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General Overview

Colorectal cancer (CRC) involves the colon, rectum, and anal canal. Colon and rectal cancer are grouped together in epidemiological studies and share similar pathophysiology, but there are distinct approaches to treatment. Conventional therapies including surgery, radiation, and chemotherapy are used depending on the stage and type of cancer. Targeted therapies, such as monoclonal antibodies and kinases inhibitors, are of increasing importance in treating advanced CRCs.


CRCs are the result of an accumulation of genetic mutations that transforms normal epithelial cells into nonmalignant adenomas or polyps, then finally malignant adenocarcinomas. Mutations originate due to hereditary syndromes or acquired through lifestyle or environmental risk factors.

Key Definitions

Adenocarcinoma—malignant neoplasm of epithelial cells with glandular or glandlike features.

Adjuvant—in oncology, treatment added after primary therapy, usually a surgery, with the goal to reduce recurrence.

CEA—carcinoembryonic antigen, tumor marker found in the serum for CRC but is also elevated in other malignant and nonmalignant conditions such as smoking.

Chemoradiation—chemotherapy given concomitantly with radiation, usually with radiosensitizing agents like fluoropyrimidines or platinums.

Microsatellite instability—when microsatellites, repeated sequences of DNA that are usually of a set length, accumulate errors and become longer or shorter than normal.

Neoadjuvant—in oncology, treatment added before primary therapy, usually a surgery, with the goal to improve outcomes of that curative therapy.

TNM staging—method of classifying cancers by T: tumor size, N: lymph node involvement, and M: presence of distant metastases; the combination of these three factors categorizes a cancer into “stages”; the higher the stage number the more widespread the cancer and generally the worse the prognosis.

Clinical Presentation/Signs and Symptoms

The clinical presentation of CRCs can be nonspecific including gastrointestinal (GI) bleeding, abdominal pain, and change in bowel habits (constipation, abnormal stools). Patients sometimes experience significant weight loss and a partial or complete bowel obstruction. The pattern of spread to distant sites primarily involves the liver and lungs (liver more common for colon and lung for rectal cancer).


The diagnosis of CRC is accomplished through colonoscopy and biopsies. A colonoscopy can visualize the entire colon and remove polyps for pathology review. If a full colonoscopy is not possible (eg, due to an obstruction), a postoperative colonoscopy is still recommended to rule out any synchronous tumors that may occur. Barium enemas with flexible sigmoidoscopy (FSIG) can diagnose tumors in the sigmoid colon but could miss any tumors in the remaining two-thirds of the colon. Sometimes a bowel obstruction or other barriers preclude a complete colonoscopy necessitating a radiographic diagnosis.

During colonoscopy, a biopsy of the suspicious mass is taken to confirm diagnosis of CRC. CRCs typically arise from glandular tissue and are thusly classified as adenocarcinomas. Additional pathologic testing should be performed to determine if the tumor has mutations in KRAS, NRAS, ...

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