583P A rapid blood test for the earlier detection of colorectal cancer

Abstract

Background
The detection of colorectal cancer (CRC) in early stages can enable the removal of pre-cancerous lesions and allow earlier treatment. Most CRCs develop from adenomas, with “advanced” adenoma (AA) considered to be clinically relevant precursor of CRC. Screening for CRC is recommended for average-risk adults using faecal immunochemical testing (FIT), but the performance of FIT is limited. FIT reportedly has false positive rate of ∼93%, and ∼10% of CRC diagnoses have a negative FIT result. Moreover, the sensitivity for detecting AA is only 24%, highlighting the need for alternative strategies.

Methods
The Dxcover® Colorectal Cancer Liquid Biopsy is a spectroscopic test that interrogates a blood sample with infrared light and generates a distinctive signature that represents the whole biomolecular profile of the sample. Patient samples (n=296) were retrospectively collected for this discovery study, and the full cohort consisted of 100 CRC, 99 adenoma (A) and 97 colonoscopy screening controls with a non-cancer (NC) diagnosis. Machine learning algorithms have been developed with the resultant spectral profiles to predict CRC and AA. Feature importance analysis has also been carried out to identify the spectral regions found to be most significant for each classification.

Results
The CRC v NC model achieved an area under the receiver operating characteristic curve (AUROC) of 0.93. At 90% specificity, the overall CRC sensitivity was 80%, and the detection rates were consistent across stages: 83% (I), 73% (II), 76% (III), and 100% (IV). The CRC+A v NC model reported an AUROC of 0.88, and at 90% specificity, the overall CRC sensitivity was 78%. The test successfully detected 83% of stage I, 73% of stage II, 76% of stage III and 87% of stage IV CRC. Furthermore, 59% of AA patients were identified with this classifier, which is greater than the current performance levels of FIT.

Conclusions
A rapid blood test that is sensitive to AA and early-stage CRC could substantially improve patient outcomes. This liquid biopsy can be fine-tuned to give a different balance of sensitivity and specificity depending on international healthcare markets. Current screening programmes have addressable shortcomings, and the emergence of new technologies is essential to support earlier CRC detection.