Rectal adenocarcinoma

An adenocarcinoma arising from the rectum. It is more frequently seen in populations with a western type diet and in patients with a history of chronic inflammatory bowel disease.

Rectal Adenocarcinoma Arising in Villous Adenoma

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 2020, there were an estimated 1.93 million new cases of colorectal cancer and 935,173 deaths.

Estimated new cases and deaths from rectal and colon cancer in the United States in 2021:

New cases of rectal cancer: 45,230. New cases of colon cancer: 104,270. Deaths: 52,980 (rectal and colon 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.

Risk Factors

Increasing age is the most important risk factor for most cancers. Other risk factors for colorectal cancer include the following:

• Family history of colorectal cancer in a first-degree relative.
• Personal history of colorectal adenomas, colorectal cancer, or ovarian cancer.
• Hereditary conditions, including familial adenomatous polyposis (FAP) and Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]).
• Personal history of long-standing chronic ulcerative colitis or Crohn colitis.
• Excessive alcohol use.
• Cigarette smoking.
• Race/ethnicity: African American.
• Obesity.
• Screening

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:

• 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.

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. Laboratory examination may reveal iron-deficiency anemia and electrolyte and liver function abnormalities.

Staging

he AJCC has designated staging by TNM (tumor, node, metastasis) classification to define rectal cancer. The same classification is used for both clinical and pathologic staging. Treatment decisions are made with reference to the TNM classification system, rather than the older Dukes or Modified Astler-Coller classification schema. See staging info here

Prognostic Factors

The prognosis of patients with rectal cancer is related to several factors, including the following:

• Tumor adherence to or invasion of adjacent organs.
• Presence or absence of tumor involvement in the lymph nodes and the number of positive lymph nodes.
• Presence or absence of distant metastases.
• Perforation or obstruction of the bowel.
• Presence or absence of high-risk pathologic features, including the following:
• 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.[6,25,30] 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. 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.

A large number of studies have evaluated other clinical, pathologic, and molecular parameters. As yet, none has been validated in multi-institutional prospective trials. For example, microsatellite 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. 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 fluorouracil-based chemoradiation therapy.

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.

Follow-up After Treatment

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

• To assess the efficacy of initial therapy.
• To detect new or metachronous malignancies.
• To detect potentially curable recurrent or metastatic cancers.

Routine, periodic studies following treatment for rectal cancer may lead to earlier identification and management of recurrent disease. 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.

Surveillance

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. 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:

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.

Types

Adenocarcinomas account for the vast majority of rectal tumors in the United States. Other histologic types account for an estimated 2% to 5% of colorectal tumors.

According to the degree of cellular differentiation, rectal adenocarcinomas are divided into well, moderately, and poorly differentiated.

Histological variants

Histologic variants include mucinous adenocarcinoma, signet ring cell carcinoma, medullary carcinoma, serrated adenocarcinoma, cribriform comedo-type adenocarcinoma, and micropapillary adenocarcinoma.

Treatment

Standard Treatment Options for Stages 0–III Rectal Cancer

Stage (TNM Definitions)

Standard Treatment Options

Stage 0 Rectal Cancer Polypectomy or surgery Stage I Rectal Cancer Surgery with or without chemoradiation therapy Stages II and III Rectal Cancer Surgery Preoperative chemoradiation therapy Short-course preoperative radiation therapy followed by surgery and chemotherapy Postoperative chemoradiation therapy Primary chemoradiation therapy followed by intensive surveillance for complete clinical responders

Treatment Options for Stage IV and Recurrent Rectal Cancer

Stage (TNM Definitions) Treatment Options Stage IV and Recurrent Rectal Cancer Surgery with or without chemotherapy or radiation therapy First-line chemotherapy and targeted therapy Second-line chemotherapy Palliative therapy Liver Metastases Surgery Neoadjuvant chemotherapy Local ablation Adjuvant chemotherapy Intra-arterial chemotherapy after liver resection

Prevention

For the great majority of people, the major factor that increases a person’s risk for colorectal cancer (CRC) is increasing age. Risk increases dramatically after age 50 years; 90% of all CRCs are diagnosed after this age. Incidence and mortality rates are higher in African Americans compared with other races; however, a meta-analysis found no evidence that African Americans have higher rates of precancerous lesions. The history of CRC in a first-degree relative, especially if before the age of 55 years, roughly doubles the risk. A personal history of CRC, high-risk adenomas, or ovarian cancer also increases the risk. Other risk factors are weaker than age and family history. People with an inflammatory bowel disease, such as ulcerative colitis or Crohn disease, have a much higher risk of CRC starting about 8 years after disease onset and are recommended to have frequent colonoscopic surveillance. A small percentage (<5%) of CRCs occur in people with a genetic predisposition, including familial adenomatous polyposis and hereditary nonpolyposis coli.

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