Colorectal Cancer Initial Assessment

Clinical Presentation

Right-sided colonic lesions may present as vague abdominal pain, weight loss, anemia secondary to chronic blood loss, weakness, and abdominal mass. Left-sided colonic lesions may present as colicky abdominal pain, changes in bowel habits (constipation alternating with diarrhea), narrowing of stools, and obstructive symptoms like nausea and vomiting. Lesions in the rectum may present as changes in bowel habits, new onset or recurrent or persistent rectal bleeding, rectal urgency or fullness, and tenesmus. 

Physical Examination

Digital rectal examination (DRE) is an important part of the physical examination. It can detect lesions located up to 7 cm from the anal verge. 

Screening

The primary goals of colorectal cancer screening are prevention and early detection. Screening for colorectal cancer substantially reduces mortality rates in individuals between the age of 50 to 70 years. It may either be done among high-risk groups (eg those with inflammatory bowel disease or with adenomatous polyps) or to the general population. No single screening test is 100% sensitive. Screening inflammatory bowel disease patients helps detect colorectal cancer at an earlier stage but does not reduce mortality from colorectal cancer.    

Screening for the General Population  

Colonoscopy  

Colonoscopy is the best screening modality for high-risk patients and the best follow-up strategy for evaluating patients with positive guaiac-based fecal occult blood testing (gFOBT). It is the only screening test shown to reduce the incidence of colorectal cancer among screened individuals.  

Its advantages include wide availability, the capability to allow single-session diagnosis and treatment, the ability to examine the entire colon, comfortability when done with sedation, and the only test recommended at 10-year intervals. The interval for colonoscopy depends on factors such as a family history of colorectal cancer (especially in first-degree relatives <50 years old), age at colitis diagnosis, presence of primary sclerosing cholangitis (PSC), and severity of inflammation.  

Flexible Sigmoidoscopy  

Flexible sigmoidoscopy is recommended as a direct visualization test used for the detection of adenomatous polyps and carcinoma. Studies have shown that this test helps reduce mortality risk from colorectal cancer.    

Its advantage is that it only requires less preparation and no sedation. The disadvantage of this procedure includes colonic perforations, bleeding, and examination being limited only to the distal colon.  

Carcinoembryonic Antigen (CEA)  

CEA determination may be considered a screening tool for colorectal cancer although some medical societies do not recommend this due to its low sensitivity (46%) and specificity (89%). It is also used in the monitoring of treatment response and cancer recurrence.  

Chromoendoscopy with Dye-spraying or Image-enhanced Endoscopy (IEE)  

This procedure yields higher results in detecting dysplasia compared with standard white-light endoscopy. The use of indigo carmine dye, although more costly, is preferred over methylene blue (as the former does not induce DNA damage).  

CT Colonography (Virtual Colonoscopy or CTC)  

CT colonography is a non-invasive technique that may be used to detect polyps or carcinomas >10 mm in size. It is not suitable for detecting lateral spread and polyps measuring <1 cm. It does not require sedation and is noninvasive and cost-effective, with very low test-related complications.  

Capsule Colonoscopy (PillCam^TM Colon 2)  

Capsule colonoscopy is an approved imaging test for screening of the proximal colon for individuals at high risk for colorectal cancer who have undergone colonoscopy but were not able to complete the procedure, and have contraindications to colonoscopy, CT colonography, and sedation. The reported polyp detection rate is at 24% and 74%; and the sensitivity rate for polyps >6 mm at 79-96%, and 84-97% in polyps ≥10 mm.  

Its advantage is that it is a non-invasive imaging tool with a lesser risk for complications compared to a colonoscopy. Its disadvantage is that the needed bowel preparations are more extensive compared to colonoscopy.  

Guaiac-based Fecal Occult Blood Testing (gFOBT)  

gFOBT is a stool-based screening test shown by several studies to reduce mortality from colorectal cancer.  A negative result does not ensure that the patient is free from colorectal cancer. Its advantage is its high specificity (94%) in detecting colorectal cancer. Its disadvantages include the possibility to miss tumors that are not bleeding or only slightly bleeding and high false-positive rates due to reactions from non-heme in food or blood in the upper gastrointestinal tract.  

