Incidence and Mortality

It is difficult to separate epidemiological considerations of rectal cancer from those of colon cancer because epidemiological studies often consider colon and rectal cancer (i.e., colorectal cancer) together.

Worldwide, colorectal cancer is the third most common form of cancer. In 2012, there were an estimated 1.36 million new cases of colorectal cancer and 694,000 deaths[1].

Estimated new cases and deaths from rectal cancer in the United States in 2016:[2]

New cases of rectal cancer: 39,220.

New cases of colon cancer: 95,270.

Deaths: 49,190 (colon and rectal cancers combined).

Colorectal cancer affects men and women almost equally. Among all racial groups in the United States, African Americans have the highest sporadic colorectal cancer incidence and mortality rates[3][4].

Anatomy

Anatomy of the lower gastrointestinal system.

The rectum is located within the pelvis, extending from the transitional mucosa of the anal dentate line to the sigmoid colon at the peritoneal reflection; by rigid sigmoidoscopy, the rectum measures between 10 cm and 15 cm from the anal verge[5]. The location of a rectal tumor is usually indicated by the distance between the anal verge, dentate line, or anorectal ring and the lower edge of the tumor, with measurements differing depending on the use of a rigid or flexible endoscope or digital examination[6].

The distance of the tumor from the anal sphincter musculature has implications for the ability to perform sphincter-sparing surgery. The bony constraints of the pelvis limit surgical access to the rectum, which results in a lesser likelihood of attaining widely negative margins and a higher risk of local recurrence[5].

Risk Factors

Hereditary syndromes

Individuals with certain known single-gene disorders are at an increased risk of developing rectal cancer. Single-gene disorders related to known syndromes account for 10% to 15% of colorectal cancers. (Refer to the PDQ summary on Genetics of Colorectal Cancer for more information.)

The hereditary colorectal cancer syndromes and related genes that are involved include the following:[6][7][8]

Nonpolyposis disorders

Lynch syndrome (hereditary nonpolyposis colorectal cancer) mismatch repair genes: Defects in mismatch repair genes (involving MSH2, MLH1, PMS1, PMS2, or MSH6) represent the most common form of hereditary colorectal cancer and account for approximately 3% to 5% of all colorectal malignancies[7]. The majority of genetically defined cases involve MSH2 on chromosome 2p and MLH1 on chromosome 3p. In affected families, 15% to 60% of family members are found to have mutations in MSH2 or MLH1; the mutation prevalence depends on features of the family history[9]. (Refer to the Lynch syndrome section in the PDQ summary on Genetics of Colorectal Cancer for more information.)

Polyposis disorders

Familial adenomatous polyposis: APC gene.

Attenuated familial adenomatous polyposis: APC gene.

Turcot syndrome: APC gene; mismatch repair genes.

Hyperplastic polyposis syndrome: BRAF and KRAS2 genes.

MYH-associated polyposis: MYH gene.

Ashkenazi Jews also have an increased risk of colorectal cancer related to a mutation in the APC gene (I1307K), which occurs in 6% to 7% of the Ashkenazi Jewish population[10].

Hamartomatous disorders

Peutz-Jeghers syndrome: STK11/LKB1 gene.

Juvenile polyposis syndrome: SMAD4/DPC4 and BMPR1A genes.

Cowden syndrome: PTEN gene.

Ruvalcaba–Myhre–Smith syndrome: PTEN gene.

Hereditary mixed polyposis syndrome.

Other genetic risk factors

Other factors more common than hereditary syndromes that increase the risk of rectal cancer include the following:

Personal history of colorectal cancer or colorectal adenomas.

First-degree relative (parent, sibling, or offspring) with a history of colorectal cancer or colorectal adenomas[11].

Personal history of ovarian, endometrial, or breast cancer[12][13].

These high-risk groups account for only 23% of all colorectal cancers. Limiting screening or early cancer detection to only these high-risk groups would miss the majority of colorectal cancers[14]. (Refer to the PDQ summary on Colorectal Cancer Prevention for more information.)

Screening

Evidence supports screening for rectal cancer as a part of routine care for all adults aged 50 years and older, especially for those with first-degree relatives with colorectal cancer, for the following reasons:

Incidence of the disease in those 50 years and older.

Ability to identify high-risk groups.

Slow growth of primary lesions.

Better survival of patients with early-stage lesions.

Relative simplicity and accuracy of screening tests.

(Refer to the PDQ summary on Colorectal Cancer Screening for more information.)

Clinical Features

Similar to colon cancer, symptoms of rectal cancer may include the following:[15]

Rectal bleeding.

Change in bowel habits.

Abdominal pain.

Intestinal obstruction.

Change in appetite.

Weight loss.

Weakness.

