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NIHR Signal Intensive routine follow-up after bowel cancer treatment may not be necessary

Published on 29 January 2020

doi: 10.3310/signal-000869

More intensive follow-up strategies for patients who have surgery to cure bowel cancer do not result in an overall survival benefit when compared with less intensive follow-up. More intensive strategies include increased frequency of clinic visits, blood tests and scans.

This Cochrane review did find that those people followed up intensively had more frequent surgery to try and cure a recurrence, but this did not translate into a measurable benefit in survival. This suggests that people do not need a more intensive regime, which may be more expensive for health services and burdensome for patients.

This was the fourth update of this Cochrane review. It did not change the conclusions from the last update in 2016, but the four new studies that were included (with an additional 6,238 participants) now strengthen confidence in the conclusions.

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Why was this study needed?

Colorectal, or bowel cancer, is cancer of the colon or rectum. It is the fourth most common cancer in the UK, with about 42,000 people diagnosed each year. For about two-thirds of patients, the cancer is curable with surgery and sometimes chemotherapy.

It is common practice to follow patients up for several years, to check whether the cancer has returned. However, there is considerable uncertainty over whether patients benefit from being seen more often and what tests should be used. Follow-up can be expensive, inconvenient, and cause anxiety, and some tests can have side effects.

This study aimed to answer these questions by assessing the effect of a variety of follow-up programmes on overall survival, cancer-specific and relapse-free survival, and quality of life. It also investigated the harms and costs of follow-up.

What did this study do?

This update of a Cochrane systematic review included four new trials since the last update in 2016, giving nineteen trials with 13,216 participants. Participants had all had surgery to remove tumours in the colon or rectum. The included studies were all randomised controlled trials, comparing different follow-up strategies. Follow-up included clinic visits and examinations, CT scans, and carcinoembryonic antigen (CEA) blood tests.

More intensive strategies were defined as an increased frequency of these visits and investigations, compared to no follow-up, or less frequent investigations. The study also compared follow-up settings, and usual follow-up to follow-up with additional support materials. The individual tests were evaluated in a sub-group analysis.

The trials took place in Europe, Australia and China, with two carried out in the UK. The quality of evidence for the important outcomes was reliable.

What did it find?

  • For overall deaths, intensive follow-up made no significant difference compared with less intensive follow-up (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.80 to 1.04). The average effect was 24 fewer deaths per 1,000 patients. But the true effect could be between 60 fewer and 9 more deaths per 1,000 patients.
  • For colorectal cancer-specific deaths, the use of intensive versus less intensive follow-up made little or no difference (HR 0.93, 95% CI 0.81 to 1.07).
  • More people had salvage surgery, with curative intent, when followed up intensively (risk ratio 1.98, 95% CI 1.53 to 2.56).
  • Intensive follow-up probably made little or no difference to quality of life, anxiety or depression but data was not available for meta-analysis.
  • No benefit was found from the use of particular tests such as the CEA blood test or CT scans and harms or costs could not be estimated.

What does current guidance say on this issue?

The NICE 2020 guideline on the diagnosis and management of colorectal cancer recommends that patients are offered regular surveillance, with both CT scans of the chest, abdomen and pelvis and CEA blood tests in the first three years.

It no longer specifies how frequent these tests should be. However, the guideline committee noted that previously standard care was considered to be a minimum of two CTs of the chest, abdomen and pelvis, as well as six-monthly blood tests during these three years.

Regular follow-up should be stopped when the patient and healthcare professional have discussed and agreed that the likely benefits no longer outweigh the risks of further tests, or if the patient cannot tolerate further treatments.

What are the implications?

This research suggests that we still are not sure which follow-up strategy is best, but a less intensive regime appears adequate. The new NICE guidance does not specify the number or frequency of CTs or CEA blood tests because of remaining uncertainty around the most clinically and cost-effective regime. This means there is likely to be wide variation depending on clinician and patient preferences.

Citation and Funding

Jeffery M, Hickey BE and Hider PN. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2019;(9):CD002200.

The review was supported by Cochrane Colorectal Cancer group, New Zealand Health Technology Assessment and Princess Alexandra Hospital Cancer Collaborative Group, Australia.

Bibliography

Cancer Research UK. Bowel cancer. London: Cancer Research UK; reviewed 2018.

NHS website. Bowel cancer. London: Department of Health and Social Care; 2016.

NICE. Colorectal cancer. NG151. London: National Institute for Health and Care Excellence; 2020.

NICE. Colorectal cancer (update). Evidence review E1. Follow-up to detect recurrence after treatment for non-metastatic colorectal cancer. London: National Institute for Health and Care Excellence; 2020.

Why was this study needed?

Colorectal, or bowel cancer, is cancer of the colon or rectum. It is the fourth most common cancer in the UK, with about 42,000 people diagnosed each year. For about two-thirds of patients, the cancer is curable with surgery and sometimes chemotherapy.

