Neoadjuvant androgen ablation prior to radiotherapy for prostate cancer: reducing the potential morbidity of therapy.

OBJECTIVES: To determine the impact of neoadjuvant hormonal therapy (NHT) prior to conformal radiotherapy on the reduction of volume of normal tissue structures exposed to high doses of radiation therapy and to evaluate the overall late toxicity and response to treatment among patients treated with this approach.
METHODS: Among 214 patients treated with neoadjuvant leuprolide acetate and flutamide for 3 months prior to three-dimensional conformal radiotherapy (3D-CRT), 45 patients were prospectively evaluated with detailed dose-volume histogram (DVH) analyses to determine the extent of improvement of the geometry of the target volume after NHT. All patients underwent simulation and conformal treatment planning before and after NHT, and the pre- and posthormone DVH calculations for all normal tissue structures were compared for each patient. In addition, toxicity and response to therapy were evaluated in the 214 patients treated with this combined approach.
RESULTS: In the 45 patients evaluated, the median reduction of the rectal and bladder volumes receiving 95% of the prescription dose (D95) were 18% and 46%, respectively, while 91% showed a reduction of small bowel volume in a range of 27% to 100% of the prehormonal values. Among the entire group of 214 patients treated with NHT and 3D-CRT, no grade 3 or 4 toxicity was observed with a median follow-up of 15 months after 3D-CRT. The 3-year actuarial grade 2 late gastrointestinal and genitourinary toxicity rates were 6% and 18%, respectively.
CONCLUSIONS: Neoadjuvant hormonal therapy effectively reduces the volume of normal tissue exposed to high radiation doses in the majority of treated patients and decreases the potential morbidity of therapy.