Colorectal carcinoma (CRC) is the third most common non-skin cancer in the United States after lung cancer in both men and women, with an annual incidence of 42.9 per 100,000 people. It accounts for 8% of cancer-related deaths in the US alone.[1]
Its prevalence and incidence vary worldwide, with Australia and New-Zealand having the highest incidence, followed by North America and Europe. Africa and South-Central Asia have the lowest incidence.
Such a pattern only extrapolates that CRC incidence is attributed to dietary factors along with genetic and environmental factors. It also displays a strong correlation with increased age, the maximum rate at the age above 75 years, and lowest below 40 years. Males are affected more than females. African Americans have the highest incidence, and Asian Pacific Islanders have the lowest.
Screening is the process of looking for cancer in patient that have no symptoms. Several tests are available to screen for colorectal cancer. These tests can be divided into stool-based tests and visual exams. Any abnormal test result should be followed up with a colonoscopy. If cancer of the colon is caught early, the patient usually has a better outcome.
With the advent of newer and better screening tools, CRC related mortality rate has decreased, on average, about 2.7% between 2004 and 2013. It is expected to decrease further to about 38% for 50 to 74-year-olds and about 45% for those older than 75-years-old by 2030.[2] However, for unknown reasons, data from the United States Surveillance, Epidemiology, and End Results (SEER) database suggests that the incidence has been increasing among younger adults, below 50 years of age.[3] Rates have increased constantly at a rate of 2 percent yearly from 1992 through 2013.[3] Hence, delivering more effective and robust screening is the best preventive instrument.
Recently, a gradual shift towards right-sided or proximal colon cancers has been seen both in the United States[4][5] and internationally. Mostly, the incidence of cecal primary malignancies has increased.[6] This can be attributed to the anatomic distribution of CRCs as well as to improvements in diagnosis and treatment by screening and removal of adenomatous polyps in the distal colon. Cancer biology also seems to play a role in this recent shift since serrated adenomas, which exclusively have BRAF-V600E mutations, cause lesions that are flatter and difficult to visualize endoscopically and are more common in the right colon.[7] Wide-spread, compliant and flexible screening is the best step to prevent CRC mortality in the near future, given present epidemiological evidence.
Pathogenesis
Most CRCs begin as protuberances tethered to the inner surface of the colon or rectum, clinically knows as “polyps.” These are mainly of two types: flat or raised, relative to the inner-epithelial lining.
Raised polyps show two distinctive growth patterns of mushroomed growth:
About 10 percent of CRC patients carry one or more pathogenic “non-Lynch syndrome mutations,” including mutations in high-penetrance genes such as APC, bi-allelic MUTYH, BRCA1, BRCA2, PALB2, CDKN2A, and TP53.[8]
Right-sided CRCs tend to be diagnosed in advanced stages compared to left-sided, as the cecum and right colon have a larger caliber, and stool is more liquid, causing symptoms of partial obstruction such as pain, swelling, and constipation. Blood in stools (hematochezia or melena) isn’t readily observed and comes much later as compared to the left side, making screening tools pivotal in management for early detection and therapy.[8][7]
Risk factors for CRC
Risk factor assessment helps to categorize the patient as high, average, or low-risk. Aggressive multiple interval-based testing starts as early as the teenage years[9] in patients with a positive family history or co-existing genetic cancer syndromes. A relaxed approach towards screening and further management can be seen in the majority of cases who are at average risk.[10]
1.) Family history (especially first degree relatives)
2.) Genetic cancer syndromes
3.) Medical history
4.) Personal history
5.) Race
Screening Tools
The various modalities for early detection of CRCs are as follows:
Stool-based Tests
Visualization-based Tests
Blood-based Test
Age to Initiate Screening
The U.S. Preventive Services Task Force (USPSTF) and many other expert councils recommend 50 years of age to initiate screening for average-risk patients. In African-Americans, it can be lowered to 45 years of age due to high early-onset incidence.[1] For those with high-risk attributes (positive family history or cancer syndromes), screening can be initiated from as early as the teenage years.[9] Screening for those with a positive family history is recommended to start 10 years before the age of diagnosis of the family member. USPSTF doesn't recommend routine CRC screening in adults 86 years and older.
Contraindications for Screening
Contraindications might vary depending upon the screening method. Most stool-based tests can be carried out easily. However, other screening methods involve sedation, consumption of contrast, and further instrumentation of the colon. Bowel preparation is a vital pre-requisite, using either a laxative or non-laxative method. The type of bowel preparation should be determined based on the patient's medical conditions. Colonoscopy should generally be avoided if there is a concern for bowel perforation. Care should be taken for the following conditions:
Evidence of Effectiveness of Various Screening Tests:
1.) Guaiac FOBT (gFOBT) vs. Fecal Immune-chemical Test (FIT)
Evidence of Effectiveness
2.) Stool DNA Test
Evidence of Effectiveness
3.) Sigmoidoscopy
Evidence of Effectiveness
4.) Colonoscopy
Evidence of Effectiveness
5.) Colon Capsule Endoscopy
Evidence of Effectiveness
Studies showed that in asymptomatic patients using high-quality optic colonoscopy as the standard, capsule endoscopy identified subjects with more than one adenoma of greater than or equal to 6 mm with a sensitivity of 88 percent and specificity 82 percent, and even higher rates in larger adenomas.[27]
6.) Computed Tomography Colonography
Evidence of Effectiveness
7.) Methylated SEPT-9
Evidence of effectiveness
Screening Protocols and Algorithms (Image 1)
1.) Fecal Occult Blood Test
Guaiac FOBT (gFOBT): Consists of guaiac as the main reagent derived from a plant that exclusively grows in the Caribbean. It detects organic heme by oxidation. Therefore, the presence of dietary heme from red meat, peroxidase from some plants, and anti-oxidants like vitamin C or E can lead to false-positives. Fasting is advised before the test.
Fecal Immune-Chemical Test (FIT): Employs antibodies to specifically detect human heme-based globin. Dietary and medication restrictions prior to tests aren't required. The test is very specific for detecting colonic/rectal bleeding.
2.) Stool DNA Test
3.) Sigmoidoscopy
4.) Colonoscopy
5.) Colon Capsule Endoscopy
6.) Computed Tomography Colonography
7.) Fecal Tagging
8.) Barium Enema
Either single or double-contrast is rarely used, and neither is recommended by any other expert group, due to its poor screening indices and because of the advent of better endoscopic and CTC procedures with better results.
Screening Frequencies and Ideal Intervals for Surveillance and Follow-up (Image 2)
1.) Guaiac FOBT (gFOBT) & Fecal Immune-chemical Test (FIT)
Frequency of testing: Experts recommend sigmoidoscopy every 5 years for people at average risk who have had negative test results.[34]
2.) Stool DNA Test
Frequency of testing: The current recommendation is once every three years. If positive on any of the occasions, endoscopic studies such as colonoscopy and sigmoidoscopy are recommended.[1]
3.) Sigmoidoscopy
Screening frequency: Sigmoidoscopy should be performed at five-year intervals from baseline intervention, with gFOBT/FIT every three years.[1][24]
3.) Colonoscopy
Screening frequency: Patients undergoing colonoscopy should have a 10-year interval between screening colonoscopies if the examination is negative and of adequate quality.[1][36]
4.) Computed Tomography Colonography
Screening frequency: Current USPSTF recommends CTC every five years from baseline CTC or optical colonoscopy.
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