1. Lo stato dell’arte nello screening del CRC Roma – 28 Novembre 2009 Massimo CRESPI, Daniele LISI Istituto “Regina Elena” – Roma ASL RmB Poliamb. Don Bosco - Roma
2. 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 Physical activity Energy intake Fresh fruit and vegetable Dietary fat Calcium Fiber Anti-oxidant vitamines Selenium SCREENING Anti-inflammatory drugs Summary of action with level II or III of evidence
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4. Established concepts FOBTs For early detection only of CRC Colonoscopy For early detection and prevention of CRC and polyps
7. Mortality reduction in the active participating population - Funen : - 33 % - Nottingham : - 39% - Burgundy : - 33% - Minnesota : - 55 %
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9. Proportion of TNM stage 1 cancer in the screened and control population Downstaging 20% 16% 40% Burgundy 12% 11% 44% Nottingham 11% 9% 40% Funen Control population Test not done Positive test
10. RESULTS OF A CRUCIAL COHORT STUDY (JPHC) ON CRC SCREENING IN JAPAN 42,150 subject – 551,459 person/years f.u. (13 years) RR death from CRC in screened 0.28 (0.13 - 0.61) a 70% reduction RR death from all causes 0.70 (0.61 - 0.79) a 30% reduction Incidence of CRC similar but RR 0.41 for advanced CRC Conclusions: no need for RCTs to implement screening (not ethical) KJ Lee et al, 2007
11. Reduction in mortality beyond lead time and delay time bias Summary: effects of CRC screening as shown by RCTs achieved: -15 to -55 % Improved survival (down-staging) Reduction in incidence by removals of precancerous lesions (polyps) achieved: up to 65% achieved: up to 70%
12. Meinhard Classen THE STATUS QUO OF COLORECTAL CANCER SCREENING IN EUROPE A Pan - European Survey between November 2004 and March 2007 with support of René Lambert NETZWERK gegen Darmkrebs
13. France Germany United Kingdom Bulgaria Poland Czech Republic Slovakia Romania Hungary Austria Italy Albania (red background: countries with national CRC screening program) Luxembourg Is CRC screening established in your country? QUESTION: ANSWER: Finland United Kingdom Germany Iceland 15 / 39 countries (38 %) established CRC screening EU members: 13 / 27 (48 %) Courtesy of M. Classen daa2map.de
14. Ongoing CRC screening activities in Italy M. Zorzi et al 2006 survey - National Centre for Screening Monitoring I 5.3 – II 3.9 I 5.8 – II 4.1 I-Fobt + 46.5 % (4.8 – 81 %) 47.1% (6.7–78.1%) Compliance CRC 0.31 % AA 1.46 % CRC 0.37 % AA 1.68 % 1 st screen 81.2% (69.2 – 90.7%) 82 % (56 – 100 %) OC adherence CRC 0.13 % AA 0.77 % CRC 0.11 % AA 0.49 % 2 nd screen 56 % 55 % TNM I or II 2,107,000 827,473 Invited 69 52 Programs 2006 2005
15. Ongoing CRC screening activities in Italy 2006 Regional variations M. Zorzi et al 2006 survey - National Centre for Screening Monitoring # Population covered by organized screening programs 4.8 10.0 % South 22.8 48.5 % Center 50.2 66.1 % North Actual extension (invited) Theoretical extention #
20. CRC screening is feasible: by historical methods of proven efficacy and efficiency ( G-FOBT ) by actual methods I-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
22. Relative efficiency of G-FOBT and I-FOBT for CRC and AA (330 subj. undergoing OC) Rozen P. et al. 2009 # mostly flat lesions in right colon 68.8 53.1 53.1 Sensitivity % 2.1 91.9 I-FOBT (2 samples) 2.1 94.0 I-FOBT (1 sample) 8.1 59.4 G-FOBT (3samples) No. of OC / Neoplasia Specificity % 7 8 15 AA not identified # both I-FOBT G-FOBT
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24. sDNA - Sample Collection Collection bucket inserted into bracket and installed under toilet seat Patient supplies whole stool sample; no diet or medication restrictions Patient seals sample in outer container and freezer pack Patient seals container and ships back to designated lab (all packing materials and labels supplied)
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)
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31. Screening Colonoscopy (OC) in asymptomatic subjects Meta-analysis of 10 studies, 68,324 participants Niv Y et al, 2007 Perforation 0.01 % Bleeding 0.05 % Complication 5 % (4 – 6 %) Advanced Aden. 19 % (15 - 23 %) Adenoma 0.78 % (0.13 – 2.97 %) Stage I or II 77 % CRC 97 % (94 – 98 %) Complete (OC)
