NIHR Signal Intensive follow-up following curative bowel cancer surgery may detect recurrent cancers sooner but does not improve survival

Published on 28 February 2017

Intensive follow-up of patients who have been successfully treated for bowel cancer does not improve survival outcomes compared to less intensive follow-up.

This systematic review included 15 randomised controlled trials comparing different intensities of follow-up. Protocols varied in terms of the number of tests, appointments or their setting (e.g. GP or hospital) - none of them affected survival.

More intensive follow-up did however detect recurrent cancers sooner, and patients were twice as likely to undergo surgery again as a result. Evidence is limited for other outcomes, such as how different protocols impact cost or quality of life; on-going trials may shed light on this.  

Nevertheless, bowel cancer follow-up is time consuming and uses scarce NHS resources such as colonoscopy. If less intensive follow-up offers similar survival outcomes as more intensive approaches this may offer opportunities for savings.

Share your views on the research.

Why was this study needed?

Around 40,000 new cases of bowel cancer (colorectal cancer) are diagnosed each year in the UK. This means 1 in 20 people could develop it during their lifetime. Surgery is usually the main treatment and if caught early enough there is a good chance the cancer will be removed entirely.

However, in about 50% of successfully treated patients the cancer will return and spread to other organs (metastatic). Patients are therefore usually offered follow-up appointments after their operation. Although NICE guidance outlines what follow-up should be provided, there is some variation according to individual circumstances and local Trust policy. Follow-up is time and resource heavy, often including numerous appointments, CT scans, colonoscopies and blood tests, over a span of five years or more.

This review aimed to investigate whether more intense follow-up, in terms of the number of tests, frequency of appointments or the setting, is associated with improved patient outcomes.

What did this study do?

This systematic review identified 15 randomised controlled trials that compared different follow-up strategies for 5403 people successfully treated for non-metastatic bowel cancer.

Studies compared intensive with less intensive follow-up regimens, though intensity was variably defined. Seven trials compared more versus fewer visits and tests; four compared follow-up versus no or minimal follow-up; four compared more versus less liver imaging; four compared follow-up with and without blood tests for carcinoembryonic antigen (CEA, a cancer marker); two compared surgeon versus GP-led follow-up, and one compared surgeon versus nurse-led follow-up.

Two trials each were performed in Australia, Finland and Italy, and one in China, Denmark, France, Italy, Norway, Spain, Sweden and the UK. There was one international trial. Five pre-dated 2000. Trials were mostly of good quality.

What did it find?

  • Intensive follow-up picked up seven more recurrences per 1000 patients but the true range could be between 24 fewer and 41 more (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.90 to 1.18).
  • More intensive monitoring did not improve overall survival compared with less intensive monitoring (HR 0.90, 95% CI 0.78 to 1.02; high quality evidence from 12 trials). Mortality rates at two years or more were 22.5% in the intensive groups and 24.2% in the less intensive groups.
  • There remained no difference in survival when separately analysing studies according to how they defined intensity of follow-up. Also, removing older trials or trials with a higher risk of bias did not change the overall results.
  • More intensive follow-up also had no effect on chance of survival without recurrence of colorectal cancer (HR 1.03, 95% CI 0.90 to 1.18; moderate quality evidence from 14 trials) or risk of death due to colorectal cancer (HR 0.93, 95% CI 0.78 to 1.12; moderate evidence from seven trials).
  • More intensive follow-up did lead to more surgical interventions (risk ratio [RR] 1.98, 95% CI 1.53 to 2.56; high quality evidence from 13 trials) and fewer instances of recurrent cancers being detected in-between follow-up visits (i.e. because of a return of cancer symptoms) (RR 0.59, 95% CI 0.41 to 0.86; moderate evidence from six trials).
  • Intensive follow-up did not appear to have an effect on quality of life, anxiety or depression (reported in only three studies) or adverse effects (reported in one study).

What does current guidance say on this issue?

NICE guidance, last updated in 2014, states that following curative bowel surgery people should be offered:

  • A clinic visit 4-6 weeks after treatment
  • Blood tests to check CEA at least every six months for the first three years
  • At least two CT scans of the chest, abdomen and pelvis in the first three years
  • A colonoscopy one year after the operation and if this is normal another five years later; thereafter as determined by cancer networks.

If at any time there is a suspicion of recurrent cancer then full reinvestigation should be started. Follow-up ought to be stopped when the patient and healthcare professionals agree the risks outweigh the benefits.

What are the implications?

Clinicians are left with a dilemma. Intensive follow-up detects recurrent cancer earlier, but this does not seem to improve survival outcomes. Lower intensity follow-up may offer more efficient use of scarce resources. For example, there is unexplained variation in colonoscopy rates in England, which may reflect excess demand. The review does not propose an optimal follow-up protocol and it is unclear how the different intensity regimens studied align with current recommendations.

If increasingly effective tests or treatments are developed, then increased surveillance and earlier detection could lead to better outcomes. There is little information on cost-effectiveness and quality of life. Four large on-going trials will assess this.

