Colorectal Cancer

Epidemiology and Etiology

Colorectal cancer is the third most common malignancy worldwide. The incidence is higher in Western industrialized countries, with an estimated 147,950 new cases in the US in 2020.¹ Risk factors include age gt;50, physical inactivity, obesity, type 2 diabetes, diet with increased red meat and decreased fiber, alcohol consumption, personal history of polyps or colorectal cancer, inflammatory bowel disease, positive family history, and hereditary cancer syndromes such as Lynch syndrome and familial adenomatous polyposis.

Screening and Prevention

The USPSTF and American College of Gastroenterology recommend screening for all average-risk adults aged 45-75, as well as selected individuals aged 76-85.^13,14 Screening methods include high-sensitivity fecal occult blood tests or fecal immunochemical testing (FIT) every year, stool DNA-FIT every 1-3 years, CT colonography every 5 years, flexible sigmoidoscopy every 5 years, flexible sigmoidoscopy every 5 years plus annual FIT, and colonoscopy every 10 years. Abnormal stool-based tests should be evaluated with colonoscopy.

Clinical Presentation

The most common symptoms include rectal bleeding, microcytic anemia, abdominal pain, change in bowel habits, and obstruction. Patients can also rarely present with perforation, peritonitis, and fever. Colorectal carcinomas may also be identified through screening colonoscopies.

Diagnostic Testing

A thorough family history should be obtained to assess for hereditary cancer syndromes, especially in patients younger than 50 years. The diagnosis is typically made via colonoscopy with biopsy. Imaging studies include CT scan of the chest, abdomen, and pelvis. PET scan is not routinely indicated but is useful in patients being considered for definitive resection of oligometastatic disease.

Staging

TNM: Tis (carcinoma in situ), T1 (invades submucosa), T2 (invades muscularis propria), T3 (invades through the muscularis propria), T4 (invades adjacent structures), N0 (no lymph node involvement), N1 (1-3 regional lymph nodes), N2 (gt;4 regional lymph nodes), M1 (distant metastases).

TREATMENT

• Stage I-III (local): Localized colon cancer should be treated with surgical resection. Adjuvant chemotherapy is indicated in patients with stage III disease (defined by the presence of regional lymph node involvement) and may also be beneficial in select patients with high-risk stage II disease. The preferred regimens in the adjuvant setting are FOLFOX and CAPEOX for 3-6 months. Patients with early stage rectal cancer should be treated with surgical resection including either low anterior resection (LAR) for tumors located in the middle and upper third of the rectum or abdominoperineal resection (APR). Patients with locally advanced rectal tumors are usually treated with neoadjuvant

chemoradiotherapy followed by surgical resection and adjuvant chemotherapy.¹⁵

• Stage IV (metastatic): Patients with metastatic colorectal cancer are treated with a combination of Auoropyrimidines (5-FU/leucovorin or capecitabine) plus either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI). The survival is improved with the addition of the vascular endothelial growth factor (VEGF) mAb bevacizumab or one of the EGFR mAbs, cetuximab or panitumumab. Anti-EGFR mAbs are not used in patients with KRAS mutant tumors and are less effective than bevacizumab in right-sided tumors (cecum to hepatic flexure), while the efficacy is increased in left-sided tumors (splenic flexure to rectum).¹⁶

• Selected patients with synchronous hepatic or pulmonary metastases may be treated with neoadjuvant chemotherapy followed by colectomy and metastasectomy with curative intent.

• Second-line therapy options include a switch from an oxaliplatin-based therapy to irinotecan-based therapy or vice-versa. Other options for select patients include the combination of cetuximab or panitumumab with the BRAF inhibitor encorafenib for patients with BRAF V600E mutation, ICI therapy with pembrolizumab, nivolumab alone or nivolumab plus ipilimumab in patients with dMMR or MSI- high tumors. Other approved treatments include the multityrosine kinase inhibitor regorafenib or PiAuridine-Apiracil (TAS-102).