33. Risk of CRC after negative colonoscopy Geul K et al, 2007 About 80% subjects with CRC between 50 – 58y have already one adenoma at 50y Singh et al, 2009 Right colon Left colon Overall 0.67 0.16 0.55 RR
34. Repeated screen colonoscopy after 5y Chinese average risk Leung WK et al, 2009 RR 19.6 --- 24.6 % Any polyp Advanced Ad. No polyp Baseline findings 20.7 % 1.4 % Advanced Adenomas After 5y
35. Advanced Colorectal Neoplasia after Polypectomy (pooled 9,167 subjects - mean age 62y - follow-up 47,2 months) Martinez ME et al, 2009 AA 11.2 % (1 out of 10) – Invasive CRC 0.6 % (missed or incompletely excised lesions at baseline ?) RR 1.68 Proximal adenoma from 1.39 to 2.70 (60y or more) Older age RR 1.40 Male sex Family history High grade dysplasia No. of adenomas and size Risk factors at baseline for AA and CRC at follow-up (not significant) RR 1.08 (not significant) RR 1.32 (size RR 1.56)
36. Sex and Advanced Neoplasia Meta-analysis of 17 studies, 924,932 participants Nguyen Y et al, 2009 Women are protected until menopause and by HRT (tumor suppressor role of estrogen receptor beta) 1.53 ≥ 70 1.78 60 – 69 1.86 50 – 59 1.53 40 – 49 RR men vs women Age group
40. 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
51. Most efficient CRC screen strategies by mathem. models (starting age 50y) in term of life-years gained and mortality reduction These tests provide similar life-years gained, but only if OC adherence is 50% or more. Zauber A et al, 2008 65.7 % HeSENSA annually + Flex.S. every 5y 66.0 % Hemoccult SENSA annually 64.6 % Colonoscopy (OC) every 10y 64.6 % I-FOBT (max sensitivity) every 2 – 3 y 65.7 % Mortality reduction I-FOBT every 2 – 3 y + Flex.S. every 5y
53. A bit of culture, a minimal effort, a great yield! HOW identify them ?? … by a simple question Accuracy 80 % Church, Dis Colon Rectum, 2000 A specific dedication by General Practitioners is suggested being crucial in selecting subjects , by simple questions , for: Genetic syndromes Familiar risk These patients NEED COLONOSCOPY
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55. Conclusions: some already established concepts Any test is better than NO-test In the US 1990 – 2005 CRC Mortality Males -31.8 % Females -28.0 % FOBTs For early detection only of CRC Colonoscopy For early detection and prevention of CRC and polyps
56. CONCLUSIONS Colonoscopy is the test of choice in high risk subjects S creening c olonoscopy may be proposed today as an option in average risk subjects in the frame of a direct doctor / patient relationship Crucial to the selection of high risk subjects is the informed and conscious involvement of GPs
57. South Center North FOBT programs: adjusted compliance of single program by Region
58. AMOD study Variability of compliance to FOBT Mean 27.1 % (range 7.9 – 90.9 %) North 26.7 % South 29.9 % Center 26.1 % % GPs North 26.7 % Center 26.1 % North 26.7 % Center 26.1 % North 26.7 % South 29.9 % Center 26.1 % North 26.7 % South 29.9 % Center 26.1 % North 26.7 % Lisi D. et al, DLD 2009
59. AMOD study Variability of compliance to OC Mean 10.0 % (range 0.8 – 54.9 %) North 10.7 % South 2.8 % Center 13.3 % % GPs Lisi D. et al, DLD 2009
60. The ultimate efficiency indicator of preventive diagnostic therapeutic strategies and the frame for evaluation of Health Systems Survival of Cancer Patients
61. Colorectal Cancer (Males) 5y Survival (%) EPICENTRO.ISS.IT EUROCARE.IT Eurocare-3 study Annals of Oncology 2003 (Suppl. 5) vol. 14
62. EPICENTRO.ISS.IT EUROCARE.IT Eurocare-3 study Annals of Oncology 2003 (Suppl. 5) vol. 14 (Not EU) (Not EU) (Not EU) England Scotland Wales 5y survival of CRC from Cancer Registries
64. D.K. Podolsky (NEJM, 2000) : “ The barrier to reducing the numbers of deaths from Colorectal Cancer is not a lack of scientific data but a lack of organization, financial and societal commitment!” After 9 years barriers are still barriers!
65. Low public compliance to screening colonoscopy (from Jack Tippit, Saturday Evening Post)
