Rectal cancer is a disease in which cancer cells form in the tissues of the rectum; colorectal cancer occurs in the colon or rectum. Adenocarcinomas comprise the vast majority (98%) of colon and rectal cancers; more rare rectal cancers include lymphoma (1.3%), carcinoid (0.4%), and sarcoma (0.3%).
The incidence and epidemiology, etiology, pathogenesis, and screening recommendations are common to both colon cancer and rectal cancer. The image below depicts the staging and workup of rectal cancer.
Signs and symptoms
Bleeding is the most common symptom of rectal cancer, occurring in 60% of patients. However, many rectal cancers produce no symptoms and are discovered during digital or proctoscopic screening examinations.
Other signs and symptoms of rectal cancer may include the following:
Change in bowel habits (43%): Often in the form of diarrhea; the caliber of the stool may change; there may be a feeling of incomplete evacuation and tenesmus
Occult bleeding (26%): Detected via a fecal occult blood test (FOBT)
Abdominal pain (20%): May be colicky and accompanied by bloating
Back pain: Usually a late sign caused by a tumor invading or compressing nerve trunks
Urinary symptoms: May occur if a tumor invades or compresses the bladder or prostate
Pelvic pain (5%): Late symptom, usually indicating nerve trunk involvement
Emergencies such as peritonitis from perforation (3%) or jaundice, which may occur with liver metastases (< 1%)
See Clinical Presentation for more detail.
Perform physical examination with specific attention to the size and location of the rectal tumor in addition to possible metastatic lesions, including enlarged lymph nodes or hepatomegaly. In addition, evaluate the remainder of the colon.
Examination includes the use of the following:
Digital rectal examination (DRE): The average finger can reach approximately 8 cm above the dentate line; rectal tumors can be assessed for size, ulceration, and presence of any pararectal lymph nodes, as well as fixation to surrounding structures (eg, sphincters, prostate, vagina, coccyx and sacrum); sphincter function can be assessed
Rigid proctoscopy: This examination helps to identify the exact location of the tumor in relation to the sphincter mechanism
Routine laboratory studies in patients with suspected rectal cancer include the following:
Complete blood count
Liver and renal function tests
Carcinoembryonic antigen (CEA) test
Cancer antigen (CA) 19-9 assay, if available: May be useful for monitoring the disease
Histologic examination of tissue specimens
Screening tests may include the following:
Stool DNA screening (SDNA)
Fecal immunochemical test (FIT)
Flexible sigmoidoscopy (FSIG)
Combined glucose-based FOBT and flexible sigmoidoscopy
Double-contrast barium enema (DCBE)
Computed tomography (CT) colonography
Fiberoptic flexible colonoscopy (FFC)
If metastatic rectal cancer is suspected, the following radiologic studies may be obtained:
CT scanning of the chest, abdomen, and pelvis
Endorectal or pelvic magnetic resonance imaging (MRI)
Positron emission tomography (PET) scanning: Not routinely indicated
See Workup for more detail.
A multidisciplinary approach that includes colorectal surgery, medical oncology, and radiation oncology is required for optimal treatment of patients with rectal cancer. Surgical technique, use of radiotherapy, and method of administering chemotherapy are important factors.
Strong considerations should be given to the intent of surgery, possible functional outcome, and preservation of anal continence and genitourinary functions. The first step involves achievement of cure, because the risk of pelvic recurrence is high in patients with rectal cancer, and locally recurrent rectal cancer has a poor prognosis.
Radical resection of the rectum is the mainstay of therapy. The timing of surgical resection is dependent on the size, location, extent, and grade of the rectal carcinoma. Operative management of rectal cancer may include the following:
Transanal excision: For early-stage cancers in a select group of patients
Transanal endoscopic microsurgery: Form of local excision that uses a special operating proctoscope that distends the rectum with insufflated carbon dioxide and allows the passage of dissecting instruments
Endocavity radiotherapy: Delivered under sedation via a special proctoscope in the operating room
Sphincter-sparing procedures: Low anterior resection, coloanal anastomosis, abdominal perineal resection
Adjuvant medical management
Adjuvant medical therapy may include the following:
Adjuvant radiation therapy
Intraoperative radiation therapy
Adjuvant chemoradiation therapy
The National Comprehensive Cancer Network guidelines recommend the use of as many chemotherapy drugs as possible to maximize the effect of adjuvant therapies for colon and rectal cancer.
