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


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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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Faecal DNA vs FOBfor Colorectal Cancer Screeningin an Average Risk Population

Leo Pang

Surgical Registrar

POW Journal Club

1st 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

          • PPV 5.7% for CRC, 31.5% for adenomas


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?


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


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


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%


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


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


Discussion

  • Implications on health benefits

  • Acceptability and availability

  • Costs


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