False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening

Int J Cancer. 2009 Aug 15;125(4):746-50. doi: 10.1002/ijc.24458.


Delayed return of immunochemical fecal occult blood test (iFOBT) samples to a laboratory might cause false negatives because of hemoglobin degradation. Quantitative iFOBT's became increasingly more accepted in colorectal cancer screening. Therefore, we studied the effects of delay between sampling and laboratory delivery on iFOBT performance. IFOBT positivity (>or=50 ng/ml hemoglobin) in colorectal cancer screening participants without delay between sampling and laboratory delivery (<5 days), was compared with positivity in participants with >or=5 and >or=7 days delay. Additionally, positive tests were stored at room temperature and retested 5 times within 10-14 days. The sampling date was reported by 61% (n = 3,767) of the participants: in 19% delay was >or=5 days and in 5% >or=7 days. Compared with no-delay, the adenoma detection rate was already significantly decreased after >or=5 days delay (OR 0.6; 95%CI 0.4-0.9). We retested iFOBT samples of 170 positives of which 139 (82%) had a colonoscopy: 45 (32%) had advanced adenomas (not colorectal cancer) and 8 (6%) had colorectal cancer. Mean daily fecal hemoglobin decrease was 29 ng/ml (S.D. 38 and median 11 ng/ml). In patients with advanced adenomas, hemoglobin in the sample was <50 ng/ml in 5 (11%) 2-3 days after the initial test and in 16 (36%) after 10-14 days. Seven days after the initial test, 2 (25%) colorectal cancer patients became false negative. Both had stage I colorectal cancer and initial values below 100 ng/ml, where the average for stage I is 532 ng/ml. Delay in sample return increased false negative immunochemical FOBT's. Mainly precursor lesions, but also colorectal cancer, will be missed due to delayed sample return.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / diagnosis*
  • Adenoma / epidemiology
  • Adenoma / prevention & control
  • Colonic Polyps
  • Colonoscopy / methods
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / prevention & control
  • Computer Simulation
  • Early Detection of Cancer
  • False Negative Reactions
  • Female
  • Hemoglobins / analysis*
  • Humans
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Occult Blood*
  • Predictive Value of Tests
  • Prospective Studies
  • Specimen Handling


  • Hemoglobins

Associated data

  • ISRCTN/ISRCTN57917442