Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trialsBMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7341.813 (Published 06 April 2002) Cite this as: BMJ 2002;324:813
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Our objective was to compare two broad strategies of surveillance after curative resection for colorectal cancer: a more intensive strategy with less intensive or no follow up. We found a significant reduction in all-cause mortality with intensive follow up and suggested that this survival benefit was in part attributable to the early detection of all recurrences and the increased detection of isolated recurrent disease. We agree with Ian Badger and Graham Williams, and Mark Jeffrey and colleagues, that at present it is difficult to identify which aspects of intensified follow up are responsible for the benefit observed and we acknowledged this in the discussion section of our paper. We called for trials that are specifically designed to address this issue. The ongoing GILDA (Gruppo Italiano de Lavoro per la Diagnosi Anticipata) trial is to be applauded for its large recruitment to-date, but we have concerns that the study design, while balancing diagnostic intensity with extramural and intramural detection, has the disadvantage that no single test is directly compared between the two arms.
In response to the Mark Jeffrey and colleagues, we performed our subgroup analysis based on the a priori hypothesis that the early detection of extramural recurrent disease was more likely to be effective in improving survival related to cancer than strategies directed only at the detection of intraluminal disease. Within this definition we included the potential to salvage both local pelvic recurrences and solitary hepatic metastases. While the Danish study was the largest trial within the meta-analysis, it had distinct characteristics. It may have been designed to detect distant metastases (physical examination, chest radiograph, erythrocyte sedimentation rate, liver function tests), but these diagnostic tools were unlikely to contribute to the early detection of recurrences. While no trial directly compared a specific diagnostic tool, all four extramural studies included computed tomography and frequent measurements of serum carcinoembryonic antigen. Computed tomography and frequent measurements of carcinoembryonic antigen are the only tests that are reasonably sensitive for the detection of either hepatic metastases or local recurrences. Thus, considering these two tests together is justified.
We previously summarised the results of follow-up studies in a letter to the Lancet. This early analysis was not a systematic review but provided the impetus to undertake one. In the review protocol, we defined inclusion criteria as stated in the methods section. The unpublished trial by Lennon and colleagues was excluded because participants with a raised carcinoembryonic antigen concentration were randomised at the time of the rise in levels occurred rather than at the time of surgery.
There is currently a paucity of data on quality of life related issues and colorectal cancer follow-up. It is worth pointing out that within the Danish trial, a sub-study failed to demonstrate increased anxiety associated with frequent monitoring. The specific question of whether or not the earlier detection of recurrent disease affects quality of life is complex. It is necessary to evaluate differences in an individual whose recurrence is detected early compared with an individual who lives without disease but has awareness of the one in three chance of developing a recurrence.
Audisio and colleagues are correct to point out that results of the meta-analysis must be interpreted in light of the period when the included studies were performed. We state in our discussion that the trials “predated multidisciplinary approaches to the treatment of colorectal cancer”, and “that such strategies may increase the potential survival benefits from intensive follow-up”. We also recognise that where contemporary surgical approaches such as Total Mesorectal Excision are used, recurrence rates may be lower, and thus the number of potential salvageable cases may be reduced. This reinforces the need for continuing research in this area.
Alan Gibbs is right when pointing out that some of the confidence intervals in Figures 3 and 4 were incorrectly drawn. We corrected this error at proof stage but unfortunately the wrong version was included in the printed version. We stress that the numbers mentioned in the text and displayed in the figure are correct. We also appreciate his comment that an analysis of time-to-event data would have been superior to our analysis of aggregated data on time to first relapse. Unfortunately such data were not available.
While it is important that clinical guidelines are prescriptive, it is equally important that they are embracing. We believe that it would be inappropriate if guidelines simply ignored the available evidence that intensifying follow-up can improve survival. By implication, the practice of no follow-up is no longer acceptable. Clearly, further trials are required to identify the specific components of follow up that are most beneficial, and until then, we cannot be prescriptive. The findings of our study suggest that trials should focus on the roles of computed tomography and carcinoembyonic antigen testing.
1. Renehan AG, Egger M, Saunders MP, O'Dwyer ST. The impact on survival of intensive follow-up after curative resection for colorectal cancer: a systematic review and meta-analysis of randomised trials. BMJ 2002;324:813-816.