Citation and Funding

Jeffery M, Hickey BE, Hider PN, See AM. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2016;11:CD002200.

No funding information was provided for this study.

Bibliography

Cancer Research UK. Follow up for Bowel Cancer. London: Cancer Research UK; updated 2015.

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

NICE. Colorectal cancer: diagnosis and management. CG131. London: National Institute for Health and Care Excellence; 2014.

Public Health England. The 2nd Atlas of Variation in NHS Diagnostic Services in England. January 2017. London: Public Health England and NHS RightCare; 2017.

Why was this study needed?

Around 40,000 new cases of bowel cancer (colorectal cancer) are diagnosed each year in the UK. This means 1 in 20 people could develop it during their lifetime. Surgery is usually the main treatment and if caught early enough there is a good chance the cancer will be removed entirely.

However, in about 50% of successfully treated patients the cancer will return and spread to other organs (metastatic). Patients are therefore usually offered follow-up appointments after their operation. Although NICE guidance outlines what follow-up should be provided, there is some variation according to individual circumstances and local Trust policy. Follow-up is time and resource heavy, often including numerous appointments, CT scans, colonoscopies and blood tests, over a span of five years or more.

This review aimed to investigate whether more intense follow-up, in terms of the number of tests, frequency of appointments or the setting, is associated with improved patient outcomes.

What did this study do?

This systematic review identified 15 randomised controlled trials that compared different follow-up strategies for 5403 people successfully treated for non-metastatic bowel cancer.

Studies compared intensive with less intensive follow-up regimens, though intensity was variably defined. Seven trials compared more versus fewer visits and tests; four compared follow-up versus no or minimal follow-up; four compared more versus less liver imaging; four compared follow-up with and without blood tests for carcinoembryonic antigen (CEA, a cancer marker); two compared surgeon versus GP-led follow-up, and one compared surgeon versus nurse-led follow-up.

Two trials each were performed in Australia, Finland and Italy, and one in China, Denmark, France, Italy, Norway, Spain, Sweden and the UK. There was one international trial. Five pre-dated 2000. Trials were mostly of good quality.

What did it find?

  • Intensive follow-up picked up seven more recurrences per 1000 patients but the true range could be between 24 fewer and 41 more (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.90 to 1.18).
  • More intensive monitoring did not improve overall survival compared with less intensive monitoring (HR 0.90, 95% CI 0.78 to 1.02; high quality evidence from 12 trials). Mortality rates at two years or more were 22.5% in the intensive groups and 24.2% in the less intensive groups.
  • There remained no difference in survival when separately analysing studies according to how they defined intensity of follow-up. Also, removing older trials or trials with a higher risk of bias did not change the overall results.
  • More intensive follow-up also had no effect on chance of survival without recurrence of colorectal cancer (HR 1.03, 95% CI 0.90 to 1.18; moderate quality evidence from 14 trials) or risk of death due to colorectal cancer (HR 0.93, 95% CI 0.78 to 1.12; moderate evidence from seven trials).
  • More intensive follow-up did lead to more surgical interventions (risk ratio [RR] 1.98, 95% CI 1.53 to 2.56; high quality evidence from 13 trials) and fewer instances of recurrent cancers being detected in-between follow-up visits (i.e. because of a return of cancer symptoms) (RR 0.59, 95% CI 0.41 to 0.86; moderate evidence from six trials).
  • Intensive follow-up did not appear to have an effect on quality of life, anxiety or depression (reported in only three studies) or adverse effects (reported in one study).

What does current guidance say on this issue?

NICE guidance, last updated in 2014, states that following curative bowel surgery people should be offered:

  • A clinic visit 4-6 weeks after treatment
  • Blood tests to check CEA at least every six months for the first three years
  • At least two CT scans of the chest, abdomen and pelvis in the first three years
  • A colonoscopy one year after the operation and if this is normal another five years later; thereafter as determined by cancer networks.

If at any time there is a suspicion of recurrent cancer then full reinvestigation should be started. Follow-up ought to be stopped when the patient and healthcare professionals agree the risks outweigh the benefits.

What are the implications?

Clinicians are left with a dilemma. Intensive follow-up detects recurrent cancer earlier, but this does not seem to improve survival outcomes. Lower intensity follow-up may offer more efficient use of scarce resources. For example, there is unexplained variation in colonoscopy rates in England, which may reflect excess demand. The review does not propose an optimal follow-up protocol and it is unclear how the different intensity regimens studied align with current recommendations.

If increasingly effective tests or treatments are developed, then increased surveillance and earlier detection could lead to better outcomes. There is little information on cost-effectiveness and quality of life. Four large on-going trials will assess this.

Citation and Funding

Jeffery M, Hickey BE, Hider PN, See AM. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2016;11:CD002200.

No funding information was provided for this study.

Bibliography

Cancer Research UK. Follow up for Bowel Cancer. London: Cancer Research UK; updated 2015.

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

NICE. Colorectal cancer: diagnosis and management. CG131. London: National Institute for Health and Care Excellence; 2014.

