BOSTONNeoadjuvant therapy for adenocarcinoma of the rectum
is well tolerated and can produce substantial downstaging and high curative
resection rates, according to a retrospective study presented at the American
Society of Colon and Rectal Surgeons (ASCRS) annual meeting. The manuscript of
the study has been accepted for publication in Diseases of the Colon and
Thomas E. Read, MD, of Washington University School of
Medicine, St. Louis, and his co-authors evaluated the down-staging effect vs
toxicity of various neoadjuvant treatment regimens in 262 patients undergoing
proctectomy for rectal cancer between 1990 and 1999.
Patients underwent preoperative short-course radiation therapy
(2,000 cGy in 5 fractions), long-course radiation therapy (4,500 cGy in 25
fractions), or chemoradiation (4,500 cGy in 25 fractions with concurrent
Downtaging was determined by comparing the pretreatment T and N
stage of the tumor (based on transrectal ultrasound with or without CT) with
Although the effect of neoadjuvant therapy was probably
underestimated because the authors’ criteria mandated a reduction in T or N
stage to indicate downstaging, nearly half of the patients in the study45%
(116 of 260)had their primary tumors downstaged by neoadjuvant therapy.
There was a trend toward greater downstaging with the more
intensive neoadjuvant regimens, though these differences did not reach
statistical significance. Down-staging of one or more T stages occurred in 34
of 82 patients (42%) treated with short-course radiation, 55 of 122 patients
(45%) treated with long-course radiation, and 27 of 56 patients (48%) treated
with chemoradiation prior to proctectomy.
Downstaging of one or more nodal stage occurred in 84 of 176
patients (48%) overall. Longer neoadjuvant treatment regimens produced greater
downstaging, with the greatest effect seen in patients treated with long-course
radiation therapy (P = .003).
Downstaging of one or more N stage occurred in 12 of 45
patients (27%) treated with short-course radiation, 50 of 87 patients (58%)
treated with long-course radiation, and 22 of 44 patients (50%) treated with
chemoradiation prior to proctectomy.
Complete pathologic response (no detectable tumor on final
histology) was observed in 16 of 260 patients (6%) overall. Complete pathologic
response occurred in 4 of 82 patients (5%) treated with short-course radiation,
5 of 122 patients (4%) treated with long-course radiation, and 7 of 56 patients
(13%) treated with chemoradiation.
Although there was a trend toward higher complete pathologic
response rates with chemoradiation, these differences did not reach statistical
significance (P = .08), Dr. Read said.
Resection with negative margins (distal, proximal, and radial)
was achieved in 211 of 227 patients (93%) in whom complete radial margin data
The greater downstaging effect of more intensive neoadjuvant
treatment regimens came at the price of greater toxicity. Grade 3-4 toxicities
occurred in 22 of 260 patients (8%) overall during neoadjuvant therapy.
No patients treated with short-course radiation had toxicity; 9
toxicities occurred in 8 of 122 patients (7%) treated with long-course
radiation; 24 toxicities occurred in 14 of 56 patients (25%) treated with
chemoradiation. This trend of increasing toxicity with more intensive
neoadjuvant therapy was statistically significant (P < .0001).
The most common complications were gastrointestinal, with
enteritis being the most frequent and most severe.
Dr. Read said that his data suggest that the selective use of
neoadjuvant radiation and chemoradiation may have utility in the management of
patients with rectal cancer.
"We have typically used short-course radiation for
patients with small, mobile tumors that are ultrasound stage T3N0 or less on
pretreatment evaluation," Dr. Read told ONI in an interview.
Currently, he said, long-course radiation is used for patients
with T3N0 tumors that are bulky or tethered and for patients with nodal disease
who are too frail to tolerate chemoradiation. For such patients, he said, the
least morbid and most acceptable treatment approach may be sequential therapy:
preoperative radiation followed by surgery and then chemotherapy.
"The local control and functional results with this
approach are excellent," Dr. Read said. "There is no evidence that
delaying chemotherapy until the postoperative period will compromise its impact
on distant disease."
He noted that preoperative chemoradiation is employed
primarily for healthy patients with fixed or deeply tethered cancers, or
patients with nodal disease on transrectal ultrasound or CT.
Dr. Read said that he hoped that prospective comparisons of the
benefits vs the toxicities of various neoadjuvant regimens could help guide
selection of these treatments in the future.