Cribado del cáncer (colorrectal): las pruebas de detección precoz salvan vidas Dr. Antoni Castells Servicio de Gastroenterología Hospital Clínic nic,, Barcelona (castells@clinic.cat) Conditions for a population-based screening (Frame( and Carlson, 1975) Relevant health care problem Well-established established natural history early detection diminishes morbi-mortality mortality Effective and well-accepted treatment Adequate screening test Cost-effective strategy Cancer incidence in Spain Natural history of CRC 10 years Colorrectal 25.665 Pulmón 18.821 Mama 15.979 Vejiga Próstata 14.477 13.212 Normal mucosa Adenoma Carcinoma 0 5.000 10.000 15.000 20.000 25.000 30.000 Casos nuevos /año Advanced adenoma: Size 1 cm Villous component High-grade dysplasia Centro Nacional de Epidemiología
Endoscopic polypectomy: : CRC incidence Endoscopic polypectomy: : CRC mortality Incidencia acumulada de CCR (%) 5 4 3 2 1 Mayo Clinic St. Mark SEER Polipectomía 47% Evidence: 1b Recommendation: A 2 4 6 años 8 Winawer et al. NEJM 1993 Zauber et al. NEJM 2012 CRC screening in average-risk risk population Age No < 50 years 50 years No screen Annual or biennial FOBT and/or sigmoidoscopy / 5 years, o colonoscopy / 10 years Personal and/or familial risk factors U.S. Preventive Services Task Force U.S. Multi-Society Task Force on Colorectal Cancer American Cancer Society AEG semfyc - Cochrane Cancer screening: cost-effectiveness Cost/QALY 20.000 17.500 15.000 12.500 10.000 7.500 5.000 2.500 0 SOH-I anual 1.130 SIGMOID. cada 5a 2.305 COLONOSC. cada 10a 2.369 12.647 18.489 18.646 CRC Prostate Breast Cervical López-Bastida. Servicio Canario de Salud
Screening in average-risk risk population: fecal occult blood testing (FOBT) FOBT vs. Evidence: 1a Recommendation: A 0% -5% -10% -15% -20% -25% -30% -35% CRC mortality reduction Minnesota (1) Nottingham (2) Funen (3) -30% -15% -18% 1 Mandel et al. NEJM 1993 2 Hardcastle et al. Lancet 1996 3 Kronborg et al. Lancet 1996 Guaiac (Hemoccult II ) (OC-Sensor ) Invitated population 10,301 10,322 Stool samples 3 1 Participation no. (%) 4,836 (47%) 6,157 (60%) <0.01 Test positivity 2.4% 5.5% <0.01 Adv. adenomas no. (%) 46 (0.4%) 121 (1.1%) <0.01 CRC no. (%) 11 (0.1%) 24 (0.2%) <0.01 Van Rossum et al. Gastroenterology 2008 p Invitation process Letter of presentation 15 days later Lista Oficinas de Farmacia en donde Letter of invitation puede recoger el material Farmacia Dr.----------- Farmacia Dr.-----------
Endoscopic finding in -positive participants Screening in average-risk risk population: colonoscopy ADVANCED COLORECTAL NEOPLAMS (CRC and high-risk adenoma) LOW-RISK ADENOMAS OTHERS HEMORROIDS DIVERTICULA ABNORMAL COLONOSCOPY IRRELEVANT Courtesy of Dr. Josep M. Augé (Hospital Clínic)
Association between colonoscopy and CRC mortality reduction CRC screening in average-risk risk population No Personal and/or familial risk factors Age < 50 years 50 years No screen Annual or biennial FOBT and/or sigmoidoscopy / 5 years, o colonoscopy / 10 years Which one is the best? Evidence: 2b Recommendation: B Baxter et al. Ann Intern Med 2009 U.S. Preventive Services Task Force U.S. Multi-Society Task Force on Colorectal Cancer American Cancer Society AEG semfyc - Cochrane Screening success The ColonPrev Study Screening success = test sensitivity x compliance (x accessibility)
Study flow chart Eligible population (grouped by address) Randomization 1:1 Information + invitation ± reminding letters Appointment: Local Screening Office (questionnaire, post-randomization consent) Chronogram End of 2 nd round June 2009 2011 Inclusion period (1 st round) Analysis of participation and detection rate 2021 Screening (continued) Analysis of mortality Analysis of CRC incidence Group I: Biennial (n= 27,749) Group II: Colonoscopy (n= 27,749) Cost-efficacy 35% 30% 25% 20% 15% 10% 5% 0% Participation and cross-over over rates (intention-to-screen analysis) Participation rate 24,60% Colonoscopy p=0.0001 34,20% OR, 0.63 (95% CI, 0.60-0.65) 7% 6% 5% 4% 3% 2% 1% 0% Cross-over over rate 6,20% Colonoscopy > p=0.0001 0,40% > colonoscopy OR, 16.8; 95% CI, 13.9-20.2) Cancer 30 (0.1%) 33 (0.1%) Advanced adenoma 514 (1.9%) 231 (0.9%) Non-advanced adenoma 1109 (4.2%) 119 (0.4%) Diagnostic yield (intention-to-screen analysis) Colonoscopy 1.0 2.3 0 1 2 3 4 5 6 7 8 9 10 11 12 Odds ratio (adjusted by age, gender and participating center) 9.8
Colorectal cancer staging (as-screenedscreened analysis) Number needed to screen (per protocol analysis) 25 20 15 10 5 0 p=0.52 24 19 6 6 6 2 Stage I Stage II Stage III Individuals needed to screen 300 250 200 150 100 50 0 191 Cancer 281 10 36 Advanced neoplasia Colonoscopy Colonoscopy Individuals needed to scope Number needed to scope (per protocol analysis) 300 250 200 150 100 50 0 191 Cancer 18 10 2 Advanced neoplasia Limitations of current strategies Invasiveness: colonoscopy, sigmoidoscopy Low sensitivity: FOBT/, sigmoidoscopy Compliance: 35-55% in -based screening (ColonPrev study, Barcelona s CRC Screening Program) <30% in colonoscopy-based screening (ColonPrev study) Coverage: <15% of eligible Spanish population <50% of eligible US population (Shapiro et al. CEBP 2008) Colonoscopy
Ideal features of a test for colorectal cancer screening Highly sensitive Early CRC stages Precursor lesions Right and left neoplasms Highly specific ( false positive) Non-invasive User friendly No bowel preparation No diet restriction Affordable Widely distributable Sensitivity Compliance Accessibility CRC biomarkers The analysis of molecular markers representing the genetic and epigenetic alterations associated with CRC is an attractive strategy Exfoliation of neoplastic cells in the feces is a continuum process in patients with colorectal neoplasia Tumor cells and tumor markers also enter into the blood in patients with colorectal neoplasia Ahlquist et al. Clin Gastroenterol Hepatol 2012 Complete blood count analysis as screening tool MeScore CRC Medial Cancer Screening The best test is the one that gets done." Sidney Winawer, MD Courtesy: Dr. Bernard Levin
Cribado del cáncer (colorrectal): las pruebas de detección precoz salvan vidas Dr. Antoni Castells Servicio de Gastroenterología Hospital Clínic nic,, Barcelona (castells@clinic.cat)