Elsevier

The Lancet

Volume 383, Issue 9927, 26 April–2 May 2014, Pages 1490-1502
The Lancet

Seminar
Colorectal cancer

https://doi.org/10.1016/S0140-6736(13)61649-9 Get rights and content

Summary

More than 1·2 million patients are diagnosed with colorectal cancer every year, and more than 600 000 die from the disease. Incidence strongly varies globally and is closely linked to elements of a so-called western lifestyle. Incidence is higher in men than women and strongly increases with age; median age at diagnosis is about 70 years in developed countries. Despite strong hereditary components, most cases of colorectal cancer are sporadic and develop slowly over several years through the adenoma–carcinoma sequence. The cornerstones of therapy are surgery, neoadjuvant radiotherapy (for patients with rectal cancer), and adjuvant chemotherapy (for patients with stage III/IV and high-risk stage II colon cancer). 5-year relative survival ranges from greater than 90% in patients with stage I disease to slightly greater than 10% in patients with stage IV disease. Screening has been shown to reduce colorectal cancer incidence and mortality, but organised screening programmes are still to be implemented in most countries.

Section snippets

Incidence and mortality

Colorectal cancer is the third most common cancer and the fourth most common cancer cause of death globally, accounting for roughly 1·2 million new cases and 600 000 deaths per year.1 Incidence is low at ages younger than 50 years, but strongly increases with age. Median age at diagnosis is about 70 years in developed countries.2 The highest incidence is reported in countries of Europe, North America, and Oceania, whereas incidence is lowest in some countries of south and central Asia and

Histopathological classification

Colorectal cancers are classified according to local invasion depth (T stage), lymph node involvement (N stage), and presence of distant metastases (M stage; table 2).39 These stages are combined into an overall stage definition (table 3), which provides the basis for therapeutic decisions.39

Although classification according to TNM and Union Internationale Contre le Cancer (UICC) stage provides valuable prognostic information and guides therapy decisions, the response and outcome of individual

Molecular pathogenesis

The molecular pathogenesis of colorectal cancer is heterogeneous. The molecular mechanisms underlying development of this cancer are clinically important because they are related to the prognosis and treatment response of the patient.40, 41 The interconnections between molecular pathogenesis, prognosis, and therapy response have become increasingly apparent during the past two decades, including the identification of the molecular mechanisms and genetic changes that cause the hereditary forms

Microsatellite instability

In addition to the identification of families with hereditary colorectal cancer, microsatellite instability analysis can provide valuable information about the prognosis and therapy response of patients. Patients with MSI-H colorectal cancer have a better prognosis than do patients with microsatellite stability. A systematic review59 of 32 eligible studies (7642 patients with colorectal cancer) estimated a hazard ratio (HR) of 0·65 (95% CI 0·59–0·71) for overall survival. Additionally, the

Diagnosis and staging

Diagnosis of colorectal cancer is made histologically from biopsy samples taken during endoscopy. Complete colonoscopy or CT colonography is mandatory to detect synchronous cancers that are present in about 2–4% of patients.69, 70 If this is not possible preoperatively, complete visualisation of the colon should be done within 6 months after curative resection.

For rectal cancer, exact local staging at the time of diagnosis is essential and is the basis for requirement of neoadjuvant treatment.

Role of multidisciplinary teams

Like other patients with cancer, those with colorectal cancer should be assessed by a multidisciplinary team. The multidisciplinary team should include a colorectal surgeon, a medical oncologist, a gastroenterologist, a radiotherapist, a radiologist, and a pathologist. Depending on the tumour extent, the addition of a hepatic or thoracic surgeon is necessary. Patients with rectal cancer for whom a decision has to be made about need for neoadjuvant therapy and all patients with distant

Primary prevention

With increased knowledge about risk and preventive factors, measures to reduce those risk factors and promote preventive lifestyles have potential for primary prevention. Several risk factors, including smoking, alcohol consumption, and obesity, are shared with other common chronic diseases, and primary prevention can and should be included in comprehensive primary prevention strategies.

Although some evidence from randomised trials23, 25 shows effective chemoprevention of colorectal cancer by

Search strategy and selection criteria

Data for this Seminar were identified by searches of PubMed, Cochrane, and ISI Web of Knowledge databases, and references from relevant articles, with various combinations of the search terms “colon cancer”, “colorectal cancer”, “colorectal neoplasms”, “colorectal tumor”, “chromosomal instability”, “diagnosis”, “drug therapy”, “epidemiology”, “genomic instability”, “microsatellite instability”, “molecular pathogenesis”, “mortality”, “prevention”, “prognosis”, “radiotherapy”, “risk factors”,

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