Rectal Cancer

Cancer of the rectum is a highly treatable and often curable disease when localized. Surgery is the primary treatment and results in cure in approximately 45% of all patients. The prognosis of rectal cancer is clearly related to the degree of penetration of the tumor through the bowel wall and the presence or absence of nodal involvement.

Following treatment of rectal cancer is listed based on stages.



HOW TO TREAT RECTAL CANCER?

Stage I Rectal Cancer

Because of its localized nature, stage I has a high cure rate.

Standard treatment options:

Wide surgical resection and anastomosis when an adequate low anterior resection (LAR) can be performed, with sufficient distal rectum to allow a conventional anastomosis or colo-anal anastomosis.
Wide surgical resection with abdominoperineal resection (APR) for lesions too distal to permit low anterior resection (LAR).
Local transanal or other resection with or without perioperative external-beam irradiation plus fluorouracil (5-FU). There are no randomized trials comparing local excision with or without postoperative chemoradiation treatments to wide surgical resection (LAR and APR). One prospective multicenter phase II study and several larger retrospective series suggest that well-staged patients with small (<4 centimeters) tumors with good histologic prognostic features (well- to moderately-differentiated adenocarcinomas), mobile, and no lymphatic, venous, or perineural invasion, treated with full-thickness local excision that results in negative margins may have outcomes equivalent to APR or LAR with the selective post-operative use chemoradiation therapy. Endoscopic ultrasound studies have been helpful in defining these patients. Patients with tumors that are pathologically T1 may not need postoperative therapy. Patients with tumors that are T2 or greater have lymph node involvement of 20% or more and require additional therapy, such as radiation and chemotherapy, or more standard surgical resection. Patients with poor histologic features should consider LAR or APR and postoperative treatment as dictated by full surgical staging. The selection of patients for local excision may also be improved by newer imaging techniques, such as endorectal magnetic resonance imaging and endorectal ultrasound.
Endocavitary, with or without external-beam, radiation in selected patients with tumors less than 3 centimeters in size, with well-differentiated tumors, and without deep ulceration, tumor fixation or palpable lymph nodes. Special equipment and experience are required to achieve results equivalent to surgery.
Stage II Rectal Cancer

The uterus, vagina, parametria, ovaries, or prostate are sometimes involved. Studies employing preoperative or postoperative radiation therapy alone have demonstrated decreased locoregional failure rates. Significant improvement in overall survival has not been demonstrated with radiation therapy alone except in a single trial of preoperative radiation therapy.

A randomized trial by the Gastrointestinal Tumor Study Group demonstrated an increase in both disease-free interval and overall survival when radiation therapy is combined with chemotherapy following surgical resection in patients whose rectal cancer has penetrated through the bowel wall into the perirectal fat (stage II) or has metastasized to regional lymph nodes (stage III). A disease-free survival advantage has been observed in patients with stage II and III rectal cancer treated with chemotherapy and radiation therapy compared to those treated with radiation therapy alone. An Intergroup trial has demonstrated a 10% improved survival with the use of continuous-infusion fluorouracil (5-FU) throughout the course of radiation therapy when compared with bolus 5-FU. This method of 5-FU administration should be considered standard. The final results of Intergroup trial 0114 showed no survival benefit with the addition of leucovorin, levamisole, or both, to 5-FU administered postoperatively at a median follow-up of 7.4 years. Clinical trials further addressing 5-FU modulation are underway, including the use of oral 5-FU prodrugs. The radiation should be delivered to high-dose levels (45-55 Gy) either preoperatively or postoperatively, with meticulous attention to technique. An analysis of patients treated with postoperative chemotherapy and radiation therapy suggests that these patients may have more chronic bowel dysfunction compared to those who undergo surgical resection alone. Improved radiation planning and techniques can be used to minimize treatment-related complications. These techniques include the use of multiple pelvic fields, prone positioning, customized bowel immobilization molds (belly boards), bladder distention, visualization of the small bowel through oral contrast, and the incorporation of three-dimensional or comparative treatment planning.

Standard treatment options:

Wide surgical resection and low anterior resection with colorectal or colo-anal reanastomosis when feasible, followed by chemotherapy and postoperative radiation therapy, preferably through participation in a clinical trial.
Wide surgical resection with abdominoperineal resection with adjuvant chemotherapy and postoperative radiation therapy, preferably through participation in a clinical trial.
Partial or total pelvic exenteration in the uncommon situation where bladder, uterus, vagina, or prostate are invaded, with adjuvant chemotherapy and postoperative radiation therapy, preferably through participation in a clinical trial.
Preoperative radiation therapy with or without chemotherapy followed by surgery with an attempt to preserve sphincter function with subsequent adjuvant chemotherapy, preferably through participation in a clinical trial.
Intraoperative electron beam radiation therapy (IORT) to the sites of residual microscopic or gross residual disease following surgical extirpation can be considered at institutions where the appropriate equipment is available. When combined with external-beam radiation therapy and chemotherapy in highly selected patients, IORT with or without 5-FU has resulted in improved local control in single institution experiences.
Stage III Rectal Cancer

Stage III rectal cancer denotes disease with lymph node involvement. The number of positive lymph nodes affects prognosis: patients with 1 to 3 involved nodes have superior survival to those with 4 or more involved nodes. Studies employing preoperative or postoperative radiation therapy alone have demonstrated decreased locoregional failure rates. Significant improvement in overall survival has not been demonstrated with pre- or postoperative radiation therapy alone except in a single trial.

