Cancer of the Rectum

Summary of Key Points

• Incidence

• Approximately 43,030 cases of rectal cancer will be diagnosed in the United States in 2018.

• The lifetime risk of developing colorectal cancer is roughly 4.5%.

• Higher rates of rectal cancer are noted in industrialized nations.

• Incidence has continued to decline over the past 20 years.

• Since 2001, rectal cancer in patients younger than 50 years has increased at an average annual rate of 3.9%.

• Biologic Characteristics

• The development of rectal cancer is a multistep heterogeneous process resulting from an alteration in cell division and replication.

• Three major molecular pathways for the development of rectal cancer have been described: (1) chromosomal instability, (2) microsatellite instability, and (3) hypermethylation of DNA.

• Staging Evaluation

• Once a diagnosis of rectal cancer has been established, a thorough history, physical examination, metastatic workup, and clinical staging should to be completed to help guide treatment decisions.

• Clinical staging includes computed tomography of the chest, abdomen, and pelvis and pelvic magnetic resonance imaging with or without endorectal ultrasound.

• A baseline carcinoembryonic antigen (CEA) level should be obtained.

• The American Joint Committee on Cancer staging system is based on the depth of tumor invasion (T), extent of regional nodal involvement (N), and presence of distant metastasis (M).

• Patients with a family history suggestive of or who meet the criteria for a heritable syndrome should be referred to a genetic counselor.

• Primary Therapy

• Treatment of nonmetastatic localized rectal cancer is a complex multidisciplinary process.

• Radical oncologic surgery (proctectomy with total mesorectal excision) provides the best curative option.

• The current standard of care for stage I (T1–2N0M0) rectal cancer is to proceed with a formal oncologic resection.

• Neoadjuvant therapy is used to reduce the rate of local recurrence in stage II (T3–4N0M0) and III (TanyN+M0) mid to distal rectal cancers and should precede surgery in those undergoing an oncologic resection.

• There is no benefit in administering neoadjuvant chemoradiotherapy for stage II and III rectal cancers above the anterior peritoneal reflection, and those should be treated similarly to colon cancer.

• Adjuvant Therapy

• Stage II (T3N0M0) and III (TanyN+M0) rectal cancer patients should be treated with either preoperative chemoradiation, surgery, and adjuvant chemotherapy, or preoperative chemotherapy followed by chemoradiotherapy, then surgery.

• The benefit of administration of chemotherapy to stage II patients is not as clear as for stage III.

• Adjuvant chemotherapy reduces the risk of recurrence by approximately 25%.

• Locally Advanced Disease

• Surgery for locally advanced rectal cancer is technically challenging, with morbidity rates ranging from 20% to 80% and mortality up to 8%.

• With the potential for major complications, a multidisciplinary approach is imperative for surgical evaluation, planning, and execution.

• These high-risk operations should be performed in dedicated referral centers capable of managing such complex patients.

• Palliation

• If the potential for cure is not possible, palliation of symptoms should be sought with a combination of modalities (chemoradiotherapy, urinary and colonic stents, nephrostomy tubes, endoscopic laser ablation, surgical procedures), all of which have been shown to improve quality of life, although they rarely halt disease progression.

• Treatment of Metastatic Disease

• Approximately 20% of patients will have stage IV distant metastatic disease at presentation.

• The most common route of hematogenous spread is to the liver (70%), followed by the lung (47%), bone (12%), and brain (8%).

• The vast majority of patients with metastasis are not cured with current treatment protocols, and only 20% to 30% will have surgically resectable disease.

• Current systemic cytotoxic and biologic therapy is associated with survival rates of up to 24 months.