Chemoradiotherapy Followed by Surgery in Rectal Cancer: Improved Local Control Using a Moderately High Pelvic Radiation Dose

Abstract

To determine complete resection and sphincter preservation rates, down-staging, local control and survival associated with concurrent chemoradiotherapy (CCRT) using a moderately high pelvic radiation dose before surgery in rectal cancer. Fifty-seven patients with histologically proven adenocarcinoma of the mid to lower rectum were treated using preoperative CCRT and surgery. Median radiation dose to the pelvis was 5400 cGy (5040-5580 cGy). CCRT was administered during the first and fifth weeks of radiotherapy with bolus intravenous 5-fluorouracil (5-FU) 400 mg/m(2)/day and leucovorin (LV) 20 mg/m(2)/day for 5 days. Surgery was attempted 4-8 weeks after completing preoperative CCRT. Post-operative chemotherapy was then added for up to four cycles of intravenous 5-FU and LV. Toxicities during CCRT were generally mild and manageable: Grade 1/2 anemia, 3.5%; Grade 1/2 leukopenia, 45.6%; Grade 3 leukopenia, 3.5%; Grade 1/2 diarrhea, 22.8%; Grade 1/2 abdominal discomfort, 7%; and perianal skin reaction, 5.3%. No late complication requiring surgical intervention occurred. Complete surgical resection with a negative resection margin was achieved in 98.2% of patients, and the down-staging rate was 52.6% (30/57; 95% CI 39.6-65.6%). Complete pathologic response was obtained in 5.3% patients (3/57; 95% CI 0-11.1%) and in other 2 patients only sporadic tumor cells nests were noted in surgical specimens. The sphincter preservation rate was 77.2% (44/57; 95% CI 66.3-88.1%). Of 30 patients with tumors located within 5 cm from the anal verge, sphincter preservation was possible in 18 patients (60.0%; 95% CI 47.3-72.7%). With a median follow-up duration of 40 months, overall and disease-free survival (DFS) rates over 3 years were 91.8% (95% CI 85.5-98.2%) and 79.7% (95% CI 71.2-88.2%), respectively. At univariate analysis, significant factors for DFS was LN involvement status (P = 0.024). Local and distant failure rates over the same period were 5.3 and 21.1%, respectively. Preoperative CCRT produced encouraging down-staging rates and was found to facilitate complete resection and sphincter saving in distal rectal cancer with acceptable toxicity. Further studies are warranted using this moderately high radiation dose to the pelvis to improve the local control.