2. Kjeldsen BJ, Kronborg O, Fenger C, Jorgensen OD. A prospective randomized study of follow-up after radical surgery for colorectal cancer. Br J Surg 1997;84:666-669.
3. Kievit J. Follow-up of patients with colorectal cancer. numbers needed to test and treat. Eur J Cancer 2002;38:986-999.
4. Renehan AG, O'Dwyer ST. Surveillance after colorectal cancer resection. Lancet 2000;355:1095-1096.
5. Kjeldsen BJ, Thorsen H, Whalley D, Kronborg O. Influence of follow -up on health-related quality of life after radical surgery for colorectal cancer. Scand J Gastroenterol 1999;34:509-15.
Competing interests: No competing interests
Variation in the methods, intensity and duration of follow up (FU) after surgery for colorectal cancer may reflect the lack of evidence on which base the postoperative FU of patients. Persistence of such variation does not only mean that the problem is in the clinical guidelines.
Application of FU principles after curative surgery for colorectal cancer is not only helpful in the early detection of recurrent cancer but it is also cost-effective.
Adherence to the guidelines after surgery is the core of an intensive FU. Such component might continue lifelong if it is applied rightly on a wide range of practice, involving GPs. A valuable data from their side is highly appreciated.
Competing interests: No competing interests
Renehan et al have performed a state of the art meta-analysis on the basis of 5 trials published between 1995 and 1998, and have found that intensive follow-up reduces 5-year overall mortality by an odds ratio of 0.81.1 Convincing though this may seem, in our opinion several issues remain to be resolved, such as 1) the internal consistency and validity of the original material on which the analysis is based, 2) whether mortality reduction sufficiently proves the (cost-)effectiveness of follow-up in clinical care, and 3) for whom and how should follow-up be performed.
1) The meta-analysis is based on a small number of studies, representing 1342 patients only, 666 of whom underwent intensive follow- up. The summary table 3 of page 5 on this patient material shows several surprising findings. In spite of the lead-time effect of 8.5 months, not more but less recurrences were found in the index group, albeit that this difference is not significant. Differentiated by site, only isolated local recurrences are detected significantly more often in the index group. In contrast, both liver and lung metastases were found (insignificantly) less often in the index group, while the subset of isolated liver recurrences, most amenable to curative treatment, was of equal size in both groups.
All this suggests that gains in survival are primarily generated through the increased curative treatment of isolated local recurrences. This is not convincing for three reasons. First, differentiation between the 1 intramural and 4 extramural trials generates the opposite finding, with mortality reduction only being found in the pooled extramural detection trials.2-5 In the intramural detection trial, where diagnosis is primarily aimed at local recurrence, no mortality difference is found.6 Second, the survival gains from treatment of local recurrence are heavily influenced by the Pietra study, a study that reports such high local recurrence rates (15% for colon cancer and 37% for rectal cancer, as shown in table 3 on page 1128) that one may doubt the quality of the primary cancer surgery on which this study is based.4 Third, both surgical oncological clinical practice, and the majority of the literature on follow-up suggests that gains can primarily be achieved from the treatment of liver metastases, and not from the treatment of local recurrences (treatment of liver recurrences being reported 5-10 times more often, and contributing to far more patients with 5-year survival after recurrence, than treatment of local recurrence, as shown in a summary published by one of us7).
In all five trials, patients were randomized to intensive follow-up versus a less or no follow-up regimen in the control group. However, no blinding that we know of was used in any of the trials, and neither were there specific rules about further diagnostic analysis in the case of an abnormal routine test, nor about the standards for treatment of recurrence in the index or the control group. This leaves the majority of the decision-making and subsequent care with respect to cancer recurrences to the discretion of the non-blinded clinician. One cannot ignore the gains, ascribed to a difference in follow-up, that are in part the result of unobserved and unreported differences in post-detection care, and thereby produce an inappropriately positive picture of follow-up effectiveness.