The sensitivity in detecting colorectal cancer in an average-risk individual is lower (37-79%) compared to other non-invasive screening tests. The patient needs to adhere to a prescribed diet during the course of obtaining 3 stool specimens.  

Fecal Immunochemical Testing (FIT)  

The advantage of FIT is higher detection rates for advanced adenomas (30%) and cancer (82% sensitivity) compared to gFOBT. The sensitivity in detecting colorectal cancer is reported at 91 to 95% (average 93%). No diet restriction is necessary for the test and a single test is sufficient. Its disadvantage is that it is not recommended for screening of advanced or non-advanced adenomas.  

FIT-DNA or Multitarget Stool DNA (mt-sDNA) Testing  

FIT-DNA or multitarget stool DNA testing is a non-invasive colorectal cancer screening test that uses FIT to detect DNA biomarkers in stool samples to identify biomarkers associated with colorectal cancer and advanced adenomas in average-risk individuals. It is the recommended screening test for average-risk individuals because of its high sensitivity compared to FIT.  

Its advantage is its sensitivity in detecting colorectal cancer (92.3%), advanced precancerous lesions (42.4%), polyps with high-grade dysplasia (69.2%), and sessile serrated polyps >1 cm (42.4%) which is higher compared to FIT. Its disadvantage is its specificity in detecting colorectal cancer which is lower (86.6%) compared to FIT.  

Bacterial Biomarker LR4+FIT (M3CRC)  

Bacterial biomarker LR4+FIT is a non-invasive colorectal cancer screening test composed of a Lachnoclostridium sp marker m3, Fusobacterium nucleatum, Bacteroides clarus, and Clostridium hathewayi combined with FIT to detect DNA biomarkers for colorectal cancer in fecal samples.  

Its advantage is its sensitivity in detecting colorectal cancer (94%) and advanced adenomas (56.8%) which is higher compared to other non-invasive screening tests. Its disadvantage is its specificity in detecting colorectal cancer which is low (81%) compared to other non-invasive screening modalities.  

Methylated Septin 9 (mSEPT9) DNA Blood-based Test  

Methylated Septin 9 DNA blood-based test is a minimally invasive screening test that detects circulating mSEPT9 DNA in plasma. It is an alternative test for individuals refusing to undergo other screening procedures.  

Its advantage is its specificity in detecting colorectal cancer which is reported at 83 to 93.8% (average 89.6%). Its disadvantage is its sensitivity in detecting colorectal cancer (61.8 to 68%) and advanced adenomas (27.4%) which is low compared to other screening modalities.  

Screening Based on Risk Stratification  

Individuals at Average Risk  

For individuals at average risk, the recommended age of screening is ≥45 years. Colonoscopy is the preferred screening modality and may be done every 10 years. If colonoscopy is incomplete, repeat colonoscopy within 1 year or other screening methods (eg double-contrast barium enema) should be considered.  

Other recommended screening tests include annual fecal-based tests (ie gFOBT, FIT) or FIT-DNA every 3 years, flexible sigmoidoscopy every 5-10 years, or CTC every 5 years. Flexible sigmoidoscopy every 10 years is a proposed alternative screening strategy, combined with annual FIT, or flexible sigmoidoscopy at longer intervals without FIT (eg flexible sigmoidoscopy every 5 years with an interval FOBT).  

Individuals at Increased Risk

Following screening colonoscopy and complete polypectomy, individuals at increased risk are screened as follows:

• Low-risk adenomas (≤2 tubular adenomas measuring <1 cm): First follow-up colonoscopy within 7 to 10 years, if normal, repeat every 10 years 
• Low-risk sessile serrated polyps (≤2 polyps or measuring <1 cm without dysplasia): First follow-up colonoscopy within 5 years, if normal repeat every 10 years
• Advanced or multiple adenomas (3 to 10 polyps measuring ≥10 mm and with any villous features or high-grade dysplasia): Repeat colonoscopy within 3 years; subsequent colonoscopies within 5 years, or depending on findings 

For patients with large colorectal polyps, recommended timing of follow-up colonoscopy after receiving complete resection are as follows:

