Colorectal Cancer
last authored: Feb 2015, David LaPierre
last reviewed:
Introduction
Colorectal cancer is the third or fourth most common cancer in populations worldwide, and the second most common cause of cancer deaths in men and women after lung cancer. In the American population, the lifetime risk of developing CRC is 2.5-5% (Rudy and Zdon, 2000).
Even though it is frequently a life-thratening disease, it has a long period during which screening and early diagnosis can result in cure.
There are a number of screening tests available that vary in cost, effectiveness, and acceptability. For the general population, many countries suggest screening to begin at age 50.
Cancers may develop at various points along the colon and rectum. In general, the more distal the cancer, the better the prognosis, in part due to increased frequency of observable signs and symptoms, as well as ease of diagnosis. Industrialized countries are at greatest risk for colorectal cancer, with the notable exception of Japan.
The Case of John R.
John is a 44 year old man who attends his doctor for general fatigue. As a component of his investigations, routine bloodwork reveals a microcytic anemia. Without other evidence suggesting otherwise, John's doctor becomes worried about a diagnosis of colorectal cancer.
- Q: how would John's doctor explore the possibility of this diagnosis?
Causes and Risk Factors
Age is an important determinant of risk, as rates of disease increase with years.
A history of colon cancer in a first degree relative increase risk by 2-3 fold (Rudy and Zdon, 2000). Colorectal cancer is extremely uncommon in people under the age of 35, except in genetic syndromes.
Genetic mutations
Specific mutations can have a signficant impact on risk of developing colorectal cancer, as described below under pathophysiology. A number of these mutations contribute to genetic syndromes such as Famililar Adenomatous Polyposis Coli (FAP) or Hereditary Non-Polyposis Coli Colorectal Cancer (HNPCC).
In FAP, patients develop hundreds or thousands of polyps at an early age, and cancer is virtually guaranteed. Monitoring with colonoscopy, along with bowel resection, is necessary for survival.
In HNPCC, which is also known as Lynch syndrome, cancers may also be seen in the uterus, ovary, breast, stomach, and pancreas.
Medical conditions
Inflammatory bowel disease, especially ulcerative colitis, strongly increases the risk of CRC.
Other conditions include acromegaly and potential diabetes.
acromegaly, and potentially diabetes have higher rates of colorectal cancer.
Lifestyle factors
Smoking has been linked to colon cancer, among many others.
There has been no direct cause identified, but increased amounts of red meat and alcohol have been implicated.
Factors associated with decreased risk include physical activity and vegetable consumption.
Pathophysiology
Polyps
The majority of colorectal cancers are believed to arise from benign adenomas called polyps. While in the US, incidence of polyps averages 15-30% for older adults, only a minority of polyps progress to colon cancer. Observational studies suggest progression takes at least 10 years from normal tissue to cancer (REF). This process is longest in the distal colon, and shorter in the rectum and sigmoid colon (Rudy and Zdon, 2000).
Polyps have a variety of morphologies. Hyperplastic polyps have essentially no risk of malignancy. Between 70-90% of CRCs arise from adenomatous polyps, which may be tubular, villous, or tubulovillus. Villous adenomas are the least common, but also the most dangerous in regards to risk of malignancy. Between 10-30% of CRCs develop from sessile polyps.
Polyps also vary in size. Polyps that are <5mm in diameter care very small risk, while those with a diameter of 2 cm or larger have a 50% chance of becoming malignant (REF).
Transformation Process
Colorectal carcinogenesis is a well-theorized process involving the step-wise accumulation of various oncogenes and tumour suppressor genes. If a high-grade dysplasia is seen in a polyp, there is a higher likelihood that other abnormalities may be present in the colon.
The following videos, courtesy of the Khan academy, show histologic patterns of the progressing transformation process.
| Normal colon |
Dysplasia |
| Hyperplasia |
Cancer |
The most common is APC, or adenomatous polyposis coli gene. This is a tumour suppresor gene that is mutated in a majority of cancers. Other specific mutations involving tumour suppressor genes include DCC, MCC, and p53. Oncogenes that can be involved include ras, src, and myc, as well as potentially BRCA1. DNA repair genes such as hMLH1 may also be involved in some cases.
Cancer Morphology
Cancers can be sessile (flat) or pedunculated (stalklike), or can appear as stricures, fungated masses, or ulcerating masses.
Staging of Colorectal Cancer
The Dukes staging system is commonly used to classify CRC, providing information on prognosis. A description of the stages include:
A |
limited to mucosa and submucosa |
B1 |
extends into the muscular mucosa, but not through it |
B2 |
extends through muscle; lymph nodes not involved |
C1 |
contained within bowel wall; lymph nodes invoved |
C2 |
extends through bowel wall and involves lymph nodes |
D |
metastasis to liver, bone, lung |
Cancers may also be staged using the TNM system:
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Signs and Symptoms
The majority of colorectal cancers are asymptomatic until advanced. Often iron deficiency anemia is the first piece of clinical evidence.
- history
- physical exam
History
Gastrointestinal bleeding is the most common symptom, and may appear as:
- hematochezia (bright red bleeding)
- melena (black stools)
- maroon stools
Other common symptoms can include:
- abdominal pain from obstruction or invasion
- change in bowel habits, including constipation or diarrhea
- nonspecific symptoms of maligancy including anorexia, fatigue, or weight loss.
Liver involvement can cause abdominal fullness
Physical Exam
A digital rectal exam should be done to assess for palpable tumours.
Abdominal exam may reveal abdominal mass, including hepatomegaly. The live rmay be hard and irregular.
Investigations
Screening for CRC is described here.
- lab investigations
- diagnostic imaging
Lab Investigations
CBC should be done; occult malignancies often present via iron deficiency anemia.
Carcinoembryonic antigen (CEA) levels are measured preoperatively to establish a baseline to determine treatment success.
Diagnostic Imaging
Everyone with symptoms suggestive of colorectal cancer should undergo colonoscopy.
If cancer is found, an abdominal and pelvic CT is done to look for hepatic and lymphatic spread.
Differential Diagnosis
The differential diagnosis of colorectal cancer includes:
- causes of abdominal pain
- causes of GI bleeding
Treatments
Surgery alone is curative for early stage cancer. A colostomy may be created, or the bowel may be rejoined during the operation.
Surgery, postoperative radiation, and chemotherapy including 5-fluorocil, with or without leukovorin, are of benefit to people with Dukes stages B or C cancers.
Palliative surgery, radiation, and chemotherapy are all used in treatment of stage D cancers.
Consequences and Course
Survival is based on stage of disease. A cancer with Duke's stage A, if treated appropriately, has a survival of up to 90% at 5 years, while cancer that has metastasized has a 5 year survival of 5% (Rudy and Zdon, 2000).
Almost 50% of patients are diagnosed at stage III or IV.
Obstruction is more common with distal malignancy, as the stool is harder, the lumen is smaller, and growths tend to grow in a napkin ring pattern vs polyp.
Resources and References
Canadian Association of Gastroenterology - Canadian Digestive Health Foundation.
Qaseem A et al. 2012. Screening for colorectal cancer: a guidance statement from the American College of Physicians. Ann Intern Med. 156(5):378-86.
Rudy DR, Zdon MJ. 2000. Update on Colorectal cancer. AAFP. 61(6): 1759-1770.
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