Combined androgen blockade: the gold standard for metastatic prostate cancer

Abstract

There is no debate that both the earlier diagnosis and the treatment of men with cancer of the prostate (CaP) are having an impact on patients with this disease. In many practices there are fewer and fewer patients presenting with the classic diagnosis of 'advanced disease', i.e., stage M (D2). Only a few years ago, a large percentage of men with CaP had bony metastases when they presented to a physician. Hormonal ablation was the optimal treatment, and the only question was whether bilateral orchiectomy or medical castration should be used. The median time to progression with either type of monotherapy was 12-18 months, and the median time to survival was 24-36 months. Unfortunately, in many parts of the world, this scenario is still the norm. In the United States, Europe, and an increasing number of other countries, improved methods of detection with transrectal ultrasound and prostate-specific antigen (PSA) have resulted in a dramatic shift in the stage of disease at diagnosis. It is safe to say that in these countries the majority of prostate cancers are now being clinically diagnosed while still localized, and many organ-confined tumors are being definitively treated and cured. Nevertheless, many of these patients will be understaged at the time of diagnosis and will show progression following definitive therapy. In most surgical series approximately one half of patients will be found on pathologic examination to have pT3 disease. The use of PSA in the diagnosis of CaP has been mentioned, and it is being used extensively to monitor recurrent/residual disease. Hormonal therapy is being employed earlier in numerous clinical situations, and its use is no longer reserved solely for patients with metastatic disease. In this context combined androgen blockade has become the gold standard of treatment in neoadjuvant situations as well as for advanced CaP. Newer advances, including 3-month depot formulations of luteinizing hormone-releasing hormone analogues, the reversibility of medical castration, the preference of most patients to have medical castration, and the approval of other antiandrogens in the United States, all have further strengthened the use of combined androgen blockade. Hormonal therapy in adjuvant settings, when there is a high likelihood of disease recurrence, is also being used in many clinical situations. In addition, there appears to be a role for certain types of hormonal therapy in chemoprevention.