NIHR Signal New evidence confirms three-yearly surveillance interval for people at intermediate risk of bowel cancer

Published on 3 October 2017

People with benign growths (adenomas), who are at intermediate risk of bowel cancer, benefit from follow-up colonoscopy. However, some of the patients at the lower end of risk in this intermediate category may not benefit from more than one follow-up. 

This NIHR-funded cohort study reviewed data for 11,944 intermediate-risk patients from UK hospitals. Within this group, particular features were identified which placed them at higher risk, such as the presence of larger or highly abnormal adenomas or incomplete colonoscopy. These patients had half the risk of developing cancer if they attended one follow-up colonoscopy around three years later, and two-thirds the risk if they attended a second after around another three years. For people without these features, the benefits of ongoing surveillance were less clear.

This large-scale study showed that all intermediate-risk patients benefit from a follow-up examination, and colonoscopy at three years is an appropriate interval. This supports the current UK screening schedule. However, there is a subgroup of patients at lower risk who may not benefit from more than one follow-up examination.

It may be possible to reduce the frequency of screening for these people. A study of more recent data will be necessary to validate this finding.

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Why was this study needed?

Bowel (colorectal) cancer is the fourth most common cancer in the UK. An estimated 15,900 people died from bowel cancer in 2014. Bowel cancer costs the NHS around £1.1 billion a year. Early detection of bowel cancer is essential to give the best chance of survival.

Adenomas are small growths on the inner lining of the large bowel that can become cancerous. People with adenomas can be categorised as being at low, intermediate or high risk of cancer depending on the size and number of adenomas they have.

About half of people with adenomas are classified as intermediate risk. They currently receive colonoscopy screening for bowel cancer every three years. It’s not yet clear if this is the most effective schedule, or whether the number of examinations could be safely reduced for some people, or the time interval increased.

What did this study do?

This NIHR-funded study examined hospital records for 11,944 patients with intermediate-risk adenomas who had colonoscopies at 17 UK hospitals. Researchers compared this with data from 2,352 intermediate-risk people from two UK screening cohorts and one US screening program.  

Intermediate risk is defined as three or four adenomas smaller than10mm, or one or two adenomas with at least one of 10mm or larger. This was categorised as higher-intermediate risk if there was an adenoma of 20mm or larger, or with highly abnormal cells, polyps higher in the colon, no complete colonoscopy or poor bowel preparation. People with none of these features were defined as at lower-intermediate risk.

People with medical or hereditary conditions giving higher cancer risk were excluded.

There was a small amount of missing data, differences between those who attended follow-up or not (selection bias) and possible underestimation of the effect of surveillance and interval between screens. However, national data such as this is the best way to monitor screening outcomes on a large scale.

What did it find?

  • The UK hospital data showed an incidence rate of bowel cancer among all intermediate-risk patients of 206 per 100,000 people per year (95% confidence interval [CI] 177 to 240). A single follow-up colonoscopy reduced the risk of cancer compared with no follow-up (hazard ratio [HR] 0.51, 95% CI 0.34 to 0.77). Two follow-up visits further reduced risk (HR 0.32, 95% CI 0.17 to 0.61).
  • Over three-quarters of the people had higher-intermediate risk features. They had a higher risk of developing bowel cancer compared with the general population (standardised incidence rate [SIR] 1.26, 95% CI 1.02 to 1.53). All further follow-up reduced this risk so it was no longer statistically significant (SIR 1.13, 95% CI 0.96 to 1.32). Attending one follow-up colonoscopy reduced cancer risk by 50% (HR 0.50, 95% CI 0.34 to 0.76), and attending two or more follow-up visits further reduced risk (HR 0.36 95% CI 0.20 to 0.62).
  • Twenty-two percent of the hospital group was classed as at lower-intermediate risk. They already had lower cancer incidence than the general population (SIR 0.39, 95% CI 0.18 to 0.75). Attending a single follow-up colonoscopy did not significantly reduce cancer risk compared with not attending (HR 0.62, 95% CI 0.16 to 2.43). This suggests that risk classification could be revised for some people in the intermediate risk category, but this needs further looking into.      
  • Each yearly increase in the time interval between initial screening and first follow-up increased the chances of detecting new bowel cancer (OR [odds ratio] 1.32 95% CI 1.20 to 1.46) and advanced adenoma (OR 1.18, 95% CI 1.12 to 1.24) in all patients. The increased interval between first and second follow-up also increased the risk of advanced adenoma or cancer (OR 1.22, 1.09 to 1.36).
  • In the screening cohorts, the incidence of bowel cancer was 124 per 100,000 intermediate-risk patients per year (95% CI 88 to 176). Attending one follow-up visit reduced the risk of bowel cancer by 73% (HR 0.27, 95% CI 0.10 to 0.71). There didn’t appear to be further benefit from subsequent follow-up (HR 0.33, 95% CI 0.12 to 0.90). Unlike in the hospital patients, increasing screening interval had no effect on the detection of cancerous change. The smaller size of these cohorts suggests they be interpreted with caution.

