Lack of association between diagnostic and therapeutic delay and stage of colorectal cancer

Abstract

Background

A recent review suggests that there is no association between diagnostic and therapeutic delays and survival in colorectal cancer patients. However, the effect of tumour stage on the relationship between delay and survival in CRC should be clarified. We review here the evidence on the relationship between diagnostic and therapeutic delays and stage in colorectal cancer.

Methods

We conducted a systematic review of Medline, Embase, Cancerlit and the Cochrane Database of Systematic Reviews to identify publications published between 1965 and 2006 dealing with delay, stage and colorectal cancer. A meta-analysis was performed based on the estimation of the odds ratios (OR) and on a random effects model.

Results

We identified 50 studies, representing 18,649 patients. Thirty studies were excluded due to excessively restricted samples (e.g. exclusion of patients with intestinal obstruction or who died 1–3 months after surgery) or because they studied only a portion of the delay. Of the 37 remaining studies, great variability was noted in connection with the type of classification used for disease stage and the type of measurement used for the delay. Meta-analysis was performed based on 17 studies that included 5209 patients. The combined OR was 0.98 (95% confidence interval (CI): 0.76–1.25), suggesting a lack of association between delay and disease stage. In four studies, cancers of the colon and rectum were dealt with separately, and a meta-analysis was performed using the data for colon cancer (1001 patients) and for rectal cancer (799 patients). In both cases, the combined ORs overlapped 1.0, and showed opposite associations when studied separately: 0.86 (95% CI: 0.63–1.19) for the colon (i.e. more delay is associated with the earlier stage at diagnosis) and 1.93 (95% CI: 0.89-4.219) for the rectum (i.e. less delay is associated with the earlier stage).

Conclusions

When colorectal cancers are taken as a whole, there appears to be no association between diagnostic delay and disease stage when diagnosis is made. However, when cancers of the colon and the rectum are studied separately, there may be an opposite association. More studies about this issue are needed with larger and unrestricted samples.

Introduction

Colorectal cancer is an important public health problem worldwide, especially in wealthy countries. In Europe, when both sexes are taken together, it ranks the second highest amongst cancers in both incidence and mortality,¹ while in the United States it is the cancer with the fourth highest incidence and ranks second in terms of mortality.²

Survival amongst patients with colorectal cancer varies greatly amongst different geographic regions. In the United States, it is higher than in Europe: 69% versus 57% after 3 years,³ a fact that could be linked to earlier diagnosis, since the percentage of cases that are diagnosed in early stages, the percentage of adenocarcinomas that are found when adenomas (polyps) are removed and the percentage of tumours that are removed are all higher in the United States.⁴ Greater differences are seen amongst European countries, which may also be due to wide variability in access to diagnostic and therapeutic techniques.⁵

The stage when the tumour is diagnosed is the main prognostic factor in colorectal cancer, so that in Europe survival is 93% after 3 years for Duke stage A, between 91% and 74% for stage B, between 66% and 48% for stage C and 16% for stage D.³

There is an evidence that early diagnosis, before symptoms appear, reduces disease mortality and incidence.⁶ On the other hand, when the patient already has symptoms, there is a controversy regarding the association between how long they have been present – that is, diagnostic or therapeutic delay – and survival. In the case of breast cancer, it has been shown that early diagnosis is linked to better survival, an effect that appears to be mediated by the stage of the disease when the diagnosis is made.⁷

In a recent systematic review⁸ that was performed to assess how diagnostic and therapeutic delays affect survival, we have obtained contradictory results: in most cases, there was no association between delay and survival; in others, there was paradoxically an association between a longer delay and a greater survival, and in others still greater delay was associated with decreased survival. However, when the delay was adjusted for other variables having prognostic significance, such as disease stage, the association between delay and survival disappeared in all studies, which shows that disease stage could be acting as a confounder. At the same time, the results obtained suggested that the delay could affect survival differently in the case of cancers of the colon and rectum.

We found no review that looked at the link between delay and disease stages. This study aims to review and summarise the evidence accrued.