It is common practice to follow patients up for several years, to check whether the cancer has returned. However, there is considerable uncertainty over whether patients benefit from being seen more often and what tests should be used. Follow-up can be expensive, inconvenient, and cause anxiety, and some tests can have side effects.

This study aimed to answer these questions by assessing the effect of a variety of follow-up programmes on overall survival, cancer-specific and relapse-free survival, and quality of life. It also investigated the harms and costs of follow-up.

What did this study do?

This update of a Cochrane systematic review included four new trials since the last update in 2016, giving nineteen trials with 13,216 participants. Participants had all had surgery to remove tumours in the colon or rectum. The included studies were all randomised controlled trials, comparing different follow-up strategies. Follow-up included clinic visits and examinations, CT scans, and carcinoembryonic antigen (CEA) blood tests.

More intensive strategies were defined as an increased frequency of these visits and investigations, compared to no follow-up, or less frequent investigations. The study also compared follow-up settings, and usual follow-up to follow-up with additional support materials. The individual tests were evaluated in a sub-group analysis.

The trials took place in Europe, Australia and China, with two carried out in the UK. The quality of evidence for the important outcomes was reliable.

What did it find?

  • For overall deaths, intensive follow-up made no significant difference compared with less intensive follow-up (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.80 to 1.04). The average effect was 24 fewer deaths per 1,000 patients. But the true effect could be between 60 fewer and 9 more deaths per 1,000 patients.
  • For colorectal cancer-specific deaths, the use of intensive versus less intensive follow-up made little or no difference (HR 0.93, 95% CI 0.81 to 1.07).
  • More people had salvage surgery, with curative intent, when followed up intensively (risk ratio 1.98, 95% CI 1.53 to 2.56).
  • Intensive follow-up probably made little or no difference to quality of life, anxiety or depression but data was not available for meta-analysis.
  • No benefit was found from the use of particular tests such as the CEA blood test or CT scans and harms or costs could not be estimated.

What does current guidance say on this issue?

The NICE 2020 guideline on the diagnosis and management of colorectal cancer recommends that patients are offered regular surveillance, with both CT scans of the chest, abdomen and pelvis and CEA blood tests in the first three years.

It no longer specifies how frequent these tests should be. However, the guideline committee noted that previously standard care was considered to be a minimum of two CTs of the chest, abdomen and pelvis, as well as six-monthly blood tests during these three years.

Regular follow-up should be stopped when the patient and healthcare professional have discussed and agreed that the likely benefits no longer outweigh the risks of further tests, or if the patient cannot tolerate further treatments.

What are the implications?

This research suggests that we still are not sure which follow-up strategy is best, but a less intensive regime appears adequate. The new NICE guidance does not specify the number or frequency of CTs or CEA blood tests because of remaining uncertainty around the most clinically and cost-effective regime. This means there is likely to be wide variation depending on clinician and patient preferences.

Citation and Funding

Jeffery M, Hickey BE and Hider PN. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2019;(9):CD002200.

The review was supported by Cochrane Colorectal Cancer group, New Zealand Health Technology Assessment and Princess Alexandra Hospital Cancer Collaborative Group, Australia.

Bibliography

Cancer Research UK. Bowel cancer. London: Cancer Research UK; reviewed 2018.

NHS website. Bowel cancer. London: Department of Health and Social Care; 2016.

NICE. Colorectal cancer. NG151. London: National Institute for Health and Care Excellence; 2020.

NICE. Colorectal cancer (update). Evidence review E1. Follow-up to detect recurrence after treatment for non-metastatic colorectal cancer. London: National Institute for Health and Care Excellence; 2020.

