Skip to main content
Erschienen in: Der Urologe 11/2015

01.11.2015 | Übersichten

Testosteron im Management des metastasierten Prostatakarzinoms

verfasst von: Prof. Dr. J.M. Wolff, H.P. Schmid

Erschienen in: Die Urologie | Ausgabe 11/2015

Einloggen, um Zugang zu erhalten

Zusammenfassung

Das Prostatakarzinom (PCa) ist der häufigste maligne Tumor und die dritthäufigste Krebstodesursache bei Männern in Deutschland. Die Funktion der Prostata wird durch Testosteron bzw. dessen Metabolit Dihydrotestosteron maßgeblich beeinflusst. Über die Bedeutung von Testosteron beim metastasierten kastrationsresistenten Prostatakarzinom (mCRPC) besteht jedoch vielfach Unklarheit. Lange Zeit wurde die Korrelation des Testosteronspiegels mit der Entstehung oder der Progredienz des PCa über die Androgenhypothese erklärt. Neuere Daten haben die Androgenhypothese jedoch infrage gestellt. Ein hoher Testosteronspiegel begünstigt die Entstehung oder Progredienz eines Prostatakarzinoms nicht und ein niedriger Testosteronspiegel wirkt nicht protektiv. Die Relevanz des Testosteronspiegels beim mCRPC zeigen u. a. die Ergebnisse aus den klinischen Zulassungsstudien mit neuen Substanzen wie Abirateronacetat und Enzalutamid. Die Hinweise auf einen prognostischen Charakter des Testosteronspiegels mehren sich.
Literatur
1.
Zurück zum Zitat Attard G, Reid AH, A’Hern R et al (2009) Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol 27:3742–3748PubMedCentralCrossRefPubMed Attard G, Reid AH, A’Hern R et al (2009) Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol 27:3742–3748PubMedCentralCrossRefPubMed
2.
Zurück zum Zitat Barrie SE, Haynes BP, Potter GA et al (1997) Biochemistry and pharmacokinetics of potent non-steroidal cytochrome P450(17alpha) inhibitors. J Steroid Biochem Mol Biol 60:347–351CrossRefPubMed Barrie SE, Haynes BP, Potter GA et al (1997) Biochemistry and pharmacokinetics of potent non-steroidal cytochrome P450(17alpha) inhibitors. J Steroid Biochem Mol Biol 60:347–351CrossRefPubMed
3.
Zurück zum Zitat Calof OM, Singh AB, Lee ML et al (2005) Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 60:1451–1457CrossRefPubMed Calof OM, Singh AB, Lee ML et al (2005) Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 60:1451–1457CrossRefPubMed
4.
Zurück zum Zitat Chen CD, Welsbie DS, Tran C et al (2004) Molecular determinants of resistance to antiandrogen therapy. Nat Med 10:33–39CrossRefPubMed Chen CD, Welsbie DS, Tran C et al (2004) Molecular determinants of resistance to antiandrogen therapy. Nat Med 10:33–39CrossRefPubMed
5.
Zurück zum Zitat Cooper CS, Perry PJ, Sparks AE et al (1998) Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men. J Urol 159:441–443CrossRefPubMed Cooper CS, Perry PJ, Sparks AE et al (1998) Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men. J Urol 159:441–443CrossRefPubMed
6.
Zurück zum Zitat Crawford ED, Eisenberger MA, McLeod DG et al (1989) A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 321:419–424CrossRefPubMed Crawford ED, Eisenberger MA, McLeod DG et al (1989) A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 321:419–424CrossRefPubMed
7.
Zurück zum Zitat Efstathiou E, Titus M, Wen S et al (2014) Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol Efstathiou E, Titus M, Wen S et al (2014) Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol
8.
Zurück zum Zitat Fizazi K, Scher HI, Molina A et al (2012) Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 13:983–992CrossRefPubMed Fizazi K, Scher HI, Molina A et al (2012) Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 13:983–992CrossRefPubMed
9.
Zurück zum Zitat Geller J, Albert JD, Nachtsheim DA, Loza D (1984) Comparison of prostatic cancer tissue dihydrotestosterone levels at the time of relapse following orchiectomy or estrogen therapy. J Urol 132:693–696PubMed Geller J, Albert JD, Nachtsheim DA, Loza D (1984) Comparison of prostatic cancer tissue dihydrotestosterone levels at the time of relapse following orchiectomy or estrogen therapy. J Urol 132:693–696PubMed
