Anthony V. D’Amico, MD, PhD, discusses key factors that determine his radiotherapy treatment selection in the management of patients following radical prostatectomy.
Anthony V. D’Amico, MD, PhD, a professor and chair of genitourinary radiation oncology at Brigham and Women’s Hospital and Dana-Farber Cancer Institute, shares his expertise on the use of radiotherapy following radical prostatectomy in patients with prostate cancer.
There have been three randomized trials that have investigated the use of immediate (adjuvant) radiation following radical prostatectomy that is used before the PSA reaches 0.1 ng/mL compared to early salvage that is after the PSA arises above 0.1 ng/mL or 0.2 ng/mL. Those studies concluded that salvage was preferable and no different than adjuvant. One key issue, however, is when you want to use less as opposed to more treatment, you use a noninferiority trial design. And 2 of those 3 studies were superiority studies. The other point is that many patients on those studies didn't have high risk factors, only 9% to 16%. As a result, the question of what to do with people with 1 or multiple high-risk factors in terms of salvage or adjuvant radiation remains unanswered.
Three studies have been conducted since then by a group that I'm associated with, which is a multinational collaboration between Europe—particularly Germany, Hamburg—United States, UCSF, and Johns Hopkins, and what was discerned from this is if you have 2 high-risk factors, that is cancer extending beyond the prostate on pathologic exam at the time of radical prostatectomy, or if you had Gleason score 8, 9, or 10, those are the 2 high-risk factors, then you are at much higher risk for recurrence. So with people who have both of those—a Gleason 8, 9, or 10, and cancer beyond the prostate at prostatectomy, adjuvant radiation appears to confer a survival benefit compared to early salvage.
The next study that was done involved people who have a single risk factor. For these people, it appears that there is a PSA cut point above which the risk of death increases by 50% and below which it does not. And that cut point is 0.25 ng/mL in terms of the PSA level. So it appears for people who have a single risk factor—Gleason 8, 9, or 10, or cancer extending beyond the prostate at the time of surgery—that establishing salvage therapy by a PSA of 0.25 ng/mL would be important.
The reason why this is timely is because with the advent of advanced PSMA-PET technology, many physicians are waiting to start salvage radiation to a higher PSA level. Typically it’s 0.3 ng/mL to sometimes as high as 0.5 ng/mL because of 2 reasons One, not all insurers will reimburse the PSMA-PET at low PSA levels; some do but many don't. And second, the performance characteristics of the PET scan improve with increasing PSA level.
At our own institution, we've adopted the policy of starting salvage therapy in men with a single high-risk factor before the PSA gets to 0.2 ng/mL, andcertainly not 0.25 ng/mL. And so I think that that's an important point to take home: with one risk factor, do salvage by 0.25 ng/mL and with 2 risk factors, do adjuvant and don't wait for the PSA to rise.