Colorectal cancer (CRC) is the third most common cancer affecting men and women in the United States. When CRC is found at an early stage before it has spread, the five-year relative survival rate is about 90%, yet it remains a leading cause of cancer-related death among both genders. 

Prevention and Screening 

The American Cancer Society recommended that those at average risk begin CRC screening at age 45 with visual examination of the colon or stool-based tests (i.e., annual fecal occult blood testing, annual fecal immunochemical test, or multitargeted stool DNA test every three years). Visualization techniques include traditional colonoscopy every 10 years, flexible sigmoidoscopy every 5 years, or computed tomography colonography every 5 years.  

People at higher risk for CRC should initiate screening earlier and have it more frequently than those at average risk. This includes people with a personal history of polyps or inflammatory bowel disease, history of prior radiation to the abdomen or pelvis, or a family history of CRC and hereditary colorectal cancer syndrome, such as familial adenomatous polyposis or Lynch syndrome. Patients and healthcare providers should decide together which CRC screening options are right for them. Centers for Disease Control and Prevention (CDC) data indicate that CRC screening rates are increasing, but one in three patients who should undergo testing has never been screened. 

The most effective ways to lower CRC risk are through screening, diet, and lifestyle changes. Because most polyps take 10–15 years to develop into cancer, finding and removing polyps with screening can stop CRC before it starts. Researchers are also looking at use of aspirin for CRC prevention. 

Diagnostic Biomarkers  

The National Comprehensive Cancer Network recommended testing all metastatic CRC tumors for KRAS, NRAS, and BRAF mutations. Tumors without RAS mutations (known as the “wild type”) are more likely to respond to EGRF therapies (i.e., cetuximab and panitumumab); those with the mutations will not likely. Patients without mutated BRAF genes have a better prognosis; those with a mutated copy may benefit from cetuximab. Those without PIK3CA mutations tend to have better survival than those who do and may benefit from low-dose (325 mg) aspirin therapy

Biomarker testing may also uncover hereditary risk for developing CRC. Patients with Lynch syndrome and stage II microsatellite instability–high tumors are not likely to benefit from fluorouridine therapies and may have a better prognosis

Immunotherapy may be an option for some advanced or recurrent colon cancers.

Treatments 

The extent of disease at diagnosis, including lymph node involvement or distant metastasis, drives treatment recommendations. First-line treatment is often surgery, with or without adjuvant chemotherapy depending on stage. Systemic combination regimens such as 5-fluorouracil, leucovorin, and oxaliplatin are often prescribed. Agents targeting VEGF (e.g., bevacizumab, ramucirumab, ziv-aflibercept) are options for advanced or recurrent disease in addition to other second-line chemotherapies. EGFR inhibitors (e.g., cetuximab, panitumumab) is another targeted approach that may be used in combination with chemotherapy, although it’s not used for patients who express KRAS, NRAS, or BRAF genes.  

Immunotherapy may be an option for some advanced or recurrent colon cancers. PD-1 inhibitors, such as nivolumab and pembrolizumab, are approved for use either alone or in combination with CTLA-4 inhibitors. HER2-targeted therapies are sometimes used in patients with tumors that overexpress HER1, and TRK inhibitors are used for patients with NTRK fusion–positive disease. 

Rectal cancer is typically treated with surgery alone for early- 

stage disease or combination therapy with chemoradiation followed by surgery for more advanced stages. Localized radiation therapy is used more commonly in rectal cancers, but external radiation and brachytherapy are both used for CRC. Ablation and embolization may be options for metastatic CRC. 

Side Effects and Management  

The Colorectal Cancer Alliance listed the most frequent physical and psychosocial effects from local and systemic therapies, as well as management strategies. Surgical interventions may require ostomy care. Radiation may induce skin irritation, sexual dysfunction, rectal or urinary incontinence, scarring or adhesions, and other side effects. Systemic chemotherapy can cause dose-limiting diarrhea as well as nausea and vomiting, myelosuppression, and fatigue.  

Bevacizumab is associated with cardiovascular effects, and patients should be monitored accordingly. 

Survivorship  

CRC survivors must be monitored with visualization of the intestinal tract and rectum. Encourage patients to adhere to prescribed imaging schedules and review the results with their providers. CEA testing indicates if the CRC tumor marker returns at a suspicious level. CRC survivors should follow a healthy lifestyle with careful consideration of other cancer screening recommendations, smoking cessation, and nutritious diet. Depending on treatment, CRC survivors may need ongoing support to care for a permanent ostomy.