10.
Zurück zum Zitat Halabi S, Small EJ, Kantoff PW et al (2003) Prognostic model for predicting survival in men with hormone- refractory metastatic prostate cancer. J Clin Oncol 21:1232–1237CrossRefPubMed Halabi S, Small EJ, Kantoff PW et al (2003) Prognostic model for predicting survival in men with hormone- refractory metastatic prostate cancer. J Clin Oncol 21:1232–1237CrossRefPubMed
11.
Zurück zum Zitat Holzbeierlein J, Lal P, LaTulippe E et al (2004) Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am J Pathol 164:217–227PubMedCentralCrossRefPubMed Holzbeierlein J, Lal P, LaTulippe E et al (2004) Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. Am J Pathol 164:217–227PubMedCentralCrossRefPubMed
12.
Zurück zum Zitat Huggins C, Stevens RE, Hodges CV (1941) Studies on prostatic cancer II. The effects of castration on advanced carcinoma of the prostate. Arch Surg 43:209–223CrossRef Huggins C, Stevens RE, Hodges CV (1941) Studies on prostatic cancer II. The effects of castration on advanced carcinoma of the prostate. Arch Surg 43:209–223CrossRef
13.
Zurück zum Zitat Isbarn H, Pinthus JH, Marks LS et al (2009) Testosterone and prostate cancer: revisiting old paradigms. Eur Urol 56:48–56CrossRefPubMed Isbarn H, Pinthus JH, Marks LS et al (2009) Testosterone and prostate cancer: revisiting old paradigms. Eur Urol 56:48–56CrossRefPubMed
14.
Zurück zum Zitat Jarman M, Barrie SE, Llera JM (1998) The 16,17-double bond is needed for irreversible inhibition of human cytochrome p45017alpha by abiraterone (17-(3-pyridyl)androsta-5, 16- dien-3beta-ol) and related steroidal inhibitors. J Med Chem 41:5375–5381CrossRefPubMed Jarman M, Barrie SE, Llera JM (1998) The 16,17-double bond is needed for irreversible inhibition of human cytochrome p45017alpha by abiraterone (17-(3-pyridyl)androsta-5, 16- dien-3beta-ol) and related steroidal inhibitors. J Med Chem 41:5375–5381CrossRefPubMed
15.
Zurück zum Zitat Jastrzebska S, Walczak-Jedrzejowska R, Kramek E et al (2014) Relationship between sexual function, body mass index and levels of sex steroid hormones in young men. Endokrynol Pol 65:203–209CrossRefPubMed Jastrzebska S, Walczak-Jedrzejowska R, Kramek E et al (2014) Relationship between sexual function, body mass index and levels of sex steroid hormones in young men. Endokrynol Pol 65:203–209CrossRefPubMed
16.
Zurück zum Zitat Khera M, Crawford D, Morales A et al (2014) A new era of testosterone and prostate cancer: from physiology to clinical implications. Eur Urol 65:115–123CrossRefPubMed Khera M, Crawford D, Morales A et al (2014) A new era of testosterone and prostate cancer: from physiology to clinical implications. Eur Urol 65:115–123CrossRefPubMed
17.
Zurück zum Zitat Kim J, Coetzee GA (2004) Prostate specific antigen gene regulation by androgen receptor. J Cell Biochem 93:233–241CrossRefPubMed Kim J, Coetzee GA (2004) Prostate specific antigen gene regulation by androgen receptor. J Cell Biochem 93:233–241CrossRefPubMed
18.
Zurück zum Zitat Klotz L, Nabid A, Higano C et al (2014) Effect of dutasteride in men receiving intermittent androgen ablation therapy: the AVIAS trial. Can Urol Assoc J 8:E789–E794PubMedCentralCrossRefPubMed Klotz L, Nabid A, Higano C et al (2014) Effect of dutasteride in men receiving intermittent androgen ablation therapy: the AVIAS trial. Can Urol Assoc J 8:E789–E794PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat Klotz L, O’Callaghan C, Dearnaley D et al (2014) Nadir testosterone (T) on ADT predicts for time to castrate resistant progression: a secondary analysis of the PR-7 intermittent vs continuous ADT trial. In: 29th Annual European Association of Urology (EAU) Congress. Stockholm Klotz L, O’Callaghan C, Dearnaley D et al (2014) Nadir testosterone (T) on ADT predicts for time to castrate resistant progression: a secondary analysis of the PR-7 intermittent vs continuous ADT trial. In: 29th Annual European Association of Urology (EAU) Congress. Stockholm
20.
