We gathered some community questions on metastatic prostate cancer for Dr. Wayne Brisbane at UCLA Health and Dr. Hardeep Phull at Palomar Health during recent “Ask the Expert” webinars. Below are some of the important insights they shared on this complex diagnosis that we transcribed from the discussions.
The following questions and responses have been lightly edited for grammatical purposes.
1) When should you consider changing therapy for metastatic prostate cancer?
Dr. Brisbane: I will say I deal mostly with localized prostate cancer, but: is your PSA responding? Has the PSA bottomed out or is it starting to recur? Is your testosterone at a castrate level? What have you been on already? What kind of regimens? Have you had docetaxel, [or] have you not? Have you [been on] Radium, have you not? Then there’s obviously these newer medications [like] Pluvicto, which [targets the] PSMA where it has a beta or an alpha particle stuck onto it. Multiple companies are coming out with these now and some of the responses they’re getting are pretty impressive. I would say that’s a conversation you really have to have with the medical oncologist to see what you’re on and if it’s working. What have you seen and how was the response? Sometimes the medical oncologists will have a preference for what drugs we start with and what kind of pathway. Should we start with Zytiga or something else, and then go to androgen blockade? It’s probably up to the medical oncologist, but I do think that it’s worth a conversation.
Sometimes people come to see me and they’re like, “Hey, you do a lot of prostate cancer, what do you think about this?” I think it’s important to say, “Well, if you want a second opinion, most of the people in academic medicine are very happy to do those kinds of things.” UCLA has a second opinion service, there’s Memorial [Sloan Kettering], MD Anderson, just tons of these kinds of places where you can go and present your data and get a second opinion. It may cost a couple hundred bucks, but if it helps you sleep better at night or changes the way the therapy is going, it’s worth it.
2) Are there any other therapies for Stage IVA prostate cancer in addition to radiation and hormone therapy?
Dr. Brisbane: Stage IV usually involves the bladder, the pubis, or some kind of adjacent structure. It kind of depends on if you’re using the TNM staging or some of that more classic Stage IV, it’s hard to know exactly.
In general, the answer is going to be based on hormone therapy because that really still is the best thing we have for killing off prostate cancer that’s not castration-resistant. It’s really powerful. Sometimes, even when something is castration-resistant, we will still rely on keeping the hormone therapy on board in order to drive those testosterone receptors. It’s just amazing how testosterone-dependent prostate cancer is. By denying the testosterone, we can really make a difference.
What I will say is, radiation can be very effective. If you have T4, meaning locally invasive, prostate cancer, occasionally, we will need to do some sort of surgery. Not necessarily surgical removal of the entire prostate, but like a TURP or something to help get people out of urinary retention that could be important while we’re getting somebody ready for radiation. That kind of conversation, again, does require some nuance to discuss the individual elements of the case. Oftentimes it’s better to discuss that with somebody who can see the images and really know what the nuances are.
3) We have a patient with metastatic prostate cancer being treated with Xtandi and Orgovyx and he’s on his sixth week of radiation. His biggest complaint is lack of energy. Are there any suggestions he should investigate with his oncologist?
Dr. Phull: It seems like a lot of this gentleman’s symptoms are from the course of these agents. Sometimes prostatectomy or radiation causes urinary complaints, and then you exacerbate it with this hormonal treatment, so some people feel a little worse for a short period of time. I tell all men when they start hormone treatment of any sort, you’re basically reducing testosterone to near zero from wherever level it’s at.
If you look around America, at least here in Southern California, I see a men’s health clinic popping up everywhere to give men testosterone, sometimes inappropriately when their testosterone levels are just fine, but the same symptoms come up. “I have low energy, low libido, and low strength.”
Yes, testosterone as a hormone is related to that. When you block these things and make it near zero, and then you add Xtandi–which is the androgen receptor blocker–on top of it, I can see patients having a decrease in energy and strength and muscle loss. I’ve seen men lose dozens of pounds, of not fat, but muscle. That’s such an important issue, to have strength. Having muscle weight and that sort of strength is better than any weight as a predictor for future mortality. There’s also low libido in the bedroom, all these other factors. I’ve actually seen men in their early ages, less so in their 80s or 90s, get severe depression and I can see why. You’re bombarded with hormonal treatment that’s working and yay, your PSA is less than 0.1 or zero, but your journey now is impacted and you feel awful and the things you used to enjoy, the things that bring pleasure, are gone.
We do have medications for this. They’re not 100%, but they’re essentially an antidepressant to help deal with these, we call them vasomotor symptoms. There’s no magic pill, unfortunately, and every pill you add on has its own set of side effects, but we have these discussions with patients to say, “Here are some options. You could try this. We could watch and wait because they could get better.” I found after patients are on these treatments over months or even years, these symptoms tend to subside a little bit or get more tolerable.
Really the hardest one is what this gentleman brought up: energy. Energy is such a tough one because it’s not just “I didn’t drink caffeine this morning” or anything like that. We don’t have a perfect energy pill, but if it’s from low testosterone, the best treatment for energy is testosterone, yet that would be horrific for the prostate cancer. You’d be undoing all the treatment. I’m hoping in the future one day, as we get more and more selective treatments, maybe we can have fewer side effects doing these androgen deprivations. I do worry that it’s really hard to not have the side effects of castration. I think this is a great unmet area for future trials and medicines that actually work and aren’t just putting a Band-Aid on the problem and adding on other layers and other issues.
I would tell this gentleman, you’ve got this. I hope this is an early part of this treatment because it should and will get better. When you talk to your doctor, talk about dose reductions or breaks in treatment. By the way, I give my patients a lot of breaks at times for either holidays or other events. You’re not supposed to do that. These are supposed to be continuous treatments, but there are some patients who ask me for that. My job as a physician and a human being is to advocate for that person in front of me and put myself in their shoes and say, “Is that what I would want done for me?” That’s what that’s called empathy.
So start with a dose reduction, maybe in a conversation with your oncologist, and then consider a short break. I don’t know what it is about that magical window. For some reason, I’ve seen some patients on the restart do better for whatever reason. That may be enough to reset the system, but those are some strategies. I hope that helps.
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