Types of Cancer

Stage III Rectal Cancer

Overview

Following surgical removal of rectal cancer, the cancer is referred to as stage III or C rectal cancer if the final pathology report, after looking under the microscope, shows that the cancer has penetrated the wall of the rectum and invaded any of the local lymph nodes, but cannot be detected in other locations in the body.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage III rectal cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Surgical Treatment

Stage III (C) adenocarcinoma of the rectum is a curable cancer. Depending on features of the cancer under the microscope, approximately 40% of patients are cured without evidence of cancer recurrence following treatment with surgery alone. The standard surgical procedures used to remove stage III rectal cancer include low anterior resection (LAR) or abdominoperineal resection (APR). The choice of operation depends on the location of the rectal cancer in relation to the rectal sphincter or anus. For cancers that are located well above the anus, an LAR procedure can be performed. Following LAR procedure, the cut ends of the rectum are sewn together and anal function is preserved. For cancers close to the anus, an APR procedure is often necessary. Following an APR procedure, the anus is removed with the cancer, and the cut end of the large bowel is attached to the abdominal wall to form a permanent colostomy. The colostomy is covered by a bag, which collects stool as it empties from the bowel. Because of the inconvenience of a colostomy, physicians attempt to use sphincter-sparing treatments, when possible, that allow the patient to keep the anus.

Adjuvant Therapy

Despite undergoing complete surgical removal of cancer, 60-70% of patients with stage III rectal cancer experience recurrence of their cancer. It is important to realize that many patients with stage III disease already had small amounts of cancer that had spread outside the rectum and were not removed by surgery. These cancer cells are referred to as micrometastases and cannot be detected with any of the currently available tests. The presence of these microscopic areas of cancer causes the relapses that follow treatment with surgery alone. An effective treatment is needed to cleanse the body of micrometastases in order to improve the cure rate achieved with surgical removal of the cancer. The delivery of cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, radiation therapy and/or biologic therapy. Adjuvant therapy is administered with the goal of reducing cancer recurrences.

Adjuvant therapy for rectal cancer typically involves radiation therapy and/or chemotherapy. A combination of chemotherapy and radiation therapy is often administered after surgery to cleanse the area of the operation of microscopic cancer cells that may be remaining. The decision to treat with chemotherapy and radiation therapy after excision is based on the depth of invasion of the cancer and how aggressive the cancer appears under the microscope. Adjuvant 5-fluorouracil chemotherapy and radiation therapy have been used as treatment for patients with stage II rectal cancer to reduce cancer recurrences. Clinical trials have shown that treatment with adjuvant 5-fluorouracil chemotherapy and radiation therapy improves a patient’s survival compared to treatment with surgery alone.

A clinical trial performed by doctors in the Gastrointestinal Tumor Study Group (GITSG) directly compared surgery to surgery followed by chemotherapy and radiation therapy in patients with stage II and III rectal cancer. The results of this clinical trial demonstrated improved survival in patients treated with 5-fluorouracil chemotherapy and radiation therapy after surgery, compared to patients treated with surgery alone. Patients were treated with external beam radiation therapy to the pelvis and 5-fluorouracil chemotherapy was administered before, during and after radiation therapy for a total of 18 months. Patients treated with this adjuvant chemoradiation approach had a 6-year survival rate of about 54%, compared with a survival rate of 27% in patients treated with surgery alone.

Another clinical trial conducted by the North Central Cancer Treatment Group (NCCTG) directly compared adjuvant radiation therapy alone with adjuvant radiation therapy and chemotherapy following surgery for stage II rectal cancer. The addition of chemotherapy to radiation therapy reduced the chance of cancer recurrence. The use of combined adjuvant chemoradiation improved the 7-year survival in patients from 38%, using radiation therapy alone, to 49% when both chemotherapy and radiation were used. These and other clinical trials taken together demonstrate that adjuvant 5-fluorouracil chemotherapy for 6 months and radiation therapy following surgical resection of patients with stage III (C) rectal cancer improves a patient’s chance of cure and overall survival.

More recent clinical trials have investigated more effective methods to administer adjuvant chemotherapy to further improve survival. A second clinical trial conducted by the NCCTG directly compared adjuvant chemoradiation using 5-fluorouracil given every few weeks (bolus) with adjuvant chemoradiation using 5-fluorouracil given continuously over a prolonged period. Continuous 5-fluorouracil is given using a portable chemotherapy pump attached to a permanent intravenous catheter. There was a 10% improvement in survival in the group of patients treated with continuous infusion 5-fluorouracil chemotherapy compared with patients treated with bolus 5-fluorouracil chemotherapy. Although continuous infusion 5-fluorouracil chemotherapy produced a higher cure rate, there were also more side effects, including diarrhea and lowered blood counts.

