ADT: Sooner Better Than Later?

Gerald Chodak, MD


July 06, 2016

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Hello. I'm Dr Gerald Chodak from Medscape. Today I want to talk about the role of early androgen deprivation therapy (ADT) in men who have a rising prostate-specific antigen (PSA) after surgery or radiation, or who are not candidates for local therapy. Duchesne and colleagues[1] conducted a prospective randomized trial in Canada, Australia, and New Zealand. Men were enrolled if they had a PSA > 0.2 ng/mL after surgery, or if they had three rising PSA levels after radiation therapy. They could also be enrolled if they had noncurable disease—either local or metastatic disease. [Patients received either immediate ADT or delayed ADT.] Patients in the delayed-ADT group did not receive hormone therapy for at least 2 years, unless they had clinical indications requiring earlier therapy.

Overall, about 300 men were enrolled. The predominant number had a rising PSA after local therapy. Patients were followed for a median of 5 years. They found a statistically significant improvement in overall survival by about 5% [in the immediate-therapy arm], meaning that 1 out of 20 men is benefiting from this therapy.

There are some problems with this study. It was intended to enroll about 2000 men; the much lower enrollment could have created some problems. Also, the data are not yet available to review for subgroup analyses. Until now, we've had to tell men that there was no clear evidence that providing early ADT for a rising PSA would impact their survival. That has changed, and all men should be receiving this important information when their PSA is rising.

Important questions need to be answered. First, since men in the early–hormone therapy group started ADT when the PSA was > 0.2 ng/mL after surgery, one has to wonder whether it's really critical or beneficial to start ADT that early. Could patients do just as well by starting when the PSA is 1, or 5, or even 10 ng/mL? We would need another study to answer that question.

Another question relates to the use of intermittent ADT. Randomized studies have shown that there was no statistically significant difference in overall survival for men getting intermittent vs continuous ADT when they had nonmetastatic prostate cancer.[2] The question here is whether the same would apply in this group of patients. Could men be receiving intermittent therapy without compromising their overall survival if the ADT is started early?

Another question we can't answer yet is whether or not the study included men with cardiovascular disease (CVD) who received luteinizing hormone-releasing hormone agonist therapy. Recent data suggested that using an antagonist in men with CVD could lead to a lower risk for CV mortality than an agonist.[3] It will be important to analyze the data further to see if any of the men were receiving antagonist therapy, and if not, it suggests a way to further improve the overall survival results.

These questions are worth considering but require additional studies. For now, we have important information to convey to all men with a rising PSA after local therapy that there is a statistically significant benefit, although small, for getting early rather than late hormone therapy.

I look forward to your comments, thank you.


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