With the exception of obstructive symptoms, these symptoms do not necessarily correlate with the stage of disease or signify a particular diagnosis[16].

Diagnostic Evaluation

The initial clinical evaluation may include the following:

Physical exam and history.

Digital rectal exam.

Colonoscopy.

Biopsy.

Carcinoembryonic antigen (CEA) assay.

Reverse-transcription polymerase chain reaction test.

Immunohistochemistry.

Physical examination may reveal a palpable mass and bright blood in the rectum. Adenopathy, hepatomegaly, or pulmonary signs may be present with metastatic disease[6]. Laboratory examination may reveal iron-deficiency anemia and electrolyte and liver function abnormalities.

Prognostic Factors

The prognosis of patients with rectal cancer is related to several factors, including the following:[6][17][18][19][20][21][22][23][24][25]

Tumor adherence to or invasion of adjacent organs[17].

Presence or absence of tumor involvement in the lymph nodes and the number of positive lymph nodes[6][18][19][20][21].

Presence or absence of distant metastases[6][17].

Perforation or obstruction of the bowel[6][25].

Presence or absence of high-risk pathologic features, including the following:[23][24][26]

Positive surgical margins.

Lymphovascular invasion.

Perineural invasion.

Poorly differentiated histology.

Circumferential resection margin (CRM) or depth of penetration of the tumor through the bowel wall[6][22][27]. Measured in millimeters, CRM is defined as the retroperitoneal or peritoneal adventitial soft-tissue margin closest to the deepest penetration of tumor.

Only disease stage (designated by tumor [T], nodal status [N], and distant metastasis [M]) has been validated as a prognostic factor in multi-institutional prospective studies[17][18][19][20][21][22]. A major pooled analysis evaluating the impact of T and N stage and treatment on survival and relapse in patients with rectal cancer who are treated with adjuvant therapy has been published and confirms these findings[28].

A large number of studies have evaluated other clinical, pathologic, and molecular parameters[29][30][31][32][33][34][35]. As yet, none has been validated in multi-institutional prospective trials. For example, microsatelite instability–high, also associated with Lynch syndrome–related rectal cancer, was shown to be associated with improved survival independent of tumor stage in a population-based series of 607 patients with colorectal cancer who were 50 years old or younger at the time of diagnosis[36]. In addition, gene expression profiling has been reported to be useful in predicting the response of rectal adenocarcinomas to preoperative chemoradiation therapy and in determining the prognosis of stages II and III rectal cancer after neoadjuvant 5-fluorouracil-based chemoradiation therapy[37][38].

Racial and ethnic differences in overall survival (OS) after adjuvant therapy for rectal cancer have been observed, with shorter OS for blacks than for whites. Factors contributing to this disparity may include tumor position, type of surgical procedure, and presence of comorbid conditions[39].

Follow-up After Treatment

The primary goals of postoperative surveillance programs for rectal cancer are:[40]

Routine, periodic studies following treatment for rectal cancer may lead to earlier identification and management of recurrent disease[40][41][42][43][44]. A statistically significant survival benefit has been demonstrated for more intensive follow-up protocols in two clinical trials. A meta-analysis that combined these two trials with four others reported a statistically significant improvement in survival for patients who were intensively followed[40][45][46].

Guidelines for surveillance after initial treatment with curative intent for colorectal cancer vary between leading U.S. and European oncology societies, and optimal surveillance strategies remain uncertain[47][48]. Large, well-designed, prospective, multi-institutional, randomized studies are required to establish an evidence-based consensus for follow-up evaluation.

Carcinoembryonic antigen (CEA)

Measurement of CEA, a serum glycoprotein, is frequently used in the management and follow-up of patients with rectal cancer. A review of the use of this tumor marker for rectal cancer suggests the following:[40]

Serum CEA testing is not a valuable screening tool for rectal cancer because of its low sensitivity and low specificity.

Postoperative CEA testing is typically restricted to patients who are potential candidates for further intervention, as follows:

Patients with stage II or III rectal cancer (every 2–3 months for at least 2 years after diagnosis).

Patients with rectal cancer who would be candidates for resection of liver metastases.

In one Dutch retrospective study of total mesorectal excision for the treatment of rectal cancer, investigators found that the preoperative serum CEA level was normal in the majority of patients with rectal cancer, and yet, serum CEA levels rose by at least 50% in patients with recurrence. The authors concluded that serial, postoperative CEA testing cannot be discarded based on a normal preoperative serum CEA level in patients with rectal cancer[49][50].

Related Summaries

Other PDQ summaries containing information related to rectal cancer include the following:

Colorectal Cancer Prevention.

Colorectal Cancer Screening.

Gastrointestinal Stromal Tumors Treatment.

Genetics of Colorectal Cancer.

Unusual Cancers of Childhood Treatment (colorectal carcinoma).

References

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