Colorectal Cancer Screening and Prevention
Author / Curator: Dr. Leon D. Averbukh
Faculty Advisor: Dr. Robert J. Nardino
Top Teaching Points
- For those without any family history or personal history of Colorectal cancer (CRC), screening is generally recommended starting at age 50 until the age of 75. Variables that effect duration of screening are the modality used, family history, personal history with polyp frequency, type and size.
- Red meat, meat cooked at high temperatures, smoking, alcohol, central obesity, and Diabetes Mellitus increase the risk of CRC.
- Calcium, physical activity, COX-2 inhibitors, aspirin, and post menopausal hormones have been shown to reduce risk of CRC though the latter three are not recommended for regular risk reduction due to their side effect profiles.
More than 1 million people worldwide are diagnosed with CRC every year. As of 2012, it is the second most common cause of cancer in women, the third most common in men, and the fourth most common cause of cancer related death. In the United States however, it is the second most common cause of cancer and cancer related death in both men and women. CRC is most prevalent in developed nations, with the highest rates observed in Australia, New Zealand, Europe, and the US while the lowest rates are in Africa and South-Central Asia. From 2005 to 2009, the median age at diagnosis for CRC in the US was 69 years of age though it appears the rate of disease among younger people is increasing. Those born in 1990 have double the risk of developing colon cancer and quadruple the risk of rectal cancer compared to people born around 1950. Overall, the rate at which new CRC cases are diagnosed has been dropping in the US since the mid-1980s, though this drop has been driven by the older adult population. Individuals with inflammatory bowel disease are at increased risk of colon cancer, with the longer the duration of illness/ the worse the severity of inflammation, the higher the subsequent risk of CRC.
About a third of those afflicted by CRC will die from the condition with prognosis dependent largely on the type of cancer diagnosed. Generally, those that are symptomatic at the time of diagnosis are considered to have a poorer prognosis owing to their likely advanced stage of disease. Unfortunately, it is estimated that about 20% of people present for diagnosis when their disease has already progressed to stage IV cancer, with 25% of those individuals experiencing an isolated liver metastasis. Prognosis for metastatic CRC is very poor, and ranges on average from 4 to 14 months depending on the location of metastases.
Physiology / Pathophysiology
CRC is a cancer that arises from the epithelial cells found in the lining of the colon or rectum. Most commonly, these malignant mutations are the result of changes in the Wnt signaling pathway with the end result being increased activity of the mechanism. It is believed that these mutations most likely occur in the intestinal crypt stem cells and the mutations can either be acquired or inherited. For those individuals with inherited CRC, the most commonly implicated gene is the APC gene which produces the similarly names APC protein. However, mutation of the Wnt pathway is not enough to induce cancer as other elements of the cell signaling pathway have to be mutated as well. Protein such as p53, responsible for death of cells with defective Wnt pathways, along with other protein responsible for apoptosis including TGFbeta and DCC, have been found to be deactivated in CRC cases. This deactivation allows for the uncontrolled growth of tumor cells.
Treatment options vary based on location and severity of the disease. In individuals with a localized cancer, open laparotomy/ laparoscopy are the preferred methods of resection. In some cases, individuals with a few isolated lesions in the liver or lungs may also undergo surgical resection. In both colon and rectum, chemotherapy may be added to management, though in more advanced stages of disease (stages III, IV) chemotherapy and radiation therapy (more commonly employed in rectal cancer) are integral treatment elements. Recently, immunotherapy has been found to be useful in specific subtypes of colorectal cancer.
General Screening Guidelines by Society
|Society||Start Screening Age/ Stop Screening Age||Race/ gender accommodations||Method of testing recommendation level|
|Multi-Society Task Force of Colorectal Cancer [MSTF] (2017)||Age 50/ Age 75 if up to date on screening (85 if not up to date)||Age 45 for African Americans (weak evidence||First-tier: Colonoscopy every 10 years or FIT annually.
Second-tier: CT Colonography every five years, FIT–fecal DNA every three years, or flexible sigmoidoscopy every 5 to 10 years
Third-tier: Capsule colonoscopy every five years
|American Cancer Society (2018)||Age 45/Age 75
Age 76-85: Shared decision making with patient based on their functional status
Age over 85: Do not screen
|None||First Tier: Sigmoidoscopy every five years, colonoscopy every 10 years, or CT Colonography every five years.
