Maximal Testosterone Suppression In Prostate Cancer - Free Vs Total Testosterone

Testosterone remains a key target in the treatment of advanced prostate cancer. The relationship of free testosterone to prostate cancer treatment and outcomes remains largely unexplored. A consensus of prostate cancer experts was convened in 2013 to review current knowledge surrounding relationship of total and free testosterone to prostate cancer, discuss the free hormone hypothesis, and highlight future avenues for therapeutics. Free testosterone may better reflect prostate cancer tissue androgen levels than serum total testosterone concentration. Free testosterone deserves more research regarding its relation to clinical outcomes. © 2014 Elsevier Inc. All Rights Reserved.83612171222GSK; GlaxoSmithKlineSharifi, R., Bruskewitz, R.C., Gittleman, M.C., Leuprolide acetate 22.5 mg 12-week depot formulation in the treatment of patients with advanced prostate cancer (1996) Clin Ther, 18, pp. 647-657Oefelein, M.G., Feng, A., Scolieri, M.J., Reassessment of the definition of castrate levels of testosterone: Implications for clinical decision making (2000) Urology, 56, pp. 1021-1024Nishiyama, T., Serum testosterone levels after medical or surgical androgen deprivation: A comprehensive review of the literature (2014) Urol Oncol, 32, pp. 38e17-38e28Reis, L.O., Variations of serum testosterone levels in prostate cancer patients under LH-releasing hormone therapy: An open question (2012) Endocr Relat Cancer, 19, pp. 93-R98Wilke, T.J., Utley, D.J., Total testosterone, free-androgen index, calculated free testosterone, and free testosterone by analog RIA compared in hirsute women and in otherwise-normal women with altered binding of sex-hormone-binding globulin (1987) Clin Chem, 33, pp. 1372-1375Zlotta, A., Debruyne, F.M.J., Expert opinion on optimal testosterone control in prostate cancer (2005) Eur Urol Suppl, 4, pp. 37-41Morote, J., Esquena, S., Abascal, J.M., Behavior of free testosterone in patients with prostate cancer on androgen deprivation therapy (2005) Int J Biol Markers, 20, pp. 119-122Morote, J., Esquena, S., Abascal, J., Failure to maintain a suppressed level of serum testosterone during long-acting depot luteinizing hormone-releasing hormone agonist therapy in patients with advanced prostate cancer (2006) Urologia Int, 77, pp. 135-138Van Der Sluis, T.M., Bui, H.N., Meuleman, E.J.H., Lower testosterone levels with luteinizing hormone-releasing hormone agonist therapy than with surgical castration: New insights attained by mass spectrometry (2012) J Urol, 187, pp. 1601-1606Aschelter, A.M., Giacinti, S., Caporello, P., Marchetti, P., Genomic and epigenomic alterations in prostate cancer (2012) Front Endocrinol (Lausanne), 3, pp. 1-9Rove, K.O., Debruyne, F.M., Djavan, B., Role of testosterone in managing advanced prostate cancer (2012) Urology, 80, pp. 754-762Crawford, E.D., Rove, K.O., Incomplete testosterone suppression in prostate cancer (2010) N Engl J Med, 363, p. 1976Nishiyama, T., Hashimoto, Y., Takahashi, K., The influence of androgen deprivation therapy on dihydrotestosterone levels in the prostatic tissue of patients with prostate cancer (2004) Clin Cancer Res, 10, pp. 7121-7126Mendel, C.M., The free hormone hypothesis: A physiologically based mathematical model (1989) Endocr Rev, 10, pp. 232-274Matsumoto, A.M., Bremner, W.J., Serum testosterone assays - Accuracy matters (2004) J Clin Endocrinol Metab, 89, pp. 520-524Tombal, B., Berges, R., Optimal control of testosterone: A clinical case-based approach of modern androgen-deprivation therapy (2008) Eur Urol Suppl, 7, pp. 15-21Heidenreich, A., Porres, D., Epplen, R., Change of the LHRH analogue in progressive castration-refractory prostate cancer (2012) Urologe A, 51, pp. 1282-1287Silva, É.D., Ferreira, U., Matheus, W., Goserelin versus leuprolide in the chemical castration of patients with prostate cancer (2012) Int Urol Nephrol, 44, pp. 1039-1044Boccafoschi, C., Prostate cancer and androgen deprivation: Optimal castration? Prospects and developments (2011) Arch Ital Urol Androl, 83, pp. 63-66Novara, G., Galfano, A., Secco, S., Impact of surgical and medical castration on serum testosterone level in prostate cancer patients (2009) Urol Int, 82, pp. 249-255Perachino, M., Cavalli, V., Bravi, F., Testosterone levels in patients with metastatic prostate cancer treated with luteinizing hormone-releasing hormone therapy: Prognostic significance? (2010) BJU Int, 105, pp. 648-651Pickles, T., Tyldesley, S., (2011) Testosterone Breakthrough during LHRH Agonist Androgen Deprivation with Curative Radiation: Impact on PSA Kinetics and Subsequent Biochemical Outcomes, , Congress of the European Association of Urology Vienna, AustriaBlumberg, J.M., Kwon, E.O., Cheetham, T.C., Early development of castrate resistance varies