Early Androgen Deprivation
Recommendation 3.1
➤ Early (immediate) ADT may be offered to men who initially present
with noncastrate locally advanced non-metastatic disease who have
not undergone previous local treatment and are unwilling or unable
to undergo radiotherapy based on evidence in one meta-analysis of
a modest but statistically significant benefit in terms of both overall
survival and cancer-specific survival among the larger population
of men with locally advanced non-metastatic disease. (Moderate
recommendation; EB-B-I).
Qualifying Statements for Early versus Deferred ADT
• Discussions with patients regarding early ADT should include the risk of short- and
long-term side effects. Deferred ADT is often preferred by patients who desire to
avoid, or at least delay, potential ADT side effects. Consideration should be given
to restricting deferred ADT to those patients who are asymptomatic.
• No recommendation can be provided at this time for men with PSA relapse after
local treatment. Although existing studies suggest a potential overall survival
benefit, additional research is needed since such studies were underpowered.
Recommendation 2.2
➤ In resource-constrained settings where drugs such as abiraterone
may not be available, combined androgen blockade using ADT plus
a first-generation antiandrogen, such as flutamide, nilutamide, or
bicalutamide, may be offered to men with locally advanced non-
metastatic prostate cancer, rather than castration monotherapy based
on recent meta-analyses. (Moderate recommendation; EB-B-H).
Qualifying Statement for Combination Therapies Such as Combined
Androgen Blockade
• For men with high-risk non-metastatic prostate cancer progressing after radical
prostatectomy or radiotherapy or both, it is currently unclear whether enzalutamide
(160 mg ) plus leuprolide improves metastasis-free survival compared to
enzalutamide monotherapy or placebo. Though recruitment is complete for the
ongoing phase III EMBARK trial, which is designed to answer this question, results
are not yet available. Thus, no recommendation can be made at this time.