What does current guidance say on this issue?

NICE guidelines (2011) recommend that people with intermediate-risk adenomas are offered colonoscopy at three years. If colonoscopy is negative, they should be offered the next colonoscopy at three years, and if this is negative surveillance should stop. If there are low or intermediate risk features, the next colonoscopy should be at three years. If there are high-risk features they should be offered the next colonoscopy at one year with follow-up surveillance as for high risk.

The British Society of Gastroenterology (2010) and Public Health England (2009) similarly recommend that intermediate-risk patients are screened every three years until two consecutive examinations are negative.

What are the implications?

Colonoscopies are invasive and expensive. It’s important that patients undergo the minimum number of procedures needed for effective prevention of bowel cancer.

This study supports current recommendations that patients with intermediate-risk adenomas have follow-up surveillance after three years. They suggest that one follow-up could be sufficient for a subgroup without higher-risk features.

The quality of colonoscopy is likely to have improved over the past decades (hospital data came from 1984 to 2010). Further evaluation of recent data could help to clarify higher-risk signs and determine if some patients could safely move to a less intensive screening schedule.

Citation and Funding

Atkin W, Brenner A, Martin J, et al. The clinical effectiveness of different surveillance strategies to prevent colorectal cancer in people with intermediate-grade colorectal adenomas: a retrospective cohort analysis, and psychological and economic evaluations. Health Technol Assess. 2017;21(25):1-536.

This project was funded by the National Institute for Health Research [Health Technology Assessment Programme] (04/33/01) and supported by The Bobby Moore Fund for Cancer Research UK (C8171/A16894).

Bibliography

Atkin WS, Valori R, Kuipers EJ, et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition: Colonoscopic surveillance following adenoma removal. Endoscopy. 2012;44 Suppl 3:E151-63.

Cairns SR, Scholefield JH, Steele RJ, et al, on behalf of The British Society of Gastroenterology and the Association of Coloproctology. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002) Gut. 2010;59:666-90.

Cancer Research UK. Bowel Cancer Statistics. London: Cancer Research UK; 2014.

NHS Choices. Bowel polyps. London: Department of Health; 2014.

NHS Choices. Bowel cancer – diagnosis. London: Department of Health; 2015.

NICE. Colorectal cancer prevention: colonoscopic surveillance in adults with ulcerative colitis, Crohn’s disease or adenomas. CG118. London: National Institute for Health and Care Excellence; 2011.

Public Health England. Guidance: Health matters: improving the prevention and diagnosis of bowel cancer. Public health England; 2016

Public Health England. Guidance: Bowel cancer screening: programme overview. Public Health England; 2015.

Public Health England. Adenoma surveillance. BSCP Guidance Note. Sheffield: NHS Cancer Screening Programmes; 2009.

York Health Economics Consortium, University of York, School of Health and Related Research, University of Sheffield.  Bowel Cancer Services: costs and benefits. Summary report to the Department of Health. York Health Economics Consortium; 2007.

Why was this study needed?

