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Mediterranean Task Force for Cancer Control (MTCC)

Mediterranean Task Force for Cancer Control (MTCC). AIMS: To unify efforts to eliminate suffering and reduce mortality of cancer through decreasing incidence of adv. disease. Croatia. Cyprus. Algeria. Albania. Egypt. France. Greece. Italy. Jordan. Lebanon. Lybia. Macedonia. Malta.

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Mediterranean Task Force for Cancer Control (MTCC)

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  1. Mediterranean Task Force for Cancer Control (MTCC) AIMS: To unify efforts to eliminate suffering and reduce mortality of cancer through decreasing incidence of adv. disease Croatia Cyprus Algeria Albania Egypt France Greece Italy Jordan Lebanon Lybia Macedonia Malta Morocco Palestine Portugal Syria Slovenia Spain Tunisia Turkey

  2. How screening is crucial in ensuring better cure and improved survival Massimo CRESPI National Cancer Institute “Regina Elena”, Roma - Italy

  3. CRC Incidence and Mortality in “Less” and “More” Developed Countries In brutal figures … Globocan 2002

  4. COLON cancer Incidence and Mortality in Mediterranean area

  5. Terminology Prevalence Number of subjects diagnosed with a disease (CRC) still alive after x years (or months) Survival Time interval between diagnosis and death. Actuarial survival takes into consideration deaths by causes different from the index disease. It’s considered like an ultimate parameter of efficiency of the Health System (timely diagnosis, stage of disease, level of treatment and post-treatment care, etc.)

  6. Prevalence at 5y of CRC patients (Globocan 2002)

  7. 5y survival of CRC fromCancer Registries England (Not EU) (Not EU) EPICENTRO.ISS.IT EUROCARE.IT Scotland Eurocare-3 study Annals of Oncology 2003 (Suppl. 5) vol. 14 (Not EU) Wales

  8. Summary of action with level II or III of evidence Energy intake Physical activity Dietary fat Fresh fruit and vegetable Fiber Calcium Selenium Anti-oxidant vitamines Anti-inflammatory drugs SCREENING Possible actions for CRC Prevention Level II: Obtained from at least one properly designed RCT Level III: Obtained from a control trial without randomisation, “ “ cohort or case-control analytic studies, “ “ multiple time-series with/without the intervention

  9. . . Mass screening protocol under Health authorities selected population target covers all degrees of risk evaluation required entry test (FOBTs / CTcolonography?) + 2nd level test (Colonoscopy) or Colonoscopy as entry test when feasible and accepted . . .

  10. Opportunistic screening In volunteers subjects using primary diagnostic test as in screening Low risk less compliant than high risk Disadvantage: end-points not evaluable Ensures further coverage of the population . . .

  11. Expected effects of screening Expected effects of screening Reduction in mortality but lead time and delay time bias Improved survival down-staging Reduction in incidence in some cases like cervix and colon-rectum because of pre-cancer lesions Reduction in mortality but lead time and delay time bias Improved survival down-staging Reduction in incidence in some cases like cervix and colon-rectum because of pre-cancer lesions

  12. CRC screening is feasible: by historicalmethods of proven efficacy and efficiency (G-FOBT) by actualmethodsI-FOBT or HeSENSA Endoscopy(invasive, costly, but highly efficient in reducing also incidence by polypectomy) by methods in development Virtual Colonoscopy Pill cam Stool-DNA

  13. FOBTs: for a fair evaluation … ... an important definition application sensitivity (once only testing) vs. programmatic sensitivity (repeated testing every 1 or 2) J E Allison AJG 2010

  14. What is average risk for colorectal cancer? Getting old!

  15. INCIDENCE AND MORTALITY RATES OF CRC BY AGE (x 100,000/YEAR) Age (years) 40-44 45-50 50-54 55-59 60-64 65-69 70-74 75-79 Incidence 13.3 27.6 55.1 97.0 153.4 226.9 318.6 412.0 Mortality 4.6 9.6 19.0 34.4 55.4 85.6 125.9 171.9 from Miller et al.

  16. Who is at average risk ?

  17. Stool Tests sDNA G-FOBT Immuno FOBT

  18. Relative efficiency of G-FOBT and I-FOBT for CRC and AA (330 subj. undergoing OC) # mostly flat lesions in right colon Rozen P. et al. 2009

  19. Comparison g-FOBT vs i-FOBT (100 ng/ml) 770 subj. at average risk both FOBTs (3 samples) + Colonoscopy (CS) Park D AJG 2010

