Rectal Cancer: Treatment

Once the diagnosis has been confirmed by biopsy and the endorectal ultrasound has been performed, the clinical stage of the cancer is assigned. The staging characteristics are utilized by the treating physicians to plan the specific treatment protocol for the patient. In addition, the stage of the cancer at the time of presentation gives a statistical likelihood of the treatment outcome, the prognosis.

Clinical staging

Rectal cancer first invades locally and then progresses to spread to regional lymph nodes or to other organs as noted in the description above. Using the characteristics of the primary tumor, its depth of penetration through the rectum, local invasion into pelvic structure, and the presence or absence of regional or distant metastases, stage is derived. A CT scan of the pelvis is very helpful here because the presence of invasion into the sacrum or pelvic sidewalls may mean that surgical therapy is not initially possible. On this basis, clinical staging is used to begin treatment. The pathologic stage is defined when the results of analyzing the surgical specimen are available for assigning stage, (typically stage I and II).

Rectal cancer is assigned stages I through IV, based on the following general criteria:

• Stage I: the tumor is confined to the epithelium or has not penetrated through the first layer of muscle in the rectal wall.
• Stage II: the tumor has penetrated through to the outer wall of the rectum or has gone through it, possibly invading other local tissue or organs.
• Stage III: Any depth or size of tumor associated with regional lymph node involvement.
• Stage IV: any of previous criteria associated with distant metastasis.

Surgery

The first, or primary, treatment modality utilized in the treatment of rectal cancer is surgery. Stage I, II, and even suspected stage III disease are treated by surgical removal of the involved section of the rectum along with the complete vascular and lymphatic supply. Most Stage II and Stage III rectal cancers (based on endorectal ultrasound, CT scan, and chest x ray) are treated with radiation and possibly chemotherapy prior to surgery.

A factor that needs to be considered when considering primary treatment for rectal cancer is the surgeon's ability to reconnect the ends of the rectum. The pelvis is a confining space that makes the performance of the hook-up more difficult to do safely when the tumor is in the lower rectum. The upper rectum does not usually present a substantial problem to the surgeon restoring bowel continuity after the cancer has been removed. Mid-rectal tumors, (especially in males where the pelvis is usually smaller than a woman's), may present technical difficulties in hooking the proximal bowel to the remaining rectum. Technical advances in stapling instrumentation have largely overcome these difficulties. If the anastomosis, (hook-up), leaks postoperatively, infection will ensue and in the past was a major cause of complications in resection of rectal cancers. Today, utilizing the stapling instrumentation, a hook-up at the time of original surgery is much safer. If the surgeon feels that the hook-up is compromised or may leak, a colostomy may be performed. A colostomy is performed by bringing the colon through the abdominal wall and sewing it to the skin. In these cases the stool is thus diverted away from the hook-up, allowing it to heal and preventing the infectious complications associated with leak. Later, when the hook-up has completely healed, the colostomy can be taken down and bowel continuity thus restored.

Stapling devices have allowed the surgeon to get closer to the anus and still allow the technical performance of a hook-up but there are limits. It is generally felt that there should be at least three centimeters of normal rectum below the tumor or the risk of recurrence locally will be excessive. In addition, if there is no residual native rectum, the patient will not have normal sensation or control and will have problems with uncontrollable soilage, (incontinence). For these reasons, patients presenting with low rectal tumors may undergo total removal of the rectum and anus. This procedure is known as an abdominal-perineal resection. A colostomy is performed in the lower left abdomen and it is permanent.

Radiation

As mentioned, for many late stage II or stage III tumors, radiation therapy can shrink the tumor prior to surgery. The other roles for radiation therapy are as an aid to surgical therapy in locally advanced disease that has been removed, and in the treatment of certain distant metastases. Especially when utilized in combination with chemotherapy, radiation used postoperatively has been shown to reduce the risk of local recurrence in the pelvis by 46% and death rates by 29%. Such combined therapy is recommended in patients with locally advanced primary tumors that have been removed surgically. In the treatment of distant metastases, radiation has been helpful at reducing local effects from them, particularly in the brain.

Chemotherapy

Adjuvant chemotherapy, (treating the patient who has no evidence of residual disease but who is at high risk for recurrence), is considered in patients whose tumors deeply penetrate or locally invade (late stage II and stageIII). If the tumor was not locally advanced, this form of chemotherapeutic adjuvant therapy may be recommended without radiation. This therapy is identical to that of colon cancer and leads to similar results. Standard therapy is treatment with 5-fluorouracil, (5-FU) combined with leucovorin for a period of six to 12 months. 5-FU is an antimetabolite and leucovorin improves the response rate. Another agent, levamisole, (which seems to stimulate the immune system), may be substituted for leucovorin. These protocols reduce rate of recurrence by about 15% and reduce mortality by about 10%. The regimens do have some toxicity but usually are tolerated fairly well.

Similar chemotherapy is administered for stage IV disease or if a patient progresses and develops metastasis. Results show response rates of about 20%. A response is a temporary regression of the cancer in response to the chemotherapy. Unfortunately, these patients eventually succumb to the disease. Clinical trials have now shown that the results can be improved with the addition of another agent to this regimen. Irinotecan does not seem to increase toxicity but it improved response rates to 39%, added two-three months to disease free survival, and prolonged overall survival by a little over two months.

— Richard A. McCartney, MD