Elsevier

The Lancet

Volume 365, Issue 9454, 8–14 January 2005, Pages 153-165
The Lancet

Seminar
Colorectal cancer

https://doi.org/10.1016/S0140-6736(05)17706-XGet rights and content

Summary

Every year, more than 945 000 people develop colorectal cancer worldwide, and around 492 000 patients die. This form of cancer develops sporadically, in the setting of hereditary cancer syndromes, or on the basis of inflammatory bowel diseases. Screening and prevention programmes are available for all these causes and should be more widely publicised. The adenoma-carcinoma sequence is the basis for development of colorectal cancer, and the underlying molecular changes have largely been identified. Prognosis depends on factors related to the patient, treatment, and tumour, and the expertise of the treatment team is one of the major determinants of outcome. New information on the molecular basis of this cancer have led to the development of targeted therapeutic options, which are being tested in clinical trials. Further clinical progress will largely depend on the broader implementation of multidisciplinary treatment strategies following the principles of evidence-based medicine.

Section snippets

Epidemiology

Colorectal cancer is the third most common cancer and the fourth most frequent cause of cancer deaths worldwide. The WHO estimates that 945 000 new cases occur yearly, with 492 000 deaths.1 This cancer is more common in developed than developing countries. In developed countries, it is the second most common tumour, with a lifetime incidence of 5%, but its incidence and mortality are now decreasing.1, 2, 3 The worldwide variability of outcome is proportional to access to specialists and

Sporadic

Most cases of colorectal cancer are sporadic, and genetic and environmental factors are important (panel 1).1 About 20% of all patients with this cancer are estimated to have some component of familial risk without fulfilling the strict criteria for hereditary colorectal cancer.4 Family history should therefore always be taken when assessing a patient; the Bethesda guidelines are valuable in this context. However, taking a family history by interview often underestimates family history of

Screening and prevention

Screening is effective in reducing mortality from colorectal cancer. Screening procedures include faecal occult-blood tests, flexible sigmoidoscopy, double-contrast barium enema, and colonoscopy.18 One of these options should be offered to asymptomatic people aged 50 years or older.19 The ideal screening method is still controversial, with no test unequivocally better than another. Risk, costs, and effectiveness need to be taken into account when discussing the different options.19 Total

Pathogenesis

The adenoma-carcinoma sequence is the basis for development of colorectal cancer with corresponding accumulation of genetic changes.32, 33 Traditionally, colorectal carcinogenesis is explained by two pathways, the gatekeeper and the caretaker pathway.34 The gatekeeper pathway is responsible for about 85% of sporadic colorectal cancers, and is the mechanism of carcinogenesis in patients with FAP. Gatekeepers are genes that regulate growth. One of the key steps of this pathway is mutation of the

Prognostic factors

Prognostic factors can be divided into three main groups: patient, treatment, and tumour related factors. We mainly discuss the last two.

Diagnosis

Colonoscopy is the gold standard for diagnosis of colorectal cancer; in addition to physical examination, abdominal ultrasound and chest radiography are routinely done. The necessity of routine preoperative CT scans is still debated because this method alters the surgical approach in only a few cases.83

Better imaging of rectal cancer is important for planning of treatment. Local staging can be done by endorectal ultrasound (figure 2), CT (figure 3), or MRI (figure 4).84 High-resolution MRI is a

Treatment

Surgery is the basis of therapy for colorectal cancer, and important developments have occurred.

Radiotherapy and radiochemotherapy

Radiotherapy aims to reduce local recurrence and improve survival for patients with rectal cancer. Traditionally, adjuvant radiochemotherapy was considered standard care for patients with stage II and III rectal cancer. Neoadjuvant radiochemotherapy was reserved for advanced rectal cancers (uT4). Recently, neoadjuvant methods have been advocated for stage II and III patients too on the basis of two theoretical advantages—better local tumour control and lower morbidity.118

The Dutch CKVO 95-04

Adjuvant treatment

The use of adjuvant fluorouracil-based chemotherapy in patients with stage III colon cancer is thought to be standard care, but is not routinely recommended in stage II colon cancer.129, 130 For specific high-risk stage II patients (eg, T4-tumours, inadequate number of removed lymph nodes, perforation, bowel obstruction, poor differentiation), however, chemotherapy should be considered. Gill and colleagues62 developed a model to estimate survival benefit by adjuvant chemotherapy stratified by

Palliative chemotherapy

Palliative chemotherapy for patients with metastatic colorectal cancer aims to improve survival and quality of life. It is crucial that resectability of the metastases is assessed by experienced surgeons before and during chemotherapy to avoid missing the opportunity for potentially curative resection, since resection of metastatic disease (hepatic or pulmonary metastases) can lead to 5-year survival rates of 35–58%.137 In this context, it is important to realise that about 15% of patients with

Response prediction

Prediction of the response to chemotherapy would allow its selective use. For fluorouracil-based chemotherapy, intratumoral thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase as well as microsatellite-instability status could be such markers.154, 155, 156 For oxaliplatin, intratumoral concentrations of ERCC1 (excision repair cross-complementing), and for irinotecan, intratumoral concentrations of topoisomerase 1 seem to allow response prediction.157 However,

Follow-up

The objectives of follow-up after curative resection of colorectal cancers are improvement of survival, psychological support, quality control of medical care, and facilitation of research.158 Meta-analyses showed a significant improvement in survival after intense compared with routine follow-up (relative risk ratio 0·67–0·81).159, 160, 161 The cost for one saved year of life by follow-up is estimated at about US$6000–14000, which is judged to be acceptable.162

Because of the heterogeneity of

Future developments

The molecular genesis of colorectal cancer and therapies focusing on specific molecular targets attract the most attention and promise major advances. Individualised treatment according to genetic tumour profiles might become possible. However, we should not forget that better screening and prevention programmes could save many lives; public education should therefore be a top priority. In the future, prediction of the individual risk of colorectal cancer with individualised screening and

Search strategy and selection criteria

We searched the databases MEDLINE and PREMEDLINE from January, 1999, to July, 2004. The keywords “colorectal cancer”, “rectal cancer”, and “colon cancer” were combined with the Boolean operator “and” with the following keywords: “epidemiology”, “risk factors”, “prevention”, “screening”, “pathogenesis”, “prognostic factors”, “diagnosis”, “treatment” (“surgery”, “radiotherapy”, “chemotherapy”), and “follow-up”. We screened the bibliography of each relevant article for further relevant

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