The following agents may be used in the management of rectal cancer:
Antineoplastic agents (eg, fluorouracil, vincristine, leucovorin, irinotecan, oxaliplatin, cetuximab, bevacizumab, panitumumab)
Vaccines (eg, quadrivalent human papillomavirus [HPV] vaccine)
Colon and rectal cancer incidence was negligible before 1900. The incidence of colorectal cancer has been rising dramatically following economic development and industrialization. Currently, colorectal cancer is the third leading cause of cancer deaths in both males and females in the United States. [1, 2]
Adenocarcinomas comprise the vast majority (98%) of colon and rectal cancers. Other rare rectal cancers, including carcinoid (0.4%), lymphoma (1.3%), and sarcoma (0.3%), are not discussed in this article. Squamous cell carcinomas may develop in the transition area from the rectum to the anal verge and are considered anal carcinomas. Very rare cases of squamous cell carcinoma of the rectum have been reported. [1, 3]
Approximately 20% of colon cancers develop in the cecum, another 20% in the rectum, and an additional 10% in the rectosigmoid junction. Approximately 25% of colon cancers develop in the sigmoid colon. 
The incidence and epidemiology, etiology, pathogenesis, and screening recommendations are common to both colon cancer and rectal cancer. These areas are addressed together.
An image depicting the staging and workup of rectal cancer can be seen below.
The mucosa in the large intestine regenerates approximately every 6 days. Crypt cells migrate from the base of the crypt to the surface, where they undergo differentiation and maturation, and ultimately lose the ability to replicate.
The significant portions of colorectal carcinomas are adenocarcinomas. The adenoma-carcinoma sequence is well described in the medical literature. [1, 4] Colonic adenomas precede adenocarcinomas. Approximately 10% of adenomas will eventually develop into adenocarcinomas. This process may take up to 10 years. 
Three pathways to colon and rectal carcinoma have been described:
Adenomatous polyposis coli ( APC) gene adenoma-carcinoma pathway
Hereditary nonpolyposis colorectal cancer (HNPCC) pathway
Ulcerative colitis dysplasia
The APC adenoma carcinoma pathway involves several genetic mutations, starting with inactivation of the APC gene, which allows unchecked cellular replication at the crypt surface. With the increase in cell division, further mutations occur, resulting in activation of the K-ras oncogene in the early stages and p53 mutations in later stages. These cumulative losses in tumor suppressor gene function prevent apoptosis and prolong the cell's lifespan indefinitely. If the APC mutation is inherited, it will result in familial adenomatous polyposis syndrome.
Histologically, adenomas are classified in three groups: tubular, tubulovillous, and villous adenomas. K-ras mutations and microsatellite instability have been identified in hyperplastic polyps. Therefore, hyperplastic polyps may also have malignant potential in varying degrees. 
The other common carcinogenic pathway involves mutation in DNA mismatch repair genes. Many of these mismatched repair genes have been identified, including hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6. Mutation in mismatched repair genes negatively affects the DNA repair. This replication error is found in approximately 90% of HNPCC and 15% of sporadic colon and rectal cancers. [1, 6] A separate carcinogenic pathway is also described in inflammatory bowel disease (IBD). Chronic inflammation such as in ulcerative colitis can result in genetic alterations which then lead into dysplasia and carcinoma formation. 
Colon and rectal cancer is the third most common cancer in both females and males. The American Cancer Society (ACS) estimates that 95,270 new cases of colon cancer and 39,220 new cases of rectal cancer will occur in 2016; 23,110 cases of rectal cancer are expected in men and 16,110, in women.  For estimates of deaths, the ACS combines colon and rectal cancers; approximately 49,190 deaths from colorectal cancer are expected to occur in 2016. 
