1. Kane, Terri DNAP, CRNA


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What are the effects of early versus late androgen suppression therapy (AST) for advanced prostate cancer?



A systematic review of 10 randomized controlled trials (RCTs) involving over 10,500 participants.



Prostate cancer is a leading cause of death in men worldwide. If the cancer is localized to the prostate gland, cures can be obtained through radiation or surgery. If it has metastasized to the bones or lymph nodes, a cure is not obtainable. However, hormonal treatment, which lowers androgen levels, can slow cancer growth and help prevent associated adverse effects. Treatment is usually started either soon after diagnosis (early treatment) or after the patient is experiencing symptoms (late treatment).


AST has been the gold standard in metastatic prostate cancer treatment. Suppression of androgen both slows cancer progression and lowers levels of prostate specific antigen (PSA). Early treatment means a longer duration of hormone therapy and increased treatment-related adverse effects, including depression, fatigue, hot flashes, and cardiovascular effects. Both early and late treatment involves management of advanced disease effects.



This systematic review sought to assess the effects of early versus late AST in men with prostate cancer. Early suppression was defined as AST initiation at diagnosis or in asymptomatic patients with rising PSA levels. Late suppression was defined as AST initiation when patients were symptomatic.


In all, 10 RCTs were identified for meta-analysis involving over 10,500 participants, with an average follow-up time of five to 13 years. The two primary outcomes were time to death from any cause and serious adverse effects. Secondary outcomes included time to death from prostate cancer; adverse events such as skeletal events, fatigue, and heart failure; quality of life; and time to disease progression.


Early AST was found to reduce the risk of death from any cause. Serious adverse effects such as myocardial infarction, cerebrovascular events, or death from these events occurred equally in both the early and late AST groups.


Early AST also prolonged the time to prostate cancer-related death and slightly decreased adverse effects such as skeletal events, general pain, back pain, and urinary symptoms. Symptoms such as fatigue and heart failure were more likely to occur because of the prolonged length of time on treatment. Quality of life was assessed by a questionnaire two years after the implementation of AST. Mean differences were small for global quality of life, physical functioning, emotional functioning, and sexual function. Finally, early AST decreased clinical progression and slightly increased time to disease progression after nine years.



The data related to the primary outcomes, while not statistically significant, suggested an increase in time to death from any cause and an increase in time to death related to prostate cancer with early treatment. Secondary outcomes data suggested an early AST-related increase in fatigue and heart failure, but these effects were evaluated in a limited number of RCTs and may not be generalizable.


The early initiation of AST may prolong time to death from any cause and death related to prostate cancer. While several adverse effects increased because of longer hormone suppression, quality of life indicators such as physical functioning, emotional functioning, and sexual function were unchanged. Serious adverse effects and quality of life may be similar in both groups.




Kunath F, et al Early versus deferred standard androgen suppression therapy for advanced hormone-sensitive prostate cancer. Cochrane Database Syst Rev 2019;6:CD003506.