Androgen deprivation therapy as backbone therapy in the management of prostate cancer

Abstract

Androgen deprivation therapy (ADT) is well established as a backbone therapy for metastatic prostate cancer (mPCa), and both European and American guidelines emphasize the importance of maintaining ADT after progression to metastatic castration-resistant prostate cancer (CRPC). However, the use of ADT varies widely in clinical practice despite these recommendations. Both research and development of increasingly precise assay technologies have improved our understanding of androgen production and signaling, and the recent data have suggested that a new serum testosterone cutoff value of <0.7 nmol/L should be employed. Most clinical trials to date have used the historical 1.7 nmol/L cutoff, but the <0.7 nmol/L cutoff has been associated with improved patient outcomes. Combining agents with different mechanisms of action to achieve intense androgen blockade may improve survival both before and after progression to CRPC. Data suggest that this intensive approach to androgen deprivation could delay the transition to CPRC and hence improve survival dramatically. Various combinations of backbone ADT with chemotherapy or radiotherapy are under investigation. Administration of ADT is established in patients with intermediate or high-risk localized prostate cancer (PCa) receiving radiotherapy with curative intent. This article reviews the current and potential role of ADT as backbone therapy in both hormone-sensitive PCa and CRPC with a focus on mPCa.

Keywords: ADT; androgen deprivation therapy; chemotherapy; prostate cancer; radiotherapy; treatment guidelines.

Figure 1

Treatment patterns across Europe for patients with mCRPC receiving their first chemotherapy regimen. Note: Reproduced from Sternberg CN, Baskin-Bey ES, Watson M, Worsfold A, Rider A, Tombal B. Treatment patterns and characteristics of European patients with castration-resistant prostate cancer. BMC Urol. 2013;13:58. © Sternberg et al; licensee BioMed Central Ltd. 2013. Abbreviations: AA, antiandrogen; C, chemotherapy; LHRH, luteinizing hormone-releasing hormone; mCRPC, metastatic castration-resistant prostate cancer.

Figure 2

Kaplan–Meier estimates of OS following six cycles of docetaxel at the start of ADT versus ADT alone in the CHAARTED study. Notes: The median duration of follow-up was 28.9 months among all patients. From N Engl J Med. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. 373(8):737–746. Copyright © 2015 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Abbreviations: ADT, androgen deprivation therapy; CHAARTED, Androgen Ablation Therapy with or without Chemotherapy in Treating Patients with Metastatic Prostate Cancer; HR, hazard ratio; OS, overall survival.

Figure 3

TPP with standard androgen ablation therapy versus three cycles of systemic chemotherapy in a Phase III trial in advanced PCa. Notes: (A) TTP by assigned treatment. (B) TTP by treatment, stratified by disease volume at entry. Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved. Millikan RE, Wen S, Pagliaro LC, et al. Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol. 2008;26(36):5936–5942. Abbreviations: PCa, prostate cancer; PFS, progression-free survival; TTP, time to progression.