2) Although the meta-analysis reports a reduction in mortality, this comes at a price that remains understandably unreported because of the outcome measure chosen. The study finds that intensive follow-up detects recurrences 8 months earlier. We may assume that in this group, like in most colon cancer series reported in the literature, more than 1 out of every 3 patients (37.5% in 24,305 patients in the earlier mentioned review7) will suffer a recurrence. This means that around 250 patients out of the 666 in the intensive follow-up group will have had a cancer recurrence. For all of these patients their cancer-free survival will shortened be by an average of 8 months through the lead time effect of follow-up (as is illustrated strikingly in fig 2 on page 667 of Kjeldsen).6 This generates a considerable loss in quality of life through earlier detection of (incurable) cancer, which must be weighed against the survival gains generated in the around 32 more patients treated with curative intent. Remaining QALY-gains must then be compared with added costs, to assess whether colon cancer follow-up represents a sufficiently cost-effective use of limited resources.
3) Finally, the meta-analysis leaves open the question in whom and how follow-up should be performed. Self evidently, follow-up should not be required for those who are not fit enough to undergo surgery for recurrence, and probably not for those in whom a favorable primary cancer stage makes recurrences highly unlikely. If follow-up is performed, it remains to be demonstrated for whom, how and for how long it should be performed.
In conclusion, Renehan’s study presents a valuable summary of 5 randomized trials on colon cancer follow-up performed in the 1990’s. However, it does not eliminate deficiencies in or doubts about or the original material. Neither does it answer questions about the potential benefits of follow-up in terms of QALY gains, nor about its cost- effectiveness. In addition, new treatment methods (such as TME with preoperative RT for rectal cancer) are expected to change (local) recurrence profiles dramatically, and will thereby limit the value of these historical data. Therefore, in our opinion, this meta-analysis does not settle the issue, and is, in itself, not sufficient to set a new standard for clinical care.
J. Kievit, Leiden, the Netherlands firstname.lastname@example.org
R.A. Audisio, Liverpool, United Kingdom email@example.com
T. Wiggers, Groningen, the Netherlands firstname.lastname@example.org
K.S. Virgo, St Louis, U.S.A. email@example.com
F.E. Johnson, St Louis, U.S.A. Frank.Johnson@med.va.gov
1. 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.
2. Makela JT, Laitinen SO, Kairaluoma MI. Five-year follow-up after radical surgery for colorectal cancer. Results of a prospective randomized trial. Arch.Surg. 1995;130:1062-7.
3. Ohlsson B, Breland U, Ekberg H, Graffner H, Tranberg KG. Follow- up after curative surgery for colorectal carcinoma. Randomized comparison with no follow-up. Dis.Colon Rectum 1995;38:619-26.
4. Pietra N, Sarli L, Costi R, Ouchemi C, Grattarola M, Peracchia A. Role of follow-up in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis.Colon Rectum 1998;41:1127-33.
5. Schoemaker D, Black R, Giles L, Toouli J. Yearly colonoscopy, liver CT, and chest radiography do not influence 5- year survival of colorectal cancer patients [see comments]. Gastroenterology 1998;114:7-14.
6. Kjeldsen BJ, Kronborg O, Fenger C, Jorgensen OD. A prospective randomized study of follow-up after radical surgery for colorectal cancer. Br.J.Surg. 1997;84:666-9.
7. Kievit J. Follow-up of patients with colorectal cancer. numbers needed to test and treat. Eur.J.Cancer 2002;38:986-99.
Competing interests: No competing interests
8th May 2002
In the paper by Renehan (1) et al published in the BMJ of the 6th of April I should like to point out that 95% confidence intervals shown in Fig 2 (abridged text) for 5 year survival measures for Ohlsson (2) et al 1995, and for Kjeldsen (3) et al 1997, do not correspond to the numerical upper and lower end points and upper endpoint respectively given in the text of the figure. In addition the values for risk estimates and 95% confidence limits for recurrences, etc shown in Fig 4 are inconsistent with the values in the text given for all site recurrences, isolated hepatic metastases, intraluminal recurrences and metachronous cancers.
In addition I would question the statistical analysis of time to first relapse in patients with colorectal cancer used in Table 2. The usual approach would be based on survival analysis. The above paper follows what appears to be the analysis used in some of the original papers which used a t test approach. This raises the question of whether the numbers involved in the analysis include all patients who entered the trial or only those who had a relapse. If all patients are included what time value should be given to those patients not experiencing a relapse? A possible approach would be to allocate total follow up time, but it is clear from the value for the mean time to relapse that this is not the case here. It seems clear that the mean (and standard deviation) where given apply only to those relapsing. It is possible that those not relapsing may have been given a time value of 0, but this would be clearly inappropriate. However it appears that in the present paper where an approximate 95% confidence interval for the difference in the mean time to relapse has been calculated in Table 4 it has been assumed that the numbers involved include all patients entering the trials. The effect of this is to produce confidence intervals for the mean difference that appear to be shorter than they really should be.
