EU Perspective: Evolving Topics in Prostate Cancer - Episode 10
Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: There are new data regarding protective bone agents. Has this changed because of the trial, or can you tell us what you’ve always known and what you’re doing?
Noel Clarke, MBBS, FRCS, ChM: What I hope it will do is highlight to the urological oncology community that this is an important issue. They should be using bone protection in a way they haven’t been doing. It always interests me that clinicians, when there’s good level 1 evidence for the use of something, that they won’t use it; and when there’s no evidence at any level, they do use it. We know that this is a serious problem.
Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: In a patient beginning ADT, even for maybe nonmetastatic disease, do you think we should be looking at their bone health even at that stage?
Noel Clarke, MBBS, FRCS, ChM: Definitely, and there are very easy ways to do it. You don’t have to do a densitometry. You can use symptom fracture scoring, which will give you an index of whether a patient is at high risk of osteopenia and osteoporosis. In that way, you can just use a simple method and usually a 4-mg infusion of zoledronic acid [Reclast], which is all you need once, possibly twice a year for bone protection.
Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Is that what you do, Nick, in your practice?
Nicholas James, MD: Similar. I think we know from the SEER [Surveillance, Epidemiology, and End Results Program] data where that’s a very nice graph with the numbers of pathological fractures picked up on. They’re American insurance bills. You’ve got a huge rate of fracture by 10 years out if you’ve had more than 8 doses of Zoladex [goserelin acetate] or the equivalent. The only thing that doesn’t appear to impact the fracture rate is 1 to 4 doses of [gonadotropin-releasing hormone] analogue, which runs with prostatectomy. The fracture rate is still significant in that setting as well.
There’s the separate issue regarding what to do with men who are hormone therapy naïve—the risk of fracture is substantial. Anybody with intermediate high-risk prostate cancer is not doing a couple of years of ADT. I’m measuring their bone density. I’m not treating them but measuring. Those who start treatment are osteopenic. Those who are not yet osteopenic, I will monitor them. For the patients who are metastatic, I’m more ad hoc about it because I’m doing bone densities on men with low-body metastatic disease periodically because they will fall. If they fall, I will treat them. The trouble is the fracture score rises in these men because of their age and ADT.
We’re going to look at the STAMPEDE data. We’ve pulled out all the hospital-episode statistics on a patient in England, which is 80% in total. This allows us to pull out data on orthopedic procedures that have happened for noncancer reasons; however, we suspect these are being underreported. A patient who we treated 5 years ago won’t get reported because he fell over and had a hip replacement—that data would not get reported to the trial database. It is a similar case for cardiovascular disease as well. We’re concerned about this in multiple contexts, with abiraterone [Zytiga] in particular.
Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: A lot of these patients, especially with longer-term ADT, may not be picked up at all. It’s not really a cancer situation; it’s more so osteoporosis.
Nicholas James, MD: It’s a statistical thing. When someone is 75 years old, falling over, and needing a hip replacement, it wouldn’t necessarily be thought of as a cancer problem if they’re off treatment at that point.
Noel Clarke, MBBS, FRCS, ChM: We’re quite excited about this because we’ve got a large body of information from the control arm of the STAMPEDE trial: thousands of patients treated with ADT and then supplemented with super ADT: abiraterone and enzalutamide [Xtandi]. So not only will we be able to do what Nick has said, but we can also do some sophisticated measurements on the CT scans of sarcopenia, muscle mass, and the effect of treatment on that group. Now we’re beginning to realize that somehow a fracture might not be osteopenia or osteoporosis on its own but the combination of things. A fall may well be significant, which is muscle weakness—an ADT-related thing.
Joe O’Sullivan, MD, FRCPI, FFRRCSI, FRCR: Yeah.
Nicholas James, MD: I keenly recommend exercise to our patients because it obviously helps stop weight gain, which helps keep their muscle mass up; that’s 1 of the messages we should be really putting out there.
Transcript Edited for Clarity