Radiotherapy combined with hormonal therapy (RT-HT) in prostate cancer patients with low, intermediate, and high risk of biochemical recurrence: perspective and therapeutic gain analysis

Abstract

Treatment of prostate cancer (PC) is a challenge for both urologists and radiation oncologists. Currently, two radical methods of treatment are recommended in localized prostate cancer (PC)--i.e. radical prostatectomy (RP) and radiotherapy (RT) with excellent long-term results. However, the outcome of RT, which is the treatment of choice in locally advanced stages of the disease, is unsatisfactory due to the high risk of regional or distant metastases and local failure. Lately, hormonal therapy (HT), which had mainly been indicated for treatment of patients with distant metastases, has been added to radiotherapy to improve the efficacy of treatment. The general rationales for combining RT and HT are four-fold: decreasing prostate gland volume, diminishing the number of cancer cells, improving tumor oxygenation, and eliminating distant and regional micrometastases. Over the last 20 years several randomized clinical trials evaluating the results of combined HT and RT treatment have been carried out. The RTOG 85-31, RTOG 86-10, EORTC 22863 and RTOG 92-02 trials were completed from the mid 80s to the mid 90s and long-term follow-up data on all important end-points are now available. These data have been evaluated by panels of experts and served as the basis for the latest American (NCCN 2005) and European (EAU 2005) recommendations on prostate cancer. However, despite the long-term results of these trials, there are still no clear-cut answers to the following crucial questions: What is the optimal timing of hormonal therapy? What types of patients can benefit most from combined strategies? What is the spectrum and potential reversibility of side effects of long-term combined treatment? How does it influence the patients quality of life and care costs? Other questions concern the possible role of androgen deprivation therapy combined with brachytherapy. The only randomized trial to evaluate this issue to date was stopped due to incomplete accrual. Therefore, answers must be sought in the large body of nonrandomized studies. There is a constant need for properly designed randomized clinical trials to precisely identify the subgroup of patients who will benefit most from combined RT and HT treatment. Results of ongoing clinical trials (RTOG 9901, RTOG 9408) are expected to yield some answers to the questions mentioned above. Currently, we can conclude that in the group of patients with high risk of relapse (T3 or GS > 7 or PSA >20 ng/ml), combined hormonal and radiation therapy improves prostate cancer treatment results and should be highly recommended.