Standard treatment options:

Wide surgical resection and low anterior resection with colorectal or coloanal reanastomosis when feasible, followed by chemotherapy and postoperative radiation therapy, preferably through participation in a clinical trial.
Wide surgical resection with abdominoperineal resection with adjuvant chemotherapy and postoperative radiation therapy, preferably through participation in a clinical trial.
Partial or total pelvic exenteration in the uncommon situation where bladder, uterus, vagina, or prostate are invaded, with adjuvant chemotherapy and postoperative radiation therapy, preferably through participation in a clinical trial.
Preoperative radiation therapy with or without chemotherapy followed by surgery with an attempt to preserve sphincter function with subsequent adjuvant chemotherapy, preferably through participation in a clinical trial.
Intraoperative electron beam radiation therapy (IORT) to the sites of residual microscopic or gross residual disease following surgical extirpation can be considered at institutions where the appropriate equipment is available. When combined with external-beam radiation therapy and chemotherapy in highly selected patients, IORT has resulted in improved local control in a single institution experience.
Palliative chemoradiation.
Stage IV Rectal Cancer

Stage IV rectal cancer denotes distant metastatic disease. Local regional approaches to treating liver metastases include hepatic resection and/or intraarterial administration of chemotherapy with implantable infusion ports or pumps. For patients with limited (3 or less) hepatic metastases, resection may be considered with 5-year survival rates of 20% to 40%. Other local ablative techniques that have been used to manage liver metastases include cryosurgery, embolization, and interstitial radiation therapy. For those patients with hepatic metastases deemed unresectable (due to such factors as location, distribution, and excess number), cryosurgical ablation has been associated with long term tumor control.

Standard treatment options:

Surgical resection/anastomosis or bypass of obstructing lesions in selected cases or resection for palliation.
Surgical resection of isolated metastases (liver, lung, ovaries).
Chemoradiation for local palliation.
Chemotherapy alone for distant disease after resection of local disease.
Clinical trials evaluating new drugs and biologic therapy.
Recurrent Rectal Cancer

Locally recurrent rectal cancer may be resectable, particularly if an inadequate prior operation was performed. For patients with local recurrence alone following initial attempted curative resection, aggressive local therapy with repeat low anterior resection and coloanal anastomosis, abdominoperineal resection, or posterior or total pelvic exenteration can lead to long-term disease-free survival. The use of induction chemoradiation for previously non-irradiated patients with locally advanced (pelvic side-wall, sacral, and/or adjacent organ involvement) pelvic recurrence may increase resectability and allow for sphincter preservation. Intraoperative radiation therapy in patients who received previous external beam radiation may improve local control in patients with locally recurrent disease with acceptable morbidity. The presence of hydronephrosis associated with recurrence appears to be a contraindication to surgery with curative intent. Patients with limited pulmonary metastases and patients with both pulmonary and hepatic metastases, may also be considered for surgical resection, with 5-year survival possible in highly selected patients.

Standard treatment options:

Resection of locally recurrent rectal cancer may be palliative or curative in selected patients.
Resection of liver metastases in selected patients (5-year cure rate with resection of solitary metastases exceeds 20%).
Resection of isolated pulmonary or ovarian metastases.
Palliative radiation therapy.
Palliative chemotherapy.
Palliative chemoradiation.
Palliative endoscopic-placed stents to relieve obstruction.


HOW TO ESTIMATE PROGNOSIS OF RECTAL CANCER?

The prognosis of rectal cancer is clearly related to the degree of penetration of the tumor through the bowel wall and the presence or absence of nodal involvement. These 2 characteristics form the basis for all staging systems developed for this disease. Preoperative staging procedures include digital rectal examination, computed tomographic scan or magnetic resonance imaging scan of the abdomen and pelvis, endoscopic evaluation with biopsy, and endoscopic ultrasound (EUS).

EUS is an accurate method of evaluating tumor stage (up to 95% accuracy) and the status of the perirectal nodes (up to 74% accuracy). Accurate staging can influence therapy by helping to determine which patients may be candidates for local excision rather than more extensive surgery and which patients may be candidates for preoperative chemotherapy and radiation therapy to maximize the likelihood of resection with clear margins.

Many other prognostic markers have been evaluated retrospectively in the prognosis of patients with rectal cancer, although most, including allelic loss of chromosome 18q or thymidylate synthase expression, have not been prospectively validated.

Microsatellite instability, also associated with hereditary nonpolyposis rectal cancer, has been shown to be associated with improved survival independent of tumor stage in a population-based series of 607 patients less than 50 years of age with colorectal cancer.

Racial differences in overall survival after adjuvant therapy have been observed, without differences in disease-free survival, suggesting that comorbid conditions play a role in survival outcome in different patient populations.

A major limitation of surgery is the inability to obtain wide radial margins because of the presence of the bony pelvis. In those patients with disease penetration through the bowel wall and/or spread into lymph nodes at the time of diagnosis, local recurrence following surgery is a major problem and often ultimately results in death. The radial margin of resection of rectal primaries may also predict for local recurrence.

Following treatment of rectal cancer, periodic evaluations may lead to the earlier identification and management of recurrent disease.

To date, there have been no large-scale randomized trials documenting the efficacy of a standard, postoperative monitoring program.Carcinoembryonic antigen (CEA) is a serum glycoprotein frequently used in the management of patients with rectal cancer. A review of the use of this tumor marker suggests: that CEA is not useful as a screening test; that postoperative CEA testing be restricted to patients who would be candidates for resection of liver or lung metastases; and that routine use of CEA alone for monitoring response to treatment not be recommended. However, the optimal regimen and frequency of follow-up examinations are not well defined, since the impact on patient survival is not clear and the quality of data is poor. New surveillance methods including CEA immunoscintigraphy and positron tomography are under clinical evaluation.

Although a large number of studies have evaluated various clinical, pathological, and molecular parameters with prognosis, as yet, none have had a major impact on prognosis or therapy. Clinical stage remains the most important prognostic indicator.