The Role of Androgen Deprivation in the Definitive Management of Clinically Localized Prostate Cancer Treated with Radiation Therapy

Reviewers: Kenneth Blank, MD
Source: Int J Radiat Oncol Biol Phys 1999 Mar 1;43(4): 707-13

Introduction

The role of medications that suppress androgen production is controversial in the treatment of prostate cancer. Prostate cancer cells require androgens, such as testosterone, to survive. When medications deplete the body's androgen supply or when the testes are removed (the testes supply 97% of a man's androgen), prostate cancer cells die. Unfortunately, androgen deprivation rarely results in cure, as not all prostate cancer cells are androgen-dependent.

Many studies have been conducted to determine if androgen deprivation (surgical castration, estrogen, cyproterone, luteinizing hormone-releasing hormone agonists (LHRH), anti-androgens or a combination thereof) combined with radiotherapy is more effective than radiotherapy alone. In the March 1, 1999 issue of the International Journal of Radiation Oncology Biology and Physics, physicians from the William Beaumont Hospital in Michigan critically evaluate and synthesize these studies.

Methods

A MEDLINE search was used to identify all English language articles published between January 1990 and September 1998 in which prostate cancer patients were treated with a combination of radiotherapy and androgen deprivation. Twenty articles were selected for review and classified into one of two groups: 1) retrospective reviews (14 papers) and 2) randomized prospective trials (6 papers).

Results

Fourteen retrospective reviews were analyzed. The majority of these studies showed significant improvement in local control, disease free survival or biochemical disease free survival. Seven studies analyzed overall survival. Of these, only two found a significant improvement in survival with the addition of androgen deprivation. In addition, of the four retrospective reviews that analyzed cancer-specific survival, none found that the addition of androgen deprivation to radiotherapy improved this endpoint.

Similarly, the majority of the prospective randomized trials revealed an increase in the biochemical disease free survival but no change in overall survival. In fact, the only study that revealed a significant difference in overall survival was reported by the EORTC in 1998. In this trial, 79% for the patients treated with LHRH agonist and radiation were alive at five years compared with 62% in the radiation alone arm.

Conclusion

Based on these trials the authors conclude that combined modality therapy may improve disease free survival compared to radiotherapy alone, but the impact of androgen deprivation combined with radiotherapy on overall survival remains unclear. What does remains clear is the need for further randomized prospective trials. In fact, the RTOG has two such trials ongoing. For more information on these trials, please see OncoLink's Clinical Trials menu.