Testosterone in prostate cancer: the Bethesda consensus

BJU Int. 2012 Aug;110(3):344-52. doi: 10.1111/j.1464-410X.2011.10719.x. Epub 2011 Nov 30.

Abstract

Objective: • Androgen stimulation of prostate cancer (PCa) cells has been extensively studied. The increasing trend of using serum testosterone as an absolute surrogate for castration state means that the diagnostic measurement of testosterone and the values potentially influencing prognosis must be better understood. This is especially important when PCa progresses from an endocrine to an intracrine status.

Patients and methods: • We performed a literature review using the MEDLINE database for publications on: (i) hormonal changes with androgen deprivation therapy (ADT); (ii) monitoring hormonal therapy with testosterone measurement; (iii) the efficacy of intermittent androgen deprivation (IAD) compared with continuous androgen deprivation; (iv) the underlying mechanisms of castration-resistance; and (v) novel treatments for castration-resistant PCa (CRPCa).

Results: • The optimum serum castration levels to be achieved with ADT are still debated. Recently, the 50 ng/dL threshold has been questioned because of reports indicating worse outcomes when levels between 20 and 50 ng/dL were studied. Instead, a 20 ng/dL threshold for serum testosterone after ADT in patients with advanced prostate cancer was recommended.

Conclusion: • Understanding the mechanisms of androgen biosynthesis relating to PCa as well as prognostic implications might achieve a consensus regarding the role of ADT for both the androgen-sensitive and -insensitive disease state.

Publication types

  • Review

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Androgens / biosynthesis
  • Cholestenone 5 alpha-Reductase / metabolism
  • Consensus
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Disease Progression
  • Humans
  • Male
  • Metabolic Networks and Pathways / physiology
  • Neoplastic Stem Cells / physiology
  • Orchiectomy
  • Practice Guidelines as Topic
  • Prognosis
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Testosterone / blood
  • Testosterone / metabolism*
  • Therapies, Investigational

Substances

  • Androgen Antagonists
  • Androgens
  • Cyclooxygenase 2 Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Testosterone
  • Cholestenone 5 alpha-Reductase