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Key Clinical Updates in Colorectal Cancer

For the 50% of patients with metastatic CRC who have KRAS/NRAS/BRAF wild-type tumors, cetuximab and panitumumab (monoclonal antibodies to the epithelial growth factor receptor, in combination with chemotherapy, can extend median survival by 2 to 4 months compared with chemotherapy alone. For the 5% to 10% with BRAF V600E sequence variations, targeted combination therapy with BRAF and EGFR inhibitors extend overall survival to 9.3 months, compared with 5.9 months for those receiving standard chemotherapy.

In four randomized clinical trials (n = 458,002), intention to screen with 1- or 2-time flexible sigmoidoscopy versus no screening was associated with a significant decrease in CRC–specific mortality.

National Comprehensive Cancer Network.

National Comprehensive Cancer Network.

Shaukat A et al. Am J Gastroenterol. [PMID: 33657038]


  • Personal or family history of adenomatous or serrated polyps or colorectal cancer (CRC) is an important risk factor.

  • Symptoms or signs depend on tumor location.

    • Proximal colon: fecal occult blood, anemia.

    • Distal colon: change in bowel habits, hematochezia.

  • Diagnosis established with colonoscopy with biopsy.


CRC is the second leading cause of death due to malignancy in the United States. CRC will develop in approximately 4.2% of Americans (4.3% of men, 4.0% of women) and has a 5-year survival rate of 65%. In 2022, there will be an estimated 151,030 new CRC cases (80,690 cases in men, 70,340 in women) in the United States, with an estimated 53,200 deaths (28,400 deaths in men, 24,180 in women). Over the last 10 years, CRC incidence has declined by 1.7% per year and mortality by 3.2% per year, which is attributed to population-based CRC screening. The percentage of US adults aged 50–75 years who were up-to-date with recommended CRC screening was 67.1% in 2019.

CRCs are almost all adenocarcinomas, which tend to form bulky exophytic masses or annular constricting lesions (eFigure 39–7). Most are thought to arise from malignant transformation of an adenomatous polyp (tubular, tubulovillous, or villous adenoma) or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma). Polyps that are “advanced” (ie, polyps at least 1 cm in size, adenomas with villous features or high-grade dysplasia, or serrated polyps with dysplasia) are associated with a greater risk of cancer.

eFigure 39–7.

Colonic adenocarcinoma that is circumferential and narrowing the lumen. (Used, with permission, from Yao-Wen Cheng, MD.)

Approximately 85% of sporadic CRC arise from adenomatous polyps. They have loss of function of one or more tumor suppressor genes (eg, p53, APC, or DCC) due to a combination of spontaneous pathologic variants of one allele combined with chromosomal instability and aneuploidy (abnormal DNA content) that leads to deletion and loss of heterozygosity of the other allele (eg, 5q, 17q, or 18p deletion). Activation of oncogenes such as KRAS and BRAF is ...

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