Always beneficial?

Top Line: At ASTRO we learned in abstract form that large pooled data indicates there is no subset of prostate cancer that loses the relative advantage of androgen deprivation therapy (ADT) added to radiation.

The Study: We now have the full manuscript with subset analyses. While RTOG 0815 helps clarify the absolute clinical benefit of ADT in men with intermediate risk disease, this massive dataset covers patients across risk groups. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium compiled data on 10,853 enrollees in 12 randomized trials accrued between 1987 and 2010 evaluating the impact of adding and/or prolonging ADT in combo with definitive prostate radiation. Across this broad population, any addition of ADT improved the primary endpoint of metastasis-free survival (HR 0.83), as did prolonging ADT in the adjuvant setting (0.84) but not neoadjuvant setting. This translated to a number-needed-to-treat (NNT) in order to avoid one distant met at 10 years of 18 for intermediate-risk disease and 8 for high-risk disease. Similarly, the NNT to save a life at 10 years was 17 for intermediate-risk disease and 10 for high-risk disease. Further prolongation of ADT (from 4-6 months to 18-36 months) in 10 men with high-risk disease prevent metastases in one. Finally, the benefit of adding ADT wasn’t attenuated with increasing radiation dose, as demonstrated in 0815, nor by increasing age. Returning to the accrual periods, the big caveat to keep in mind: “Given that both stage and grade migration have occurred during the past three decades, the patients with intermediate-risk disease in this meta-analysis might be more similar to patients with unfavorable intermediate-risk, or even high-risk, prostate cancer today.”

TBL: Giving ADT during and after radiation results in a relative improvement in metastasis-free survival regardless of risk group, but men with increasing risk derive greater absolute benefit. | Kishan, Lancet Oncol 2022