Meta-analysis of colorectal cancer follow-up after potentially curative resection

Abstract

Background: After potentially curative resection of primary colorectal cancer, patients may be monitored by measurement of carcinoembryonic antigen and/or CT to detect asymptomatic metastatic disease earlier.

Methods: A systematic review and meta-analysis was conducted to find evidence for the clinical effectiveness of monitoring in advancing the diagnosis of recurrence and its effect on survival. MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases were searched for randomized comparisons of increased intensity monitoring compared with a contemporary standard policy after resection of primary colorectal cancer.

Results: There were 16 randomized comparisons, 11 with published survival data. More intensive monitoring advanced the diagnosis of recurrence by a median of 10 (i.q.r. 5-24) months. In ten of 11 studies the authors reported no demonstrable difference in overall survival. Seven RCTs, published from 1995 to 2016, randomly assigned 3325 patients to a monitoring protocol made more intensive by introducing new methods or increasing the frequency of existing follow-up protocols versus less invasive monitoring. No detectable difference in overall survival was associated with more intensive monitoring protocols (hazard ratio 0·98, 95 per cent c.i. 0·87 to 1·11).

Conclusion: Based on pooled data from randomized trials published from 1995 to 2016, the anticipated survival benefit from surgical treatment resulting from earlier detection of metastases has not been achieved.

Fig. 1

Flow chart showing selection of trials for review

Fig. 2

Forest plot showing hazard ratios for death in seven randomized comparisons of more and less intensive follow-up from which hazard ratios could be derived. An inverse-variance random-effects model was used to produce an overall estimated hazards ratio. Hazard ratios are shown with 95 per cent confidence intervals. The studies are ordered according to the year of the start of the inclusion. CEASL is dominant because the weight of the study is dependent on the follow-up time, number of events and number of patients in each treatment arm. The Kaplan–Meier curve in CEASL is plotted up to 25 years. The point estimate in favour of more intensive monitoring in studies by Rodriguez-Moranta et al. and Pietra and colleagues was attributed by the authors to detection by endoscopy and successful treatment of recurrent rectal carcinoma

Fig. 3

Forest plot showing odds ratios for death in seven randomized comparisons of more and less intensive follow-up. A Mantel–Haenszel random-effects model was used to produce an overall estimated odds ratio. Odds ratios are shown with 95 per cent confidence intervals

Fig. 4

Forest plot for death in two studies in which the difference in monitoring was confined to endoscopy, and two studies for which the difference was between a hospital/specialist setting and a general practice setting. A Mantel–Haenszel random-effects model was used to produce an overall estimated odds ratio. Odds ratios are shown with 95 per cent confidence intervals

Fig. 5

Funnel plot of studies included in meta-analysis. Reference numbers are shown

Fig. 6

Subset analysis of three large multicentre RCTs published in 2006, 2014 and 2016, which included 80·9 per cent of all patients in the full systematic review. A random-effects inverse-variance model was used to produce an overall estimated hazards ratio. Hazard ratios are shown with 95 per cent confidence intervals