From Stephen Halloran:

Hi Ihssan,

Thanks for your enquiry. I'm no longer on the ACB mail-base but several colleagues have kindly forwarded your enquiry.

You may know that I was the lead author of the EU guidelines on the CRC screening test and chair the World Endoscopy Organisations' Screening Committee on 'Fit for Screening'. This latter organisation is working to both promote the adoption of FIT across the world but also work with all involved to enhance the quality of FIT systems and their use in population-based screening programmes. I guess you will have read the recent review paper on CRC screening by my colleague Linda Rabeneck. Linda is an active member of the WEO group and she will be a good source of local knowledge and policy.

The Department of Health in England has made a commitment to move from guaiac to FIT testing as soon as possible and currently the rate limiting factors are both software development for population-based screening (all 55 year olds) of the logistics of FS rollout. I am progressing and supporting the rollout of a trial FIT programme in England in late 2013 and am currently performing a comparative evaluation of the all FIT systems which meet the minimum criteria for population-based screening (currently only 4) and this will inform tendering processes in 2014. The trial is likely to use the OC-Sensor /Diana system from Eiken and for the evaluation will adopt a cut-off of 100 ng Hb/mL buffer. Remember that this concentration relates only to that specific device / system because it will be influenced by faecal sampling mass and the volume of buffer.

Unlike many lab tests the choice of cut-off concentration is not based purely on clinical grounds. The lower the cut-off the larger the number of colonoscopies, the greater the necessary resource and cost, the larger the number of detected cancers and advanced adenomas and thus the more effective in reducing incident cancers and mortality. The further rider to this is that with a lower cut-off the greater the potential harm from perforation and in the extreme the potential for mortality amongst healthy individuals.

Companies ofter recommended on the use of two devices (a hang over from the use of guaiac cards) and a cut-off which was not very firmly based on clinical evidence. Van Rossum and Ernst Kuipers in the Netherlands have demonstrated that a single device is adequate and they have explored the relationship between cut-off concentration and numbers needed to scope (NNS), clinical outcomes and cost effectiveness using OC-Sensor. The Dutch government are now committed to start screening and a programme and timescale have been published. Tendering has resulted in them adopting the FOB Gold /Sysmex system and therefore they now have to investigate the reliability and clinical efficacy of this system prior to adoption. I know calculations have been done to convert their chosen OC-Sensor cut-off of 75ng/mL to a potential equivalent for FOB gold but they will need to test this in vitro and in vivo. Italy are using 100ng/mL with the OC Sensor (and have done so for perhaps 6 years) as are Malta and Southern Ireland. 75ng/mL is being used for the Pilot programme in New Zealand (in Auckland). Slovenia changed from Magstream to OC Sensor and I think are using 100 ng/mL. Israel do not have wide coverage and use a mixture of systems but have tried using much lower cut-offs. Scotland did a short study with a very high cut-off which gave a positivity rate of close to 2% to match their guaiac system this gave a better uptake but did not enhance clinical outcomes.

The choice is therefore mostly dictated by endoscopy resource, with OC-Sensor and a 100ng/mL cut-off you should expect 6% positivity with variation depending on the prevalence of CRC and the socioeconomic demographics, at 50ng/mL expect 9 – 12% and at 400ng/mL 2 –2.5% positivity. Remember that the tests are sensitive to Hb degradation (Australian experience of 50% reduction in positivity over a hot summer) and my published work with colleagues in Florence which shows a 13% reduction in cancer pickup during the summer – similar effect but less dramatic in the Netherlands. Companies are enhancing the preservatives properties of their buffers but, by doing so, are likely to affect the accuracy of the analysis.

Hope this is of value – happy to discuss.

I include Linda's publication and my EU chapter for interest.

overview article “European guidelines for quality assurance in colorectal cancer screening and diagnosis: Overview and introduction to the full Supplement publication” is now published online and available at:

https://www.thieme-connect.de/ejournals/issue/eFirst/10.1055/s-00000012

The article is ‘Open Access’ and may be downloaded free of charge.

Grazzini, G., Zappa, M., Ventura, L., Rubeca, T., & Halloran, S. P. (2011, September 1). Different seasons with decreased performance of immunochemical faecal occult blood tests in colorectal cancer screening Response. GUT, 60(9), 1304. doi:10.1136/gut.2010.226241

Fraser, C. G., Allison, J. E., Allison, J. E., Young, G. P., & Halloran, S. P. (2012, June). Newer fecal tests: Opportunities for professionals in laboratory medicine. Clinical Chemistry, 58(6), 963-965. doi:10.1373/clinchem.2012.185025

Young, G. P., Fraser, C. G., Halloran, S. P., & Cole, S. (2012, July). Guaiac based faecal occult blood testing for colorectal cancer screening: An obsolete strategy?. Gut, 61(7), 959-960. doi:10.1136/gutjnl-2011-301810

Fraser, C. G., Allison, J. E., Halloran, S. P., Young, G. P., & on behalf of the Expert Working Group on Fecal Immunochemical Tests for Hemoglobin, Colorectal Cancer Screening Committee, World Endoscopy Organization. (2012, April 2). A Proposal to Standardize Reporting Units for Fecal Immunochemical Tests for Hemoglobin.. J Natl Cancer Inst. doi:10.1093/jnci/djs190

Halloran, S. P. (2009, September). Bowel cancer screening. Surgery, 27(9), 397-400. doi:10.1016/j.mpsur.2009.08.013

Allison, J. E., Allison, J. E., Fraser, C. G., Halloran, S. P., & Young, G. P. (2012, March). Comparing fecal immunochemical tests: Improved standardization is needed. Gastroenterology, 142(3), 422-424. doi:10.1053/j.gastro.2012.01.015

Whyte, S., Chilcott, J., & Halloran, S. (2012, March 5). Re-appraisal of the options for colorectal cancer screening in England.. Colorectal Dis. doi:10.1111/j.1463-1318.2012.03014.x

Grazzini, G., Zappa, M., Ventura, L., Rubeca, T., & Halloran, S. P. (2011, March 1). Seasonal variations of immunochemical and gaiac faecal occult blood tests Reply. GUT, 60(3), 424. doi:10.1136/gut.2010.230573

Grazzini, G., Zappa, M., Ventura, L., Rubeca, T., & Halloran, S. P. (2011, March). The Authors' reply. Gut, 60(3), 424. doi:10.1136/gut.2010.230573

Grazzini, G., Zappa, M., & Halloran, S. P. (2012, January). The authors' reply. Gut, 61(1), 162. doi:10.1136/gut.2011.237479

Duffy, M. J., van Rossum, L. G. M., van Turenhout, S. T., Malminiemi, O., Sturgeon, C., Lamerz, R., . . . Halloran, S. P. (2011, January 1). Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper. INTERNATIONAL JOURNAL OF CANCER, 128(1), 3-11. doi:10.1002/ijc.25654

Best wishes,

Stephen

Stephen P. Halloran MBE FRCPath

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Consultant Biochemist: Royal Surrey County Hospital, Guildford Tel:- 01483 464121
Director: Bowel Cancer Screening Hub – South of England Tel:- 01483 688553
Director: GMEC Guildford Medical devices Evaluation Centre (NHS PaSA/CEP) Tel:- 01483 688553
Professor: University of Surrey

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