Short game, long results.

Top Line: Does short-term ADT improve long-term survival in men with localized prostate cancer?

The Study: We recently saw the long-term results of EORTC 22991 (intermediate risk, dose-escalated RT cohort), which showed improved event-free and disease-free survival, but not overall survival at 10 years when 6 months ADT was added to RT. RTOG 9408 previously showed that adding short-term ADT to moderate dose RT for localized prostate cancer improved overall survival from 57→ 62% at 10 years. Do those results hold up beyond 10 years? 9408 included over 2000 men with localized, cT1-2b prostate cancer with PSA ≤ 20. About 35%, 55% and just under 10% of men had low, intermediate, and high risk disease. They were treated with an initial 46.8 Gy to the pelvis followed by a cone-down boost to the prostate of 19.8 Gy for a total of 66.6 Gy in 37 fractions. They were randomized to either RT alone or 4 months of ADT, which consisted of flutamide 250mg TID and either goserelin or leuprolide, which started 2 months before RT. At 18 years, the previous difference in OS between arms was lost with both arms converging to an OS rate of 23%. The difference in restricted mean survival time (RMST) between arms at 18 years favored ADT+RT by 6 months (11.76 years with ADT vs 11.26 years without). This means 4 months of ADT translated to an average 6 month improvement in survival over 18 years. Though OS converged due to an increase in other-cause mortality, there remained a significant long-term reduction in disease specific mortality (14→ 8%), distant metastasis (13→ 9%), and biochemical failure (53→ 40%) across subgroups. So, what we see is that the addition of short-term ADT to RT improves long-term treatment outcomes across patient subgroups and risk categories. However, the absolute benefit is more pronounced as risk increases, which would be necessary to translate into a survival benefit.

TBL: The addition of 4 months of ADT to moderate dose radiation for localized (mostly low and intermediate risk) prostate cancer continued to improve disease-specific outcomes but not overall survival > 15 years after treatment in RTOG 9408. | Jones, Int J Radiat Oncol Biol Phys 2021