Initially, when first used by Huggins and Hodges hormone therapy (ADT) was recommended to be used early on in prostate cancer disease progression.

Eventually, the Veterans Administration Cooperative Urology Research Group (VACURG) studies reversed this early recommendation. After this study ADT was usually deferred until symptomatic progression. It was believed that ADT caused an alteration of the nature of metastatic lesions, thereby creating earlier androgen resistance.

Recently this debate has again come into issue. Earlier use of ADT has gained new and stronger popularity because of the advent of less-toxic and well-tolerated pharmaceutical agents, such as luteinizing hormone-releasing hormone (LHRH) agonists and antiandrogens. Laboratory studies have demonstrated that early hormone therapy does not confer early resistance. An update of the VACURG study by Byar and Corle determined that disease progression from stage C to stage D was decreased from 50% to 10% with diethylstilbestrol (DES) therapy.

[1] Crawford and associates also showed a benefit of early hormone therapy in men with distant metastases.[2]

Then the Medical Research Council performed a study that found that overall survival was significantlyextended in those who were treated early.[2] This study was a randomized study of 938 men with locally advanced or asymptomatic metastatic prostate cancer in which the men received treatment with orchiectomy or an LHRH agonist, either immediately or after symptoms occurred. The development of extra-skeletal metastases, pathologic bone fractures, spinal cord compression, and urethral obstruction was twice as common in the deferred-treatment group.[2]

In a study by the Eastern Cooperative Oncology Group (ECOG), immediate therapy significantly improved survival and reduced the risk of progression.[3] In this trial, 98 men who underwent radical prostatectomy and were found to have lymph node metastases were randomly assigned to either immediate castration (ie, LHRH agonist/orchiectomy) or therapy instituted at disease progression.
CONCLUSIONS: The early use of ADT confers a survival advantage to men with advanced prostate cancer and does not bring about early hormone resistance.
References :
• [1] Byar DP, Corle DK. Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies. NCI Monogr. 1988;(7):165-70. [Medline].
• [2] Crawford ED, Blumenstein BA, Goodman PJ, et al. Leuprolide with and without flutamide in advanced prostate cancer. Cancer. Sep 1 1990;66(5 Suppl):1039-44. [Medline].
• .[3] Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate versus deferred treatment for advanced prostatic cancer: initial results of the Medical Research Council Trial. Br J Urol. Feb 1997;79(2):235-46. [Medline].
From -Med Scape – Martha K Terris, MD, FACS; Chief Editor: Edward David Kim, MD, FACS

Joel Nowak, M.A., M.S.W.