt pathway in colorectal cancer Accumulation of β-catenin in adenoma inside a villus of the small intestine and in a small aberrant crypt focus in the colon of a min (multiple intestinal neoplasia – APC mutant) mouse. Science 2005 Radtke and Clevers SCIENCE 25 MARCH 2005 Chair of Gastroenterology, University of Udine

20. Caratteristiche fondamentali dello screening per neoplasia nella popolazione generale • Malattia frequente • Preceduta da una lesione preneoplastica asportabile in modo curativo • Che insorge su organo/tessuto “accessibile” Chair of Gastroenterology, University of Udine

21. RESEZIONE ENDOSCOPICA Courtesy Gastrolab Chair of Gastroenterology, University of Udine

22. The National Polyp Study Winawer SJ, Zauber AG, Ho MN, O’Brien MJ, Gottlieb LS, Sternberg SS, Waye JD, Schapiro M, Bond JH, Panish JF, et al. National Polyp Study Workgroup. Prevention of Colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993;329:1977-81. • Winawer SJ, Zauber AG, O’Brien MJ, et al. The National Polyp Study • Workgroup: design, methods and characteristics of patients with • newly diagnosed polyps. Cancer 1992;70:1236-45. • Winawer SJ, Zauber AG, O’Brien MJ, et al. National Polyp study Workgroup: • randomized comparison of surveillance intervals after colonoscopic • removal of newly diagnosed adenomatous polyps. N. Engl J • Med 1993;328:901-6. • Winawer SJ, Fletcher RH, Miller L, et al. Colorectal cancer screening: • clinical guidelines and rationale. Gastroenterology 1997;112:594-642. • Winawer SJ, Fletcher RH, Rex D, et al. Colorectal cancer screening and • surveillance: clinical guidelines and rationaledupdate based on new • evidence. Gastroenterology 2003;124:544-60. • Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy • surveillance and polypectomy: a consensus update by the U.S. • Multi-Society Task Force on colorectal cancer and the American • Cancer Society. Gastroenterology 2006;130:1872-85. • Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy • surveillance and polypectomy: a consensus update by the U.S. Multi- • Society Task Force on colorectal cancer and the American Cancer Society. • CA Cancer J Clin 2006;56:143-59. >90% reduction in CRC Chair of Gastroenterology, University of Udine

23. Caratteristiche fondamentali dello screening per neoplasia nella popolazione generale • Malattia frequente • Preceduta da una lesione preneoplastica asportabile in modo curativo • Che insorge su organo/tessuto “accessibile” Chair of Gastroenterology, University of Udine

24. La colonscopia ottica Courtesy Gastrolab Chair of Gastroenterology, University of Udine

25. Il razionale dello screening del cancro del colon-retto Quale screening? Chair of Gastroenterology, University of Udine

26. Tests disponibili per lo screening CRC 1. SOF annuale 2. Sigmoidoscopia ogni 5 anni 3. SOF + sigmoidoscopia annualmente e ogni 5 anni 4. Colonoscopia ogni 10 anni 6. Nuove opzioni Chair of Gastroenterology, University of Udine

27. TESTS FOR DIAGNOSIS OF CRC Colonoscopy gold standard Chair of Gastroenterology, University of Udine

28. American Gastroenterological AssociationColorectal cancer screening and surveillance: Clinical guidelines and rationale—Update based on new evidence – Gastroenterology 2003; 124: 544 • Men and women at average risk should be offered screening with one of several options beginning at age 50 years. • The rationale for presenting multiple options is that no single test is of unequivocal superiority and that giving patients a choice allows them to apply personal preferences and may increase the likelihood that screening will occur. • The strategies are not equal with regard to evidence of effectiveness, magnitude of effectiveness, risk, or up-front costs. • Reviewing the rationale section for each screening test will provide clinicians with information that they can use in presenting the relative effectiveness of each test to patients. Chair of Gastroenterology, University of Udine

