Is there an added value of faecal calprotectin and haemoglobin in the diagnostic work-up for primary care patients suspected of significant colorectal disease? A cross-sectional diagnostic study

Abstract

Background: The majority of primary care patients referred for bowel endoscopy do not have significant colorectal disease (SCD), and are - in hindsight - unnecessarily exposed to a small but realistic risk of severe endoscopy-associated complications. We developed a diagnostic strategy to better exclude SCD in these patients and evaluated the value of adding a faecal calprotectin point-of-care (POC) and/or a POC faecal immunochemical test for haemoglobin (FIT) to routine clinical information.

Methods: We used data from a prospective diagnostic study in SCD-suspected patients from 266 Dutch primary care practices referred for endoscopy to develop a diagnostic model for SCD with routine clinical information, which we extended with faecal calprotectin POC (quantitatively in μg/g faeces) and/or POC FIT results (qualitatively with a 6 μg/g faeces detection limit). We defined SCD as colorectal cancer (CRC), inflammatory bowel disease, diverticulitis, or advanced adenoma (>1 cm).

Results: Of 810 patients, 141 (17.4 %) had SCD. A diagnostic model with routine clinical data discriminated between patients with and without SCD with an area under the receiver operating characteristic curve (AUC) of 0.741 (95 % CI, 0.694-0.789). This AUC increased to 0.763 (95 % CI, 0.718-0.809; P = 0.078) when adding the calprotectin POC test, to 0.831 (95 % CI, 0.791-0.872; P < 0.001) when adding the POC FIT, and to 0.837 (95 % CI, 0.798-0.876; P < 0.001) upon combined extension. At a ≥ 5.0 % SCD probability threshold for endoscopy referral, 30.4 % of the patients tested negative based on this combined POC-tests extended model (95 % CI, 25.7-35.3 %), with 96.4 % negative predictive value (95 % CI, 93.1-98.2 %) and 93.7 % sensitivity (95 % CI, 88.2-96.8 %). Excluding the calprotectin POC test from this model still yielded 30.1 % test negatives (95 % CI, 24.7-35.6 %) and 96.0 % negative predictive value (95 % CI, 92.6-97.9 %), with 93.0 % sensitivity (95 % CI, 87.4-96.4 %).

Conclusions: FIT - and to a much lesser extent calprotectin - POC testing showed incremental value for SCD diagnosis beyond standard clinical information. A diagnostic strategy with routine clinical data and a POC FIT test may safely rule out SCD and prevent unnecessary endoscopy referral in approximately one third of SCD-suspected primary care patients. Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0694-3 .

Fig. 1

Flowchart of Dutch primary care patients with lower abdominal complaints for at least 2 weeks and referred for endoscopy, and their enrolment in the CEDAR study from July 2009 through January 2012. CEDAR Cost-Effectiveness of a Decision rule for Abdominal complaints in primary care; GP general practitioner; SCD significant colorectal disease. ¹ Non-SCD was established by other bowel tests for six patients (abdominal ultrasound in five and barium enema in one patient) and by the gastroenterologist based on bowel investigations performed before recruitment in the study for four patients. ² SCD was established by the gastroenterologist for one patient on the basis of bowel investigations performed before recruitment in the study

Fig. 2

Receiver operating characteristic curves for diagnosing SCD for the basic diagnostic model, and the POC FIT and the calprotectin POC test extended models. FIT faecal immunochemical test for haemoglobin; POC point-of-care; SCD significant colorectal disease. Areas under the curve (before optimism-correction): basic model 0.741 (95 % CI, 0.694–0.789); calprotectin POC test extended 0.763 (95 % CI, 0.718–0.809); POC FIT extended 0.831 (95 % CI, 0.791–0.872); Both faecal POC tests extended 0.837 (95 % CI, 0.798–0.876). Dashed line is reference line