Background: Androgen ablation as a treatment for patients with prostate carcinoma was described 60 years ago. Despite the long pedigree for this treatment, the optimal use of androgen ablation therapy remains extremely controversial. Monitoring the level of prostate specific antigen (PSA) has created a dramatic shift in the population of patients in whom androgen ablation is initiated. This has resulted in a number of changing concepts of treatment. Patients with recurrent prostate carcinoma after the failure of local therapy are now diagnosed with recurrent disease on the basis of a rising PSA level. These patients have a median life expectancy of 10-15 years compared with 3 years for patients who present with metastatic disease. This means that the systemic side effects of androgen ablation and the impact on quality of life have become more important. Controversies exist with respect to the timing of therapy, the use of intermittent androgen ablation, and the role of total androgen blockade.
Methods: A critical review of the literature, with an emphasis on quality of life and recent publications, was performed.
Results: Data support the early initiation of androgen ablation for patients with locally advanced or lymph node positive prostate carcinoma. There are no data supporting a particular PSA trigger point or a PSA doubling time for the initiation of androgen ablation therapy after the failure of local radical therapy. The combined results of 27 prospective randomized trials of total androgen blockade support the finding of a modest survival benefit for patients who undergo androgen ablation with combined therapy. The average, absolute 5-year survival rate was improved by 3% (a 10% reduction in the risk of dying), with a 95% confidence interval between 0.4% and 6.0%. Intermittent therapy resulted in an improved quality of life in the off-treatment interval. Uncertainty remains with respect to the long term effect of intermittent androgen ablation therapy on patient survival. This is being studied in a prospective intergroup trial comparing continuous therapy with intermittent therapy carried out by the National Cancer Institute Criteria/Canadian Uro-Oncology Group and the Southwest Oncology Group.
Conclusions: Androgen ablation therapy is an effective treatment for patients with advanced prostate carcinoma. It has serious limitations, however. Although it improves patient survival, it is not curative, and it is associated with a substantial adverse impact on the quality of life for patients, particularly when its use is prolonged. The advent of intermittent therapy may reduce this impact. The real challenge, however, is to develop better means to avert hormone-refractory prostate carcinoma and better treatments for patients with hormone-refractory disease when it occurs.