Optimizing androgen deprivation therapy with radiation therapy for aggressive localized and locally advanced prostate cancer

Radiation therapy with androgen deprivation therapy (ADT) has historically been one of the mainstays of treatment for intermediate- and high-risk prostate cancer. The benefit of ADT likely derives from both enhancing local control and inhibiting micrometastatic disease. While level 1 evidence has demonstrated the benefits of 4–6 months of ADT for all men with intermediate-risk disease, further stratification of intermediate-risk prostate cancer into favorable and unfavorable subgroups indicates that ADT may not be necessary for favorable intermediate-risk disease but likely still provides a survival advantage for unfavorable intermediate-risk disease, even in the dose escalation era. Long-course ADT, consisting of 2–3 years of treatment, is the standard of care for high-risk prostate cancer managed with RT based on phase III trials. However, emerging data from a randomized trial raises the possibility that 18 months of ADT could be sufficient for select high-risk patients. The desire to minimize exposure to ADT lies in its many adverse effects, including the potential for cardiovascular harm in certain patients with significant coexisting comorbidity, possibly increased risk for neurocognitive and psychiatric events, and the well-documented metabolic changes. Providers need to carefully weigh these potential risks with the known survival benefits of ADT in aggressive localized and locally advanced prostate cancer.