COMMENTARY

Does Radiation Therapy Right After Prostatectomy Save Lives?

Gerald Chodak, MD

Disclosures

April 02, 2015

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Hello. I am Dr Gerald Chodak for Medscape. Today I want to talk about adjuvant or salvage radiation after radical prostatectomy for men with high-risk disease. "High risk" includes those with a Gleason score of 8-10 or those who have extracapsular disease at the time of their radical prostatectomy.

We do not have a lot of information about this approach from randomized trials. One well-done US trial[1] found a small improvement in survival, benefiting about 1 in 9 men after about 12.5 years. A European randomized trial[2] did not show a survival benefit at a median follow-up of 10.6 years.

Hsu and colleagues[3] from the University of California at San Francisco recently conducted a nonrandomized study. They reviewed the CaPSURE database and found more than 300 men who had received radiation therapy, either as adjuvant or as salvage. They defined "salvage" as men who had a measurable prostate-specific antigen (PSA) level. The problem with the study is that it was not randomized, and therefore interpreting the results must be done with great care.

The study found that those men who received adjuvant radiation therapy had the best overall survival. Men who received radiation when their PSA level was relatively low, meaning < 1 ng/ mL, did almost as well as the men who received adjuvant therapy, but those who did not receive salvage therapy until the PSA was > 1 ng/mL had the worst outcomes. The authors concluded that waiting until the PSA is > 1 ng/mL translates to the worst overall survival and cancer-specific survival.

Still Need a Randomized Trial

There are several problems as we try to interpret these results. First, the radiation dose was not standardized. It appears that men who received around 70 Gy had better outcomes than those who received 60 or 66 Gy; however, interpretation of those outcomes is difficult.

Second, using a nonrandom method to select the PSA levels at which to institute salvage radiation lends itself to a very difficult interpretation. Perhaps there is an optimal PSA level for delivering adjuvant or salvage radiation therapy. The problem with giving radiation to everyone with high-risk disease regardless of their PSA level is that many men may be overtreated to help a small number.

We are left with the same dilemma of not knowing whether adjuvant radiation is clearly better than salvage radiation when the PSA becomes detectable. What that magical PSA detectable level is remains unclear. We know that a measurable PSA > 0.2 ng/mL is a real change. Although there can be fluctuations that indicate when men are more likely to develop a recurrence, why wait until a PSA level gets to be > 1 before instituting therapy? By waiting until there is at least a measurable PSA, you can reduce the number of men who would get radiation they would never need, but ultimately the question comes down to whether immediate adjuvant radiation therapy in men with high-risk disease is clearly better than waiting until the PSA becomes detectable. We will need a randomized trial to answer that question.

For now, I still believe we can offer men who have high-risk disease adjuvant therapy, recognizing that perhaps about 90% of them will receive a treatment that does not help them. Fortunately, quality-of-life surveys have demonstrated a relatively small negative impact from receiving adjuvant radiotherapy. Nevertheless, it would be much better if we could tailor the treatment to those men who really need it and avoid it in those who do not.

At this point in time, despite the findings from this uncontrolled trial, we still do not have a good answer on how best to approach men who have high-risk findings after radical prostatectomy.

I look forward to your comments. Thank you.

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