Decipher May Help Identify Who Really Needs ADT With Radiotherapy

A new analysis from the randomised phase 3 NRG/RTOG 0815 trial suggests that the Decipher genomic classifier may do more than estimate prognosis: it may help predict which men with intermediate-risk prostate cancer actually benefit from adding short-term androgen deprivation therapy to dose-escalated radiotherapy.

Researchers analysed tumour samples from 395 men, with a median follow-up of 10.2 years. The interaction between Decipher score and ADT benefit for distant metastasis was statistically significant, suggesting that the treatment effect differed according to tumour biology rather than clinical risk group alone.
Among patients with intermediate or high Decipher scores, adding short-term ADT reduced the absolute risk of distant metastasis at 10 years by about 8 percentage points. By contrast, among the 44% of patients with low Decipher scores, the absolute difference was only around 1 percentage point. Decipher was also independently associated with biochemical failure, distant metastasis and prostate cancer-specific mortality.
The result is important because intermediate-risk prostate cancer is biologically heterogeneous. Some men may gain meaningful protection from metastasis with ADT, while others may receive months of hormonal treatment, with its metabolic, sexual and quality-of-life effects, for very little absolute benefit.
These findings are not yet the same as proving that low-Decipher patients can routinely omit ADT. That question is being tested prospectively in the phase 3 NRG-GU010 GUIDANCE trial, where men with lower genomic risk are randomised between radiotherapy alone and radiotherapy plus six months of ADT, while higher-risk patients are being studied with treatment intensification.
Still, the new RTOG 0815 analysis strengthens the idea that future treatment decisions may rely less on broad clinical labels such as “intermediate risk” and more on the molecular biology of the individual tumour.

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