Early, early, early.

Top Line: The long-term results of RTOG 9601 were practice changing and led to widespread use of androgen deprivation in men receiving salvage prostate radiation. 

The Study: But at ASTRO 2019, we learned that adding ADT to salvage RT and broadly improving survival wasn’t quite that simple. Here we have the final manuscript of that analysis to hammer home some key concepts regarding the use of ADT in the salvage setting. The 760 men enrolled in 9601 had a pre-treatment PSA between 0.2 and 4.0. They were stratified by PSA above or below 1.5. While 85% fell into the PSA ≤ 1.5 stratum, 60% had a pre-treatment PSA > 0.5 and 44% never even had an undetectable PSA after surgery. The main analysis showed that men with a PSA ≤ 1.5 derived no survival benefit from ADT while those with PSA > 1.5 had a 25% absolute improvement at 12 years. There was a strong interaction between PSA (as a continuous variable) and OS benefit from ADT. The PSA ≤ 1.5 group was further categorized as receiving early (PSA 0.2-0.6) or late (0.61-1.5) salvage RT. The early salvage group had no improvement in OS and appeared to have increased other-cause mortality (OCM) and non-cancer events with ADT. In contrast, the late salvage group (as with the PSA > 1.5 group) saw a significant improvement in OS with ADT. The forest plot of OS, DM, and OCM gives us the big picture. Adding ADT reduces distant events while also increasing the risk of non-cancer events. For men with PSA ≤ 0.6, there is a low risk of DM, low cancer benefit from ADT, and increased risk of non-cancer events. As pre-treatment PSA rises beyond 0.6, the risk of occult DM and the cancer-specific benefit of ADT outweigh the risk of non-cancer events.

TBL: Pre-treatment PSA is an important factor in predicting the potential benefit (and detriment) of adding ADT to salvage post-prostatectomy RT. | Dess, JAMA Oncol 2020