ReviewRelationship of diagnostic and therapeutic delay with survival in colorectal cancer: A review
Introduction
Colorectal cancer (CRC) is the second most frequent malignant tumour in the developed world in either sex. In Europe it is estimated that in the year 2006 there were 412,000 new cases of CRC, with incidence rates of 55.4 per 100,000 in men and 34.6 per 100,000 in women, and that 207,400 people died of this disease (mortality rates, 27.3 per 100,000 in men and 16.6 per 100,000 in women).1
The 5-year survival rate of CRC patients in Europe is 52%, although there is considerable variation among countries, with rates for colon tumours ranging from 26% to 56% for men and from 29% to 59% for women, and rates for rectal tumours ranging from 26% to 56% for men and from 28% to 62% for women. These differences in survival have been attributed to the stage and timing of diagnosis and, in some regions, to the quality of medical care.2
CRC is diagnosed principally by the presence of clinical signs, since although screening has proven effective, it is still not widespread.3 Its clinical presentation is often ill-defined and insidious, especially when the tumour is situated in the right colon. The most frequent symptoms are rectorrhagia, changes in frequency of evacuation, abdominal pain, loss of weight, anaemia and intestinal obstruction,4, 5, 6, 7, 8 with obstruction being an indication of poor prognosis.9, 10, 11, 12 Patients with cancer of the rectum tend to present first with rectorrhagias and changes in frequency of evacuation, accompanied by rectal pain or tenesmus, which together have been termed the ‘distal cluster’.13 In contrast, cancers of the colon become apparent through non-specific symptoms such as anaemia, anorexia, abdominal pain and fatigue.14
The time between the first symptoms and the diagnosis of a cancer is termed the diagnostic delay, whereas the time between first symptoms and initiation of treatment is termed the therapeutic delay. In general, however, the duration of symptoms is referred to without specifying the end point of the period. The diagnostic and therapeutic delays are complex concepts involving various factors, including the biology of the tumour, the interaction between the tumour and the host, the behaviour of the patient, the conduct of the physician and the operation of the healthcare system. Intuitively, a reduction in the diagnostic or therapeutic delay should be accompanied by an improved survival rate. This has been shown in breast cancer,15 but it is not so clear in cancers of other parts of the body.16, 17
In CRC, the effect of delay on survival has been studied since the 1960s. Between 1937 and 1960 there was a decrease in the mean delay of CRC diagnosis, an increase in the rate of tumour removal, a decrease in the number of cases with obstruction, and a substantial improvement in 5-year survival rate18 .These observations, however, have not been confirmed, with studies showing either no association between delay and survival,9, 19, 20 or that longer delay was associated with a better survival rate.21, 22, 23, 24 We have therefore sought to determine whether diagnostic or therapeutic delay influences survival in CRC.
Section snippets
Methods
A systematic review of Medline, Cancerlit, Embase and the Cochrane Database of Systematic Reviews was performed using the keywords colorectal neoplasms OR gastrointestinal neoplasms AND early diagnosis OR diagnostic delay OR patient delay OR provider delay OR survival OR prognosis OR time factors. The search covered systematic reviews and original studies published between 1962 and 2006, with traditional reviews, editorials and letters of opinion excluded. A review was considered to be
Results
Forty-one studies were identified: Ten from Medline, two from Embase and the rest from the secondary review. No systematic review was identified, and one that did not comply with the definition was excluded.32 The characteristics of the remaining 40 studies5, 9, 18, 19, 20, 21, 22, 23, 24, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 are shown in Table 2. All were original articles, except for one unpublished doctoral
Discussion
The systematic review did not produce an unequivocal answer to the question of whether diagnostic or therapeutic delay influences survival in CRC. Our review, however, enabled us to identify deficiencies in the studies reviewed, and to put forward several hypotheses. Although the results of the meta-analysis suggest that longer delay in CRC is related to improved survival, this is by no means certain.
Limitations of the systematic review. The term ‘delay’ is not a descriptor, nor is it present
Conflict of interest statement
None declared.
Acknowledgement
This study has received a grant from the Balearic Department of Health in 2003. In addition, it has received the support of the Health Promotion and Preventive Health in Primary Health Care Network, sustained by the Ministry of Health (ISCIII-RETCI G03/170 and RD 06/0018) and of the Health Sciences University Institute (IUNICS), belonging to the University of the Balearics Islands. The authors would like to thank Rebeca Isabel and Amador Ruiz for their help in the bibliographic review and David
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