Impact of changes to the interscreening interval and faecal immunochemical test threshold in the national bowel cancer screening programme in England: results from the FIT pilot study

“The Bowel Cancer Screening Programme is one of the best ways to diagnose bowel cancer early, or in some cases prevent it from developing in the first place.” Genevieve Edwards, Chief Executive, Bowel Cancer UK
Impact of changes to the interscreening interval and faecal immunochemical test threshold in the national bowel cancer screening programme in England: results from the FIT pilot study
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Why is bowel cancer screening important?

Colorectal Cancer (CRC), also known as bowel cancer, is the fourth most common cancer and the second most common cause of cancer death in the UK. 1 Cancer Research UK has estimated that 54% of CRC cases are preventable, and that almost all (98%) people with bowel cancer will survive their disease for one year or more when diagnosed at its earliest stage. 1 Both accentuate the importance of an efficient screening programme for reducing incidence and mortality rates from CRC.

Current bowel cancer screening in England

Currently in England, women and men aged 60 to 74 years* are invited for a CRC screening every two years. They are first sent a home testing kit faecal immunochemical test (FIT), which measures the faecal haemoglobin concentration (f-Hb), i.e., blood level in collected faecal sample. If the f-Hb is 120 μg/g (positivity threshold) or more, they are referred a hospital visit, and typically an colonoscopy for further diagnostics. 2

FIT has high sensitivity depending on the positivity threshold used, 2,3 and has been shown to lead to more favourable stage at diagnosis and reduced mortality from the disease. It can also detect bleeding from adenomas which can then be removed during a colonoscopy , preventing progression to cancer and reducing cancer incidence, but sensitivity to adenomas is low unless the f-Hb threshold is very low, and therefore the effect on incidence is generally small. On the other hand, endoscopic screening (such as colonoscopy) can detect precancerous adenomas in large numbers, substantially reducing cancer incidence. 4,5

 * Some regions may have adopted a lower starting age, as low as 50, depending on local health resources.

What’s the issue?

The screening service, particularly the colonoscopy capacity is stretched by recovering from the COVID-19 pandemic, additional hygiene procedures to minimise risk of transmitting COVID-19, and the recent move to a lowered starting age of between 50 to 60 years (depending on local resources). It may be timely to consider other screening options, starting with estimating the impact of alternative intervals between screens and/or f-Hb thresholds for FIT positivity, to identify options to minimise effects of increasing demand and/or restrictions in capacity.   

What have we estimated?

In this paper, we based all our estimates on every 100,000 individuals screened, and over a 15-year period as it is the typical lifetime span of screening. Firstly, we estimated sensitivity and the mean sojourn time (MST: the average duration of the presymptomatic screen-detectable phase of the cancer) for a range of f-Hb thresholds; then for different combinations of interval and threshold, the consequent demand on colonoscopy; lastly we derived estimates on the number of benefiting individuals in terms CRC (both screen-prevented and screen-detected), adenomas and advanced adenomas detected; as well as interval cancers prevented (the cancer which would have arisen in-between two screens had it not been detected at screening), and the number deaths prevented. Estimates are derived from the FIT pilot study performed in England in 2014, in which 27,238 persons were screened with FIT. 4, 16

What did we find?

As one would expect, both the frequency of screening (interscreening interval) and the positive threshold for referral have very strong effects on the benefits in terms of early detection, prevention, and reduction in mortality, and on the numbers of colonoscopies required. The number of colonoscopy slots available is an unavoidable constraint on screening, and our results suggest that in tailoring the programme to colonoscopy availability, alteration of the threshold for a positive test seems to be a more effective tactic than changing the interval (although both could be done at once). For example, if we needed to reduce the current numbers of colonoscopies by about one third, this could be achieved by either changing the interval from two to three years or changing the threshold from 120 µg/g to 180µg/g. (Figures 1&2) However, we estimated the lives lost due to the latter change would be considerably fewer – around 400 lives for every 3 million screened over 15 years.  