Zurück zum Zitat Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft DK, AWMF) (2014) Konsultationsfassung: Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 2.2; AWMF Registernummer: 034/022OL. http://leitlinienprogramm-onklogie.de/Leitlinien.7.0.html Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft DK, AWMF) (2014) Konsultationsfassung: Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 2.2; AWMF Registernummer: 034/022OL. http://​leitlinienprogra​mm-onklogie.​de/​Leitlinien.​7.​0.​html
21.
Zurück zum Zitat Miyatake A, Morimoto Y, Oishi T et al (1980) Circadian rhythm of serum testosterone and its relation to sleep: comparison with the variation in serum luteinizing hormone, prolactin, and cortisol in normal men. J Clin Endocrinol Metab 51:1365–1371CrossRefPubMed Miyatake A, Morimoto Y, Oishi T et al (1980) Circadian rhythm of serum testosterone and its relation to sleep: comparison with the variation in serum luteinizing hormone, prolactin, and cortisol in normal men. J Clin Endocrinol Metab 51:1365–1371CrossRefPubMed
22.
Zurück zum Zitat Molina A, Belldegrun A (2011) Novel therapeutic strategies for castration resistant prostate cancer: inhibition of persistent androgen production and androgen receptor mediated signaling. J Urol 185:787–794CrossRefPubMed Molina A, Belldegrun A (2011) Novel therapeutic strategies for castration resistant prostate cancer: inhibition of persistent androgen production and androgen receptor mediated signaling. J Urol 185:787–794CrossRefPubMed
23.
Zurück zum Zitat Morgentaler A (2006) Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 50:935–939CrossRefPubMed Morgentaler A (2006) Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 50:935–939CrossRefPubMed
24.
Zurück zum Zitat Morgentaler A, Traish AM (2009) Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 55:310–320CrossRefPubMed Morgentaler A, Traish AM (2009) Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 55:310–320CrossRefPubMed
25.
Zurück zum Zitat Mostaghel EA, Page ST, Lin DW et al (2007) Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res 67:5033–5041CrossRefPubMed Mostaghel EA, Page ST, Lin DW et al (2007) Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res 67:5033–5041CrossRefPubMed
26.
Zurück zum Zitat Mottet N, Bastian PJ, Bellmunt J et al (2014) EAU guidelines on prostate cancer. http://www.uroweb.org Mottet N, Bastian PJ, Bellmunt J et al (2014) EAU guidelines on prostate cancer. http://​www.​uroweb.​org
27.
Zurück zum Zitat Muller RL, Gerber L, Moreira DM et al (2012) Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the reduction by dutasteride of prostate cancer events trial. Eur Urol 62:757–764CrossRefPubMed Muller RL, Gerber L, Moreira DM et al (2012) Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the reduction by dutasteride of prostate cancer events trial. Eur Urol 62:757–764CrossRefPubMed
28.
Zurück zum Zitat Rathkopf DE, Smith MR, Bono JS de et al (2014) Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Eur Urol 66(5):815–825PubMedCentralCrossRefPubMed Rathkopf DE, Smith MR, Bono JS de et al (2014) Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Eur Urol 66(5):815–825PubMedCentralCrossRefPubMed
29.
Zurück zum Zitat Roder MA, Christensen IJ, Berg KD et al (2012) Serum testosterone level as a predictor of biochemical failure after radical prostatectomy for localized prostate cancer. BJU Int 109:520–524CrossRefPubMed Roder MA, Christensen IJ, Berg KD et al (2012) Serum testosterone level as a predictor of biochemical failure after radical prostatectomy for localized prostate cancer. BJU Int 109:520–524CrossRefPubMed
30.
Zurück zum Zitat Rosner W, Auchus RJ, Azziz R et al (2007) Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 92:405–413CrossRefPubMed Rosner W, Auchus RJ, Azziz R et al (2007) Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 92:405–413CrossRefPubMed
31.
