Multimodality radiotherapy and androgen ablation in the treatment of clinically localized prostate cancer: early results in high risk patients

In patients presenting with clinically localized prostate cancer, the risk of biochemical failure increases significantly with higher Gleason scores, prostate specific antigen (PSA) levels, and clinical stages. Current surgical and radiotherapeutic approaches appear to offer limited success in patients with highly adverse prognostic factors. In an attempt to improve on these outcomes, we have combined external beam radiotherapy (EBRT) with a brachytherapy (BT) boost and neo adjuvant and adjuvant androgen ablation in a population at significant risk of biochemical failure. Here we present early biochemical progression data for this approach. From October 1997 to July 1999, 72 men with a serum PSA >or=10 ng/ml or Gleason score >or=7 or clinical stage >or=T2c (AJC/UICC 1992) underwent EBRT followed by palladium-103 BT. All patients underwent 8 months of combined androgen ablation with leuprolide and an oral antiandrogen beginning 3 months prior to initiation of EBRT. Patients were followed by PSA and digital rectal examination (DRE) at 3-month intervals and a chart review on all patients was carried out during July 2001. To allow comparisons to contemporary literature, Kaplan-Meier survival curves were generated utilizing three alternate definitions of biochemical recurrence: PSA >0.2 ng/ml, PSA >1.0 ng/ml, and the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition of three consecutive rising PSAs. Our results indicate that when PSA >0.2 ng/ml was used to define biochemical progression, 88% (95% CI 80-97) of patients remained free of disease at 24 months. When PSA >1.0 ng/ml was used, 97% (CI 92-100) of patients remained disease free at 24 months. ASTRO criteria yielded 90% (CI 82-98) recurrence-free survival at 24 months. In conclusion, this very early report indicates that in patients who are at increased risk of biochemical failure, EBRT with a BT boost in conjunction with short-term androgen ablation offers potentially superior biochemical disease-free survival to contemporary alternative approaches in the literature. Clearly, longer follow-up is required to confirm the durability of this approach.