|Mechanisms of improved survival from intensive followup in colorectal cancer: a hypothesis
|Renehan A G, Egger M, Saunders M P, O'Dwyer S T
The review explored the mechanism underlying survival associated with intensive follow-up in colorectal cancer. The authors concluded that intensive follow-up is associated with a mortality reduction but only 2% are attributable to cure from salvage reoperations; other factors may contribute to the remaining lives saved and form important future research questions. The conclusions are reliable.
To explore the survival mechanism associated with intensive follow-up in colorectal cancer.
MEDLINE, EMBASE, Cancerlit and the Cochrane Controlled Trials Register were searched up to December 2003; the search terms were reported. In addition, reference lists of selected articles, reviews and commentaries were screened, meeting proceedings and national trial registers were searched, and the editorial base of the Cochrane Colorectal Cancer Group was contacted. Trials published in any language were eligible.
Study designs of evaluations included in the review
Randomised controlled trials (RCTs), where randomisation took place at or shortly after surgery, were eligible for inclusion.
Specific interventions included in the review
Studies comparing intensive follow-up strategies with control follow-up regimes (as defined by the individual trials) were eligible for inclusion. The surveillance tests and their frequency varied considerable; several studies reviewed patients every 3 months for the first 2 years and then 6 monthly.
Participants included in the review
Studies in patients with colorectal cancer treated surgically with curative intent were eligible. Studies that included patients with advanced disease (Dukes' stage D) when curative resection was generally not possible were excluded. The majority of patients in the included studies were diagnosed with Dukes' stage B and had cancer of the colon. Their mean age ranged from 62 to 69 years.
Outcomes assessed in the review
The studies had to report survival data at the 5-year follow-up to cancer to be eligible. The review reported all-cause deaths, all site recurrences, reoperation rates, salvage cure rates, and absolute risk differences for overall lives gained, lives gained through salvage and lives gained through factors other than salvage.
How were decisions on the relevance of primary studies made?
The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.
Assessment of study quality
The criteria used to assess validity were adequacy of concealment of the patient's allocation to treatment group, double-blinding and withdrawals. Two reviewers independently assessed the validity of the studies, with any differences resolved by consensus.
Two reviewers independently extracted the data, with any disagreements resolved by a third reviewer. The data were extracted from the final report for each trial, but preliminary reports were also consulted for additional details on the methodology. The extracted data included the proportion of survivors at 5 years, overall deaths, cancer-related deaths, all site recurrences, mean time to detection (months and standard error of measurement), number of recurrences, recurrences by site, number with intraluminal disease, curative reoperation rates and number of patients disease-free after reoperation.
Methods of synthesis
How were the studies combined?
Comparisons of events for intensive versus conventional follow-up were performed, and pooled risk ratios (RR) were computed with 95% confidence intervals (CIs) using a random-effects model. The proportion of overall lives gained, and lives gained through salvage reoperation were calculated using absolute risk differences and 95% CIs.
How were differences between studies investigated?
Statistical heterogeneity was assessed using the chi-squared test. If significant, the sources of heterogeneity were explored.
Results of the review
Six RCTs (n=1,679) were included in the review.
Trial methodology was moderate.
There were significantly fewer (all-cause) deaths in patients followed intensively than in patients followed by conventional regimes (31% versus 40%; RR 0.76, 95% CI: 0.67, 0.86), based on 1,679 patients in 6 studies. The reoperation rates were significantly better for intensively followed patients (9 versus 6%; RR 2.12, 95% CI: 1.43, 3.15). The recurrence rates for all sites (36% versus 37%) and the proportions successfully salvaged (4% versus 2%) were similar for both arms.
The absolute risk difference for overall lives gained from intensive follow-up was 10% (95% CI: 4, 16), with 2% (95% CI: 0, 5) attributable to cure from salvage reoperation. The difference (4 to 11%) suggested to the authors that factors other than salvage may contribute to survival from intensive follow-up.
There was significant statistical heterogeneity (p=0.009) which was traced to one study with a high reoperation rate among patients intensively followed. After excluding this study, the absolute risk difference for all lives gained was 9% (95% CI: 2, 16) and the number of lives gained through salvage was 1% (95% CI: 0, 3).
Intensive follow-up in colorectal cancer is associated with an absolute reduction in all-cause 5-year mortality. However, only 2% were attributable to cure from salvage reoperations; other factors such as increased psychological well-being and/or altered lifestyle, and/or improved treatment of coincidental disease, may contribute to the remaining lives saved and form important future research questions.
This was a review with a clear research question and well-defined inclusion criteria. The searches were extensive and efforts were made to identify published and unpublished studies written in any language; this reduces the probability of publication and language bias. An earlier paper on the topic (see Other Publications of Related Interest) did not find indications of publication bias. The reviewers undertook measures to reduce errors and bias in the data abstraction and quality assessment, although this was not reported for the process of study selection. Further details were reported in web tables (currently these can only be obtained from the authors directly).
The synthesis of the included studies was appropriate and sources of heterogeneity were explored. The conclusions follow from a well-conducted review: the conclusion that intensive follow-up can reduce mortality, of which only a small percentage seems to be due to salvage reoperations, is reliable; however, the question of what other factors may contribute to the reduction was outside the scope of the included primary studies.
Implications of the review for practice and research
Practice: The authors stated that colorectal nurse specialists working parallel with colorectal cancer specialists using protocol-driven protocols is an alternative care strategy for colorectal cancer follow-up. There may also be a role for additional allied disciplines such as cancer nutritionists and psychologists.
Research: The authors stated that colorectal nurse specialists working parallel with colorectal cancer specialists using protocol-driven protocols for colorectal cancer follow-up and the role of additional allied disciplines (e.g. cancer nutritionists and psychologists) are possibilities for future research.
Renehan A G, Egger M, Saunders M P, O'Dwyer S T. Mechanisms of improved survival from intensive followup in colorectal cancer: a hypothesis. British Journal of Cancer 2005; 92(3): 430-433
Other publications of related interest
Renehan AG, Egger M, Saunders MP, O'Dwyer ST. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. BMJ 2002;324:813-816.
Subject indexing assigned by NLM
Colorectal Neoplasms /mortality /psychology; Follow-Up Studies; Humans; Models, Biological; Randomized Controlled Trials as Topic; Salvage Therapy; Survival Analysis
Date bibliographic record published
Date abstract record published
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.