Zurück zum Zitat Rosner W, Vesper H (2008) Preface. CDC workshop report improving steroid hormone measurements in patient care and research translation. Steroids 73:1285CrossRefPubMed Rosner W, Vesper H (2008) Preface. CDC workshop report improving steroid hormone measurements in patient care and research translation. Steroids 73:1285CrossRefPubMed
32.
Zurück zum Zitat Rosner W, Vesper H (2010) Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metab 95:4542–4548CrossRefPubMed Rosner W, Vesper H (2010) Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metab 95:4542–4548CrossRefPubMed
33.
Zurück zum Zitat Ryan CJ (2014) Final analysis of phase 3 COU-AA-302 study. In: European Society for Medical Oncology (ESMO). Madrid, p abstract 753O Ryan CJ (2014) Final analysis of phase 3 COU-AA-302 study. In: European Society for Medical Oncology (ESMO). Madrid, p abstract 753O
34.
Zurück zum Zitat Ryan CJ, Cheng ML (2013) Abiraterone acetate for the treatment of prostate cancer. Expert Opin Pharmacother 14:91–96CrossRefPubMed Ryan CJ, Cheng ML (2013) Abiraterone acetate for the treatment of prostate cancer. Expert Opin Pharmacother 14:91–96CrossRefPubMed
35.
Zurück zum Zitat Ryan CJ, Molina A, Li J et al (2013) Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. J Clin Oncol 31:2791–2798CrossRefPubMed Ryan CJ, Molina A, Li J et al (2013) Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. J Clin Oncol 31:2791–2798CrossRefPubMed
36.
Zurück zum Zitat Ryan CJ, Peng W, Kheoh T et al (2014) Androgen dynamics and serum PSA in patients treated with abiraterone acetate. Prostate Cancer Prostatic Dis 17:192–198PubMedCentralCrossRefPubMed Ryan CJ, Peng W, Kheoh T et al (2014) Androgen dynamics and serum PSA in patients treated with abiraterone acetate. Prostate Cancer Prostatic Dis 17:192–198PubMedCentralCrossRefPubMed
37.
38.
Zurück zum Zitat Scher HI, Halabi S, Tannock I et al (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26:1148–1159PubMedCentralCrossRefPubMed Scher HI, Halabi S, Tannock I et al (2008) Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 26:1148–1159PubMedCentralCrossRefPubMed
39.
Zurück zum Zitat Shaneyfelt T, Husein R, Bubley G, Mantzoros CS (2000) Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol 18:847–853PubMed Shaneyfelt T, Husein R, Bubley G, Mantzoros CS (2000) Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol 18:847–853PubMed
40.
Zurück zum Zitat Tindall DJ, Rittmaster RS (2008) The rationale for inhibiting 5alpha-reductase isoenzymes in the prevention and treatment of prostate cancer. J Urol 179:1235–1242PubMedCentralCrossRefPubMed Tindall DJ, Rittmaster RS (2008) The rationale for inhibiting 5alpha-reductase isoenzymes in the prevention and treatment of prostate cancer. J Urol 179:1235–1242PubMedCentralCrossRefPubMed
41.
Zurück zum Zitat Titus MA, Schell MJ, Lih FB et al (2005) Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin Cancer Res 11:4653–4657CrossRefPubMed Titus MA, Schell MJ, Lih FB et al (2005) Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin Cancer Res 11:4653–4657CrossRefPubMed
42.
Zurück zum Zitat Traish AM, Miner MM, Morgentaler A, Zitzmann M (2011) Testosterone deficiency. Am J Med 124:578–587CrossRefPubMed Traish AM, Miner MM, Morgentaler A, Zitzmann M (2011) Testosterone deficiency. Am J Med 124:578–587CrossRefPubMed
43.
Zurück zum Zitat Wang C, Catlin DH, Demers LM et al (2004) Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 89:534–543CrossRefPubMed Wang C, Catlin DH, Demers LM et al (2004) Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 89:534–543CrossRefPubMed
Metadaten
Titel
Testosteron im Management des metastasierten Prostatakarzinoms
verfasst von
Prof. Dr. J.M. Wolff
H.P. Schmid
Publikationsdatum
01.11.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Die Urologie / Ausgabe 11/2015
Print ISSN: 2731-7064
Elektronische ISSN: 2731-7072
DOI
https://doi.org/10.1007/s00120-015-3813-4

Weitere Artikel der Ausgabe 11/2015

Der Urologe 11/2015 Zur Ausgabe

Berufspolitik BDU

Berufspolitik BDU

CME Zertifizierte Fortbildung

Priapismus

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.