To Evaluate the Sensitivity and Specificity of a Test Kit in Hong Kong Clinical Trial
Official title:
The Diagnostic Accuracy of Using Faecal-DNA Test (COLOSAFE) for Colorectal Cancer Screening
To evaluate the sensitivity and specificity of the test kit "COLOSAFE' in Hong Kong
Colorectal cancer (CRC) remains to be a leading cause of cancer mortality [1]. It induces a
substantial financial burden in terms of healthcare utilization and quality-adjusted life
years (QALY) lost [2]. Fecal Occult Blood Tests (FOBT) and colonoscopy were proven effective
in reducing CRC mortality by 33% and 68%, respectively [3-5]. Both tests have been proposed
as primary screening modalities for asymptomatic subjects by international guidelines and
Asia Pacific consensus statements [6-8]. However, colonoscopy has a low compliance rate at
approximately 20% in Chinese populations, and has been perceived by screening participants as
invasive, expensive and inconvenient due to the need for bowel preparation [9, 10]. In
addition, the accuracy of FOBT is limited and its adherence declined sharply over time [11,
12]. Hence, the recent decade witnessed a rapid development of non-invasive biomarkers to
detect CRC.
Faecal-DNA test is a novel screening test for CRC, using molecular techniques to identify
CRC-relevant biomarkers in stool. One of its toolkits, branded 'ColoGuard' (sDNA, Exact
Sciences), was first approved by the FDA in 2014 for its application in clinical practice
[13]. It consists of quantitative molecular assays for KRAS mutations, aberrant NDRG4 and
BMP3 methylation, and β-actin, and a hemoglobin immunoassay [13], which has been widely
promoted in US. In 2016, it was endorsed by the United States Preventive Service Task Force
(USPSTF) as one of the recommended screening tests [14].
Recently, a test kit named 'COLOSAFE' (or namedChang An Xin) has been developed as a
faecal-DNA product targeted to improve diagnostic accuracy of CRC screening [15]. It is a
stool test of methylated SDC2 for detection of CRC. This stool test of methylated SDC2
detected 81.1% of CRC and 58.2% of adenomas at a specificity of 93.3%. SDC2 is also named
fibroglycan, encoding a type I trans-membrane heparansulfate proteoglycan. In certain cancers,
hypermethylation of SDC2 had been reported. Recent studies showed that methylated SDC2 was
detected at high frequency in blood from CRC patients [16, 17]. As tumor cells are exfoliated
into the gut lumen earlier than vascular invasion when CRC develops [18], faecal sample could
represent a more suitable specimen than plasma for detection of early cancer.
A recent study involving 1,200 subjects from 2015 to 2017 by the Sixth Affiliated Hospital of
Sun Yat-sen University, Nanfang Hospital of Southern Medical University and Shandong Cancer
Hospital showed that the 'COLOSAFE' test kit attained a sensitivity of 85% while maintaining
a specificity of 98% (unpublished data). Because of its novelty, the 'COLOSAFEtest kit was
recognized as a 'creative medical apparatus' by the National CFDA in March 2017. In June
2017, the project 'Screening and intervention research of Chinese CRC' (2017YFC 1308800) was
launched with national key project for non-communicable disease control. Nevertheless, there
are limitations with the design of the original study [15]. For instance, it involved a
small, single-centre that recruited a homogeneous sample of individuals only. An important
knowledge gap exists and additional clinical trials are required to further validate its
diagnostic accuracy in other populations.
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