Colorectal Cancer

Background

• Colorectal cancer most commonly affects elderly persons ≥ 60 years old, and more men are affected than women.
• The causes of the disease are accumulation of genetic and epigenetic alterations.
• Likely risk factors include:
  • hereditary syndromes, such as Lynch syndrome and familial adenomatous polyposis;
  • diet, including consumption of processed and red meat, consumption of alcohol, and low consumption of nonstarchy vegetables and fruits;
  • lifestyle factors, including sedentary lifestyle and smoking;
  • concurrent diseases, particularly inflammatory bowel disease.
• Common presenting symptoms include rectal bleeding, occult blood in stool, weight loss, abdominal pain, and change in bowel habit.
• The 5-year relative survival is 71%-90% for locoregional disease and 14% for distant stage disease in the United States.

Evaluation

• Perform assessment with a multidisciplinary team of radiologists, surgeons, radiation oncologists, medical oncologists, pathologists, and gastroenterologists (Strong recommendation).
• For initial testing to establish diagnosis:
  • Perform a complete history and physical examination, including digital rectal examination for rectal cancer.
  • Perform a total colonoscopy (Strong recommendation).
  • Perform a biopsy for histopathological confirmation of diagnosis (Strong recommendation).
• For staging after diagnosis:
  • Perform abdominal, pelvic, and chest computed tomography (CT) ( Strong recommendation).
  • Consider magnetic resonance imaging (MRI) and contrast-enhanced ultrasound for lesion characterization in case of uncertainty in CT findings (Weak recommendation).
• Pretreatment testing aimed at staging and treatment planning typically includes blood tests, imaging studies (CT, MRI, and endorectal ultrasound), pathology review, and tumor testing (microsatellite instability or DNA mismatch repair testing); also consider genetic testing based on age, personal medical history, and family history of colorectal cancer syndromes such as Lynch syndrome - see Lynch syndrome for details.

Management

Management of nonmetastatic colon cancer

• Management of malignant polyps after endoscopic polypectomy:
  • Perform complete endoscopic polypectomy to remove all adenomatous tissue if possible.
  • For single polyp that has been completely removed with favorable histology and clear margins:
    • If the polyp is pedunculated, perform surveillance (Strong recommendation).
    • If the polyp is sessile with invasive carcinoma, consider either surveillance (Weak recommendation) or colectomy with en bloc removal of regional lymph nodes (Weak recommendation).
  • For a fragmented specimen, or if the margin cannot be assessed, or if the polyp has unfavorable histology, consider colectomy with en bloc removal of regional lymph nodes (Weak recommendation).
  • For stage 0 (Tis, N0, M0) disease, consider segmentary en bloc resection for larger lesions not amenable to local excision.
• Management of possibly resectable nonmetastatic colon cancer:
  • If the tumor is nonobstructing, offer colectomy with en bloc removal of regional lymph nodes (Strong recommendation), and then follow with adjuvant therapy.
  • If the tumor is obstructing, options include 1-stage colectomy with en bloc removal of regional lymph nodes (Weak recommendation), resection with diversion (Weak recommendation), colonic stent (depending on tumor location) followed by colectomy (Weak recommendation), or diversion followed by colectomy with en bloc removal of regional lymph nodes (Weak recommendation); then, follow with adjuvant therapy.
  • If clinical T4b tumor, consider colectomy with en bloc removal of regional lymph nodes (Weak recommendation) after neoadjuvant chemotherapy (Weak recommendation); then, follow with adjuvant therapy.
  • If the tumor is locally unresectable or medically inoperable, consider neoadjuvant therapy and evaluation for conversion to resectable disease, and then consider following with surgery with or without intraoperative radiation therapy, if possible (Weak recommendation).
• Adjuvant therapy includes either chemotherapy or chemoradiation therapy; the choice of appropriate adjuvant treatment is based on pathologic stage.

Management of nonmetastatic rectal cancer

• Management of malignant polyps:
  • Consider en bloc resection of polyps to accurately assess the level of invasion in the resection margin and the deepest area (Weak Recommendation).
  • For single specimen that has been completely removed with favorable histology and clear margins (T1 only):
    • If the polyp is pedunculated, consider surveillance (Weak recommendation) or perform transanal excision with transanal endoscopic microsurgery (Strong recommendation).
    • If the polyp is sessile, consider surveillance, transanal excision if appropriate, or transabdominal resection (Weak recommendation).
  • For fragmented specimen, or if the margin cannot be assessed, or if the polyp has unfavorable histologic features, consider transanal excision if appropriate based on risk assessment (Weak recommendation), or perform transabdominal resection with removal of lymph nodes (Strong recommendation).
• Management of nonmetastatic rectal cancer:
  • For very early disease, for patients who are poor surgical candidates, consider local radiation therapy, either alone or in combination with chemoradiation therapy, with brachytherapy or contact therapy using Papillon technique as an alternative to local surgery (Weak recommendation).
  • For T1-T2, N0, or early disease, consider transanal excision if appropriate based on risk assessment (after neoadjuvant radiation or chemoradiation therapy if indicated) (Weak recommendation), or perform transabdominal resection with total mesorectal excision (TME) (Strong recommendation); then, follow resection with adjuvant therapy.
  • For T3, N0, or any T, N1-N2, or T4 and/or locally unresectable or medically inoperable disease, consider either:
    • transabdominal resection using TME (Strong recommendation for TME) after neoadjuvant therapy with chemoradiation or short-course radiation therapy (Strong recommendation); then, follow with adjuvant therapy
    • transabdominal resection after neoadjuvant chemotherapy and primary chemoradiation therapy (Weak recommendation)
• Adjuvant therapy includes either chemotherapy or chemoradiation therapy; the choice of appropriate adjuvant treatment is based on pathologic stage.