Bowel (colorectal) cancer is the fourth most common cancer in the UK. An estimated 15,900 people died from bowel cancer in 2014. Bowel cancer costs the NHS around £1.1 billion a year. Early detection of bowel cancer is essential to give the best chance of survival.

Adenomas are small growths on the inner lining of the large bowel that can become cancerous. People with adenomas can be categorised as being at low, intermediate or high risk of cancer depending on the size and number of adenomas they have.

About half of people with adenomas are classified as intermediate risk. They currently receive colonoscopy screening for bowel cancer every three years. It’s not yet clear if this is the most effective schedule, or whether the number of examinations could be safely reduced for some people, or the time interval increased.

What did this study do?

This NIHR-funded study examined hospital records for 11,944 patients with intermediate-risk adenomas who had colonoscopies at 17 UK hospitals. Researchers compared this with data from 2,352 intermediate-risk people from two UK screening cohorts and one US screening program.  

Intermediate risk is defined as three or four adenomas smaller than10mm, or one or two adenomas with at least one of 10mm or larger. This was categorised as higher-intermediate risk if there was an adenoma of 20mm or larger, or with highly abnormal cells, polyps higher in the colon, no complete colonoscopy or poor bowel preparation. People with none of these features were defined as at lower-intermediate risk.

People with medical or hereditary conditions giving higher cancer risk were excluded.

There was a small amount of missing data, differences between those who attended follow-up or not (selection bias) and possible underestimation of the effect of surveillance and interval between screens. However, national data such as this is the best way to monitor screening outcomes on a large scale.

What did it find?

  • The UK hospital data showed an incidence rate of bowel cancer among all intermediate-risk patients of 206 per 100,000 people per year (95% confidence interval [CI] 177 to 240). A single follow-up colonoscopy reduced the risk of cancer compared with no follow-up (hazard ratio [HR] 0.51, 95% CI 0.34 to 0.77). Two follow-up visits further reduced risk (HR 0.32, 95% CI 0.17 to 0.61).
  • Over three-quarters of the people had higher-intermediate risk features. They had a higher risk of developing bowel cancer compared with the general population (standardised incidence rate [SIR] 1.26, 95% CI 1.02 to 1.53). All further follow-up reduced this risk so it was no longer statistically significant (SIR 1.13, 95% CI 0.96 to 1.32). Attending one follow-up colonoscopy reduced cancer risk by 50% (HR 0.50, 95% CI 0.34 to 0.76), and attending two or more follow-up visits further reduced risk (HR 0.36 95% CI 0.20 to 0.62).
  • Twenty-two percent of the hospital group was classed as at lower-intermediate risk. They already had lower cancer incidence than the general population (SIR 0.39, 95% CI 0.18 to 0.75). Attending a single follow-up colonoscopy did not significantly reduce cancer risk compared with not attending (HR 0.62, 95% CI 0.16 to 2.43). This suggests that risk classification could be revised for some people in the intermediate risk category, but this needs further looking into.      
  • Each yearly increase in the time interval between initial screening and first follow-up increased the chances of detecting new bowel cancer (OR [odds ratio] 1.32 95% CI 1.20 to 1.46) and advanced adenoma (OR 1.18, 95% CI 1.12 to 1.24) in all patients. The increased interval between first and second follow-up also increased the risk of advanced adenoma or cancer (OR 1.22, 1.09 to 1.36).
  • In the screening cohorts, the incidence of bowel cancer was 124 per 100,000 intermediate-risk patients per year (95% CI 88 to 176). Attending one follow-up visit reduced the risk of bowel cancer by 73% (HR 0.27, 95% CI 0.10 to 0.71). There didn’t appear to be further benefit from subsequent follow-up (HR 0.33, 95% CI 0.12 to 0.90). Unlike in the hospital patients, increasing screening interval had no effect on the detection of cancerous change. The smaller size of these cohorts suggests they be interpreted with caution.

What does current guidance say on this issue?

