Factors Impacting Treatment Approach in Advanced Prostate Cancer
Panelists:Raoul S. Concepcion, MD, FACS, Urology Associates; Michael S. Cookson, MD, MMHC, University of Oklahoma Health Sciences Center; Daniel P. Petrylak, MD, Yale School of Medicine; Daniel I. Quinn, MBBS, PhD, FRACP, FACP, University of Southern California; Neal D. Shore, MD, FACS, Carolina Urologic Research Center; Charles J. Ryan, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Raoul S. Concepcion, MD: Let’s just say that, again, for the discussion, this guy, he’s very active, he’s already received his sipuleucel-T. We know he has multiple areas on his bone scan to the axial skeleton, the ribs, and sacrum. He’s got minimal nodal disease, less than 1 cm. So, we talk to him, and say he is getting up at night and taking more and more NSAIDs, occasionally takes an opioid. Dan, with all the different therapies that are out there, this guy’s already failed, he’s progressing past his immunotherapy. How do you look at this gentleman now?
Daniel P. Petrylak, MD: The first thing that strikes me about this case is he’s only had a sodium fluoride PET scan, and recently, in my experience, there is a CT scan that’s often done with that. But the CT scan generally is not a high resolution CT scan, so you may be missing visceral disease in patients such as this. So, the first thing I would do in this patient is get a standard CT scan of the chest, abdomen, and pelvis with contrast to be sure he doesn’t have liver metastasis or something else that we’re missing in this situation. And that’s going to affect my treatment, because clearly if he has visceral disease, I’m going to tend to go more towards chemotherapy. If he has bone-only disease or nodal disease, I would like to go with enzalutamide or abiraterone in that situation. I think that that’s going to be one of my checkpoints.
Raoul S. Concepcion, MD: So, let’s just say he’s got a full-blown CT, no visceral metastasis, multiple bone metastases, 1-cm node, ECOG 1, and some symptomatology that seems to be related to his bone metastasis, in terms of some mild pain requiring NSAIDs, but, occasionally, will drop an opiate.
Daniel P. Petrylak, MD: I think that either abiraterone or enzalutamide would be appropriate in this patient. Certainly, there are selection criteria for both drugs. Somebody who is older or frail, I would not tend to give enzalutamide to because of some of the CNS (central nervous system) effects that go on with that, the fatigue that goes on with the drug. But I would either consider abiraterone or enzalutamide in this patient. I think it’s a toss-up as to which one to use in this situation.
Raoul S. Concepcion, MD: Mike?
Michael S. Cookson, MD, MMHC: I think his point is well taken. One of the things that I’m impressed with as an urologist is that we see windows of opportunity for treatment, and sometimes we get complacent with what we’re doing and then we lose those opportunities. So, for example, yes, the oral agents would be appropriate in this setting, but if he’s having pain and it’s related to the bone and he doesn’t have visceral metastases, there’s a window open there for you to give radium. If we don’t do it, and let’s say it’s a year later and now he does blossom visceral metastases, we’re taught not to give the drug in that setting. I think that there’s a lot of competing issues, but one of the things that I worry about—and the same is true of immunotherapy—we lose some opportunities while we’re watching. We don’t watch often enough. So, I think the agents we’ve discussed for bone metastases. And if there is soft tissue disease—visceral metastases—the trend is more towards chemotherapy in that setting.
Raoul S. Concepcion, MD: David, obviously pre-2010, docetaxel was the only thing out there. How does docetaxel fit into this patient? It’s clearly an option.
David I. Quinn, MBBS, PhD: Right, but most patients want to wait with the chemotherapy. I think that we have other options now. So, this is a patient we’re also like, ‘Okay, chemotherapy is a well-tested treatment.’ It’s going to be in your future unless they’re really not a candidate for it, but I would tend to reserve that for a patient that either has major opioid-requiring pain or visceral metastases. In this patient, the discussion I’d be having is between one of the novel anti-androgen drugs, either enzalutamide or abiraterone. He’s 63, I think he’d tolerate either reasonably well. Or consider whether we start now with radium because he’s kind of in the window. And what do I mean by the window? He doesn’t have visceral disease and I would do the CT scan with contrast, just as Dan Petrylak would, because that’s something you really need to know if you’re considering radium. I would talk to this guy about radium, and I would then say if we do radium we’re going to have to watch you closely. We’ll see you each month, we’ll look at your PSA (prostate-specific antigen), we’ll look at any responding, we’ll look at your alkaline phosphatase, and I think he might do well with that for a period of time because he has an active bone milieu. One thing that would worry me about radium is that he has a PSA doubling time that is now less than 6 or 7 months, and radium is not great at controlling the PSA. So, the discussion then is, well, if we need to add something to control that, what are we going to do? And, so, I would potentially start him on radium and then say, look, my threshold for starting either enzalutamide or abiraterone if I’ve got to control your PSA is low.
And then the other thing is I do a scan between the third and fourth radium treatments. I don’t even do a bone scan anymore because usually the radium is very effective. If it’s not, the patient is getting increased pain and that hones you in. But I’ve had a number of people who have started to develop visceral metastases, and in this guy I wouldn’t be so worried because I think I can control that with enzalutamide or abiraterone. But, when you’re looking at giving radium a bit later, and you start to get visceral metastases in either the lung, or the liver, or elsewhere... Sometimes if they’re resistant to enzalutamide or abiraterone or both. So, there’s a lot of different considerations there.
Raoul S. Concepcion, MD: Clearly, if you got a scan—maybe not in this particular patient but a rapidly progressing patient in between third and fourth injections of radium—and you picked up newly diagnosed visceral disease, you would have probably had them on another agent as well. Would you complete the last three cycles of your radium-223?
David I. Quinn, MBBS, PhD: The answer is maybe. The guy at the moment I think has got evidence of an active bone milieu. So, if he says, ‘Look, my pain has improved,’ and the spouse agrees, and he’s getting benefit from it, you’ve then got a difficult decision to make, and it depends what drugs they’ve had before. For this guy, if he’s not had enzalutamide or abiraterone, they’re good choices. The more difficult choice is when you’ve got small liver metastasis, and it’s the first time. Do you add docetaxel to the radium which has excess toxicity? We know from the phase I/II studies, done by Mike Morris and other people out of Memorial Sloan Kettering, that you can’t give full doses of both. So, it’s an issue of whether you’re going to change it up and extend the interval of radium, and reduce the dose of docetaxel in that setting. I think that’s a difficult question. Will they do as well with just switching to full dose docetaxel at that setting? This doesn’t come up that often. But when it does, I’ve learned that we may be going over a cliff with a patient, and you need to be prepared to react pretty quickly.