Colorectal Cancer Screening and Prevention

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In Process

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.

Background

Epidemiology

More than 1 million people worldwide are diagnosed with CRC every year.[1] 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.[2] In the United States however, it is the second most common cause of cancer and cancer related death in both men and women.[2] 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.[3] 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.[4] 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.[5]

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.[6] Prognosis for metastatic CRC is very poor, and ranges on average from 4 to 14 months depending on the location of metastases.[7]

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.[8] 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.[9] This deactivation allows for the uncontrolled growth of tumor cells. 

Treatment

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.[1] 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.[1]  Recently, immunotherapy has been found to be useful in specific subtypes of colorectal cancer.[10] 

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)[11] 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)[12] 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)[13] 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
  • Colonoscopy
Every 2 years until 40, then annualy thereafter
Familial Adenomatous Polyposis  N/A
  • Sigmoidoscopy or Colonoscopy
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
  • Colonoscopy
Every 3-5 years
American

Cancer Society

Familial Adenomatous Polyposis (FAP) Age 10-12
  • Flexible Sigmoidoscopy
  • Genetic testing if not done previously
Yearly
Lynch Syndrome (Hereditary non-polyposis colon cancer) Age 20-25 OR,

10 years before youngest case in immediate family

  • Colonoscopy
  • Genetic testing if not done previously
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

  • Colonoscopy
Every 1-2 years with biopsies for dysplasia

Screening Guidelines for Older Populations

USPSTF

  • 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.

MSTF:

  • 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
  • Non existent or weak association between dietary fiber intake and colon cancer.[14]
  • Increasing intake of fruits, vegetables, or fiber is unlikely to prevent colorectal cancer.[15]
Red Meat, Fat, and Carbohydrates Increases
  • Limiting intake of processed and red meat and replacing it with alternative protein sources may reduce risk of colorectal cancer.[16]
  • Reducing consumption of meat undergoing high-temperature cooking may reduce risk of colorectal cancer.[14]
Calcium and Vitamin D Calcium: Decreases

Vitamin D: Potentially decreases

  • Significant though modest finding supporting the ability of calcium intake to prevent colorectal cancer.[17]
  • Though an inverse relationship has been identified between vitamin D levels and CRC incidence, no definitive association between CRC risk and Vitamin D supplementation has been proven[18]
B Vitamins Unclear
  • Conflicting evidence on whether increased intake of Vitamin B6 reduces or increases (in certain populations) the risk of CRC. At this time, it is not recommended to consume additional B6 to reduce CRC risk.[14]
Folate Unclear
  • Unclear whether high doses of folate increase or decrease the risk of CRC in non folate deficient populations.[14]
  • Folate deficient populations could benefit from supplementation of folate to reduce risk of CRC.[19]
Micronutrients None
  • Randomized trials have no shown any reduction in CRC rates with antioxidant vitamin supplements including beta-carotene, Vitamins A, C, or E.[14]
Lifestyle Traits Effect on CRC risk Implications
Alcohol Increases
  • High intake of alcohol increases the risk of CRC.[20]
  • Men that drink more than 2 drinks of alcohol per day have a 2 fold higher risk of colon cancer when compared to men who drink less than .25 drinks per day.[21]
Smoking Increases
  • In the US, it is estimated that 15-20% of CRC can be attributed to smoking.[14]
  • Increased risk of rectal cancer with smoking is considered to be greater than the increased risk of CRC.[22]
Body Mass and Fat Distribution Increases
  • Central adiposity in particular appears to increase risk of CRC.[14]
  • Individuals with DM are also at an increased risk of CRC.[23]
  • It is believed that hyperinsulinemia increases risk of CRC.[24]
Physical Activity Decreases
  • Routine physical activity in addition to healthy body weight significantly lowers risk of CRC.[14]
  • Physically active individuals have a 20-30% lower risk of CRC compared to less active individuals.[14]
Medications Implications
COX-2 inhibitors Decreases
  • COX-2 selective inhibitors prevent adenoma recurrence amongst populations with previous history of adenoma.[25]
  • COX-2 selective inhibitors reduce risk of CRC.[14]
  • Generally not recommended as a preventative method for CRC in the general population due to associated toxicities.[26]
Aspirin Decreases
  • Aspirin reduces the risk of CRC.[27]
  • Those with higher BMI's that were given daily Aspirin 325mg had a greater risk reduction of recurrent adenoma than those of a normal weight.[28]
  • Not recommended for routine CRC prevention.[26]
Post Menopausal Hormones Decreases
  • Has been found to lower risk of CRC though it is unclear which preparations are optimal.[29]
  • Not recommended in the use of CRC risk reduction due to increased risk of breast cancer and cardiovascular events associated with their use.[14]

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.[30]

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.[31]

References

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