Alan CC Gibbs
1: Renehan A, Egger M, Saunders M, O’Dwyer S. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta analysis of randomised trials. BMJ 2002, 813- 816
2: Ohlsson B, Breland U, Ekberg H, Graffner H, Tranberg KG. Follow- up after curative surgery for colorectal carcinoma. Randomised comparison with no follow-up. Dis Colon Rectum 1995; 38: 619-626
3: Kjeldsen BJ, Kronborg O, Fenger C, Jorgensen OD. A prospective randomised study of follow-up after radical surgery for colorectal cancer. Br J Surg 1997; 84: 666-669
No competing interests
Competing interests: No competing interests
The factors that control survival after malignancy are many and complex. The meta-analysis from Renehan et al suggests a survival benefit from intensive investigation following colorectal cancer1. However recent evidence in gynaecological malignancies has suggested that the use of routine follow up may delay presentation in individuals who are symptomatic with recurrence2. Even with intensive follow-up symptomatic recurrence in colonic cancer accounts for 27-50% of all recurrences3-5. Since curative intervention is not limited to those with asymptomatic recurrence, education of all patients about possible symptoms of recurrence and the shortcomings of follow up is important in order to produce optimal outcome in this group of patients.
1 Renehan A, Egger M et al. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta -analysis of randomised trials. BMJ. 2002; 324:813-6 2 Olaitan A, Murdoch J et al. A critical evaluation of current protocols for the follow up of women treated for gynaecological malignancies. International Journal of Gynaecological Cancer. 2001. 11:349-353. 3 Makela J, Laitinen S and Kairiluoma M. Five year follow-up after radical surgery for colorectal cancer: results of a prospective randomized trial. Archives of Surgery. 130:1062-1067. Oct 1995. 4 Ohlsson B, Breland U, et al. Follow-up after curative surgery for colorectal carcinoma: randomized comparison with no follow-up. Diseases of Colon and Rectum. 38(6): 619-626. June 1995. 5 Kjeldsen B, Kronborg O, et al. A prospective randomised study of follow- up after radical surgery for colorectal cancer. British Journal of Surgery. 84: 666-669. 1997.
Competing interests: No competing interests
Renehan et al. have conducted a thorough systematic review of randomised controlled trials (RCTs) exploring the impact of intensifying follow up in patients with colorectal cancer following curative resections 1. Not surprisingly the results of their meta-analysis are very similar to our own published several months ago as part of a Cochrane Review 2. There are however, some errors in their description and interpretation of the data which require comment. Furthermore their recommendation that “clinical guidelines should be revised” is not justified.
Renehan et al state that “in four trials computed tomography and frequent measurements of carcinoembryonic antigen (CEA) were limited to the intensive arms”. In fact in 3 of the quoted studies CEA was measured with equal frequency in both arms of the trials 3 4 5. Only in the study by Ohlsson et al (which showed no difference in mortality) was CEA measurement limited to the intensive arm 6. Therefore the conclusion that there is an absolute reduction in mortality of 9 – 13% “…using modern follow up regimens (including computed tomography or frequent measurements of serum carcinoembryonic antigen or both)…” is not justified. The only other study which looked specifically at the utility of measuring CEA is the study by Lennon et al which (although only published in abstract form to date) was reported as showing no improvement in survival 7. We find it confusing that Renehan et al chose to exclude the study by Lennon et al from their current systematic review, whereas in the previous publication of their meta-analysis of follow-up trials they chose to include this study 8.
Renehan et al have divided the 5 trials into those designed to look for “intramural recurrences” or “extramural recurrences”. This division seems somewhat arbitrary and leads to the exclusion (from a sub-group analysis on mortality) of the Danish trial 9 which contributed 597 (45%) of the 1332 patients included in the overall meta-analysis. The Danish trial included measures designed to look for distant metastases (physical examination, CXR, ESR, liver function tests) and it was the intent of the study investigators to look for all types of recurrences; not just “intramural” ones 10. We would need reassurance that the exclusion from analysis of these 2 studies was not a post-hoc decision.