NICE guidelines (2011) recommend that people with intermediate-risk adenomas are offered colonoscopy at three years. If colonoscopy is negative, they should be offered the next colonoscopy at three years, and if this is negative surveillance should stop. If there are low or intermediate risk features, the next colonoscopy should be at three years. If there are high-risk features they should be offered the next colonoscopy at one year with follow-up surveillance as for high risk.

The British Society of Gastroenterology (2010) and Public Health England (2009) similarly recommend that intermediate-risk patients are screened every three years until two consecutive examinations are negative.

What are the implications?

Colonoscopies are invasive and expensive. It’s important that patients undergo the minimum number of procedures needed for effective prevention of bowel cancer.

This study supports current recommendations that patients with intermediate-risk adenomas have follow-up surveillance after three years. They suggest that one follow-up could be sufficient for a subgroup without higher-risk features.

The quality of colonoscopy is likely to have improved over the past decades (hospital data came from 1984 to 2010). Further evaluation of recent data could help to clarify higher-risk signs and determine if some patients could safely move to a less intensive screening schedule.

Citation and Funding

Atkin W, Brenner A, Martin J, et al. The clinical effectiveness of different surveillance strategies to prevent colorectal cancer in people with intermediate-grade colorectal adenomas: a retrospective cohort analysis, and psychological and economic evaluations. Health Technol Assess. 2017;21(25):1-536.

This project was funded by the National Institute for Health Research [Health Technology Assessment Programme] (04/33/01) and supported by The Bobby Moore Fund for Cancer Research UK (C8171/A16894).

Bibliography

Atkin WS, Valori R, Kuipers EJ, et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First edition: Colonoscopic surveillance following adenoma removal. Endoscopy. 2012;44 Suppl 3:E151-63.

Cairns SR, Scholefield JH, Steele RJ, et al, on behalf of The British Society of Gastroenterology and the Association of Coloproctology. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002) Gut. 2010;59:666-90.

Cancer Research UK. Bowel Cancer Statistics. London: Cancer Research UK; 2014.

NHS Choices. Bowel polyps. London: Department of Health; 2014.

NHS Choices. Bowel cancer – diagnosis. London: Department of Health; 2015.

NICE. Colorectal cancer prevention: colonoscopic surveillance in adults with ulcerative colitis, Crohn’s disease or adenomas. CG118. London: National Institute for Health and Care Excellence; 2011.

Public Health England. Guidance: Health matters: improving the prevention and diagnosis of bowel cancer. Public health England; 2016

Public Health England. Guidance: Bowel cancer screening: programme overview. Public Health England; 2015.

Public Health England. Adenoma surveillance. BSCP Guidance Note. Sheffield: NHS Cancer Screening Programmes; 2009.

York Health Economics Consortium, University of York, School of Health and Related Research, University of Sheffield.  Bowel Cancer Services: costs and benefits. Summary report to the Department of Health. York Health Economics Consortium; 2007.

The clinical effectiveness of different surveillance strategies to prevent colorectal cancer in people with intermediate-grade colorectal adenomas: a retrospective cohort analysis, and psychological and economic evaluations

Published on 3 May 2017

Atkin W, Brenner A, Martin J, Wooldrage K, Shah U, Lucas F, Greliak P, Pack K, Kralj-Hans I, Thomson A, Perera S, Wood J, Miles A, Wardle J, Kearns B, Tappenden P, Myles J, Veitch A & Duffy S W.

