Information was found by an electronic search of PubMed using the terms “colorectal cancer pathology”, “colon cancer pathology”, “rectal cancer pathology”, “circumferential resection margin”, and “TNM staging”. Only papers published in English between 1980 and 2007 were used.
Personal ViewThe future of the TNM staging system in colorectal cancer: time for a debate?
Introduction
The Tumour, Nodes, and Metastasis (TNM) staging system was initially developed to predict cancer prognosis, but its function has expanded and it is now used to determine treatment and entry into clinical trials. The objectives of the TNM system have been stated as: to aid in the planning of treatment; to give some indication of prognosis; to assist in assessing the effects of treatment; to help with the exchange of information between treatment centres; and to contribute to the continuing investigation of human cancers.1
In view of the continually expanding knowledge of cancer, the TNM system is revised every few years to allow for the incorporation of new evidence and, therefore, keep classifications up to date. However, revisions of the system can cause problems, especially with regard to treatment. Modification of a component of the system could lead to the upstaging or downstaging of the disease, resulting in a change in treatment by the oncologist. For example, if the criteria for the presence of a lymph-node metastasis changes,2, 3 then the stage of cancer in many patients will change, leading to a situation where patients might be offered treatment based on one edition of the TNM system but not if an earlier edition is used, or vice versa. Changes in the TNM system can also lead to an inability to compare results from new clinical trials with older trials, and such changes are especially difficult for ongoing clinical trials, where a decision needs to be made on how to revise the entry criteria or treatment patterns in light of the new changes. Almost all large clinical trials need to cope with these problems, because most will take 5–10 years to recruit and follow-up. The pragmatic approach in this situation is to keep the TNM version that was decided on at the outset of the trial. However, this approach can bring problems for the pathologists who might not know that a patient was being considered for a postoperative clinical trial and, might, therefore, apply the new version of the TNM system instead. The more frequent the revisions the greater these problems become.
In 2004, a study was published that highlighted many deficiencies of the TNM system and its revision process.4 Major changes were proposed for future management of TNM classifications, which included open submission of proposals for revisions, a process of continued monitoring of the published work, and a wider consultation process. These are laudable changes if they are introduced and could solve many of the current problems. But do they go far enough in rectifying the issues and has a chance to optimise the benefits that can be gained from a universally respected staging system been missed? A glaring omission from the recommendations of the 2004 report4 was a commitment to introduce changes only on the basis of high-quality evidence. This omission was surprising, because such a commitment is a key feature of most practice guidelines and a defining feature of the oncology community. As gastrointestinal pathologists, we wish to highlight some of the problems that have occurred with the TNM system and the classification of colorectal cancer (figure 1) in the past, with particular focus on the sixth TNM revision (TNM6). On the basis of these problems, we reject some of the recent changes to the system, urge that the same mistakes are not made again, and suggest further improvements that could be made to help keep the TNM system at the heart of the staging process worldwide.
Section snippets
Revisions of the TNM system
The staging of colorectal cancer has seen several changes over the past 10 years.1, 2, 3 Such changes, along with their evidence base, are a major area of concern, highlighted by the fact that some of these changes have been withdrawn in subsequent revisions of the system. Such withdrawals could be attributed to the fact that some recommendations for change seem to have been based on postulations rather than on fact and others have been drawn from evidence from other tumour sites without
Problems with revisions of the TNM system
The changes made to the TNM5 edition for the TNM6 definitions of lymph-node involvement and venous invasion, highlight some of the fundamental flaws in the revision process. Five major problems exist with these changes: first, the clinical evidence base on which these changes were made was very poor; second, the published work did not support the biological basis for the classification of tumour nodules as solely lymph-node involvement or venous involvement; third, tumour deposits might be
Overwhelming evidence
Overwhelming evidence has been ignored when revising the TNM system. The introduction of the R classification in 1978 was a major step forward, with R0 denoting a complete resection with no residual tumour, R1 a microscopically incomplete resection with 0 mm clearance, and R2 macroscopic residual tumour.17, 18, 19 However, this R1 definition is inappropriate because a resection margin of 0 mm is not routinely used in practice.20, 21, 22, 23, 24
The TNM committee have commented on this problem by
Confusion over statements
Many publications have been required to further clarify confusion about the TNM staging system.24, 35, 36, 37 For example, major confusion was caused by the statements by the TNM committee,2 the AJCC,38 the American College of Pathologists,39 and the American College of Surgeons.40 These statements suggested that a minimum of 12 lymph nodes needed to be assessed before a tumour could be staged properly, a suggestion that was interpreted as a rule rather than a recommendation by pathologists. As
Should we revert to TNM5?
As a result of the flaws in TNM6, the UK continues to apply TNM5 because this version was previously used in everyday practice and was the version used in the most recent generation of clinical trials and population studies. Although TNM5 contains the controversial 3-mm rule that seems to lack an evidence base, this rule does, at least, have the advantage of being quantitative and, therefore, reproducible. Additionally, persisting with TNM5 has avoided adoption of the contentious node and vein
Positive changes in TNM6
The subdivision of stage II into IIA (T3 N0 M0) and IIB (T4 N0 M0) is helpful because patients classified as T4 N0 M0 have a significantly worse prognosis than those classified T3 N0 M0 and are frequently given adjuvant treatment; however, so are other patients who are classed as high–risk, such as those with extramural vascular invasion or extensive extramural spread. Extramural spread cannot be identified by the TNM system and vascular invasion is compromised by the TNM6 definition of venous
Suggested improvements for the revision process
The recommendations made in 2004 to allow more transparent and robust changes to the TNM system4 were commendable, but did not go far enough. Levels of evidence are now internationally accepted as the best way forward for developing guidelines for practice and we argue that this approach would be the way forward for the TNM system. Clinicians in England and Wales,42, 43 Scotland,44 France,45 and the USA40 who specialise in colorectal cancer have all published guidelines for the management of
Conclusions
We hope that our concerns for the use of the TNM6 staging system in colorectal cancer are shared by the oncology community. This system is an essential cornerstone for the management of patients with cancer, but we believe that unless modern standards of evidence are adopted, along with wide consultation about proposed changes and evidence of reproducibility, this system will become discredited and a valuable international resource will be lost. As cancer clinicians strive to improve survival
Search strategy and selection criteria
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