Renehan et al state that follow-up “…..may also be associated with ……improved psychological wellbeing in patients.” Although this may be true, follow-up may also be associated with psychological harms that deserve equal mention. These include increased anxiety, false reassurance, labelling and the earlier detection of incurable metastatic disease.
The final conclusion in Renehan’s paper is that “…we believe that clinical guidelines should be revised”. Given the varied components and intensity of follow-up (different tests and frequency of tests) across the 5 trials it is impossible to deduce which aspect of follow-up is responsible for the survival benefit. Even Renehan et al acknowledge “We could not evaluate the efficacy of individual investigations used in colorectal cancer surveillance.” In the circumstances it is not feasible to rewrite guidelines based on the current evidence. In addition explicit evidence based guidelines require simultaneous consideration of the benefits, harms & costs of an intervention and clear information on the impact of the proposed intervention(s) on patient outcomes and resources. The completed trials to date are conspicuously devoid of data on the harms and costs of follow-up.
The conclusions of our Cochrane review were more cautious and more accurately reflect the validity of the data: “The results of this review support the general principle of clinical follow-up for patients with CRC after curative treatment. The exact details of the optimal follow-up regimen still need clarification” 2.
We would strongly encourage practitioners to enter patients into ongoing RCTs in Italy and the UK which address the effectiveness of follow -up more rigorously and should provide valuable data on the harms and costs of such follow-up.
1. 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; 324:1- 8.
2. Jeffery GM, Hickey BE, Hider PN. Follow-up strategies for patients treated for non-metastatic colorectal cancer (Cochrane Review) in: The Cochrane Library, Issue 1,2002:Update Software
3. Makela JT, Laitinen SO, Kairaluoma MI. Fiveyear followup after radical surgery for colorectal cancer. Results of a prospective randomized trial. Arch Surg 1995;130:10627.
4. Schoemaker D, Black R, Giles L, Toouli J. Yearly colonoscopy, liver CT, and chest radiography do not influence 5year survival of colorectal cancer patients. Gastroenterology 1998;114:714.
5. Pietra N, Sarli L, Costi R, Ouchemi C, Grattarola M, Peracchia A. Role of followup in management of local recurrences of colorectal cancer: a prospective, randomized study. Dis Colon Rectum 1998;41:112733.
6. Ohlsson B, Breland U, Ekberg H, Graffner H, Tranberg K-G. Followup after curative surgery for colorectal carcinoma. Randomized comparison with no followup. Dis Colon Rectum 1995;38:61926.
7. Lennon T, Houghton J, Northover J, on behalf of CRC/NIH CEA Trial Working Party. Post-operative CEA monitoring and second-look surgery in colorectal cancer: trial results British Journal of Cancer. Proceedings of Ninth Annual Scientific Meeting of the British Oncological Association; 1994 10-12 July; Guildford
8. Renehan AG, O’Dwyer ST. Surveillance after colorectal cancer resection. (letter) Lancet 2000;355:1095-96.
9. Kjeldsen BJ, Kronborg O, Fenger C, Jorgensen OD. A prospective randomized study of followup after radical surgery for colorectal cancer. Br J Surg 1997;84:6669.
10. Kronborg O. Personal communication April 2002.
Competing interests: No competing interests
AG Renehan et al have recently published a systematic review and meta- analysis showing that intensive follow-up after curative resection for colorectal cancer was associated with an earlier detection of all recurrences and a reduction in all cause mortality (RR 0.81, 95% CI 0.70- 0.94) (1). The authors claim that the effect was more evident in trials designed to compare follow up regimens having major differences in extramural recurrences detection power. While dividing trials into such categories is not always straightforward (i.e in Schoemaker et al. (2) regimens had also different intensity in detecting intramural recurrences) the expected differences in the number of isolated local recurrences (23/156 – 10/157=13 cases) and isolated liver metastases (20/323 – 15/315= 5 cases) seem far from conclusive.
A Cochrane Collaboration systematic review has been recently published on the same topic (3). In this meta-analysis statistically significant differences in mortality emerged in overall analysis and in two subgroup analyses where the same five trials were split into the categories “more tests versus fewer tests” (three studies) and “liver imaging versus no liver imaging” (three studies).
