Rectal Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage II Rectal Cancer
The NSABP R-03 similarly compared preoperative versus postoperative chemoradiation therapy for patients with clinically staged T3 or T4 or node-positive rectal cancer. Chemotherapy consisted of 5-FU/LV with 45 Gy in 25 fractions with a 5.4 Gy boost. Although the intended sample size was 900 patients, the study closed early because of poor accrual, with 267 patients. With a median follow-up of 8.4 years, preoperative chemoradiation was found to confer a significant improvement in 5-year DFS (64.7% vs. 53.4% for postoperative patients, P = .011). Similar to the German Rectal Study, there was no significant difference seen in OS between treatment arms (74.5% vs. 65.6%, P =. 065 for preoperative vs. postoperative chemoradiation).[Level of evidence: 1iiA]
Preoperative chemoradiation therapy has become the standard of care for patients with clinically staged T3 or T4 or node-positive disease, based on the results of several studies.
Retrospective studies have demonstrated that some patients with pathological T3, N0 disease treated with no further therapy after surgery have a very low risk of local and systemic recurrence. In addition, a pooled analysis of 3,791 patients enrolled in clinical trials demonstrated that, for patients with T3, N0 disease, the 5-year OS rate with surgery plus chemotherapy (84%) compared favorably with the survival rates of patients treated with surgery plus radiation and bolus chemotherapy (76%) or surgery plus radiation and protracted-infusion chemotherapy (80%). However, a multi-institutional retrospective analysis demonstrated that 22% of patients thought to have clinically node-negative T3 disease by ultrasound or magnetic resonance imaging (MRI) were found, at the time of resection, to have positive mesorectal lymph nodes even after chemoradiation.
Short-course Preoperative Radiation Therapy
Short-course radiation therapy before surgery has been a standard approach in parts of Europe and Australia. The use of short-course radiation therapy was evaluated in a randomized study in the Swedish Rectal Cancer Trial (NCT00337545).[Level of evidence: 1iiA] In the trial, 1,168 patients younger than 80 years with stage I to III resectable rectal adenocarcinoma were randomly assigned to receive preoperative radiation therapy (25 Gy in five fractions) or taken directly to surgery. Patients did not receive adjuvant chemotherapy. The 5-year OS rate was 58% in the radiation group and 48% in the surgery group (P = .005). The rate of local control was 11% in the radiation group and 27% in the surgery group (P < .001). Subsequently, the following two studies compared short-course preoperative radiation therapy with the standard, long-course radiation therapy administered with 5-FU:
- In the Polish Rectal Trial, 312 patients with clinical stage T3 or T4 rectal cancer were randomly assigned to preoperative radiation therapy (25 Gy in five fractions) followed by TME within 7 days, 6 months of adjuvant 5-FU/LV or preoperative chemoradiation (50.4 Gy in 28 fractions with concurrent bolus 5-FU/LV), TME in 4 to 6 weeks after completion of radiation, and 4 months of adjuvant 5-FU/LV. The primary endpoint of the study was to detect a difference of at least 15% in sphincter preservation with a power of 80%. The rates of sphincter preservation were 61.2% in the short-course group and 58% in the chemoradiation group (P = .570). The actuarial 4-year survival rate was 67.2% in the short-course group and 66.2% in the chemoradiation group (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.69-1.48; P = .960). The HR for local recurrence in the short-course group compared with the chemoradiation group was 0.65 (95% CI, 0.32-1.28; P = .210). There was no difference in late toxicity.
- In the Trans-Tasmanian Radiation Oncology Group (TROG) trial (TROG 01.04 [NCT00145769]), 326 patients with ultrasound- or MRI-staged T3 N0-2 M0 rectal adenocarcinoma within 12 cm from the anal verge were randomly assigned to short-course radiation therapy (25 Gy in five fractions) followed by surgery 3 to 7 days later or long-course chemoradiation (50.4 Gy in 28 fractions with concurrent continuous infusional 5-FU) followed by surgery in 4 to 6 weeks. All patients received adjuvant chemotherapy (5-FU/LV) after surgery. The trial was designed to have 80% power to detect a 10% difference in local recurrence at 3 years with a two-sided test at the 5% level of significance. Cumulative incidence of local recurrence at 3 years was 7.5% for the short-course group and 4.4% for the long-course group (P = .24). OS at 5 years was 74% for the short-course group and 70% for the long-course group (HR, 1.12; 95% CI, 0.76-1.67; P =.62).