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

Published on 5 September 2019

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

Cochrane Database Syst Rev Volume 9 , 2019

BACKGROUND: This is the fourth update of a Cochrane Review first published in 2002 and last updated in 2016.It is common clinical practice to follow patients with colorectal cancer 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. OBJECTIVES: To assess the effect of follow-up programmes (follow-up versus no follow-up, follow-up strategies of varying intensity, and follow-up in different healthcare settings) on overall survival for patients with colorectal cancer treated with curative intent. Secondary objectives are to assess relapse-free survival, salvage surgery, interval recurrences, quality of life, and the harms and costs of surveillance and investigations. SEARCH METHODS: For this update, on 5 April 2109 we searched CENTRAL, MEDLINE, Embase, CINAHL, and Science Citation Index. We also searched reference lists of articles, and handsearched the Proceedings of the American Society for Radiation Oncology. In addition, we searched the following trials registries: ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We contacted study authors. We applied no language or publication restrictions to the search strategies. SELECTION CRITERIA: We included only randomised controlled trials comparing different follow-up strategies for participants with non-metastatic colorectal cancer treated with curative intent. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently determined study eligibility, performed data extraction, and assessed risk of bias and methodological quality. We used GRADE to assess evidence quality. MAIN RESULTS: We identified 19 studies, which enrolled 13,216 participants (we included four new studies in this second update). Sixteen out of the 19 studies were eligible for quantitative synthesis. 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 intensive follow-up made little or no difference (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.80 to 1.04: I(2) = 18%; high-quality evidence). There were 1453 deaths among 12,528 participants in 15 studies. In absolute terms, the average effect of intensive follow-up on overall survival was 24 fewer deaths per 1000 patients, but the true effect could lie between 60 fewer to 9 more per 1000 patients.Colorectal cancer-specific survival: we found intensive follow-up probably made little or no difference (HR 0.93, 95% CI 0.81 to 1.07: I(2) = 0%; moderate-quality evidence). There were 925 colorectal cancer deaths among 11,771 participants enrolled in 11 studies. In absolute terms, the average effect of intensive follow-up on colorectal cancer-specific survival was 15 fewer colorectal cancer-specific survival deaths per 1000 patients, but the true effect could lie between 47 fewer to 12 more per 1000 patients.Relapse-free survival: we found intensive follow-up made little or no difference (HR 1.05, 95% CI 0.92 to 1.21; I(2) = 41%; high-quality evidence). There were 2254 relapses among 8047 participants enrolled in 16 studies. The average effect of intensive follow-up on relapse-free survival was 17 more relapses per 1000 patients, but the true effect could lie between 30 fewer and 66 more per 1000 patients.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%; high-quality evidence). There were 457 episodes of salvage surgery in 5157 participants enrolled in 13 studies. In absolute terms, the effect of intensive follow-up on salvage surgery was 60 more episodes of salvage surgery per 1000 patients, but the true effect could lie between 33 to 96 more episodes per 1000 patients.Interval (symptomatic) recurrences: these were less frequent with intensive follow-up (RR 0.59, 95% CI 0.41 to 0.86; I(2) = 66%; moderate-quality evidence). There were 376 interval recurrences reported in 3933 participants enrolled in seven studies. Intensive follow-up was associated with fewer interval recurrences (52 fewer per 1000 patients); the true effect is between 18 and 75 fewer per 1000 patients.Intensive follow-up probably makes little or no difference to quality of life, anxiety, or depression (reported in 7 studies; moderate-quality evidence). The data were not available in a form that allowed analysis.Intensive follow-up may increase the complications (perforation or haemorrhage) from colonoscopies (OR 7.30, 95% CI 0.75 to 70.69; 1 study, 326 participants; very low-quality evidence). Two studies reported seven colonoscopic complications in 2292 colonoscopies, three perforations and four gastrointestinal haemorrhages requiring transfusion. We could not combine the data, as they were not reported by study arm in one study.The limited data on costs suggests that the cost of more intensive follow-up may be increased in comparison with less intense follow-up (low-quality evidence). The data were not available in a form that allowed analysis. 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 groups, this was not associated with improved survival. Harms related to intensive follow-up and salvage therapy were not well reported.

Expert commentary

Conventional thought has been that more intensive follow-up increases early detection of relapse thereby improving survival outcomes in early-stage colorectal cancer. This has been challenged by finding no improvement in survival with more intensive follow-up in patients treated with curative intent. Despite an increase in salvage surgery (curative intent) following relapse detection, this did not translate to improved survival. Practice still varies considerably from centre to centre, and this review reassures clinicians against the requirement for intensive follow-up.

Although there was no effect on overall quality of life with more frequent follow-up, it is important to determine if the increase in salvage surgery and earlier detection of recurrences improve patients’ symptom burden and global health.

Further evidence is required regarding the cost and benefits of less frequent follow-up and the risk of harm from frequent imaging/intervention. This will guide clinicians and standardise practice; however, follow-up strategy should be tailored according to individual patient needs.

Dr Nalinie Joharatnam-Hogan, Clinical Research Fellow, MRC Clinical Trials Unit, UCL, London

Dr Khurum Khan, Professor and Consultant Medical Oncologist, Gastrointestinal Oncology Service, Cancer of Unknown Primary Service, University College London Hospital, UCL Cancer Institute and North Middlesex University Hospital

The commentators declare no conflicting interests

Expert commentary

The benefits of intensive follow-up after curative resection of colorectal cancer have been debated for many years. These benefits do not extend to the population level. The challenge for the clinician is to balance the hopes and expectations of individual cancer patients against the issues of cost and resource use.

Intensive follow-up results in less than a 10% chance of patients undergoing salvage surgery, but that represents the only chance of cure in the setting of recurrent disease. At least intensive follow-up is not associated with loss of quality of life or harm.

Professor James Hill, Consultant General and Colorectal Surgeon, Manchester University NHS Foundation Trust

The commentator declares no conflicting interests