While we welcome this new pieces of evidence that should allow to better weigh up the clinical relevance of postoperative follow-up policies, we also felt encouraged to continue our randomised clinical trial (GILDA - Gruppo Italiano di Lavoro per la Diagnosi Anticipata) (4) since both meta- analyses’ authors call for new trials to assess the role of individual investigations and underscore the importance of adding psychological well being and cost-effectiveness as outcome measures. The GILDA trial is a project we launched after publishing the results of the GIVIO study on early breast cancer patients follow-up. In this regard, we would like to point out that the GIVIO trial did not include psychological support as an intervention, as wrongly reported by Rehen et al., while showed that health related quality of life was not affected by postoperative surveillance intensity (5).
The GILDA trial is aimed at testing the impact on survival, health-related quality of life and costs of two follow-up regimens with rather balanced differences in both extramural and intramural diagnostic intensity, in patients with colorectal carcinoma. We report details of the follow-up schedules in the table below (“B” stands for both intensive and minimalist regimens, and “I” stands for intensive regimen only). Thirty-seven centers, most located in Italy (one center in Spain -Barcelona- and, more recently, one in the US - St. Louis), participate in this trial that was initially sponsored by the Associazione Italiana per la Ricerca sul Cancro (AIRC), a non-profit private association and by the Mario Negri Institute thereafter. Trial recruitment started in April 1998 and as March 2002, 670 patients have been enrolled into the study. GILDA is the largest randomised trial conducted in this field up to now and is the only protocol where health-related quality of life and economic aspects of follow-up besides the usual clinical end points are addressed. The trial is still ongoing and new interested participants are very welcomed to contact the Coordinating Center.
Months from randomization Procedure 4 8 12 16 20 24 30 36 42 48 60 Office visit B B B B B B B B B B B Hematologic tests I I I I I I I I I I I CEA B B B B B B B B B B B Colonoscopy B I I B I Chest X-ray I I I I I Liver US B I I B I I I I Abdominal CT (rectum only) I I I I
on behalf of GIVIO and GILDA Investigators.
Laboratory of Clinical Research,
Department of Oncology,
Istituto di Ricerche Farmacologiche “Mario Negri”,
1) Renehan AG, Egger M, Saunder MP, O’Dwyer. Impact on survival of intensive follow up after curative resection for colorectal cancer: a systematic review and meta-analysis of randomised trials. BMJ 2002;234:1-8
2) Schoemaker D, Black R, Giles L, Toouli J. Yearly colonoscopy, liver CT, and chest radiography do not influence 5-year survival of colorectal cancer patients. Gastroenterology 1998;114:7-14
3) Jeffrey GM, Hickey BE, Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer (Cochrane Review) In: The Cochrane Library, Issue 1, 2002. Oxford: Update Software
4) Mosconi P, Andreoni B, Confalonieri C, Fossati R, Labianca R, Martignoni G. A randomized trial of intensive versus minimalist follow-up of patients with resected Dukes B2-C colorectal carcinoma. The pilot phase. Proc Am Soc Clin Oncol 17:276a, 1998 (abstr 1063)
5) The GIVIO Investigators. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomised controlled trial. JAMA 1994;271:1587-92
Competing interests: No competing interests
Editor – Renehan et al1 have combined the data from five dissimilar trials in a meta- analysis of follow up protocols after surgical resection of colorectal carcinoma. They conclude that computerised tomography and frequent serum carcinoembryonic antigen measurements can reduce the mortality from recurrent colorectal cancer. Their data do not support this conclusion. One of the studies included in the meta-analysis did not use carcinoembryonic antigen measurements. Of the remaining four, three used carcinoembryonic antigen measurements in both the experimental and control groups, and only one restricted its use to the intervention arm only. Their conclusion is misleading, particularly as they recommend their paper should form the basis for economic modelling of follow up protocols and for a revision of current clinical guidelines.
Ian Badger, Consultant Surgeon, New Cross Hospital, Wolverhampton WV10 0QP
Graham Williams, Consultant Surgeon, New Cross Hospital, Wolverhampton WV10 0QP
1. Renehan A. G. Egger M. Saunders M. P. O’Dwyer S. T. Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials. Br. J. Med. 2002;324:813-815.
Competing interests: No competing interests