Mendenhall WH, Rout WR, Vouthey J-N et al,
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001
Reviewers: John Han-Chih Chang, M.D. and Kenneth Blank, M.D.
Source: Journal of Clinical Oncology October 1997, Volume 15: pp 3241 - 8.
Along with cure of the disease, sphincter (anal) preservation is an ultimate goal in the treatment in early stage rectal cancer. Advanced stage disease or rectal muscle invasive cancer with lymph node involvement and cancer invading the full thickness of rectal wall are usually treated with radical resection and chemosensitized radiation therapy. Sphincter preservation is varied, with some having to rely on a permanent colostomy. Those few patients with early stage disease are all eligible for sphincter sparing curative modalities such as endocavitary radiation therapy or wide local excision and postoperative radiation therapy.
Results of endocavitary radiation therapy have been previously described by the French, Cleveland Clinic, UCLA, Mayo Clinic and Washington University. They reveal a local-regional control rate of 75 - 95%, cause specific survival of 91 - 97% and sphincter preservation (no colostomy) rate of 83 - 91%. Wide local excision is used in cases of early stage or submucosal lesions and radiation is added adjuvantly in cases were the surgery discovered "unfavorable" pathology. Historically, patients have done well with this treatment schema. Data from St Mark's Hospital, Germany, France, Mayo Clinic, UCLA and Massachusetts General Hospital all reflect a local-regional control of 73 - 98%, cause specific survival of 85 - 99% and sphincter preservation of 84 - 96% in patients with "favorable" early stage rectal cancer and wide local excision alone. The addition of radiation therapy used in unfavorable pathology postoperatively yields local-regional control rates of 76 - 94%, cause specific survivals of 88 - 93% and sphincter preservation rates of 88 - 100%.
This publication was a retrospective review on the experience at the University of Florida in Gainesville. The patients were treated between 1974 to 1994. All patients were followed two years or until death. Favorable lesions were well to moderately differentiated, mobile, exophytic and no greater than three centimeters. Wide local excision was performed via a trans-anal or trans-sacral approach. Post-operative radiation was given to 45 patients with equivocal, close (? 5mm) or positive margins, invasion into or through the muscularis propria, fragmented excision or perineural invasion. The radiation post-operatively was with external-beam (EBRT) to 4500 - 6000 rads or cGy and occasionally an interstitial radiation implant to boost the dose to the tumor bed. The Endocavitary irradiation was administered to 20 patients in four separate fractions to a total dose of 11000 - 12000 cGy with a 50 KvP x-rays. Two weeks were given between fractions. Only 2 patients received chemotherapy.
The local control rates at five years were 80% for the endocavitary radiation group and 86% for the post-operative radiation group. The ultimate five-year local control rate for endocavitary patients is 85% and post-operatively radiation group is 92%. Sphincter preservation after endocavitary irradiation was 80% and 84% for post-operative radiation. The rate of distant metastases was 5% in endocavitary versus 4% in the post-operative radiation groups. Five-year absolute survival and cause specific survival for the endocavitary group was 76% and 84%, respectively. For the post-operative radiation group, it was 80% and 88%, respectively. Ulceration was found to be a significant poor prognostic factor.
No grade 5 (fatal) toxicities were reported. In the endocavitary group, no acute toxicities were noted. Twenty percent grade 3 to 4 toxicity was seen in the endocavitary group. All of these resolved with medical management. Three patients required a colostomy secondary to rectal perforation after wide local excision, but only 2 were permanent. One patient had severe cystitis with postoperative EBRT, but completed therapy with interstitial brachytherapy radiation.
Favorable early stage rectal cancers can be very well treated with endocavitary radiation or wide local excision alone. The past literature certainly supports this, but the data presented did not present the University of Florida's experience with wide local excision alone. It would have been useful to compare this data with those that received post-operative radiation therapy for unfavorable factors, since it is their contention that post-operative radiation can make the unfavorable cancer outcomes similar to the favorable disease's outcome. The historical data do show that adjuvant radiation therapy post-operatively for patients with disease beyond the submucosa (unfavorable) has better local control and overall survival than those treated with surgery alone. Also, there is the question of the lack of chemotherapy used. Major randomized trials have looked at post-operative radiation, chemotherapy, and radiation combined with chemotherapy as adjuvant therapy for unfavorable rectal cancers. These have shown a significant disease free and overall survival advantage to using a combination of radiation and chemotherapy post-operatively in these patients. Overall, this review did provide more support in the use of endocavitary radiation in early stage, favorable rectal cancers for cure. Also, post-operative radiation therapy data provided continued support to using adjuvant radiation therapy for rectal cancers that have spread beyond the submucosa. The future to treatment of rectal cancer, will look at the role of pre-operative chemoradiation therapy. There are on-going trials and studies trying to answer that very question.