Video: How do Provenge or Xofigo Prolong Life When They Don’t Drop PSA? | Helpline Questions

Helpline Questions | Transcription

Hi, I'm Dr. Scholz. A common question we get at the PCRI is, "Why do Provenge and Xofigo prolong life, but not necessarily cause the PSA to decline?" 

First, let me tell you that I do see PSA declines with both of these agents. Just to review, Provenge is an FDA approved immune therapy; Xofigo is a targeted form of injected radiation therapy that goes into the blood and targets bone metastases. 

So with most treatments, [e.g.] hormone therapy, chemotherapy, we'll see consistent declines in PSA and that will confirm that the disease is regressing under the influence of therapy. Since that has been the norm for many decades when Provenge and Xofigo came on the market and claimed to be able to make people live longer without a PSA decline many people questioned the validity of that claim, that these things are actually working. 

Now first, let's lay to rest any idea that they're not working, that it is some sort of spoof. The type of studies that have been done—double-blind, randomized, placebo-controlled trials—unequivocally show that both of these agents prolong life, so there's really no disputing that. That being the case, how can we explain the fact that the PSA levels are not consistently dropping like they do with other therapies? 

 I don't think it's a very difficult concept honestly. These medicines have a long protracted effect. Chemotherapy and hormone therapy only work as long as you're administering them. When you stop them, the effect wears off and the cancer starts to grow again; the PSA rises again. When you administer something like Provenge the whole immune system nature is altered permanently in favor of suppressing the disease. So what happens is, although the disease doesn't regress, it progresses much more slowly. The immune system inhibits progression and so studies have actually shown that if you look at PSA rates of rise prior to treatment and after treatment, the rate of PSA rise is slowed and thus people live longer. 

Brand new technologies that work by methods we've never had before are expected to have methods of action that aren't what we originally anticipated. Both Provenge and Xofigo have the capacity to prolong life, but they're not universally going to cause PSA to decline. That should never be taken as an indication that the treatments are ineffective. The studies that have been performed are unequivocal.