Health Technology Assessment Volume 21 Issue 25 , 2017

Background The UK guideline recommends 3-yearly surveillance for patients with intermediate-risk (IR) adenomas. No study has examined whether or not this group has heterogeneity in surveillance needs. Objectives To examine the effect of surveillance on colorectal cancer (CRC) incidence; assess heterogeneity in risk; and identify the optimum frequency of surveillance, the psychological impact of surveillance, and the cost-effectiveness of alternative follow-up strategies. Design Retrospective multicentre cohort study. Setting Routine endoscopy and pathology data from 17 UK hospitals (n = 11,944), and a screening data set comprising three pooled cohorts (n = 2352), followed up using cancer registries. Subjects Patients with IR adenoma(s) (three or four small adenomas or one or two large adenomas). Primary outcomes Advanced adenoma (AA) and CRC detected at follow-up visits, and CRC incidence after baseline and first follow-up. Methods The effects of surveillance on long-term CRC incidence and of interval length on findings at follow-up were examined using proportional hazards and logistic regression, adjusting for patient, procedural and polyp characteristics. Lower-intermediate-risk (LIR) subgroups and higher-intermediate-risk (HIR) subgroups were defined, based on predictors of CRC risk. A model-based cost–utility analysis compared 13 surveillance strategies. Between-group analyses of variance were used to test for differences in bowel cancer worry between screening outcome groups (n = 35,700). A limitation of using routine hospital data is the potential for missed examinations and underestimation of the effect of interval and surveillance. Results In the hospital data set, 168 CRCs occurred during 81,442 person-years (pys) of follow-up [206 per 100,000 pys, 95% confidence interval (CI) 177 to 240 pys]. One surveillance significantly lowered CRC incidence, both overall [hazard ratio (HR) 0.51, 95% CI 0.34 to 0.77] and in the HIR subgroup (n = 9265; HR 0.50, 95% CI 0.34 to 0.76). In the LIR subgroup (n = 2679) the benefit of surveillance was less clear (HR 0.62, 95% CI 0.16 to 2.43). Additional surveillance lowered CRC risk in the HIR subgroup by a further 15% (HR 0.36, 95% CI 0.20 to 0.62). The odds of detecting AA and CRC at first follow-up (FUV1) increased by 18% [odds ratio (OR) 1.18, 95% CI 1.12 to 1.24] and 32% (OR 1.32, 95% CI 1.20 to 1.46) per year increase in interval, respectively, and the odds of advanced neoplasia at second follow-up increased by 22% (OR 1.22, 95% CI 1.09 to 1.36), after adjustment. Detection rates of AA and CRC remained below 10% and 1%, respectively, with intervals to 3 years. In the screening data set, 32 CRCs occurred during 25,745 pys of follow-up (124 per 100,000 pys, 95% CI 88 to 176 pys). One follow-up conferred a significant 73% reduction in CRC incidence (HR 0.27, 95% CI 0.10 to 0.71). Owing to the small number of end points in this data set, no other outcome was significant. Although post-screening bowel cancer worry was higher in people who were offered surveillance, worry was due to polyp detection rather than surveillance. The economic evaluation, using data from the hospital data set, suggested that 3-yearly colonoscopic surveillance without an age cut-off would produce the greatest health gain. Conclusions A single surveillance benefited all IR patients by lowering their CRC risk. We identified a higher-risk subgroup that benefited from further surveillance, and a lower-risk subgroup that may require only one follow-up. A surveillance interval of 3 years seems suitable for most IR patients. These findings should be validated in other studies to confirm whether or not one surveillance visit provides adequate protection for the lower-risk subgroup of intermediate-risk patients. Funding The National Institute for Health Research Health Technology Assessment programme.

Adenoma risk classification:

  • Low risk: one or two small adenomas measuring <10mm in diameter.
  • Intermediate risk: three or four small adenomas <10mm, or at least one measuring ≥10mm.
  • High risk: five or more small adenomas <10mm, or three or more measuring ≥10mm.

Advanced adenoma was defined as one adenoma measuring >10mm, or with villous or tubulo-villous structure or highly abnormal cells on microscopic examination.

Expert commentary

Current practice for surveillance of patients with intermediate-risk adenomas is a colonoscopy at three years. The value of this study is to add evidence to the fact that this timeframe is correct. In addition, this study confirms that one surveillance endoscopy in this group reduces the risk of them developing colorectal cancer.

Another important finding is that patient anxiety about the procedure is offset by their concerns about developing cancer, which may be useful when explaining follow-up to patients. The finding of cohorts that receive more or less benefit from surveillance should prompt further research into those patients.

Mr Kenneth Keogh, ST8 Colorectal Surgery, Royal Devon and Exeter Hospital

Categories

  •   Cancers, Gastrointestinal disorders, Screening, Acute and general medicine