Combined changes to both threshold and frequency can be very powerful. For example, we could increase the numbers of lives saved by around 40% by screening annually instead of two-yearly and maintaining the current threshold. However, this would require an almost 100% increase in the number of colonoscopies needed. Changing the interval to three-yearly but lowering the threshold to 40 would achieve a similar saving of lives while only increasing colonoscopies by around 50%.

Figure 1. Estimated number of CRC prevented, detected and benefited from screening over 15 years on per 100,000 individuals.Caption

Figure 2. Estimated demand on colonoscopy and benefit in adenoma and advanced adenoma detection from screening over 15 years on per 100,000 individuals.Caption

Something different?

Our paper also recommends an alternative multi-pathway programme which utilise the fact FIT can measure the exact blood level in faecal samples (as opposed to binary results). Below is an example:

  • Undetectable f-Hb: delay next screen to three years;
  • Very low f-Hb: next screen in two years;
  • Low f-Hb: repeat screening test in three months to assess persistence of bleeding;
  • Medium f-Hb: flexible sigmoidoscopy to examine the lower part of the colon (distal), and remove any abnormalities found, followed by a further FIT to ascertain whether the cause of the bleeding has been removed;
  • High f-Hb: colonoscopy.

So…?

In conclusion, our results provide an evidence base for policymakers to optimise the programme based on the dynamic capacity of endoscopy and National Health Service (NHS) resource. Additionally, our paper highlighted the potential in utilising the FIT results more fully, with multiple diagnostic pathways depending on the level of f-Hb.7

Behind the paper story

In this paper, we estimated the impact on pre-cancerous lesions such as adenomas and advanced adenomas in addition to that of cancers and deaths. For this, we give special thanks to Professor Steve Coad and Professor Charles Knowles, who emphasised the need to value one’s quality of life no less than one’s actually life. They noted that clinically, although patients detected with the earliest stage of bowel cancer have good survival, their normal lives may not return; however, patients treated for pre-cancerous lesions such as adenomas are much more likely to regain their usual quality of life back after treatment. Therefore, in designing an effective screening programme, we must consider beyond the number of lives saved and cancers detected, to also estimate the impact on prevention. Ultimately CRC screening is for both detection and prevention.

Reference

  1. Cancer research UK. Bowel cancer statistics: bowel cancer incidence [Internet]; [cited 23rd June 2022]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer#heading-Zero.
  2. Moss S, Mathews C, Day TJ, Smith S, Seaman HE, Snowball J, et al. Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England. Gut. 2017;66(9):1631-44.
  3. Lee, Jeffrey K et al. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Annals of internal medicine vol. 160(3): 171. (2014)
  4. Roselló S, Simón S, Cervantes A. Programmed colorectal cancer screening decreases incidence and mortality. Translational gastroenterology and hepatology. 2019;4:84.
  5. Cardoso R, Guo F, Heisser T, Hackl M, Ihle P, De Schutter H. et al. Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study. The Lancet Oncology. 2021 Jul 1;22(7):1002-13.
  6. NHS England and NHS Improvement. Roll out of the new bowel cancer screening test – faecal immunochemical test (FIT) briefing for GPs: not for wider distribution (PAC reference 000603)[Internet]; 2019 [cited 23rd October 2020]. Available from: https://www.england.nhs.uk/south/wp-content/uploads/sites/6/2019/06/fit-gp-briefing-sheet.pdf.
  7. Li SJ, Sharples LD, Benton SC, Blyuss O, Mathews C, Sasieni P, Duffy SW. Faecal immunochemical testing in bowel cancer screening: Estimating outcomes for different diagnostic policies. J Med Screen. 2020 Dec 20:969141320980501.

 

Contributions and Funding

SJL and TS were supported by the National Institute for Health Research (NIHR) Research Methods Fellowship & Internship 2017 (Grant number RM-FI-2017-09-004). SWD and PS’s contribution to this work was part-funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis, PR-PRU-1217-21601. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

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