Chapter 147: Colorectal Cancer

Update Summary

The following updates to this chapter were made on February 7, 2021:

• Metastatic Disease Initial Therapy section and Table 147-6 updated: Removed fluorouracil/leucovorin + bevacizumab and capecitabine + bevacizumab as no longer recommended as first-line therapy in patients appropriate for intensive therapy; added pembrolizumab for patients with dMMR/MSI-H appropriate for intensive therapy; updated dosing intervals for checkpoint inhibitors; and added trastuzumab + [pertuzumab or lapatinib] for patients not appropriate for intensive therapy with HER amplified and RAS and BRAF WT

• Table 147-7 in Metastatic Disease: Second-Line and Subsequent Therapy section updated: Removed binimetinib as no longer recommended in combination with encorafenib if BRAF V600 mutation positive; removed section on second-line options following first-line fluorouracil-based regimens; and added regimens for BRAF V600 mutation mutation-positive patients for second- or subsequent-line regimens

KEY CONCEPTS

• Advancing age, high-risk adenomatous polyps, inherited and acquired genetic susceptibilities, inflammatory bowel disease, diabetes mellitus, and lifestyle factors are associated with colorectal cancer risk.

• Regular use of aspirin and other nonsteroidal anti-inflammatory drugs reduces risk of colorectal cancer, but is not currently recommended for routine cancer prevention.

• Effective colorectal cancer detection programs incorporate routine screening starting at age 50 years for average-risk individuals. Colorectal adenomas can progress to cancer and should be removed.

• The treatment goal for stages I, II, and III colon cancer is cure; surgery should be offered to all eligible patients for this purpose. Six months of fluoropyrimidine-based adjuvant systemic therapy reduces the risk of cancer recurrence and overall mortality in patients with stage III and select patients with stage II colon cancer. An oxaliplatin-containing regimen further reduces risk as compared with fluoropyrimidine alone in stage III patients.

• Combined modality neoadjuvant therapy consists of fluoropyrimidine-based chemosensitized radiation therapy and surgery for patients with stage II or III cancer of the rectum and is considered standard of care to decrease risk of local and distant disease recurrence.

• Preoperative chemotherapy may reduce tumor size and convert unresectable disease to resectable disease in selected patients with metastatic colorectal cancer. This strategy offers the potential for prolonging overall survival and cure for metastatic disease.

• Chemotherapy is palliative for metastatic disease. A fluoropyrimidine with oxaliplatin or irinotecan improves survival compared to fluoropyrimidine monotherapy and should be offered to patients who are candidates for aggressive treatment. The ability for patients to receive all active cytotoxic agents (eg, fluoropyrimidine, oxaliplatin, and irinotecan) during the course of their disease improves their overall survival.

• Bevacizumab plus fluoropyrimidine-based chemotherapy as initial therapy for metastatic disease is considered standard of care and provides a survival benefit as compared with combination chemotherapy alone.

• The addition of an epidermal growth factor receptor (EGFR) inhibitor (cetuximab or panitumumab) to initial treatment for RAS and BRAF...