Screening for CRC in Wolff Schmiegel. Medizinische Universitätsklinik Knappschaftskrankenhaus Bochum

Transkript

1 Screening for CRC in 2014 Wolff Schmiegel Medizinische Universitätsklinik Knappschaftskrankenhaus Bochum

2 Colorectal cancer screening - methods FOBT guaiac immunochemical sigmoidoscopy colonoscopy CT-colonography capsule endoscopy faecal testing Genetic stool tests M2-PK blood tests

3 guaiac FOBT

4 guaiac FOBT CRC mortality reduction mortality reduction biennial annual screened participants Minnesota 21% 33% 45% 47,000/18 years Funen 18% 30% 140,000/13 years Nottingham 13% 27% 153,000/11 years Burgundy 16% 33% 91,000/11 years Göteburg 16% 24% 34,144/19 years Winawer et al. Gastroenterology 1997, Jorgensen et al. Gut 2002, Scholefield et al. Gut 2002, Faivre et al. Gastroenterology 2004, Lindholm et al. Brit J Surg 2008

5 gfobt long term mortality data Minnesota trial Shaukat et al. N Engl J Med 2013;369:

6 gfobt-screening easy to perform, low costs proven efficacy in reducing CRC-related mortality +ive tests require colonoscopy -> not performed in up to 30% moderate sensitivity for carcinomas (about 40%) low sensitivity for adenomas (10-20%) benefit due to early diagnosis of carcinoma, prevention of carcinoma unlikely

7 immunochemical FOBT (FIT)

8 FIT Sensitivity for CRC (meta-analysis) Lee et al. Ann Intern Med 2014;160:171-81

9 FIT vs. gfobt vs. sigmoidoscopy Prospect. randomised trial from NL, pat y. gfobt vs FIT (100 ng/ml) gfobt FIT Sigmo Attendance rate 49,5% 61,5% 32,4% Positive Test 2,8% 4,8% 10,2% Cancers 6 (0,3%) 14 (0,5%) 8 (0,6%) Advanced adenomas 22 (0,9%) 59 (2,0%) 103 (7,4%) Rate adv. neoplasia/ 0,6% 1,5% 2,4% 100 invited colonoscopy after pos. test 95% 96% 99% Hol et al. Gut 2010; 59:62-8

10 FIT vs. colonoscopy prospect. randomised trial Spain, 26,703 pat y.; ifobt (75 ng/ml) vs colonoscopy colonoscopy FIT odds ratio attendance 24.6% 34.2% 0.63 positive Test - 7.5% cancers 30 (0.1%) 33 (0.1%) 0.99 advanced adenomas 514 (1.9%) 231 (0.9%) 2.30 adenomas 1109 (4.2%) 119 (4.2%) 9.80 Quintero et al. N Engl J Med. 2012;366:

11 FIT - comparison of different tests prospective trial from Germany, asymptomatic individuals, comparison of colonoscopy with FOBT Cut-off 40 ng/ml 25 ng/ml 10 ng/ml 50 ng/ml 40 ng/ml 50 ng/ml Hundt et al. Ann Intern Med 2009;150:162-9

12 FIT in some countries already standard screening test (Japan) sensitivity for cancers > gfobt sensitivitity for advanced adenomas > gfobt sensitivity and specificity vary according to test and cut-off non bleeding lesions not detected more expensive (about 3-4 times) number of stool specimen that need to be tested? optimal cut-off? local test analysis vs. central test analysis? => Likely to replace guaic FOBT in the near future

13 National Polyp Study (NPS) mortality polypectomy reduces CRC-mortality by 53% Zauber et al. N Engl J Med 2012;366:687-96

14 Sigmoidoscopy UK trial Prospective rand. trial, 1 x sigmoidoscopy vs. Ø screening, Follow-up 11.2 years Mortality reduction by 43% Atkin et al. Lancet 2010;375:

15 Sigmoidoscopy UK trial Prospective rand. trial, 1 x sigmoidoscopy vs. Ø screening, Follow-up 11.2 years Incidence reduction of distal cancers by 50% Atkin et al. Lancet 2010;375:

16 CRC mortality reduction due to lower endoscopy Secondary analysis of 2 large US-cohorts Nishihara et al. N Engl J Med 2013;369:

17 before October 2002: CRC screening Germany 45 annual FOBT starting October 2002: annual FOBT at 55 colonoscopy (if neg. repeated after 10 y.) alternatively: biennial FOBT -> Free of charge