Neoadjuvant Therapy

Rectal cancer may not be diagnosed until it has grown to the point that surgery would be unlikely to result in complete removal of the cancer. These cancers that lie close to the anus can be treated before surgery to permit an operation that preserves the rectal sphincter or anus. Neoadjuvant therapy is treatment that is delivered prior to surgery in order to help shrink the cancer, thereby facilitating more complete surgical removal. When sphincter-sparing treatment is used for treatment of larger rectal cancers that lie close to the rectal sphincter or anus, a combination of chemotherapy and radiation therapy may be administered before surgery to help shrink the cancer. The 5-fluorouracil chemotherapy and radiation therapy is delivered in a manner similar to adjuvant treatment following surgery. If there is sufficient shrinkage with neoadjuvant chemotherapy and radiation, a low anterior resection can be performed to remove the rectal cancer and still keep the anus. The benefits of neoadjuvant chemoradiation therapy compared with chemotherapy after surgical resection are being evaluated in ongoing clinical trials.

In one small study, 30 patients with locally advanced rectal cancer received neoadjuvant therapy consisting of chemotherapy and radiation therapy. The results showed that 71% of patients had a response, with 14% being complete. The cancer was “down staged” in 53% of patients, allowing for a less drastic type of surgery to be performed.

A large multi-institutional clinical trial was recently completed that directly compared treatment of neoadjuvant radiation plus surgery to surgery alone in over 1,800 patients with rectal cancer that had not spread to distant sites. Two years following treatment, there was no difference in survival between the two groups of patients. However, local cancer recurrences had occurred in only 2.4% of patients treated with radiation plus surgery, compared to 8.2% of patients treated with surgery alone.

Strategies to Improve Treatment

The progress that has been made in the treatment of rectal cancer has resulted from improved surgical techniques, the development of adjuvant and neoadjuvant chemotherapy and radiation therapy treatments and participation in clinical trials. Future progress in the treatment of rectal cancer will result from continued participation in appropriate clinical trials. Currently, there are several areas of active exploration aimed at improving the treatment of stage III (C) rectal cancer.

New Adjuvant Chemotherapy Regimens: Several new chemotherapy drugs show promising activity for the treatment of advanced or recurrent rectal cancer. Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies for use as adjuvant treatment is an active area of clinical research. Camptosar® and oxaliplatin are newer chemotherapeutic drugs being evaluated in various combinations with 5-fluorouracil for adjuvant treatment of rectal cancer.

Biological Modifier Therapy: Biologic response modifiers are naturally occurring or synthesized substances that direct, facilitate or enhance the body’s normal immune defenses. Biologic response modifiers include interferons, interleukins and monoclonal antibodies. In an attempt to improve survival rates, these and other agents are being tested alone or in combination with chemotherapy in clinical trials.

Cytoprotective Agents: Over the past 50 years, many drugs, called radiation protection or cytoprotective agents, have been treated for the prevention of toxicity of normal cells from radiation. Ethyol® is the only agent in this category to be approved by the U.S. Food and Drug administration for use in patients receiving radiation therapy for cancer of the head and neck. This drug has been shown to reduce the side effects from chemotherapy in patients with ovarian cancer. In one study, 30 patients with advanced (stage II-III) rectal cancer were randomly allocated to receive radiation and chemotherapy with or without Ethyol®. The results showed that Ethyol® was associated with a reduction in side effects of the skin, bowel and blood. Ethyol®, and possibly other drugs in the future, may also allow the delivery of higher doses of chemotherapy and/or radiation therapy.

Improved Sphincter-Sparing Treatments: Because of the inconvenience of a permanent colostomy, physicians are using sphincter-sparing treatments that allow patients with low-lying rectal cancers to keep the rectal sphincter or anus. Improved methods to select patients who can be treated with limited surgery followed by adjuvant chemotherapy and radiation therapy are being developed. In addition, more aggressive use of preoperative chemoradiation may allow more patients with larger low-lying rectal cancers a chance to maintain control of bowel function.

Neoadjuvant Treatment: When rectal cancer cannot be completely removed with surgery, a patient’s chance of cure is greatly diminished. Pre-operative radiation and/or chemotherapy is referred to as neoadjuvant therapy. Neoadjuvant therapy can shrink some rectal cancers and therefore allow complete surgical removal. Determining the optimal neoadjuvant chemotherapy and radiation therapy is an area of current research.

Improvement in Predicting Need for Adjuvant Chemotherapy: Although staging is currently important in order to determine proper treatment and outcome, current tests are not reliable enough to accurately predict patients who will relapse if they do not receive adjuvant chemotherapy.

One technique that may help predict an increased risk of cancer recurrence is Doppler ultrasound. Doppler ultrasound has been used to measure blood flow in the artery to the liver (hepatic artery) and total liver flow in patients with rectal cancer. This measurement may be helpful because abnormalities occurring in hepatic artery blood flow can be used to detect early cancer metastasis to the liver. In one recent clinical study, 120 patients with colorectal cancer underwent curative surgery. Patients with stage I (A) or II (B) cancer had a recurrence-free survival rate of 57% and patients with stage III (C) had a recurrence-free survival of 39%. Of the 47 patients who had a normal Doppler perfusion before surgery, the survival was 89%, with no recurrence of cancer. Of 73 patients who had an abnormal value, only 22% survived with no recurrence of cancer. This study suggests that Doppler ultrasound may identify patients who need additional adjuvant treatment.