Elsevier

The Lancet Oncology

Volume 7, Issue 2, February 2006, Pages 127-131
The Lancet Oncology

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Immunochemical testing of individuals positive for guaiac faecal occult blood test in a screening programme for colorectal cancer: an observational study

https://doi.org/10.1016/S1470-2045(05)70473-3Get rights and content

Summary

Background

Screening for colorectal cancer by use of guaiac-based faecal occult blood tests (FOBT) reduces disease-specific mortality. However, due to imperfect specificity, about half of individuals positive for guaiac FOBT are negative for neoplasia on colonoscopy. We aimed to assess whether the testing of individuals positive for guaiac FOBT in a screening programme for colorectal cancer by use of a sensitive immunochemical FOBT could select more appropriately those who should receive colonoscopy.

Methods

We invited individuals who were guaiac FOBT positive in the second screening round of a pilot study in Scotland, UK, to give two samples, each from separate stools, for immunochemical FOBT while awaiting colonoscopy. Results were classed as: both samples negative (N/N), one sample negative and one positive (N/P), and both samples positive (P/P); data were assessed for sampling bias. We compared immunochemical findings with those from colonoscopy using odds ratios of positive samples (P/P) versus negative (N/N and N/P). Sensitivity, specificity, and positive and negative likelihood ratios for cancer, and for cancer and high-risk adenomatous polyps were also calculated.

Findings

1486 participants were invited and 801 (54%) sets of duplicate samples were returned. We found no evidence of sampling bias with regard to sex, age, or degree of positivity on guaiac FOBT. Of 800 sets returned with consent and analysed, 173 (22%) were N/N, 129 (16%) were N/P, and 498 (62%) were P/P. χ2 test showed a highly significant positive correlation between degree of positivity on guaiac FOBT and on immunochemical FOBT (p<0·003). 795 individuals had data for colonoscopy: one (<1%) of 171 N/N participants and one (<1%) of 127 N/P participants had colorectal cancer, compared with 38 (8%) of 497 P/P participants; adenomatous polyps were found in 28 (16%) N/N individuals, 24 (19%) N/P individuals, and 193 (39%) P/P individuals. Normal colonoscopy was less common in the P/P group (85 [17%]) than in the N/N (67 [39%]) and N/P (49 [39%]) groups. The odds ratio for P/P being associated with cancer was 7·57 (95% CI 1·84–31·4) and with high-risk adenomatous polyps was 3·11 (1·86–5·18). Sensitivity of a P/P result for cancer was 95·0% (81·8–99·1), and for cancer and high-risk adenomatous polyps was 90·1% (84·4–94·0); specificity was 39·5% (36·0–43·1) and 47·8% (43·9–51·8), respectively.

Interpretation

Immunochemical FOBT for individuals with positive guaiac FOBT could decrease substantially the number of false positives in a screening programme for colorectal cancer.

Introduction

Randomised trials have shown that regular annual or biennial screening with a guaiac faecal occult blood test (FOBT) significantly reduce deaths from colorectal cancer.1, 2, 3 On the basis of this evidence, a pilot study was established in the UK to assess whether a national screening programme for colorectal cancer was feasible.4 The results of this pilot have shown that screening with guaiac FOBT is feasible within the context of the UK's National Health Service (NHS) and that screening should reduce deaths from colorectal cancer.5

However, this type of screening is imperfect. First, guaiac FOBT has fairly low clinical sensitivity and specificity.6 Second, independent assessment of the pilot study highlighted that most positive guaiac FOBT results arose from repeat testing of initially weak positive tests, which increased the screening period for many participants, and might be overly burdensome in a national screening programme. For these reasons, attention has been given to alternative tests.7 The choice of FOBT for screening is not easy, however, and recommendations from WHO and the World Organisation for Digestive Endoscopy (OMED) suggest that no extensively studied FOBT meets the needs for all target populations worldwide.8 Interest in the use of immunochemical FOBT has increased, and evidence suggests that this test, by use of one or preferably two samples of faeces, has better clinical sensitivity than does guaiac FOBT.8 Moreover, because immunochemical FOBT is specific for human haemoglobin, no dietary restriction is needed.

Immunochemical FOBT is more expensive than is guaiac, and has a lower limit of analytical detection, leading to a substantially higher frequency of positive results than guaiac—factors that might place unacceptable burdens on a publicly funded screening programme. To overcome these issues a two-tier approach has been suggested,9 in which faecal samples for both guaiac FOBT and immunochemical FOBT are obtained simultaneously without dietary restriction. A positive guaiac FOBT is confirmed or refuted by use of the immunochemical FOBT; however, obtaining faeces for both FOBT at the same time might hinder implementation of this procedure. As suggested previously,10 but to our knowledge not studied to date, we aimed to assess a two-tier approach in the second round of the Scottish group in the UK pilot study of screening for colorectal cancer. All participants with a positive guaiac FOBT were offered immunochemical FOBT before colonoscopy. We did an observational study to assess whether testing individuals who were positive on guaiac FOBT with immunochemical FOBT could direct investigation, by use of colonoscopy, to those most likely to have neoplastic pathology.

Section snippets

Methods

All participants in the final 13 months of the second round of the Scottish group in the UK pilot study of screening for colorectal cancer who had a positive guaiac FOBT were offered colonoscopy.4, 5 The UK pilot was coordinated from England (in Coventry and Warwick) and from Scotland (in Tayside, Grampian, and Fife). The population invited for screening in every round were individuals aged 50–69 years; the population invited in the first round (2000–02) was much the same as that for the second

Results

Table 1 shows the number of participants by interview location, sex, age, and guaiac FOBT positivity. 1486 potential participants attended for interview with specialist nurses. 801 sets of samples were returned and, of 800 with consent, 173 (22%) were N/N, 129 (16%) were N/P, and 498 (62%) were P/P.

We found no evidence of sampling bias. The number of men and women who returned samples was much the same, as was median age and range (table 1). For those with availavble data, 368 (46%) of 799

Discussion

We have shown a positive relation between strength of positivity on guaiac FOBT and the results of immunochemical FOBT. Most participants classed as strong positive on first guaiac FOBT were P/P on immunochemical FOBT, compared with about half of those classed as positive on the third guaiac FOBT; those classed as positive on second guaiac FOBT were intermediate between these two groups.

Our findings suggest that the small number of individuals who are strongly positive on first guaiac FOBT

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