The short of it.

Headline: The addition of androgen deprivation therapy (ADT) to modern (read: dose-escalated) prostate radiation across a broad population of intermediate risk disease does not improve overall survival but clearly slashes biochemical recurrence, distant mets and prostate cancer death.

The Study: Why no translation to an overall survival benefit? Because the absolute benefit to aforementioned outcomes were, while detectable, tiny. Let’s delve in. RTOG 0815 was designed in the early 2000s and recruited roughly 1500 men from 2009 to 2016. As was standard at the time, radiation was conventionally fractionated to either 79.2 Gy (89%) or 45 Gy followed by a brachytherapy boost (remaining 11%) and ADT with something like Lupron included the addition of an oral antiandrogen both for a duration of 6 months. Eligibility was intentionally very broad with one (as was the case for 67% of enrollees) or any combo (remaining 33%) of intermediate risk factor, meaning as mean as two-thirds would fall in our current “favorable” intermediate risk category—but probably much less given 92% had Gleason 7 disease. The primary endpoint of overall survival was 90-91% at 5 years either way. To no surprise, biochemical failure at 8 years was halved with ADT, 21% versus 10% with ADT, which persisted across subgroups, even Gleason 3+4. Arguably more importantly, it also delayed salvage therapy. While statistically significant, rates of distant mets at 5 years were only 3% versus 0.6% and of prostate cancer mortality 1% versus 0%. Finally, as always, prostate cancer data maturation is outpaced by other advancements, and genomic scores will likely add importantly granularity to which individuals are most likely to benefit—our money is on a post-hoc secondary analysis stratified by Decipher score.

TBL: You're now armed with the pros part of your pros and cons discussion of adding ADT to radiation for intermediate risk prostate cancer. If this leaves you less than crystal clear on how to approach this in clinic, take a listen to how Dr. Kraus himself does it. | Kraus, ASTRO 2021

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