Testosterone in prostate cancer: the Bethesda consensus

• Published in: BJU international Vol. 110; no. 3; pp. 344 - 352
• Main Authors: Djavan, Bob, Eastham, James, Gomella, Leonard, Tombal, Bertrand, Taneja, Samir, Dianat, Seyed Saeid, Kazzazi, Amir, Shore, Neal, Abrahamsson, Per‐Anders, Cheetham, Philippa, Moul, Judd, Lepor, Herbert, Crawford, E. David
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Aging; Androgen Antagonists - therapeutic use; Androgens; Androgens - biosynthesis; Biological and medical sciences; castration level; castration resistance; Cholestenone 5 alpha-Reductase - metabolism; Clinical Medicine; Consensus; Cyclooxygenase 2 Inhibitors - pharmacology; Disease Progression; Gynecology. Andrology. Obstetrics; hormonal therapy; Humans; intermittent androgen deprivation; Klinisk medicin; Male; Male genital diseases; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Men; Metabolic Networks and Pathways - physiology; Neoplastic Stem Cells - physiology; Nephrology. Urinary tract diseases; Orchiectomy; Practice Guidelines as Topic; Prognosis; Prostate cancer; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Proto-Oncogene Proteins c-bcl-2 - metabolism; serum testosterone; Testosterone; Testosterone - blood; Testosterone - metabolism; Therapies, Investigational; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Nephrology; Prostate disease; Hormone therapy; Urology; castration level; Castration; Intermittent; Androgen deprivation; intermittent androgen deprivation; Serum; Testicular hormone; serum testosterone; Male genital diseases; Urinary system disease; Androgen deprivation therapy; Androgen; castration resistance; Malignant tumor; Consensus; Resistance; hormonal therapy; Testosterone; Sex steroid hormone; Prostate cancer; Cancer
• ISSN: 1464-4096; 1464-410X; 1464-410X
• DOI: 10.1111/j.1464-410X.2011.10719.x

What's known on the subject? and What does the study add? Androgen stimulation of prostate cancer (PCa) cells has been the basis for extensive studies evaluating the role of androgen in PCa but the diagnostic measurement of androgen as well as androgen values that potentially influence prognosis are unclear in patients with PCa. The 50 ng/dL threshold has been questioned as a result of reports indicating worse outcomes for levels between 20 and 50 ng/dL. Instead, a 20 ng/dL threshold for serum testosterone after androgren deprivation therapy in patients with advanced PCa was recommended. 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.