Until 1980, the greatest advances in the management of rectal cancer were technical ones. Whereas in the past most patients with rectal cancer underwent an abdominoperineal resection, it became possible in the 1980s to maintain intestinal continuity in the majority of patients with a low anterior resection and colorectal anastomosis and, more recently, with a low anterio resection and coloanal anastomosis. These advances were due, in part, to the development of stapling devices, which allowed surgeons to perform anastomoses that were technically difficult to perform by hand. More importantly, it became clear that in tumors identified at a relatively early stage, retrograde tumor spread was uncommon, and a 2-cm distal margin was generally adequate.
In the late 1960s and early '70s, adjuvant radiation studies reported better local control in patients with locally advanced disease but no overall survival benefit. These studies provided important information about the risk of local recurrence and identified the subset of patients who benefited from adjuvant radiation therapy.
Single-agent adjuvant chemotherapy trials also failed to show a survival benefit when such therapy was given with radiation therapy for rectal cancer. However, recognition of the high risk of local recurrence in patients with tumors involving the full thickness of the bowel wall, or in patients with lymph node metastases, led to randomized trials using combined-modality chemotherapy and radiation therapy.
In 1986, the Gastrointestinal Tumor Study Group (GITSG) reported the first evidence that an overall survival benefit could be achieved using adjuvant chemotherapy and radiation therapy. The chemotherapy employed incorporated fluorouracil(Drug information on fluorouracil) (5-FU), vincristine, and methyl-CCNU (semustine). Chemotherapy alone did not produce a survival benefit, but combined-modality therapy did. In a study reported 3 years later by the National Surgical Adjuvant Breast and Bowel Project (NSABP), chemotherapy did confer a survival benefit in a select subset of patients. The Mayo/North Central Cancer Treatment Group (NCCTG) randomized trial comparing radiation therapy alone with chemotherapy and radiation therapy also demonstrated a survival advantage afforded by combined adjuvant chemoradiation.
Focus Shifts to Adjuvant Therapy
These studies changed the focus of rectal cancer management for the next generation. Surgical management took a back seat to this new and exciting work on adjuvant chemotherapy and radiation therapy, and the focus in the 1990s has been to maximize the benefit of adjuvant therapy. During this decade, national cooperative group studies have attempted to address numerous questions about the optimal administration of adjuvant therapy. The NSABP is studying the necessity of using radiation therapy in combination with chemotherapy. The intergroup has demonstrated that the leukemogenic methyl-CCNU is not necessary. Ongoing studies are examining other 5-FU regimens, which include levamisole(Drug information on levamisole)
(Ergamisol) and leucovorin, and are comparing bolus with prolonged IV infusion of 5-FU. Clearly, the optimal regimen that minimizes toxicity and produces maximal tumor control has yet to be defined.
Another direction for adjuvant treatment of rectal cancer under investigation for the past decade is preoperative adjuvant therapy. This approach requires preoperative identification of a tumor that penetrates the full thickness of the bowel wall. Improved CT scans, pelvic MRI, and the advent of intraluminal ultrasound have made this possible with a high degree of accuracy. The newest Radiation Therapy Oncology Group (RTOG) and NSABP protocols compare preoperative with postoperative adjuvant therapy.
Review of Surgery Is Timely
Dr. Enker's excellent review of the surgical management of rectal cancer is timely. He reminds us that, in this group of patients with rectal cancer that is through the bowel wall or node-positive, surgery alone cures about 50% of patients.
Dr. Enker makes an appropriate plea for a universal definition of the rectum anatomically, for the location of the tumor in the rectum, and for the type of operation. This will become vital as we enter a new generation of clinical trials in which quality-of-life issues assume greater importance.
Dr. Enker reviews the anatomy of the rectum, its blood and lymphatic supply, and the anatomy and function of the pelvic nerves. He also discusses results of surgery with respect to tumor control; sphincter preservation; bowel, bladder, and sexual function; and complications. Significant advances in nerve preservation have been made in the past decade but have been poorly disseminated throughout the surgical community, in contrast to the widespread acceptance of adjuvant chemoradiation therapy.
Total Mesorectal Excision--A Significant Advance
Perhaps the most significant advance in this decade has been in the surgical management of the disease. Dr. Enker compares the standard blunt dissection taught and practiced in most centers with the superior results of a sharp dissection along anatomic planes of the mesorectum. With total mesorectal excision, the 5-year survival rate is 75% without adjuvant therapy, as compared with rates of 50% with blunt dissection and about 60% with blunt dissection and adjuvant chemoradiation. Although the studies of total mesorectal excision may have some selection biases, these results have been reproduced often enough to be accepted. In this era of managed care and cost containment, perhaps we should spend more time improving surgical management of rectal cancer, rather than trying to play a costly game of "catch-up" with adjuvant therapy.