Both colon and rectal cancer incidences, as well as mortality rates, have been decreasing for the last several decades, from 66.3 per 100,000 population in 1985 to 45.5 in 2006.  The rate of decrease accelerated from 1998-2006 (to 3% per year in men and 2.2% per year in women), in part because of increased screening, allowing the detection and removal of colorectal polyps before they progress to cancer. The lifetime risk of developing a colorectal malignancy is approximately 6% in the general US population. This decrease is due to a declining incidence and improvements in both early detection and treatment.
Although the incidence of colon and rectal cancer varies considerably by country, an estimated 944,717 cases were identified worldwide in 2000. High incidences of colon and rectal cancer cases are identified in the US, Canada, Japan, parts of Europe, New Zealand, Israel, and Australia. Low colorectal cancer rates are identified in Algeria and India. The majority of colorectal cancers still occur in industrialized countries. Recent rises in colorectal cancer incidence have been observed in many parts of the Japan, China (Shanghai) and in several Eastern European countries. 
The American Cancer Society estimates that in 2015, colorectal cancer will account for 8% of cancer deaths in men and 9% of cancer deaths in women. In the US, mortality rates have been decreasing in both sexes for the past 2 decades. (The 1- and 5-year rates for patients with colon and rectal cancer are 83% and 64%, respectively.) When colorectal cancers are detected early and localized, the 5-year survival rate is 90%. 
A review of eight trials by Rothwell et al found allocation to aspirin reduced death caused by cancer. Individual patient data were available from seven of the eight trials. Benefit was apparent after 5 years of follow-up. The 20-year risk of cancer death was also lower in the aspirin group for all solid cancers. A latent period of 5 years was observed before risk of death was decreased for esophageal, pancreatic, brain, and lung cancers. A more delayed latent period was observed for stomach, colorectal, and prostate cancer. Benefit was only seen for adenocarcinomas in lung and esophageal cancers. The overall effect on 20-year risk of cancer death was greatest for adenocarcinomas. 
A study by Banks et al showed the benefit of aspirin in preventing colon adenocarcinoma among patients with hereditary risk of colorectal cancer. In a study of 861 patients, 600 mg of aspirin daily for a mean of 25 months substantially reduced cancer incidence after 55.7 months among carriers of hereditary colorectal cancer. Further studies are needed to determine the ideal dosage and duration. 
In a review of 51 randomized controlled trials, Rothwell et al found that aspirin reduced the short-term incidence of cancer and the short- and long-term risk of cancer death. The authors conclude that their results support the use of daily aspirin for cancer prevention. 
The incidence of colorectal cancer tends to be higher in Western nations than in Asian and African countries; however, within the United States, minor differences in incidence exist among whites, African Americans, and Asian Americans. Five-year survival rates are lower among blacks (55%) than whites (66%). Among religious denominations, colorectal cancer occurs more frequently in the Jewish population. 
A study by Yothers et al found that black patients with resected stage II and stage III colon cancer had worse overall and recurrence-free survival compared with white patients who underwent the same therapy. 
A study of racial disparities in mortality rates between black and white individuals with colorectal cancer by Robbins et al showed earlier and larger reductions in death rates for whites from 1985-2008.  This racial disparity could be decreased with greater education to the black population regarding colorectal cancer prevention and access to treatment, including colonoscopies and polypectomies.
The incidence of colorectal malignancy is slightly higher in males than in females. The overall age-adjusted incidence of colorectal cancer in all races was 48.9 per 100,000 for males and 37.1 per 100,000 for females in 2008-2012, yielding a male-female ratio of 1.32:1. Mortality rates for colorectal cancer were also higher in males (18.6 per 100,000) than in females (13.1 per 100,000) in 2008-2012.  Left colon carcinomas were more likely to be observed in males and right colon carcinomas were more likely to be observed in females. 
The incidence of colorectal cancer starts to increase after age 35 and rises rapidly after age 50, peaking in the seventh decade. More than 90% of colon cancers occur after age 50. However, cases have been reported in young children and adolescents.  The incidence rates of colorectal cancer increased by 1.8% per year in adults younger than age 50 from 2007 to 2011. 
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