Why is there a benefit of ADT for high risk prostate cancer treated with radiation, yet no large trials describing benefit of adjuvant ADT after radical prostatectomy?

From a high level, the magnitude of the benefit of ADT with radiation seems proportional to the aggressiveness of the disease (i.e. low risk has no significant benefit, int risk weighs risk features and cardiac health, and high risk the benefit of ADT can trump cardiac risk).

In that context, we have seen a benefit of ADT in the salvage setting including from the RTOG 0534/SPPORT trial as well as the 6 vs. 24 month RADICALS-HD comparison. Taken together, the two RADICALS-HD papers suggest that there isn't in fact anything special about the prostatectomy space, but rather that lower-risk patients might not benefit from ADT while higher-risk patients might benefit from longer ADT. For comparison of 0vs6 and 6vs24, there were 11% vs 29% GS 8-1...

All interesting commentaries. Could there be a synergistic effect between RT and ADT whereby a diminished testosterone level enhances the sensitivity of the malignant cells in which RT is more effective in the local +/- the regional space, and could there be an abscopal effect in the distant space where micro- met may exist. Thus, there may not be an "apple to apple" comparison between RT and surgery. Until/unless there are high-level data from surgery and ADT, we will continue to engage in speculative analysis. James Benton, Rad Onc, ATL

My 2 cents on this topic.

Historically, "definitive" RT often cytoreduces a prostate cancer by something like 99.999% or a similar magnitude concept, rather than flat wiping it out forever (treated every cell but didn't kill every cell. It takes something like another 8 years for that outcome to be expressed clinically in a typical "local relapse" RT scenario).

RP often does that 99.999% thing too, but in a different way (treated 99.999% of the cells by removing them entirely, but did not do a thing to the other 0.001%).

Paired with the concept that ADT also cytoreduces but is not curative.

So, since RT treated every cell, but did not kill every cell, ADT "weakening the thing" is arguably good enough to get 99.999% to 100%.

Whereas, since s...

Many moons ago, a famous urologist had quipped: “Prostatectomy only cures those prostate cancers that didn’t need to be cured and it doesn’t cure any cancers that needed to be cured”. In other words, prostatectomy only provides a generous biopsy. It adds little to the likelihood of a cure beyond what irradiation and/or systemic therapy can accomplish without prostatectomy.