Colorectal Cancer
Clinical Performance
The clinical performance of the Epi proColon realtime PCR kit was tested in a case–control design comprising specimens from histologically confirmed invasive colorectal adenocarcinoma patients of all stages and specimens from colonoscopy-verified negative individuals with no apparent disease. Bisulphite-converted DNA was prepared using the Epi proColon Plasma DNA Preparation kit from 261 plasma aliquots from individual subjects and converted DNA was assayed with the Epi proColon realtime PCR kit. Based on internal and external control values for each run, valid mSEPT9 measurements were determined for 257 out of 261 specimens (98.5%). Of the 154 subjects with no evidence of disease (controls), 135 specimens were determined mSEPT9-negative, resulting in an estimated clinical specificity of 88% (95% confidence interval [CI] 82–92%). Of the 103 subjects diagnosed with invasive colorectal adenocarcinoma (cases), 69 specimens were determined mSEPT9- positive, resulting in an estimated clinical sensitivity of 67% (95% CI 57–76%). mSEPT9 was positive in 44 of the 66 patients with cancer in early, still localised disease states (44 stage I, 22 stage II). Table 2 summarises the results.
PRESEPT
Prospective Evaluation of Septin 9 Performance for Colorectal Cancer Screening (PRESEPT) is a multicentre clinical study sponsored by
Epigenomics to prospectively evaluate the clinical performance of mSEPT9 for colorectal cancer screening, as defined by the US Multisociety Task Force on Colorectal Cancer. This study provided data within the framework of a real screening setting with a presumably low prevalence of CRC (estimated 50 cancers from about 7,500 screening cases), in contrast to many other tests with data only from case–control studies. Clinical data obtained under International Conference on Harmonisation/World Health Organization Good Clinical Practice (ICH/GCP) control focus mainly on CRC detection as the main outcome measure, but will also provide data on polyp detection such as advanced adenomas and others as secondary study aims. Health economic analyses will be performed to assess the possible economic benefit. The study was closed in December 2009 with 7,914 individuals enrolled and 51 cancers detected, and the first
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preliminary results are to be expected in April 2010 after plasma has been tested at three testing centres, two in the US and one in Germany. Results of the PRESEPT study will provide objective evidence of the performance of mSEPT9-based CRC screening.
Conclusions and Outlook
The newly developed mSEPT9 early detection assay (Epi proColon) is the first CE-marked IVD assay for early detection of CRC in a blood plasma specimen. The design and robustness of the IVD assay enables its use in standard routine laboratory procedures. The convenience of the test for the patient and the PCP has the potential to improve patient compliance with CRC screening. The Epi proColon test now makes it possible to screen patients for CRC who might not otherwise be detected due to their denial of other screening modalities. What role this test will play in the concert of screening measures has to be determined after the results of the PRESEPT trial and further studies on compliance and cost–benefit. n
Gunter Weiss is Vice President of Product Development at Epigenomics AG, where he heads the development of colorectal-cancer-related diagnostic products. Previously, he worked at the Max Planck Institute for Evolutionary Anthropology in Leipzig, and latterly as a Professor of Bioinformatics at the University of Düsseldorf. His research interests include the molecular evolution of cancer and molecular diagnostics. Dr Weiss received both his diploma in statistics and his PhD in biology from the University of Munich.
Thomas Rösch is Director of the Department of Interdisciplinary Endoscopy at the University Hospital Hamburg-Eppendorf and a Full Professor of Medicine in the Department of Internal Medicine II at the Technical University of Medicine in Munich. In 2004, he was appointed Chief of Endoscopy and Professor of Diagnostic and Therapeutic Endoscopy at the University of Medicine Berlin. Professor Rösch is the author of over 230 publications and numerous review articles, and has
been Editor in Chief of Endoscopy since 2004. He is a member of the boards of the German Society of Gastroenterology (DGVS) and of its endoscopic section. Since 2008, Professor Rösch has been a member of the organisational board of Endoclub Nord, the largest endoscopic live demonstration meeting worldwide.
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