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A patient who had repeatedly refused routine screening for colorectal cancer (CRC), despite having lost his 80-year-old father to the disease, was again advised to undergo a colonoscopy at age 56. He insisted on having less invasive screening tests first, reported John M. Carethers, MD, of the University of California San Diego, in .

The patient denied having any blood in his stool or abnormal bowel movements. Blood tests showed that his hemoglobin level was 13.7 g/dL (reference 13.5-17.0 g/dL).

As Carethers explained to his patient, "colonoscopy, instead of stool-based testing, is recommended for screening individuals with a personal or family history of polyps or CRC, inflammatory bowel disease, or those with inherited cancer syndromes." Furthermore, when stool-based screening returns a positive result, a colonoscopy is required to confirm the diagnosis of CRC.

Given this patient's first-degree family history of CRC, he should have undergone an initial screening colonoscopy. For asymptomatic patients not at increased risk of CRC, the U.S. Preventive Services Task Force (USPSTF) one of the following:

• Colonoscopy every 10 years
• CT colonography every 5 years
• Flexible sigmoidoscopy every 10 years along with fecal immunochemical testing (FIT) yearly
• Flexible sigmoidoscopy every 5 years

There are three stool-based tests recommended by the USPSTF for CRC screening in asymptomatic persons at average risk of CRC beginning at age 45 years, Carethers noted. These include high-sensitivity guaiac fecal occult blood testing (gFOBT), FIT, and multi-target stool DNA-FIT (s-DNA-FIT), which Carethers advised for this patient.

uses a chemical to detect heme in a stool sample, while FIT uses antibodies to detect human hemoglobin in the stool sample; more than 20 μg of hemoglobin/g of feces returns a positive finding, Carethers explained.

Meanwhile, " includes FIT along with detection of DNA biomarkers for cancer, such as mutant KRAS, aberrant methylation of BMP3, and NDGR4, in cells that are shed into the stool from the lining of the colon and rectum." Results are positive if either the FIT or DNA biomarker findings are abnormal.

Stool-based screening tests for CRC are all for home use, and don't require fasting or bowel preparation. Frequency of screening varies depending on the test used.

The high-sensitivity gFOBT test kit uses a portion of three consecutive stool samples smeared onto a slide or test card, and mailed or delivered to the clinician's office. Patients may be advised to avoid taking anticoagulants, nonsteroidal anti-inflammatory drugs, vitamin C, and iron for a few days prior to the test, and told not to eat red meat such as rare beef or lamb. The USPSTF recommends yearly screening with this test.

FIT is available from a clinic, pharmacy, or by mail. A small stool sample is placed in the container provided and mailed within 24 hours of collection to avoid hemoglobin degradation. If FIT is used, the USPSTF recommends yearly screening.

s-DNA-FIT is a prescribed test kit that is mailed to the patient. This test requires a full stool sample to be collected in a bucket with a buffer for DNA stability, as well as a small stool sample collected for the FIT portion of the test. The USPSTF recommends this screening every 1 to 3 years.

The sensitivity and specificity of stool-based screening tests for CRC are 0.50-0.75 and 0.96-0.98 for high-sensitivity gFOBT, 0.74 and 0.94 for FIT, and 0.93 and 0.84 for s-DNA-FIT, respectively.

" has shown that 13.5% of s-DNA-FIT tests are positive compared with 6.4% of FIT, and 45% of patients with a positive s-DNA-FIT result have no ," Carethers wrote. "According to the 2022 Medicare fee schedule, reimbursement for high-sensitivity gFOBT was $4.38, for FIT was $18.05, and for s-DNA-FIT was $509."

The patient reported in this case underwent stool-based testing with s-DNA-FIT, which returned a positive test result. At that point, the patient agreed to have a colonoscopy, which was performed 5 weeks later.

Colonoscopy findings included "3 sessile cecal polyps (2-3 mm in diameter), one 3-mm polyp in the transverse colon, 2 sessile sigmoid polyps (2-6 mm in diameter), and a 5-cm rectal mass," Carethers noted. "On histological examination, 5 of the polyps were adenomas, 1 was a benign mucosal polyp, and the rectal mass was an invasive well-differentiated microsatellite stable adenocarcinoma, staged by CT imaging as T3N0 rectal adenocarcinoma."

Blood tests identified a serum carcinoembryonic antigen (CEA) level of less than 1 ng/mL (reference <3.0 ng/mL). Recommended treatment included 8 cycles of neoadjuvant chemotherapy with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) over a 4-month period. This was followed by 28 sessions of radiation therapy provided over a 5.5-week period.

The patient underwent low anterior resection of the rectum 2 months later. In light of the patient's age, family history of CRC, and detection of several adenomas, he also underwent a genetic evaluation with a 58-gene custom cancer panel; no germline mutations were found.

In January 2023, the patient returned to the clinic; he looked well and reported being free of abdominal symptoms. He will undergo a follow-up abdominal CT and serum CEA at 1 year after surgery, Carethers reported.

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