with different dosing regimens of luteinizing hormone releasing hormone agonist in primary hormonal therapy for prostate cancer (2011) Urology, 77, pp. 412-416Hussain, M., Tangen, C.M., Berry, D.L., Intermittent versus continuous androgen deprivation in prostate cancer (2013) N Engl J Med, 368, pp. 1314-1325Klotz, L., O'Callaghan, C.J., Goldenberg, S.L., (2013) Nadir Testosterone on ADT Predicts for Time to Castrate Resistant Progression: A Secondary Analysis of the PR-7 Intermittent Vs. Continuous ADT Trial, , Canadian Urological Association Annual Meeting Niagra Falls, Ontario, CanadaDreicer, R., Gleave, M., Kibel, A.S., Targeting the androgen receptor - Theory and practice (2011) Urology, 78 (5 SUPPL.), pp. 482-S484Djavan, B., Eastham, J., Gomella, L., Testosterone in prostate cancer: The Bethesda consensus (2012) BJU Int, 110, pp. 344-352Attard, G., Richards, J., De Bono, J.S., New strategies in metastatic prostate cancer: Targeting the androgen receptor signaling pathway (2011) Clin Cancer Res, 17, pp. 1649-1657Scher, H.I., Fizazi, K., Saad, F., Increased survival with enzalutamide in prostate cancer after chemotherapy (2012) N Engl J Med, 367, pp. 1187-1197De Bono, J.S., Logothetis, C.J., Molina, A., Abiraterone and increased survival in metastatic prostate cancer (2011) N Engl J Med, 364, pp. 1995-2005Schulman, C.C., Irani, J., Morote, J., Testosterone measurement in patients with prostate cancer (2010) Eur Urol, 58, pp. 65-74Nelson, P.S., Molecular states underlying androgen receptor activation: A framework for therapeutics targeting androgen signaling in prostate cancer (2012) J Clin Oncol, 30, pp. 644-646Siddiqui, K., Abbas, F., Biyabani, S.R., Role of estrogens in the secondary hormonal manipulation of hormone refractory prostate cancer (2004) J Pak Med Assoc, 54, pp. 445-447Levell, M.J., Siddall, J.K., Rowe, E., Relationship of testosterone, sex hormone binding globulin, and calculated free testosterone to subsequent clinical progress in patients with carcinoma of the prostate treated with bilateral orchidectomy or estrogens (1987) Prostate, 11, pp. 17-21Karr, J.P., Wajsman, Z., Kirdani, R.Y., Effects of diethylstilbestrol and estramustine phosphate on serum sex hormone binding globulin and testosterone levels in prostate cancer patients (1980) J Urol, 124, pp. 232-236Oh, W.K., The evolving role of estrogen therapy in prostate cancer (2002) Clin Prostate Cancer, 1, pp. 81-89Clemons, J., Glode, L.M., Gao, D., Flaig, T.W., Low-dose diethylstilbestrol for the treatment of advanced prostate cancer (2013) Urol Oncol, 31, pp. 198-204Molina, A., Belldegrun, A., Novel therapeutic strategies for castration resistant prostate cancer: Inhibition of persistent androgen production and androgen receptor mediated signaling (2011) J Urol, 185, pp. 787-794Bellmunt, J., Oh, W.K., Castration-resistant prostate cancer: New science and therapeutic prospects (2010) Ther Adv Med Oncol, 2, pp. 189-207Attard, G., Reid, A.H.M., Yap, T., Phase i clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven (2008) J Clin Oncol, 26, pp. 4563-4571Aggarwal, R., Weinberg, V., Small, E.J., The mechanism of action of estrogen in castration-resistant prostate cancer: Clues from hormone levels (2009) Clin Genitourin Cancer, 7, pp. 71-E76Montgomery, B., Nelson, P.S., Vessella, R., Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer (2010) BMC Cancer, 10, p. 244Getzenberg, R.H., Coss, C.C., Hancock, M.L., GTx-758, an ERα agonist, reduces serum free testosterone lower than can be achieved by leuprolide with a significantly lower rate of hot flashes in men with advanced prostate cancer (2013) Eur Urol Suppl, 12, pp. 102-e103Petrylak, D.P., Tangen, C.M., Hussain, M.H., Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer (2004) N Engl J Med, 351, pp. 1513-1520Yu, E.Y., Gittelman, M., Keane, T.E., Effect of GTx-758, an ERα agonist, on serum-free testosterone and serum PSA in men with advanced prostate cancer (2013) J Clin Oncol (Meeting Abstracts), 31 (SUPPL. 6). , http://meetinglibrary.asco.org/content/107554-134, Abstract 104. Available at Accessed September 4, 2013Takizawa, I., Nishiyama, T., Hara, N., Serum prostate-specific antigen levels reflect the androgen milieu in patients with localized prostate cancer receiving androgen deprivation therapy: Tumor malignant potential and androgen milieu (2010) Prostate, 70, pp. 1395-1401Dias, E., Mendonça, G., Zani, E., Reis, L.O., (2013) No Equivalence and Sufficiency of Leuprolide and Goserelin Acetates to Suppress Serum Total Testosterone and PSA Levels, , Congress of the Société Internationale d'Urologie Vancouver, CanadaRosner, W., Vesper, H., Toward excellence in testosterone testing: A consensus statement (2010) J Clin Endocrinol Metab, 95, pp. 4542-4548. , on behalf of The Endocrine Society the endorsing organization