Preoperative versus postoperative chemoradiotherapy for rectal cancer.
BACKGROUND
Postoperative chemoradiotherapy is the recommended standard therapy for patients with locally advanced rectal cancer. In recent years, encouraging results with preoperative radiotherapy have been reported. We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer.


METHODS
We randomly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy. The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day, five days per week, and fluorouracil, given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy. Surgery was performed six weeks after the completion of chemoradiotherapy. One month after surgery, four five-day cycles of fluorouracil (500 mg per square meter per day) were given. Chemoradiotherapy was identical in the postoperative-treatment group, except for the delivery of a boost of 540 cGy. The primary end point was overall survival.


RESULTS
Four hundred twenty-one patients were randomly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy. The overall five-year survival rates were 76 percent and 74 percent, respectively (P=0.80). The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group (P=0.006). Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group, as compared with 40 percent of the patients in the postoperative-treatment group (P=0.001); the corresponding rates of long-term toxic effects were 14 percent and 24 percent, respectively (P=0.01).


CONCLUSIONS
Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, improved local control and was associated with reduced toxicity but did not improve overall survival.
Sauer
Rolf
R
Department of Radiation Therapy, University of Erlangen, Erlangen, Germany. sekretariat@strahlen.med.uni-erlangen.de
Becker
Heinz
H
Hohenberger
Werner
W
Rödel
Claus
C
Wittekind
Christian
C
Fietkau
Rainer
R
Martus
Peter
P
Tschmelitsch
Jörg
J
Hager
Eva
E
Hess
Clemens F
CF
Karstens
Johann-H
JH
Liersch
Torsten
T
Schmidberger
Heinz
H
Raab
Rudolf
R
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009367:Neoplasm Staging; D011182:Postoperative Care; D011183:Postoperative Complications; D011300:Preoperative Care; D016016:Proportional Hazards Models; D011786:Quality Control; D011878:Radiotherapy / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis
D000970:Antineoplastic Agents; D005472:Fluorouracil