• For patients without high-risk features, invasive cancer and unfavorable risk factors for recurrence receiving complete resection: 1-3 years
• Patients without recurrence after first surveillance colonoscopy: Every 3 years
• Patients with risk factors: Within 6 months
• Patients with history of complete resection and no disease recurrence: Within 1 year and every 3 years subsequently; repeat endoscopic therapy if with disease recurrence
• Pedunculated polyps without disease recurrence: Follow-up colonoscopy in 3 years

Screening for Patients with Inflammatory Bowel Disease  

Colonoscopy should be done in all ulcerative colitis and Crohn’s colitis patients every 1-2 years and should be started 8 years after the onset of symptoms or when in remission. In the presence of primary sclerosing cholangitis (PSC), surveillance colonoscopy must be done annually independent of the onset of symptoms. Colonoscopy with chromoendoscopy is recommended if standard-definition white light endoscopy (SD-WLE) is used.  

Strictures (especially in ulcerative colitis) should be assessed thoroughly through biopsy and brush cytology. When deemed appropriate, chromoendoscopy with biopsies of surrounding mucosa are done to check for dysplasia.  

Screening for Patients with Personal History of Colorectal Cancer  

Colonoscopy 1 year post-operatively (within 3-6 months if preoperative colonoscopy is incomplete) is recommended.  If normal, this is repeated in 3 years then every 5 years. If sessile serrated polyps or adenomas are found, a colonoscopy is done annually. Subsequent colonoscopic intervals will vary among patients but should not exceed 5 years.  

Screening for mismatch repair (MMR) deficiency and/or Lynch syndrome with routine tumor testing at the time of diagnosis is recommended. Immunohistochemical and/or MSI testing may be used as the primary approach for tumor testing.  

For patients with rectal cancer treated with transanal local excision, proctoscopy with endorectal ultrasound (EUS) or MRI of the rectal anastomosis should be done. This should be repeated every 3-6 months for the first 2 years, then every 6 months until 5 years.  

Screening for Patients with Personal History of Cystic Fibrosis  

In patients with personal history of cystic fibrosis, surveillance is recommended at ≥30 years old or within 2 years post-transplantation in patients with history of organ transplant. For those who have not undergone organ transplant, surveillance should begin at ≥40 years of age. For patients with negative colonoscopy, repeat colonoscopy every 5 years is recommended.  

Screening for Individuals with Positive Family History of Colorectal Cancer  

For individuals with ≥first-degree relative with colorectal cancer at any age, a colonoscopy beginning 10 years before the earliest diagnosis in the family or at age 40 and repeated every 5 years should be done; if positive, may repeat according to colonoscopy results.  

For individuals with second- to third-degree relatives with colorectal cancer diagnosed at any age, a colonoscopy beginning at age 45 and repeated every 10 years should be done; if positive, may repeat according to colonoscopy results.  

For individuals with first-degree relatives with advanced adenomas, colonoscopy beginning at the relative’s age of onset of adenoma or at age 40 years and repeated every 5 to 10 years or according to findings.  

Screening for Patients After Surgical or Endoscopic Removal of Adenomatous Polyps or Sessile Serrated Polyps  

In patients who underwent surgical or endoscopic removal of adenomatous polyps or sessile serrated polyps, surveillance colonoscopy is recommended for adults aged 45 to 75 years. Surveillance colonoscopy between 75 to 85 years of age should be individualized.  

The risk of colorectal cancer is increased in patients with ≥3 adenomas or sessile serrated polyps measuring ≥1 cm at first colonoscopy, those with villous or tubulovillous histology, or high-grade dysplastic components.  

Low-risk patients are those with ≤2 adenomas or sessile serrated polyps measuring <1 cm without villous or high-grade dysplastic features and may not require colonoscopic surveillance; however, a colonoscopy may be performed at 7 to 10 years for those with adenomas or 5 years for those with sessile serrated polyps if other factors are present (eg family history).  

Patients with either one adenoma measuring >1 cm in size or 3 to 4 small adenomas measuring <1 cm are considered intermediate risk and surveillance colonoscopy is recommended every 3 years.  

Screening for Special Population  

Obese People  

Screening should be initiated as early as 45 years of age for obese individuals.  

Smokers  

Based on various studies, screening is recommended among active smokers and those with a >20 pack-years of smoking. Screen as early as 45 years of age, especially for those with >20 pack-years of smoking.