Management of metastatic colorectal cancer

• Management of metastatic disease depends on whether metastases are synchronous or metachronous as well as tumor resectability.
• Management of synchronous metastatic colon cancer:
  • For resectable liver and/or lung synchronous metastases, consider any of the following treatment options:
    • synchronous or staged colectomy with surgical resection of liver or lung (preferred) and/or local ablative procedures (Weak recommendation), followed by adjuvant chemotherapy
    • colectomy, followed by 2-3 months of chemotherapy, then staged resection of metastatic disease, followed by adjuvant chemotherapy (Weak recommendation)
    • neoadjuvant chemotherapy (2-3 month course) prior to synchronous or staged colectomy with surgical resection of liver or lung, followed by adjuvant chemotherapy (Weak recommendation)
  • For unresectable liver and/or lung synchronous metastases:
    • consider primary treatment with systemic chemotherapy with or without targeted therapy (Weak recommendation);
    • reevaluate patient for conversion to resectable disease every 2 months, if conversion is a reasonable goal (Weak recommendation). Base subsequent treatment on resectability after reevaluation
  • For management of synchronous abdominal or peritoneal metastases:
    • if metastases are nonobstructing, consider systemic chemotherapy (Weak recommendation)
    • if colon is obstructed or obstruction is imminent, consider any of colon resection, diverting ostomy, bypass of impending obstruction, or stenting, followed by systemic chemotherapy (Weak recommendation)
• Management of synchronous metastatic rectal cancer:
  • For resectable synchronous metastases:
    • Consider neoadjuvant treatment with any of chemotherapy (2-3 month course), chemoradiation, or short-course radiation therapy (not recommended for T4 tumors) (Weak recommendation).
    • After neoadjuvant chemotherapy, consider primary and adjuvant treatment with any of the following options:
      • staged or synchronous resection (preferred over local ablative procedures), and/or local ablative procedures for metastases and resection of rectal lesion plus adjuvant chemoradiation (Weak recommendation)
      • primary chemoradiation or short-course radiation therapy (not recommended for T4 tumors) plus adjuvant treatment with staged or synchronous resection (preferred over local ablative procedures), and/or local ablative procedures for metastases and resection of rectal lesion with optional adjuvant chemotherapy using the same regimen as neoadjuvant chemotherapy (Weak recommendation)
    • After neoadjuvant chemoradiation or short-course radiation therapy, consider primary treatment with staged or synchronous resection (preferred over local ablative procedures), and/or local ablative procedures for metastases and resection of rectal lesion plus adjuvant chemotherapy (Weak recommendation).
  • For unresectable synchronous metastases:
    • If the patient is symptomatic, consider primary treatment with any of systemic chemotherapy, chemoradiation, resection of the involved rectal segment, diverting ostomy, stenting, or short-course radiation therapy (not recommended for T4 primary tumors) (Weak recommendation); then, consider subsequent treatment with systemic chemotherapy (Weak recommendation).
    • If the patient is asymptomatic, consider systemic chemotherapy (Weak recommendation).
• Management of metachronous metastatic colorectal cancer:
  • For resectable metachronous metastases:
    • surgical resection (preferred over local ablative procedures) and/or local ablative procedures are primary treatment options, with or without neoadjuvant chemotherapy (Weak recommendation)
    • base decision on adjuvant treatment on whether neoadjuvant chemotherapy was given, and whether there was tumor growth during neoadjuvant chemotherapy
  • For unresectable metachronous metastases:
    • consider chemotherapy and/or targeted therapy (Weak recommendation)
    • reevaluate patient for conversion to resectable disease every 2 months, if conversion is a reasonable goal (Weak recommendation). Base subsequent treatment on resectability after reevaluation
• Management of oligometastatic disease:
  • Use systemic chemotherapy as initial part of any treatment approach;
  • Evaluate response to systemic chemotherapy at 6-8 weeks with multi-disciplinary team to determine the best treatment strategies (Weak recommendation); options include surgery and local ablative procedures.
  • After surgery or local ablative procedures, consider re-introduction of systemic chemotherapy, but total duration should be ≤ 6 months.
  • Consider ablative therapy with noncurative intent to eradicate all visible metastatic lesions in suitable patients despite the lack of high-quality evidence (Weak recommendation).