Elsevier

European Journal of Cancer

Volume 43, Issue 17, November 2007, Pages 2467-2478
European Journal of Cancer

Review
Relationship of diagnostic and therapeutic delay with survival in colorectal cancer: A review

https://doi.org/10.1016/j.ejca.2007.08.023Get rights and content

Abstract

Background. Early diagnosis of colorectal cancer before the onset of symptoms improves survival. Once symptoms have occurred, however, the effect of delay on survival is unclear. We review here evidence on the relationship of diagnostic and therapeutic delay with survival in colorectal cancer.

Methods. We conducted a systematic of Medline, Embase, Cancerlit and the Cochrane Database of Systematic Reviews to identify publications published between 1962 and 2006 dealing with delay, survival and colon cancer. A meta-analysis was performed based on the calculation of the relative risk (RR) and on a model of random effects.

Results. We identified 40 studies, representing 20,440 patients. Fourteen studies were excluded due to excessively restricted samples (e.g. exclusion of patients with intestinal obstruction, with tumours at stage C or D at the time of diagnosis, or who died 1–3 months after surgery); or because they studied only a portion of the delay. Of the 26 remaining studies, 20 showed no association between delay and survival. In contrast, four studies showed that delay was a factor contributing to better prognosis, and two showed that it contributed to poorer prognosis. There was no association between delay and survival when the colon and rectum were considered separately, when a multivariate analysis was performed, and when the effects of tumour stage and degree of differentiation were taken into account. To perform a meta-analysis, 18 additional studies were excluded, since the published articles did not specify the absolute numbers. In the remaining eight studies, the combined relative risk (RR) of delay was 0.92 (confidence interval (CI) 95%: 0.87–0.97).

Conclusions. The results of the review suggest that there is no association between diagnostic and therapeutic delay and survival in colorectal cancer patients. Colon and rectum should be assessed separately, and it is necessary to adjust for other relevant variables such as tumour stage.

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

References (93)

  • A. Maguire et al.

    Cancer survival and the duration of symptoms. An analysis of possible forms of the risk function. ISDS II Project Investigators

    Eur J Cancer

    (1994)
  • M. Korsgaard et al.

    Delay of treatment is associated with advanced stage of rectal cancer but not of colon cancer

    Cancer Detect Prev

    (2006)
  • L. Roncucci et al.

    Survival for colon and rectal cancer in a population-based cancer registry

    Eur J Cancer

    (1996)
  • M. Akhter et al.

    Alcohol consumption is associated with an increased risk of distal colon and rectal cancer in Japanese men: the Miyagi Cohort Study

    Eur J Cancer

    (2007)
  • A.S. Coates

    Breast cancer: delays, dilemmas and delusions

    Lancet

    (1999)
  • M. Porta et al.

    Semiology, proteomics, and the early detection of symptomatic cancer

    J Clin Epidemiol

    (2003)
  • E. Robinson et al.

    Colorectal cancer: incidence, delay in diagnosis and stage of disease

    Eur J Cancer Clin Oncol

    (1986)
  • H.W. Holliday et al.

    Delay in diagnosis and treatment of symptomatic colorectal cancer

    Lancet

    (1979)
  • L.S. Freedman et al.

    Multivariate analysis of prognostic factors for operable rectal cancer

    Lancet

    (1984)
  • S. Winawer et al.

    Workgroup II: the screening process. UICC International Workshop on Facilitating Screening for Colorectal Cancer, Oslo, Norway (29 and 30 June 2002)

    Ann Oncol

    (2005)
  • P.R. Kiran et al.

    Duration of symptoms and spread of colorectal cancer: a short history does not mean early disease

    Ann R Coll Surg Engl

    (2002)
  • P. Barillari et al.

    Relationship of symptom duration and survival in patients with colorectal carcinoma

    Eur J Surg Oncol

    (1989)
  • H. Graffner et al.

    Patient’s and doctor’s delay in carcinoma of the colon and rectum

    J Surg Oncol

    (1986)
  • A.J. Stellon et al.

    Iron deficiency anaemia in general practice: presentations and investigations

    Br J Clin Pract

    (1997)
  • E. Nilsson et al.

    Carcinoma of the colon and rectum

    Delay in diagnosis. Acta Chir Scand

    (1982)
  • M. Porta et al.

    Emergency admission for cancer: a matter of survival?

    Br J Cancer

    (1998)
  • A.P. Polednak

    Inpatient hospital admission through an emergency department in relation to stage at diagnosis of colorectal cancer

    Cancer Detect Prev

    (2000)
  • M. Korsgaard et al.

    Reported symptoms, diagnostic delay and stage of colorectal cancer: a population-based study in Denmark

    Colorectal Dis

    (2006)
  • V.L. Allgar et al.

    Delays in the diagnosis of six cancers: analysis of data from the National Survey of NHS Patients: Cancer

    Br J Cancer

    (2005)
  • Cabeza E, Esteva M, Ramos M, Roca J, Ruiz A. Demora diagnóstica o terapéutica en cáncer. Palma:RedIAPP; 2007 [in...
  • C.E. Welch et al.

    Carcinoma of the colon and rectum

    New Engl J Med

    (1962)
  • T.T. Irvin et al.

    Duration of symptoms and prognosis of carcinoma of the colon and rectum

    Surg Gynecol Obstet

    (1977)
  • F.T. McDermott et al.

    Prognosis in relation to symptom duration in colon cancer

    Br J Surg

    (1981)
  • F. McDermott et al.

    Symptom duration and survival prospects in carcinoma of the rectum

    Surg Gynecol Obstet

    (1981)
  • M. Pescatori et al.

    Site, emergency, and duration of symptoms in the prognosis of colorectal cancer

    Dis Colon Rectum

    (1982)
  • M. Porta et al.

    Influence of diagnostic delay” upon cancer survival: an analysis of five tumours sites

    J Epidemiol Community Health

    (1991)
  • A.D. Oxman

    Checklists for review articles

    BMJ

    (1994)
  • D.F. Stroup et al.

    Meta-analysis of observational studies in epidemiology: a proposal for reporting

    Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA

    (2000)
  • D.G. Altman

    Systematic reviews of evaluations of prognostic variables

    BMJ

    (2001)
  • S.H. Downs et al.

    The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions

    J Epidemiol Community Health

    (1998)
  • J. Huang et al.

    Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review

    J Clin Oncol

    (2003)
  • S.G. Thompson et al.

    How should meta-regression analyses be undertaken and interpreted?

    Stat Med

    (2002)
  • X. Hervada et al.

    Epidat 3.0. Programa para análisis epidemiológico de datos tabulados

    Rev Esp Salud Pública

    (2004)
  • S. Carter et al.

    Delay in the presentation of colorectal carcinoma: a review of causation

    Int J Colorectal Dis

    (1998)
  • J.H. MacLeod et al.

    Survivorship following treatment for cancer of the colon and rectum

    Cancer

    (1970)
  • L. Polissar et al.

    Survival of colorectal cancer patients in relation to duration of symptoms and other prognostic factors

    Dis Colon Rectum

    (1981)
  • Cited by (0)

    View full text