What is the timing of hormone therapy for the treatment of metastatic and advanced prostate cancer?

Updated: Dec 29, 2020
  • Author: Martha K Terris, MD, FACS; Chief Editor: Edward David Kim, MD, FACS  more...
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In the years following the introduction by Huggins and Hodges of hormone therapy for prostate cancer, [32] early institution of such treatment was recommended based on comparison with historical controls. [33]

Later, the Veterans Administration Cooperative Urology Research Group (VACURG) studies reversed the recommendation of early hormone therapy; instead, hormone therapy was deferred until symptomatic progression. In addition, prolongation of survival was believed to be secondary to the alteration of the nature of metastatic lesions, thereby creating earlier androgen resistance, rather than a result of early hormone manipulation.

In more recent years, the old controversy of appropriate androgen-deprivation therapy (ADT) timing 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. [34] Crawford and associates also showed a benefit of early hormone therapy in patients with distant metastases. [35]

The Medical Research Council study found that overall survival was significantly prolonged in patients who were treated early. [36] This was a randomized study of 938 patients with locally advanced or asymptomatic metastatic prostate cancer in which individuals received treatment with orchiectomy or an LHRH agonist, either immediately or after symptoms occurred. Development of extraskeletal metastases, pathologic bone fractures, spinal cord compression, and ureteral obstruction was twice as common in the deferred-treatment group. [36]

In a study by the Eastern Cooperative Oncology Group (ECOG), immediate therapy significantly improved survival and reduced the risk of progression. [37] In this trial, 98 patients 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.

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