29. AGA proposed algorithm for CRC screening Chair of Gastroenterology, University of Udine

30. Chair of Gastroenterology, University of Udine

31. Recommended CRC screening tests in different countries Chair of Gastroenterology, University of Udine

32. Il razionale dello screening del cancro del colon-retto In Italia? Chair of Gastroenterology, University of Udine

33. Sorrentino D, Paduano R, Bernardis V, Piccolo A, Bartoli E. Colorectal cancer screening in Italy: feasibility and cost-effectiveness in a model area. Eur J Gastroenterol Hepatol. 1999 Jun;11(6):655-60. OBJECTIVE: To evaluate the feasibility and cost-effectiveness of screening programmes for colorectal cancer in Italy. DESIGN; We compared five types of programmes: annual faecal occult blood testing, sigmoidoscopy (every 5 years), faecal occult blood testing plus sigmoidoscopy (every 1 and 5 years), colonoscopy (every 10 years) (all in the age group 55-69 years, last examination at 70 years) and 'filter' colonoscopy. The latter had to be performed in persons at 50 years of age and repeated every 10 years until the age of 70. Costs for the tests and colon cancer care were paid by the Regional Health Office to the hospitals performing the procedures/treatments. SETTING: Data were applied to a small model area in northern Italy (Gemona, 80,000 inhabitants) with well-known demographic (age distribution) and epidemiological (colon cancer incidence) features. RESULTS: All-inclusive 10-year costs per screenee and per death prevented (in US dollars) were: 965 and 77,200 for faecal occult blood testing; 436 and 15,500 for sigmoidoscopy; 1521 and 35,000 for sigmoidoscopy plus faecal occult blood testing; 510 and 15,100 for colonoscopy; 510 and 14,000 for 'filter' colonoscopy. With 'filter' colonoscopy the programme required 870 colonoscopies per year, while with colonoscopy 13,700 colonoscopies were needed at time zero. CONCLUSIONS: In Italy, screening programmes based on sigmoidoscopy/colonoscopy are more cost effective than those based on faecal occult blood testing. 'Filter' colonoscopy at age 50 appears superior to the other types of endoscopy-based screening programmes because it utilizes, at any point in time, a much smaller fraction of available resources. Chair of Gastroenterology, University of Udine

34. COLORECTAL CANCER SCREENING IN ITALY: FEASIBILITY AND COST-EFFECTIVENESS IN A MODEL AREA RESULTS Chair of Gastroenterology, University of Udine

35. COLORECTAL CANCER SCREENING IN ITALY: FEASIBILITY AND COST-EFFECTIVENESS IN A MODEL AREA RESULTS Costs include administration of the test plus all the procedures requested by the result of the test itself Chair of Gastroenterology, University of Udine

36. COLORECTAL CANCER SCREENING IN ITALY: FEASIBILITY AND COST-EFFECTIVENESS IN A MODEL AREA RESULTS Costs per death prevented: costs of a given screening program divided the number of lives saved by that program Chair of Gastroenterology, University of Udine

37. COLORECTAL CANCER SCREENING IN ITALY: FEASIBILITY AND COST-EFFECTIVENESS IN A MODEL AREA FEASIBILITY • The screening plans based on sigmoidoscopy or on colonoscopy require 13700 procedures at time 0 and 18700 every 5 or 10 years. • With "filter" colonoscopy the program requires 872 colonoscopies per year. Chair of Gastroenterology, University of Udine

38. C. Hassan, A. Zullo, A. Laghi, I. Reitano, F. Taggi, P. Cerro, F. Iafrate, M. Giustini, S. Winn and S. Morini Colon cancer prevention in Italy: Cost-effectiveness analysis with CT colonography and endoscopy Dig Liver Dis. 2007;39:242-50 To compare the efficacy and cost-effectiveness of CTC screening in a simulated Italian population with those of colonoscopy and flexible sigmoidoscopy (FS). Methods The cost-effectiveness of different screening strategies was compared using a Markov process computer model, in which in a hypothetical population of 100 000 50 year-olds were investigated by CTC, colonoscopy or FS every decade. Outcomes were projected to the Italian national level. Results CRC incidence reduction was calculated at 40.9%, 38.2%, and 31.8% with colonoscopy, CTC and FS, respectively. As compared to no screening, all screening programs were shown to be cost-saving, allowing a saving of 11€, 17€, and 48€ per person with colonoscopy, FS and CTC, respectively. FS appeared to be less cost-effective than CTC, whilst colonoscopy appeared to be an expensive option as compared to CTC. Undiscounted national expenditure was calculated to be €1042489512, €1093268285, and €1198783428 for FS, CTC and colonoscopy, respectively, as compared to €695818078 without screening. Conclusion CRC screening is cost-saving in Italy, irrespective of the technique applied. CTC appeared to be more cost-effective than FS, and it may also become a valid alternative to colonoscopy. Chair of Gastroenterology, University of Udine

39. Il razionale dello screening del cancro del colon-retto Dove siamo in Italia Chair of Gastroenterology, University of Udine

40. N.of CRC deaths. Males, Italy 2009 ??? Debate over CRC screening Milestones: Cervical K screening Adenoma-K sequence known First FOBT screening study Minnesota study First colonscopy screening study Chair of Gastroenterology, University of Udine

41. Il razionale dello screening del cancro del colon-retto Altrove… Chair of Gastroenterology, University of Udine

42. Chair of Gastroenterology, University of Udine

43. Chair of Gastroenterology, University of Udine

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46. N.of CRC deaths. Males, US Chair of Gastroenterology, University of Udine

47. Nei Paesi Occidentali Benchè la compliance rimane un ostacolo è difficile al giorno d’oggi giustificare l’assenza di uno screening per CRC nella popolazione generale. Chair of Gastroenterology, University of Udine