Public Health England. The 2nd Atlas of Variation in NHS Diagnostic Services in England. January 2017. London: Public Health England and NHS RightCare; 2017.

Follow-up strategies for patients treated for non-metastatic colorectal cancer

Published on 25 November 2016

Jeffery, M.,Hickey, B. E.,Hider, P. N.,See, A. M.

Cochrane Database Syst Rev Volume 11 , 2016

BACKGROUND: It is common clinical practice to follow patients with colorectal cancer (CRC) for several years following their curative surgery or adjuvant therapy, or both. Despite this widespread practice, there is considerable controversy about how often patients should be seen, what tests should be performed, and whether these varying strategies have any significant impact on patient outcomes. This is the second update of a Cochrane Review first published in 2002 and first updated in 2007. OBJECTIVES: To assess the effects of intensive follow-up for patients with non-metastatic colorectal cancer treated with curative intent. SEARCH METHODS: For this update, we searched CENTRAL (2016, Issue 3), MEDLINE (1950 to May 20th, 2016), Embase (1974 to May 20th, 2016), CINAHL (1981 to May 20th, 2016), and Science Citation Index (1900 to May 20th, 2016). We also searched reference lists of articles, and handsearched the Proceedings of the American Society for Radiation Oncology (2011 to 2014). In addition, we searched the following trials registries (May 20th, 2016): ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We further contacted study authors. No language or publication restrictions were applied to the search strategies. SELECTION CRITERIA: We included only randomised controlled trials comparing different follow-up strategies for participants with non-metastatic CRC treated with curative intent. DATA COLLECTION AND ANALYSIS: Two authors independently determined trial eligibility, performed data extraction, and assessed methodological quality. MAIN RESULTS: We studied 5403 participants enrolled in 15 studies. (We included two new studies in this second update.) Although the studies varied in setting (general practitioner (GP)-led, nurse-led, or surgeon-led) and "intensity" of follow-up, there was very little inconsistency in the results.Overall survival: we found no evidence of a statistical effect with intensive follow-up (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.78 to 1.02; I(2) = 4%; P = 0.41; high-quality evidence). There were 1098 deaths among 4786 participants enrolled in 12 studies.Colorectal cancer-specific survival: this did not differ with intensive follow-up (HR 0.93, 95% CI 0.78 to 1.12; I(2) = 0%; P = 0.45; moderate-quality evidence). There were 432 colorectal cancer deaths among 3769 participants enrolled in seven studies.Relapse-free survival: we found no statistical evidence of effect with intensive follow-up (HR 1.03, 95% CI 0.90 to 1.18; I(2) = 5%; P = 0.39; moderate-quality evidence). There were 1416 relapses among 5253 participants enrolled in 14 studies.Salvage surgery with curative intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98, 95% CI 1.53 to 2.56; I(2) = 31%; P = 0.14; high-quality evidence). There were 457 episodes of salvage surgery in 5157 participants enrolled in 13 studies.Interval (symptomatic) recurrences: these were less frequent with intensive follow-up (RR 0.59, 95% CI 0.41 to 0.86; I(2) = 66%; P = 0.007; moderate-quality evidence). Three hundred and seventy-six interval recurrences were reported in 3933 participants enrolled in seven studies.Intensive follow-up did not appear to affect quality of life, anxiety, nor depression (reported in three studies).Harms from colonoscopies did not differ with intensive follow-up (RR 2.08, 95% CI 0.11 to 40.17; moderate-quality evidence). In two studies, there were seven colonoscopic complications in 2112 colonoscopies. AUTHORS' CONCLUSIONS: The results of our review suggest that there is no overall survival benefit for intensifying the follow-up of patients after curative surgery for colorectal cancer. Although more participants were treated with salvage surgery with curative intent in the intensive follow-up group, this was not associated with improved survival. Harms related to intensive follow-up and salvage therapy were not well reported.

Carcinoembryonic antigen test: A carcinoembryonic antigen (CEA) test is used to check how well treatment is working in certain types of cancer, particularly colon cancer. Carcinoembryonic antigens are harmful substances (usually proteins) that are produced by some types of cancer.

Computerised tomography (CT) scan: A CT scan uses X-rays to produce detailed images of structures inside the body. They can be used to diagnose and track development of conditions, including cancer.

Colonoscopy: In colonoscopy, a thin flexible tube (called a colonoscope) with a tiny camera on the end is used to look inside the bowel to identify cancer.

Expert commentary

This review updates the randomised trial evidence of intensive follow-up after treatment of non-metastatic colorectal cancer treated by curative intent. Fifteen studies of 5403 participants provide a significant amount of reliable evidence. Healthcare providers will be interested in the overall benefit of follow up strategies; patients are more likely to look for benefit to individuals. As the studies show no overall survival benefit, but a greater chance of patients undergoing potentially curative salvage surgery, we are left with the resulting tension between what an individual patient would want for follow-up and what healthcare providers might consider most effective use of resources.

James Hill, Clinical Professor of Colorectal Surgery, Manchester Royal Infirmary