A Three-Pronged Attack on Recurring Prostate Cancer: Ready for Prime Time?

Gerald Chodak, MD


November 29, 2018

Hello. I'm Dr Gerald Chodak for Medscape. Today's topic is: managing men with a rising prostate-specific antigen (PSA) after radical prostatectomy.

Pollack and coworkers[1] recently presented their 10-year results from a randomized trial involving almost 1800 men. The patients were divided into three groups. One group received radiation to the prostate bed; the second group received radiation to the prostate bed plus 4-6 months of androgen deprivation using an LHRH agonist and an antiandrogen; and the third group received prostate bed radiation, radiation to the pelvic lymph nodes, and the hormone therapy.

The inclusion criteria were the following: At 6 weeks after prostatectomy, the PSA could not be higher than 1 ng/mL; nothing could be palpable in the prostate bed or if [a mass was palpable], it had to be biopsy negative; lymph nodes had to be negative at the time of surgery or less than 1.5 cm in diameter seen on MRI or CT; and the PSA level could reach no higher than 2 ng/mL at entry.

What were the results? At 5 years, the progression-free survival, defined as a rise in PSA of 2 ng/mL from nadir, was significantly better in the men who received the combination therapy of radiation to the pelvis and to the prostate bed, plus the hormone therapy. Progression-free survival was 72% in the men who received the radiation alone; 83% in the men who received radiation to the bed plus the hormones; and 89% in the men who received all three treatments.

What does this mean going forward? First, investigators had results at 8 years that did not reach statistical significance. There was a benefit for the combination therapy, but in the men whose PSAs were 1 ng/mL or less, the benefit disappeared.

So we have to ask ourselves: Are these results sufficient to make recommendations going forward? I don't think so. First, giving radiation to the pelvis of a man whose PSA is low—meaning, less than 1 ng/mL—could result in overtreatment, and the treatment did have a higher risk for side effects. Second, the results have not yet reached statistical significance for metastasis-free survival, and a longer follow-up is needed to see if that does occur. Third, we still have no information about overall survival, and it's still preliminary to conclude that a benefit for metastasis-free survival will definitely translate into a benefit for overall survival.

Nevertheless, going forward, it is reasonable to have a conversation with your patients about these early results. And men whose PSA is higher can be offered the more aggressive therapy, but realizing that the results are not definitive.

I look forward to your comments. Thank you.


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