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

What is the issue?

Colorectal cancer affects about 1 in 20 people in high-income countries. Most patients (about two thirds) have curable disease. Follow-up after surgical resection +/- chemotherapy treatment usually means visits to the doctor as well as having some tests. Many people believe that follow-up saves lives, but we are not sure how often the patient should see the doctor and what tests they should have, and when.

Why is it important?

Follow-up is expensive, it can make patients anxious around the time of their visit, and can be inconvenient. Tests are expensive and can have side effects. If tests find that cancer has come back in a person who feels well, but treatment cannot cure them, finding the recurrent cancer may not have helped that person or their family.

We asked...

We asked if follow-up (i.e. tests and doctor visits) after colorectal cancer has been treated curatively is helpful. We looked at all different kinds of follow-up: some versus none; more tests versus fewer tests; and follow-up done by surgeons, general practitioners (GPs), or nurses.

We found...

We found 19 studies, including 13,216 participants. Our results are presented along with a judgement of quality which reflects how certain we are about the results. We found that follow-up did not improve overall survival (high-quality evidence), colorectal cancer-specific survival (moderate-quality evidence), or relapse-free survival (high-quality evidence). If patients have follow-up, they are much more likely to have surgery if the cancer is detected again (high-quality evidence). With follow-up, more asymptomatic 'silent' cancer relapses are likely to be found at planned visits (moderate-quality evidence). Harmful side effects (harms) from tests were not common, but more intensive follow-up may increase harms (reported in two studies; very low-quality evidence). Costs may be increased with more intensive follow-up (low-quality evidence). More intensive follow-up probably makes little or no difference for quality of life (moderate-quality evidence).

This means...

The information we have now suggests that there is little benefit from intensifying follow-up, but there is also little evidence about quality of life, harms, and costs. We do not know what is the best way to follow patients treated for non-metastatic (no secondaries) colorectal cancer, or if we should at all. We know little about the costs of follow-up in this setting. Consumer needs and concerns with respect to the value of follow-up require further research.

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.

Read the full abstract...
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 strategy: 

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: I² = 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: I² = 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; I² = 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; I² = 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; I² = 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.

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