Neoadjuvant total androgen suppression and radiotherapy in the management of locally advanced prostate cancer

The combination of radiation therapy and total androgen suppression shows potential for improving the outcome in patients with locally advanced prostate cancer. Both radiation and androgen ablation induce apoptosis through different mechanisms, and a synergistic interaction has been reported between the two modalities in vitro. Studies of neoadjuvant hormonal therapy before radical prostatectomy have shown considerable tumor shrinkage, a change that would greatly facilitate subsequent radiotherapy. A recent randomized trial involving patients with bulky disease has shown that the use of androgen ablation therapy before and during radiation therapy substantially improved local control and decreased the time to biochemical failure. Still another randomized trial performed in patients with locally advanced disease has shown that the positive biopsy rate was strikingly lower in patients who received neoadjuvant hormonal therapy before radiation than in those who underwent radiotherapy alone, and was even lower in patients who were treated with both neoadjuvant and adjuvant total androgen suppression. The combination of hormonal therapy and radiation has not yet been proven to prolong survival. Nevertheless, given the limitations of conventional radiotherapy, it is recommended that patients at high risk for failure be entered into one of the ongoing Radiation Therapy Oncology Group (RTOG) trials. These trials are attempting to clarify such questions as the role of adjuvant therapy following neoadjuvant therapy and radiation, the optimal timing of hormonal therapy, and the role of whole pelvic irradiation.