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Meta-Analysis
. 2015 Dec 10;2015(12):CD011134.
doi: 10.1002/14651858.CD011134.pub2.

Blood CEA levels for detecting recurrent colorectal cancer

Brian D Nicholson  1 , Bethany Shinkins, Indika Pathiraja, Nia W Roberts, Tim J James, Susan Mallett, Rafael Perera, John N Primrose, David Mant
Affiliations
Meta-Analysis

Blood CEA levels for detecting recurrent colorectal cancer

Brian D Nicholson et al. Cochrane Database Syst Rev. .

Abstract

Background: Testing for carcino-embryonic antigen (CEA) in the blood is a recommended part of follow-up to detect recurrence of colorectal cancer following primary curative treatment. There is substantial clinical variation in the cut-off level applied to trigger further investigation.

Objectives: To determine the diagnostic performance of different blood CEA levels in identifying people with colorectal cancer recurrence in order to inform clinical practice.

Search methods: We conducted all searches to January 29 2014. We applied no language limits to the searches, and translated non-English manuscripts. We searched for relevant reviews in the MEDLINE, EMBASE, MEDION and DARE databases. We searched for primary studies (including conference abstracts) in the Cochrane Central Register of Controlled Trials (CENTRAL), in MEDLINE, EMBASE, and the Science Citation Index & Conference Proceedings Citation Index - Science. We identified ongoing studies by searching WHO ICTRP and the ASCO meeting library.

Selection criteria: We included cross-sectional diagnostic test accuracy studies, cohort studies, and randomised controlled trials (RCTs) of post-resection colorectal cancer follow-up that compared CEA to a reference standard. We included studies only if we could extract 2 x 2 accuracy data. We excluded case-control studies, as the ratio of cases to controls is determined by the study design, making the data unsuitable for assessing test accuracy.

Data collection and analysis: Two review authors (BDN, IP) assessed the quality of all articles independently, discussing any disagreements. Where we could not reach consensus, a third author (BS) acted as moderator. We assessed methodological quality against QUADAS-2 criteria. We extracted binary diagnostic accuracy data from all included studies as 2 x 2 tables. We conducted a bivariate meta-analysis. We used the xtmelogit command in Stata to produce the pooled estimates of sensitivity and specificity and we also produced hierarchical summary ROC plots.

Main results: In the 52 included studies, sensitivity ranged from 41% to 97% and specificity from 52% to 100%. In the seven studies reporting the impact of applying a threshold of 2.5 µg/L, pooled sensitivity was 82% (95% confidence interval (CI) 78% to 86%) and pooled specificity 80% (95% CI 59% to 92%). In the 23 studies reporting the impact of applying a threshold of 5 µg/L, pooled sensitivity was 71% (95% CI 64% to 76%) and pooled specificity 88% (95% CI 84% to 92%). In the seven studies reporting the impact of applying a threshold of 10 µg/L, pooled sensitivity was 68% (95% CI 53% to 79%) and pooled specificity 97% (95% CI 90% to 99%).

Authors' conclusions: CEA is insufficiently sensitive to be used alone, even with a low threshold. It is therefore essential to augment CEA monitoring with another diagnostic modality in order to avoid missed cases. Trying to improve sensitivity by adopting a low threshold is a poor strategy because of the high numbers of false alarms generated. We therefore recommend monitoring for colorectal cancer recurrence with more than one diagnostic modality but applying the highest CEA cut-off assessed (10 µg/L).

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Conflict of interest statement

None

Figures

1
1
PRISMA flow diagram: results of the search for studies evaluating the diagnostic accuracy of blood CEA to detect recurrent colorectal cancer in patients following curative resection.
2
2
QUADAS‐2 risk of bias and applicability concerns summary including review authors' judgements about each domain for each included study
3
3
QUADAS‐2 risk of bias and applicability concerns graph including review authors' judgements about each domain presented as percentages across included studies
4
4
Forest plot for all 52 included studies for the threshold reported closest to 5 µg/L TP = true positive; FP = false positive; FN = false negative; TN = true negative The blue square depicts the sensitivity and specificity for each study and the horizontal line represents the corresponding 95% confidence interval for these estimates.
5
5
Scatter plot of sensitivity versus specificity for all 52 studies, regardless of threshold. Each box represents the 2 x 2 data extracted from each study, with the width of the boxes being proportional to the inverse standard error of the specificity and the height of the boxes proportional to the inverse standard error of the sensitivity.
6
6
Forest plot broken down by threshold: CEA at 2.5µg/L, CEA at 5µg/L, CEA at 10µg/L. TP = true positive; FP = false positive; FN = false negative; TN = true negative The blue square depicts the sensitivity and specificity for each study and the horizontal line represents the corresponding 95% confidence intervals for these estimates.
7
7
Summary ROC plot of accuracy at a threshold of 2.5 µg/L. Each box represents the 2 x 2 data extracted from each study. The width of the box is proportional to the number of patients who did not experience recurrence in each study, and the height is proportional to the number of patients that did develop recurrent CRC. The filled circle is the pooled estimate for sensitivity and specificity and the line running through it is the summary ROC curve. The smaller dotted ellipse represents the 95% credible region around the summary estimate; the larger dashed ellipse represents the 95% prediction region.
8
8
Summary ROC plot of accuracy at a threshold of 5 µg/L. Each box represents the 2 x 2 data extracted from each study. The width of the box is proportional to the number of patients who did not experience recurrence in each study, and the height is proportional to the number of patients that did develop recurrent CRC. The filled circle is the pooled estimate for sensitivity and specificity and the line running through it is the summary ROC curve. The smaller dotted ellipse represents the 95% credible region around the summary estimate; the larger dashed ellipse represents the 95% prediction region.
9
9
Summary ROC plot of accuracy at a threshold of 10 µg/L. Each box represents the 2 x 2 data extracted from each study. The width of the box is proportional to the number of patients who did not experience recurrence in each study, and the height is proportional to the number of patients that did develop recurrent CRC. The filled circle is the pooled estimate for sensitivity and specificity and the line running through it is the summary ROC curve. The smaller dotted ellipse represents the 95% credible region around the summary estimate; the larger dashed ellipse represents the 95% prediction region.
1
1. Test
CEA ‐ all thresholds.
2
2. Test
CEA at 2.5µg/L.
3
3. Test
CEA at 5µg/L.
4
4. Test
CEA at 10µg/L.
See this image and copyright information in PMC

Comment in

References

References to studies included in this review

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References to studies excluded from this review

Afsaneh 2012 {published data only}
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Cho 2007 {published data only}
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Dalton 2010 {published data only}
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Dash 2012 {published data only}
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Fernandes 2006 {published data only}
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Fora 2012 {published data only}
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Fucini 1983 {published data only}
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Fucini 1985 {published data only}
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Gaudagni 1999 {published data only}
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Graham 1998 {published data only}
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Grossetti 1981 {published data only}
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Grossmann 2007 {published data only}
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Humphreys 2011 {published data only}
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Huyghe 1983 {published data only}
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Ito 2002 {published data only}
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