Second Tier: Take-home gFOBT yearly, take-home FIT yearly, or a stool-DNA test every three years. If any tests positive, need to do colonoscopy
|US Preventative Services Task Force [USPSTF] (2015)||Age 50/ Age 75||None||Does not list preferred screening methods, only age range for screening.|
Screening Guidelines for Higher Risk Populations
Family History of Colorectal Cancer or Adenomatous Polyps
|Society||Type of Risk||Screening Start Age||Screening Type||Screening Interval|
|MSTF||CRC or an advanced adenoma in two first degree relatives diagnosed at any age OR CRC or an advanced adenoma in a single first-degree relative at age less than 60 years||Colonoscopy every 5 years beginning 10 years before the age of diagnosis of the youngest affected relative OR age 40, whichever is earlier. For those with single first degree relative with CRC in whom no significant neoplasia appears by age 60 years, physicians can offer expanding the interval between colonoscopies.*||Colonoscopy||Every 5 years|
|CRC or an advanced adenoma in a single first-degree relative diagnosed at age over or equal to 60 years||Begin screening at age 40 years; tests and intervals are as per the average- risk screening recommendations||same as regular risk||same as regular risk|
|American Cancer Society||CRC or Adenomatous Polyps in 1st degree relative before 60 OR in 2 or more first degree relatives at any age.||Age 40, or 10 years before youngest case in immediate family, whichever is earlier.||Colonoscopy||Every 5 years|
|CRC or Adenomatous polyps in any first degree relative aged 60 or older, or in at least 2 second degree relatives of any age.||Age 40||same as regular risk||same as regular risk|
*Patient with 1 or more first degree relatives with CRC/ advanced adenoma should be offered annual FIT if they decline colonoscopy.
|Society||Type of Risk||Screening Start Age||Screening Type||Screening Interval|
|MSTF||Lynch Syndrome (Hereditary non-polyposis colon cancer)||Age 20–25||
||Every 2 years until 40, then annualy thereafter|
|Familial Adenomatous Polyposis||N/A||
||Every year until colectomy is deemed the best treatment|
|Family Colon Cancer Syndrome X||10 years before the age of diagnosis of the youngest affected relative||
||Every 3-5 years|
|Familial Adenomatous Polyposis (FAP)||Age 10-12||
|Lynch Syndrome (Hereditary non-polyposis colon cancer)||Age 20-25 OR,
10 years before youngest case in immediate family
||Every 1-2 years|
|Inflammatory Bowel disease (Ulcerative Colitis & Crohn's Disease)||8 years after the onset of pancolitis OR,
12-15 years of the onset of left sided colitis
||Every 1-2 years with biopsies for dysplasia|
Screening Guidelines for Older Populations
- Patients over the age of 85 should not be screened and the decision to screen adults aged 76 to 85 should be individualized, taking into account the patient’s overall health and prior screening history.
- Discontinuation of screening should be considered in individuals that are up to date with screening, have prior negative screening results (particularly colonoscopy) and have reached the age of 75 or have <10 years of life expectancy.
- Those without prior screening should be considered for screening up to age 85, depending on age and co-morbidities.
Colorectal Cancer Prevention
|Diet and Supplements||Effect on CRC Risk||Implications|
|Fruits, Vegetables, and Fiber||None|
|Red Meat, Fat, and Carbohydrates||Increases|
|Calcium and Vitamin D||Calcium: Decreases
Vitamin D: Potentially decreases
|Lifestyle Traits||Effect on CRC risk||Implications|
|Body Mass and Fat Distribution||Increases|
|Post Menopausal Hormones||Decreases|
Ongoing controversies- CT Colonography
CT colonogrpahy is a relatively new method of CRC screening which is not without its controversy. For one, its accuracy has been questioned and it has been further argued that if patients screen postivive for polyps during testing, a colonoscopy would then still be necessary for biopsy. A recent study from Martin-Lopez et. al. recently found that the specificity of CT colonography in screening for CRC is generally high, though it decreases as the diameter of polyp investigated decreases. The sensitivity of CT colonography for the detection of polyps < 6 mm in diameter was found to be low and heterogeneous, although the sensitivity was significantly higher for polyps > 10 mm. A strength of the CT colonography is its low incidence of adverse effects. Martin-Lopez et. al. concluded that CT colonography could therefore be useful as a screening test for populations with an average risk of CRC.
In the United States, the predmoninat method of CRC screening is via colonoscopy at 10 years intervals starting at either 45 or 50 depending on which guideline is being used. In Europe on the other hand, FIT is used at 1-2 years intervals, and if positive, then leads to the use of colonoscopy for further investigation. While there is no date of yet to support one method over the other at this time, there is a significant difference in cost and patient compliance between the two methods. COLONPREV is a study that is currently ongoing with ten-year outcome reports due in 2021. As per the findings already released from the trial, the FIT method of testing had a 39% greater compliance from patients and the same rate of CRC detection when compared to colonoscopies after the first FIT exam.
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