  20. CRC stool screening tests Imperiale TF et al, NEJM (2008) 351:274-14

  21. SCREENING STRATEGIES AND AVAILABLE RESOURCES In most developing nations, Africa, Asia (3.8 billion population), CRC screening is not a priority, resources are limited, awareness still low or restricted to the more affluent (private care) The preferred and more affordable screening strategy worldwide is FOBT (trend towards iFOBT). Bleeding from worm infestation is a problem in developing countries Primary TC / FS screening offered only in a few affluent nations (US, UK Germany, Italy, Austria, Luxemburg, Poland), FOBT as alternative

  22. Alternate strategies in low resource settings To aim at familiar / genetic risk for CRC (just few key questions by a health professional) In subjects aged <45 years (rates on total cases)

  23. Endoscopy

  24. What is HIGH RISK for CRC: impact of familiar and hereditary factors High risk Average risk Rosalind U. Clinics of North America Gastro. End. 2002

  25. Who is at high risk ? COLONOSCOPY 25%

  26. A specific dedication by General Practitioners is suggested being crucial in selecting subjects, by simple questions, for: Ö Genetic syndromes Ö Familiar risk These patients NEED COLONOSCOPY HOW identify them ?? … by a simple question Accuracy 80 % Church, Dis Colon Rectum, 2000 A bit of culture, a minimal effort, a great yield!

  27. Advanced Adenoma (AA) AA includes a range of lesions with variable (or different) cancer risk that was established as surrogate endpoint, more frequent than CRC

  28. Flexible sigmoidoscopy Endoscopic screening of CRC Colonoscopy

  29. Miss rate of Flexible Sigmoidoscopy for proximal lesions in subjects with no-distal lesions Range from 22.8 % to 65 % (results of more than 50 studies)

  30. Efficacy of colonoscopy in reducing incidence of CRC An alternative screening method • Results of two multi-center studies based on long-term follow-up of asymptomatic subjects after a colonoscopy with polypectomy US National Polyp Study (prospective) - 76 % Italian Multicenter Study (retrospective) - 66 % But COMPLIANCE in general population is low

  31. Screening Colonoscopy (OC) in asymptomatic subjects Meta-analysis of 10 studies, 68,324 participants Niv Y et al, 2007

  32. Miss rate of right sided CRC by colonoscopy in Ontario in usual clinical practice (1997 – 2001) CRC patients database: 4920 subjects Missed cancers: 4% by colonoscopy performed between 6 – 36 months before CRC diagnosis. (Byrd RL 1989: missed lesions: 3%) CRC cannot be completely eliminated even with very intensive screening Bressler B et al 2004

  33. Risk of CRC after negative colonoscopy About 80% subjects with CRC between 50 – 58y have already one adenoma at 50y Geul K et al, 2007 QUALITY of OC !? Fast-growing lesions !?

  34. Differences in protection against right/left sided CRC after a negative index CS ? Quality of CS (gastroent. Vs non-gastroent.?) Flat non polypoid lesions (more in right colon ?) Biology of proximal lesion (MSI and CIMP status ?) Why women worst ? (RR 0.99 vs 0.89 men)

  35. Low public compliance to screening colonoscopy (from Jack Tippit, Saturday Evening Post)

  36. Virtual Colonoscopy (CTC)

  37. CTC ACCURACY Johnson CD, NEJM 2008

  38. Distribution of advanced neoplasia according to polyp size at screening colonoscopy (data from 4 studies with 20,562 subjects) Advanced adenomas detected in 1155 subjects (5.6% overall) of these in diminutive polyps (≤ 5mm) 4.6% in small polyps (6-9mm) 7.9% in large polyps (≥ 10mm) 87.5% Hassan C et al, 2009

  39. Colon capsule (CE) Ø11 mm 31 mm

  40. Courtesy Dr Hassan

  41. Important factors to improve compliance to screening Awareness !! The data from US and Europe show substantial differences

  42. Trends in Incidence (M + F) of CRC in Europe vs USA Seer selected Countries Estimated

  43. Prevalence of lower GI testing (CS, FS, FOBTs) in the last 10 years Result of the SHARE program on 18,139 subj. aged more than 50y in 11 European Countries Lower GI Endoscopy from 6.1% Greece to 25.1 % France FOBTs from 4.1 % Netherlands to 61.1 % Austria WHAT A DISASTER !! Stock C, Brenner H 2010

  44. Ongoing CRC screening activities in Italy M. Zorzi et al 2006 survey - National Centre for Screening Monitoring

  45. Ongoing CRC screening activities in Italy 2006 Regional variations # Population covered by organized screening programs M. Zorzi et al 2006 survey - National Centre for Screening Monitoring

  46. 11.3 14.2 2.8 Screened by TC

  47. Compliance to screening tests in average practice (in the real world !!) • Population based extent of CRC screening in Ontario (Canada) <20% (Rabeneck L. et al. 2004) • Participation in colonoscopy population screening in Australia 18.2% (Scott RG et al. 2004)

  48. The problem is: compliance to any screening test … … ? How to increase compliance ?

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