Hormone-refractory (D3) prostate cancer: refining the concept

Urology. 1995 Aug;46(2):142-8. doi: 10.1016/s0090-4295(99)80182-4.


Objectives: A wide range of responses have been reported to second-line hormonal therapies, including corticosteroids and the withdrawal of antiandrogens in patients with hormone-refractory prostate cancers. This suggested the need to classify patients on the basis of hormonal sensitivity. A schema was developed by assessing the differences in entry criteria in relation to outcomes for clinical protocols with hydrocortisone alone or in combination with other agents for patients who had progressed after primary hormone therapy.

Methods: Published clinical trials of patients who had progressed after primary hormone treatment, which included glucocorticoids, were retrieved from Medline listings. The trials included patients treated with hydrocortisone alone, hydrocortisone and aminoglutethimide, hydrocortisone plus suramin, dexamethasone, and prednisone alone or in combination with chemotherapy.

Results: The definitions used for refractory disease ranged from none, to "progression", to "unsuccessful second medical or surgical castration. "None of the trials included a definition for hormone-refractory disease based on objective criteria. Details were lacking on most trials with respect to the response to and specific types of hormonal therapies. Furthermore, few trials controlled for the potential contribution of the "flutamide withdrawal syndrome" on outcome.

Conclusions: The term "hormone-refractory" prostate cancer has evolved to include patients with a spectrum of diseases. As utilized in clinical trials of second-line hormonal therapies, patients who have received one and as many as six different treatments have been included in the same study. A new classification of patients based on hormonal sensitivity is proposed to recognize that androgen-independent proliferation, progression of disease despite castrate levels of testosterone, does not necessarily mean that a tumor is refractory to hormonal manipulations. Future trials in hormonally relapsed patients must include more details of the hormonal therapies utilized.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aminoglutethimide / therapeutic use
  • Clinical Trials as Topic
  • Cortisone / analogs & derivatives
  • Cortisone / therapeutic use
  • Dexamethasone / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Hydrocortisone / therapeutic use
  • Male
  • Medroxyprogesterone / therapeutic use
  • Mitoxantrone / therapeutic use
  • Neoplasm Recurrence, Local*
  • Prednisone / therapeutic use
  • Prostatic Neoplasms / classification*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / epidemiology
  • Randomized Controlled Trials as Topic
  • Suramin / therapeutic use
  • Treatment Outcome


  • Aminoglutethimide
  • Suramin
  • Dexamethasone
  • Mitoxantrone
  • Medroxyprogesterone
  • Cortisone
  • Prednisone
  • Hydrocortisone