Redefining Advanced Prostate Cancer with Novel Imaging - Episode 4
Raoul S. Concepcion, MD, FACS: Let’s talk about this next setting, patients who I believe all of us are seeing more and more frequently, who are presenting with metastatic disease, newly diagnosed. We know, over the past few years—partly due to the US Preventive Services Task Force recommendation of a “D” with PSA, that’s obviously now changed—especially in the urology office, that patients were coming in not having been PSA screened. They had higher Gleason patterns and metastatic disease. Obviously, they’ve not been hormonally treated, up until this point. Fortunately, over the past few years, there have been a number of trials that have addressed how these patients should be treated, initially. Dan, can you walk us through a summary of these trials?
Daniel George, MD: Sure, I’m happy to Raoul. This field really started, I think, back in 2004 or 2005, following the approval of docetaxel for the treatment of metastatic castration-resistant prostate cancer. At that time, it was recognized that we needed to see if we could do better with this agent, by using it in an earlier disease setting. There was really a labor of love in developing and convincing people that this was an important study to do—recognizing this hormone-sensitive metastatic disease state as a potentially different biology then the natural progression that we’ve outlined from radical prostatectomy to radiation to PSA relapse to hormonal therapy. We recognized patients who were kind of de novo, coming in the door with metastatic disease. They may have had a more aggressive biology and may benefit from that more accelerated early use of hormonal therapy and chemotherapy, in combination. I think it was a great breakthrough. It took 8 to 10 years.
But over the course of that time, it read out as a dramatically positive study in favor of that early use of docetaxel. We see positive results, in terms of a greater overall survival, for sure, but also a longer time to castration resistance and a greater percentage of patients getting a PSA nadir of less than 0.2. These are all really good surrogates to tell us that we’re having a deeper and more durable effect on the tumor than with just primary ADT alone.
So, along comes the 2000s, and we have the approval of abiraterone in castration-resistant disease that’s chemotherapy refractory. It gets studied in the chemo-naïve setting, but it’s also getting studied, largely, in Europe with the same population—with metastatic hormone-sensitive disease. It’s important to recognize that in Europe, that population is even greater. These are countries that historically haven’t screened very much for prostate cancer. And they’re countries who are more prone to hold on hormonal therapy until metastatic disease is established, when patients relapse after local therapy.
You’ve got a higher percentage of these metastatic hormone-sensitive patients in the urology practices. There is an opportunity to really accrue well to these studies. And they did. LATITUDE was a large study that looked at up-front abiraterone with ADT versus ADT alone. Again, they were treated until there were signs of castration resistance or unacceptable toxicity.
STAMPEDE is a different kind of study. This was more of a rolling study. They added arms to this multi-armed large, almost registry, study through the UK. It looked at patients receiving hormonal therapies for metastatic hormone-sensitive disease coupled with everything from zoledronic acid to docetaxel to abiraterone.
And in that setting, they were able to look at a control arm of ADT alone versus each of these arms, separately. So, those 2 studies mirrored each other. Both of them read out, last year, demonstrating a significant survival benefit associated with abiraterone. It’s almost uncanny how similar the benefit was to docetaxel. But, of course, a hormonal therapy pill versus chemotherapy, that’s kind of a no-brainer for most people to say, “You know, this is the way to go.”
We’re beginning to recognize that not all of these patients are the same. Maybe there are some patients in whom drugs like abiraterone are more than enough to get that benefit? Maybe we do need to do more, like with docetaxel, in others? Maybe there are some patients who tolerate docetaxel really well? So, I think there’s more work to be done in this space. But we are recognizing that it is no longer acceptable to take a patient with metastatic disease at presentation, particularly extensive disease—more than 4 metastases at presentation—and treat them with ADT alone. We really need to consider these other approaches.
Transcript Edited for Clarity