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.
Until 1980, the greatest advances in the management of rectalcancer were technical ones. Whereas in the past most patientswith rectal cancer underwent an abdominoperineal resection, itbecame possible in the 1980s to maintain intestinal continuityin the majority of patients with a low anterior resection andcolorectal anastomosis and, more recently, with a low anterioresection and coloanal anastomosis. These advances were due, inpart, to the development of stapling devices, which allowed surgeonsto perform anastomoses that were technically difficult to performby hand. More importantly, it became clear that in tumors identifiedat 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 reportedbetter local control in patients with locally advanced diseasebut no overall survival benefit. These studies provided importantinformation about the risk of local recurrence and identifiedthe subset of patients who benefited from adjuvant radiation therapy.
Single-agent adjuvant chemotherapy trials also failed to showa survival benefit when such therapy was given with radiationtherapy for rectal cancer. However, recognition of the high riskof local recurrence in patients with tumors involving the fullthickness of the bowel wall, or in patients with lymph node metastases,led to randomized trials using combined-modality chemotherapyand radiation therapy.
In 1986, the Gastrointestinal Tumor Study Group (GITSG) reportedthe first evidence that an overall survival benefit could be achievedusing adjuvant chemotherapy and radiation therapy. The chemotherapyemployed incorporated 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 yearslater by the National Surgical Adjuvant Breast and Bowel Project(NSABP), chemotherapy did confer a survival benefit in a selectsubset of patients. The Mayo/North Central Cancer Treatment Group(NCCTG) randomized trial comparing radiation therapy alone withchemotherapy and radiation therapy also demonstrated a survivaladvantage afforded by combined adjuvant chemoradiation.
Focus Shifts to Adjuvant Therapy
These studies changed the focus of rectal cancer management forthe next generation. Surgical management took a back seat to thisnew and exciting work on adjuvant chemotherapy and radiation therapy,and the focus in the 1990s has been to maximize the benefit ofadjuvant therapy. During this decade, national cooperative groupstudies have attempted to address numerous questions about theoptimal administration of adjuvant therapy. The NSABP is studyingthe necessity of using radiation therapy in combination with chemotherapy.The intergroup has demonstrated that the leukemogenic methyl-CCNUis not necessary. Ongoing studies are examining other 5-FU regimens,which include levamisole
(Ergamisol) and leucovorin, and are comparing bolus with prolongedIV infusion of 5-FU. Clearly, the optimal regimen that minimizestoxicity and produces maximal tumor control has yet to be defined.
Another direction for adjuvant treatment of rectal cancer underinvestigation for the past decade is preoperative adjuvant therapy.This approach requires preoperative identification of a tumorthat penetrates the full thickness of the bowel wall. ImprovedCT scans, pelvic MRI, and the advent of intraluminal ultrasoundhave made this possible with a high degree of accuracy. The newestRadiation Therapy Oncology Group (RTOG) and NSABP protocols comparepreoperative with postoperative adjuvant therapy.
Review of Surgery Is Timely
Dr. Enker's excellent review of the surgical management of rectalcancer is timely. He reminds us that, in this group of patientswith 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 definitionof the rectum anatomically, for the location of the tumor in therectum, and for the type of operation. This will become vitalas we enter a new generation of clinical trials in which quality-of-lifeissues assume greater importance.
Dr. Enker reviews the anatomy of the rectum, its blood and lymphaticsupply, and the anatomy and function of the pelvic nerves. Healso discusses results of surgery with respect to tumor control;sphincter preservation; bowel, bladder, and sexual function; andcomplications. Significant advances in nerve preservation havebeen made in the past decade but have been poorly disseminatedthroughout the surgical community, in contrast to the widespreadacceptance of adjuvant chemoradiation therapy.
Total Mesorectal Excision--A Significant Advance
Perhaps the most significant advance in this decade has been inthe surgical management of the disease. Dr. Enker compares thestandard blunt dissection taught and practiced in most centerswith the superior results of a sharp dissection along anatomicplanes of the mesorectum. With total mesorectal excision, the5-year survival rate is 75% without adjuvant therapy, as comparedwith rates of 50% with blunt dissection and about 60% with bluntdissection and adjuvant chemoradiation. Although the studies oftotal mesorectal excision may have some selection biases, theseresults have been reproduced often enough to be accepted. In thisera of managed care and cost containment, perhaps we should spendmore time improving surgical management of rectal cancer, ratherthan trying to play a costly game of "catch-up" withadjuvant therapy.