18 Cumulative participation ( ) Age group males females > Age group Cumulative participitation rate

19 CRC colonoscopy screening: findings colonoscopies 303, , , , , ,253 cancer 0.70% 0.75% 0.99% 0.99% 1.06% 1.07% adenoma 17.7% 18.8% 20.1% 20.9% 22.7% 23.2% advanced adenoma 5.8% 6.1% 6.6% 6.7% 7.0% 6.9% 35.7% of cancers % of adenomas located proximal to the sigmoid colon Pox... Schmiegel Gastroenterology 2012;142:

20 Screening colonoscopy Tumor Stages Pox... Schmiegel Gastroenterology 2012;142:

21 Number needed to screen to detect one advanced neoplasia Pox... Schmiegel Gastroenterology 2012;142:

22 CRC screening influence of endoscopist speciality 45% gastroenterologists, 45% internists, 5% surgeons 5% unknown adenoma OR (95% CI) detection rate Non-gastroenterologists 22.3% 1.00 gastroenterologists 25.1% 1.18 ( ) Pox... Schmiegel Gastroenterology 2012;142:

23 Screening colonoscopy Complications n Bleeding Perforation others Lieberman 3, % 0% 0.13% Imperiale 2, % 0.04% Atkin 2, % 0.17% Regula 50, % 0.01% 0.05% Germany (2005-8) total 1,977, % 0.02% 0.07% diagnostic1,325, % 0.02% 0.07% therapeutic 652, % 0.07% 0.07%

24 Screening colonoscopy influence on incidence Epidemiolog analysis screening colonoscopy and CRC-incidence RKI, n=1, Brenner et al. Eur J Cancer 2009

25 CRC screening colonoscopy no randomized studies + indirect evidence resources side effects quality control issues compliance Likely most effective screening method if high quality colonoscopy available

26 CRC-Screening: capsule endoscopy Prospective trial, 320 pat. with increased risk Van Gossum et al. N Engl J Med 2009; 361:

27 CRC-Screening: capsule endoscopy Meta-analysis, 873 pat. with increased risk 6 mm polyps and/or 3 polyps Spada et al. Clin Gastro Hepatol 2010;8:516-22

28 capsule endoscopy next generation Prospective trial, 117 pat. with indication for colonoscopy (21 screening), PillCam Colon 2 and colonoscopy Spada et al. GIE 2011;74:581-9

29 CRC-screening: genetic stool test vs. FIT 9989 asymptomatic persons y. in US Stool DNA-Test (2 methylated genes, KRAS + Hb) + FIT (cut off 100 ng/ml) + colonoscopy number pos. DNA-Test pos. FIT cancers % 73.8% cancers % 63.5% high grade dysplasia advanced precancerous % 23.8% lesions non-advanced % 7.6% adenomas normal colonoscopy % 3.6% No result due to technical problems DNA-Test 6.3%, FIT 0,3% Imperiale et al. N Engl J Med 2014;370:

30 CRC-screening: Septin 9 test 7941 asymptomatic persons 50 y. in US + Germany Blood test for methylated SEP9 + colonoscopy number sensitivity specificity cancers 53 48% UICC I 22 35% UICC II 14 63% UICC III 12 46% UICC IV 5 77% advanced adenomas % No pathology ,5% Church et al. Gut 2014;63:317-25

31 CRC risk groups 20% 75% sporadic IBD FAP HNPCC familial Winawer et al. Gastroenterology 1997

32 CRC Familial Risk Lifetime risk average population 6% risk-increase 1 relative 1 with CRC 2-3-fold 1 relative 1 with CRC < 50 y. 3-4-fold 2 relatives 1 with CRC 3-4-fold 1 relative 2 with CRC 1.5-fold 2 relatives 2 with CRC 2-3-fold 1 relative 1 with Adenoma 2-fold Winawer et al. Gastroenterology 2003;124:544-60

33 Is FIT the ideal test for CRC risk groups? Prospect. study, 373 patients with negative FIT and screening colonoscopy => 17 w. advanced neoplasia Cha et al. Digestion 2012;86:283-7

34 Proposal for an algorithm for a databank for acquisiton of results of screening colonoscopies in persons w. familal CRC risk Risk persons: first degree relatives* of CRC-patients first degree relatives* of patients with adenomas 50 years colonoscopy (10 years before CRC diagnosis of index patients, no later than 40 years) repeated every 5 years documentation (eg. Central Institute): Characterisation of increased risk, documentation of examination result with neoplasia and complication rate * parents, children, siblings

35 Colorectal cancer screening - conclusion past current future gfobt gfobt + ifobt Sigmoidoscopy Colonoscopy (CT-colonography) FIT, endoscopy Stool DNA-testing? Capsule endoscopy? Blood DNA-testing? Surveillance of patients with famial risk mandatory