Abstract
BackgroundAndrogen 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.MethodsThis 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.Results and conclusionsModern 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.
Highlights
Adenocarcinoma of the prostate is the most common type of cancer afflicting men in the United States, with more than 11.6% of males being diagnosed with prostate cancer (PCa) at some point during their lifetime [1,2,3]
Limited headto-head studies of LHRH agonists have not generally demonstrated differences in extent of T suppression; improved clinical outcomes have been identified in patients achieving T levels of
It has been observed from comparative studies with abarelix that LHRH agonists cause a surge in serum FSH on day 2 followed by a decline, whereas the antagonist led to a rapid and sustained decrease [91]
Summary
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
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