Androgen deprivation therapy (ADT) is foundational in the management of advanced prostate cancer (PCa) and has benefitted from a recent explosion in scientific advances. These include approval of new therapies that suppress testosterone (T) levels or inactivate its function, improvements in diagnostic and assay technologies, identification of lower therapeutic targets for T, discovery of the relevance of germline genetic mutations and identification of the benefits of sequential and combination therapies.
This review discusses the clinical profiles of the most up-to-date options for ADT, best practices for managing patients with advanced PCa and future directions in therapy.
Modern assay technologies reveal that bilateral orchiectomy results in a serum T level of approximately 15 ng/dL as compared to the historical definition of castration of T < 50 ng/dL. Evidence shows that lowering T levels to <20 ng/dL improves patient survival and delays disease progression. Routine monitoring of T in addition to prostate-specific antigen throughout treatment is important to ensure continuing efficacy of T suppression. New drugs that inhibit androgen signaling in combination with traditional ADT suppress T activity to near zero and have significantly improved patient survival. When personalizing ADT regimens physicians should consider a number of factors including initiation and duration of ADT, monitoring of T levels and PSA, the possibility of switching monotherapies if a patient does not achieve adequate T suppression, and consideration of intermittent vs. continuous ADT according to patients' lifestyles, comorbidities, risk factors and tolerance to treatment.
Prostate cancer and prostatic diseases. 2018 Aug 21 [Epub ahead of print]
E David Crawford, Axel Heidenreich, Nathan Lawrentschuk, Bertrand Tombal, Antonio C L Pompeo, Arturo Mendoza-Valdes, Kurt Miller, Frans M J Debruyne, Laurence Klotz
University of Colorado School of Medicine, Denver, CO, USA. ., University of Cologne, Cologne, Germany., University of Melbourne, Melbourne, Australia., Cliniques Universitaires Saint-Luc, Brussels, Belgium., Faculdade de Medicina do ABC, São Paulo, Brazil., Hospital Médica Sur, Ciudad de México, Mexico., Charité Universitätsmedizin Berlin, Berlin, Germany., Andros Mannenkliniek, Arnhem, Netherlands., Sunnybrook Health Sciences Centre, Toronto, Canada.