Conformal preoperative endorectal brachytherapy treatment for locally advanced rectal cancer: early results of a phase I/II study.

PURPOSE: Downstaging rectal carcinoma by preoperative radiotherapy decreases local recurrence, and recent phase II studies suggest that, in the lower one-third lesions, sphincter-preserving surgery can be considered. The purpose of the current study was to assess the efficacy and the toxicity of endorectal high dose-rate brachytherapy as a preoperative downstaging treatment modality.
METHODS: Patients with newly diagnosed invasive rectal adenocarcinoma, T2 to very early T4, operable tumors were eligible. A dose of 26 Gy was given over four consecutive daily treatments of 6.5 Gy prescribed at the tumor radial margin using endorectal brachytherapy with high dose-rate delivery system. Surgery as planned initially was done four to eight weeks later to allow for tumor downstaging. Patients found to have pathologic positive nodes received postoperative external beam (45 Gy/25 fractions) to the pelvis and systemic 5-fluorouracil-leucovorin chemotherapy.
RESULTS: Forty-nine patients entered the study. Tumors were in the lower one-third in 24 patients, middle one-third in 22, and upper one-third in 3. With preoperative endorectal ultrasound and magnetic resonance imaging, the clinical staging of the tumors was: 3 T2, 42 T3, 4 T4, and 16 N1-2. Acute toxicity related to brachytherapy was limited to a moderate proctitis (Radiation Therapy Oncology Group acute toxicity scoring system, Grade 2) in all patients, with two patients with tumors extending into the anal canal having Grade 3 dermatitis. Forty-seven patients underwent surgery. Two patients refused their operation based on a normal endoscopic rectal ultrasound after treatment. A complete clinical response was obtained in 32 of 47 (68 percent) patients with 32 percent pathologically pT0N0-1, and 36 percent had only residual microfoci of carcinoma. The surgical approaches did not yield more complications than expected.
CONCLUSION: Preoperative high dose-rate endorectal brachytherapy seems to be safe, because acute toxicity was mainly local, with moderate proctitis (Grade 2) and occasional dermatitis (Grade 3) for very low tumors. Finally, this modality, by providing high rate of tumor downstaging and downsizing especially for patients with lesions in the lower one-third of the rectum, represents a definite potential for sphincter-preserving surgery for investigation in future studies.