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 (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
(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