Prognostic Significance of Monitoring Serum Testosterone in Primary ADT for Prostate Cancer

  • Shinichi SakamotoEmail author


In the 1940s, Charles Huggins et al. published a paper describing the clinical benefits of surgical castration and estrogen administration in prostate cancer patients. Later, Huggins was awarded the Nobel Prize to acknowledge the importance of his findings in this field. Since that time, androgen deprivation therapy (ADT) remains a standard therapy for metastatic prostate cancer. Although the main aim of ADT is the control of the serum testosterone (TST) level below the castration level, a series of evidences indicated the clinical significance of controlling the serum TST level even below the standard castration level. In terms of TST production, multiple pathways exist, such as “classical pathway” and “backdoor pathway.” Upregulation of such pathways, even inside the tumor, contributes to the acquisition of castration resistance. Thus, monitoring serum TST levels provides us further understanding of tumor behavior in individual patients. In this chapter, we will discuss the prognostic significance of monitoring serum TST levels in primary ADT for prostate cancer.


Androgen deprivation therapy Testosterone Prostate cancer LHRH analog GnRH antagonist 


  1. 1.
    Regis L, Iztueta I, Servian P, Kosntantinidis C, Planas J, Celma A, et al. Free serum testosterone versus total testosterone as surrogate marker for the clinical benefit of androgen suppression in prostate cancer patients. J Urol. 2014;191(4):E856-E.CrossRefGoogle Scholar
  2. 2.
    Hoffman MA, DeWolf WC, Morgentaler A. Is low serum free testosterone a marker for high grade prostate cancer? J Urol. 2000;163(3):824–7.CrossRefGoogle Scholar
  3. 3.
    Schatzl G, Madersbacher S, Thurridl T, Waldmuller J, Kramer G, Haitel A, et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate. 2001;47(1):52–8.CrossRefGoogle Scholar
  4. 4.
    Neuzillet Y, Pichon A, Ghoneim T, Lebret T, Radulescu C, Molinie V, et al. High incidence of predominant gleason pattern 4 is associated with low testosterone serum level in localized prostate cancer: an update with 937 patients. J Urol. 2014;191(4):E412-E.CrossRefGoogle Scholar
  5. 5.
    Isom-Batz G, Bianco FJ, Kattan MW, Mulhall JP, Lilja H, Eastham JA. Testosterone as a predictor of pathological stage in clinically localized prostate cancer. J Urol. 2005;173(6):1935–7.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Suzuki H, Yano M, Imamoto T, Kato T, Komiya A, Naya Y, et al. Pretreatment serum testosterone level can improve the efficiency of prostate cancer screening. J. Urology. 2007;177(4):573.CrossRefGoogle Scholar
  7. 7.
    Massengill JC, Sun L, Moul JW, HY W, McLeod DG, Amling C, et al. Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. J Urol. 2003;169(5):1670–5.CrossRefPubMedGoogle Scholar
  8. 8.
    Yamamoto S, Yonese J, Kawakami S, Ohkubo Y, Tatokoro M, Komai Y, et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol. 2007;52(3):696–701.CrossRefGoogle Scholar
  9. 9.
    Bertaglia V, Tucci M, Fiori C, Aroasio E, Poggio M, Buttigliero C, et al. Effects of serum testosterone levels after 6 months of androgen deprivation therapy on the outcome of patients with prostate cancer. Clin Genitourin Cancer. 2013;11(3):325–30. e1CrossRefPubMedGoogle Scholar
  10. 10.
    Morote J, Orsola A, Planas J, Trilla E, Raventos CX, Cecchini L, et al. Redefining clinically significant castration levels in patients with prostate cancer receiving continuous androgen deprivation therapy. J Urol. 2007;178(4 Pt 1):1290–5.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Tombal B. The importance of testosterone control in prostate cancer. Eur Urol Suppl. 2007;6(15):834–9.CrossRefGoogle Scholar
  12. 12.
    van der Sluis TM, Bui HN, Meuleman EJ, Heijboer AC, Hartman JF, van Adrichem N, et al. Lower testosterone levels with luteinizing hormone-releasing hormone agonist therapy than with surgical castration: new insights attained by mass spectrometry. J Urol. 2012;187(5):1601–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Perachino M, Cavalli V, Bravi F. Testosterone levels in patients with metastatic prostate cancer treated with luteinizing hormone-releasing hormone therapy: prognostic significance? BJU Int. 2010;105(5):648–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Yasuda Y, Fujii Y, Yuasa T, Yamamoto S, Yonese J, Fukui I. Do testosterone levels have prognostic significance in patients with metastatic prostate cancer treated with combined androgen blockade? Int J Urol. 2015;22(1):132–3.CrossRefPubMedGoogle Scholar
  15. 15.
    Kamada S, Sakamoto S, Ando K, Muroi A, Fuse M, Kawamura K, et al. Nadir testosterone after long-term follow-up predicts prognosis of prostate cancer patients treated with combined androgen blockade. J Urol. 2015;193(4):E1086-E.CrossRefGoogle Scholar
  16. 16.
    Klotz L, O’Callaghan C, Ding K, Toren P, Dearnaley D, Higano CS. Nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: a secondary analysis of the PR-7 trial of intermittent versus continuous ADT (vol 33, pg 1151, 2015). J Clin Oncol. 2016;34(16):1965.CrossRefGoogle Scholar
  17. 17.
    Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, et al. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008;102(11):1531–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Klotz L, Miller K, Crawford ED, Shore N, Tombal B, Karup C, et al. Disease control outcomes from analysis of pooled individual patient data from five comparative randomised clinical trials of degarelix versus luteinising hormone-releasing hormone agonists. Eur Urol. 2014;66(6):1101–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Montgomery RB, Mostaghel EA, Vessella R, Hess DL, Kalhorn TF, Higano CS, et al. Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth. Cancer Res. 2008;68(11):4447–54.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Locke JA, Guns ES, Lubik AA, Adomat HH, Hendy SC, Wood CA, et al. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Res. 2008;68(15):6407–15.CrossRefGoogle Scholar
  21. 21.
    Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60.CrossRefPubMedGoogle Scholar
  22. 22.
    James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338–51.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Qu F, Xie W, Nakabayashi M, Zhang H, Jeong SH, Wang X, et al. Association of AR-V7 and prostate-specific antigen RNA levels in blood with efficacy of abiraterone acetate and enzalutamide treatment in men with prostate cancer. Clin Cancer Res. 2017;23(3):726–34.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Chiba University Graduate School of MedicineChibaJapan

Personalised recommendations