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Faecal DNA vs FOB for Colorectal Cancer Screening in an Average Risk Population

Faecal DNA vs FOB for Colorectal Cancer Screening in an Average Risk Population. Leo Pang Surgical Registrar POW Journal Club 1 st August 2005. Background. FOBT UK (2004) 271,646 patients 1.9% +ve FOBT PPV 10.9% for CRC, 35% for adenomas Tuscany (2004) 78,505 5.8% +ve FOBT

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Faecal DNA vs FOB for Colorectal Cancer Screening in an Average Risk Population

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  1. Faecal DNA vs FOBfor Colorectal Cancer Screeningin an Average Risk Population Leo Pang Surgical Registrar POW Journal Club 1st August 2005

  2. Background • FOBT • UK (2004) • 271,646 patients • 1.9% +ve FOBT • PPV 10.9% for CRC, 35% for adenomas • Tuscany (2004) • 78,505 • 5.8% +ve FOBT • PPV 5.7% for CRC, 31.5% for adenomas

  3. Background • Previous studies on faecal DNA • Sensitivity 62-91% for CRC • Sensitivity 27-82% for adenomas • Specificity 93-96% • Performed on patients with known advanced and symptomatic lesions • Detection rates for CRC and adenomas between FOBT and faecal DNA?

  4. Faecal DNA vs. FOBT • NEJM December 2004 • Imperiale et. al, Indiana University • 81 sites between 2001-2003 • Asymptomatic, >50yrs, average risk • Faecal DNA – 21 mutation panel • K-ras, APC, p53, BAT-26, long DNA • Haemoccult II x3 • Colonoscopy • Blinded prospective trial • Exclusion criteria • Analysed subgroup

  5. Faecal DNA vs. FOBT • Results: • 5486 patients, 4404 fully evaluated • Mean age 68.6 • Males 44.6% • Caucasian 87.3% • 31 Adenocarcinomas (TNM I/II/III) • Faecal DNA 16/31 (51.6%) – 13 missed by FOBT • FOBT 4/31 (12.9) – 1 missed by FDNA • P = 0.003 • TNM I/II: FDNA 56.5%, FOBT 13% p=0.006 • TNM 0/I/II/III: FDNA 40.8%, FOBT 14.1% p<0.001

  6. Faecal DNA vs. FOBT • 40 Advanced adenomas with high grade dysplasia • Faecal DNA 13/40 (32.5%) • FOBT 6/40 (15%) • Other advanced adenomas • Both tests consistently <20% sensitivity • False positives • Faecal DNA 79/1423 (Specificity 94.4%) • FOBT 68/1423 (Specificity 95.2%) • All cases of advanced colorectal cancer • Faecal DNA 18.2% • FOBT 10.8%

  7. Discussion • First large study to compare average risk patients prospectively • FDNA more than 4 times more sensitive than FOBT for cancer, 2 times more sensitive for adenomas with high grade dysplasia • Not powered enough to analyse different stages of cancer • Advantages of DNA analysis

  8. Discussion • Disproportionate representation of patients over 65 – generalisable? • ? Repeat testing • ? Variablity of DNA analysis • Issues: • Test • Risk • Cost • Interval between tests • Compliance • Lower detection rates compared to previous studies

  9. Discussion • Implications on health benefits • Acceptability and availability • Costs

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