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  • Although the overall incidence of incidence of colorectal cancer (CRC) has decreased, its incidence in those younger than 50 years of age (ie, early-onset CRC) has significantly increased over the past 2 to 3 decades, accounting for an estimated one of every 10 cases currently being diagnosed in the United States.

  • Surgery is the cornerstone of curative therapy in locoregional CRC. Adjuvant chemotherapy with a fluoropyrimidine typically in combination with oxaliplatin is standard-of-care adjuvant therapy for patients with stage III and IV and high-risk stage II colon cancer. Recent data support tailoring duration of therapy (3 months vs 6 months) based on pathologic stage for stage III colon cancer.

  • In patients with locally advanced rectal adenocarcinoma, the paradigm has shifted to a total neoadjuvant therapy approach in which systemic chemotherapy in addition to neoadjuvant radiation is administered before surgery. Ongoing studies are evaluating deintensifying such trimodality therapy by omitting surgery or radiation in select patients.

  • Biomarker testing that includes mismatch repair deficiency should be performed in all patients with CRC; expanded RAS (KRAS and NRAS exons 2,3, 4), BRAFV600E mutation, and HER2neu amplification should be performed in all patients with metastatic CRC. NTRK fusion and POLE mutations are rare but targetable aberrations in metastatic CRC (mCRC). All patients with mCRC should be evaluated for resectable disease at diagnosis and at each restaging.

  • Most patients with mCRC are treated with fluoropyrimidine-based combination chemotherapy with oxaliplatin, irinotecan, or both in the first- and second-line settings. Monoclonal antibodies (mAbs) against the vascular endothelial growth factor axis or epidermal growth factor receptor (EGFR) may be used in combination with such chemotherapy. The use of anti-EGFR antibodies should be limited to RAS wild-type patients and to those with tumors arising in the left colon at least in the first-line setting. Patients with incurable metastatic disease should be considered for periods of less intensive therapy during their treatment course as the clinical situation warrants. Patients with mismatch repair–deficient mCRC are responsive to immunotherapy and should be treated with such agents, including in the first-line setting.

  • A biologic doublet therapy of encorafenib (BRAF inhibitor) in combination with cetuximab (EGFR mAb) is now standard of care for patients with previously treated BRAFV600E mutant mCRC. Regorafenib and TAS-102 are oral agents for patients with refractory disease in later lines of therapy. Ongoing trials are evaluating role of anti-Her2neu therapy in patients with Her-2neu amplification and rechallenge with anti-EGFR antibodies in patients with prior clinical benefit and subsequent progression.


Colorectal cancer (CRC) is currently the third most common cancer in incidence in the United States and accounts for about 8.5% of all cancer-related deaths (nearly 148,000 new cases and 53,000 deaths each year).1 This chapter reviews our current understanding of CRC; describes the known genetic mutations and risk factors; and outlines emerging screening, prevention, and therapeutic strategies, with particular emphasis on the approach taken at MD Anderson Cancer Center (MDACC).

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