Managing Side Effects of Treatment for Advanced Prostate Cancer

— Beyond Diagnosis continues with Christopher Wee on balancing treatment and quality of life

In "Beyond Diagnosis: Metastatic Castration-Sensitive Prostate Cancer," Cleveland Clinic oncologist Christopher Wee, MD, and host John Mangels discuss how clinicians can guide patients through the initial complexities of a metastatic diagnosis.

Each installment of this series explores the key moments in patient care, including building trust, navigating evolving therapies, aligning treatment goals, and supporting shared decision-making.

In this third episode, Wee discusses balancing treatment efficacy with quality of life, managing adverse effects of androgen deprivation therapy (ADT), and tailoring treatment intensity to patients' overall health, frailty, and individual priorities.

The following is a transcript of their remarks:

Mangels: Welcome to "Beyond Diagnosis," where we talk with doctors about treatment decisions and communicating with patients. I'm your host, John Mangels.

Treatment of metastatic castration-sensitive prostate cancer has changed significantly in the last decade. Those changes are creating new opportunities and new complexities for both physicians and patients. How do clinicians choose among expanded treatment options? How do they navigate decisions involving efficacy and risk, quality of life, and patient preferences?

We'll explore those issues and more with our guest, Dr. Christopher Wee. Dr. Wee is a physician in Cleveland Clinic's genitourinary medical oncology program. A large part of his practice involves patients with prostate cancer. Dr. Wee, thanks so much for joining us today.

Wee: Thank you for having me.

Mangels: Choosing the right treatment is only the beginning. Helping patients successfully navigate that treatment is obviously equally important. How do you talk to your patients about their goals for treatment?

Wee: Yeah, so most patients' top priority in treating this disease is to extend overall survival as long as possible while maintaining their quality of life. And that is exactly the goal. Understandably, patients can sometimes be concerned about the toxicities of a treatment and how that may impact a quality of life. Fortunately, with these pills, whether it's androgen receptor pathway inhibitor [ARPI] or chemotherapy, if you stop the treatment, those quality of life concerns can ameliorate. So I usually am able to work out, say, "Hey, let's at least try it and see how things go."

One thing that we sometimes don't consider is maintaining quality of life by preventing or delaying bad things from happening. And I think that's another consideration of treatment. And we don't necessarily see it because it's very challenging to, understandably, for a patient to grasp, "Hey, I'm taking these meds that are causing some side effects, but I feel fine right now. Why would I want to make myself not feel as good?"

Part of the goal of this though is to prevent bad things from happening such as a skeletal-related event or a fracture or pain from progressive disease. And sometimes it requires discussing those things as well.

Mangels: Let's talk about that discussion and what that sounds like and looks like. Obviously you have to talk about risk as well as benefit. What level of detail do you go into and do you think about what impact that might have on whether a patient actually stays with treatment or doesn't?

Wee: Right. And so the androgen deprivation therapy generally contributes the majority of the side effects, I would say, not the ARPI or the chemo. And unfortunately, these side effects can be problematic for some patients. I would say that most patients get through with manageable toxicity, that they don't have to necessarily upend their lifestyle, but some people get it worse and it's hard to predict that. Hot flashes, fatigue, muscle loss, bone density loss, sexual dysfunction, mood swings, weight gain, slight increased risk of heart attacks -- so these are nothing to really completely ignore by any means. These can be serious.

What I usually say though is this is one of the most important parts of systemic therapy against metastatic castration-sensitive prostate cancer and to at least try it to see if these side effects will become an issue.

More recently, within the past 5 years or so, relugolix [Orgovyx]opens in a new tab or window, an oral agent has become an option. And many patients like that option because historically we've been pursuing androgen deprivation with shots, GnRH [gonadotropin-releasing hormone] agonists most commonly, such as leuprolide. But relugolix patients like it because it's quick on/quick off with the testosterone suppression so they can feel empowered that should they have terrible toxicity, they can stop taking the pill, they're not stuck for months, and hopefully their testosterone will rebound and their side effects will subside.

Mangels: Do you find that there's a part of them that is a little reluctant to have intermittent treatment worrying about the continuity of the treatment effect?

Wee: So for metastatic disease, intermittent therapy is not preferred. The standard of care for metastatic disease is still continuous therapy. They did a trial where they randomized patients to intermittent versus continuous ADT and they were unable to prove that intermittent was non-inferior. So that's why current standard of care is that patients with metastatic disease need to be on it continuous.

However, if a patient is really having a lot of trouble with therapy, knowing these risks and benefits, patients can make informed decisions for themselves what makes most sense for them. But the default answer is they should be on it continuously.

Mangels: What adverse effects require the greatest attention on your part?

Wee: Yeah, so I think the fatigue can be very problematic for a lot of patients. And in those situations, I try to optimize every other fatigue thing that could be done just as much as possible. So for example, if someone's having nocturia or if they're snoring, see if they have untreated sleep apnea, those type of things.

Exercise can actually help with fatigue as well, though certainly it's challenging to motivate yourself if you're already feeling fatigued. But I think those are some common things. And sometimes we go with our palliative care colleagues and our symptom management colleagues to help find other ways to help manage some of these side effects.

When it comes to hot flashes, there are some agents that have some efficacy at reducing the intensity and frequency of those.

And when it comes to cardiovascular risk, relugolix specifically can be helpful, especially in patients with prior major adverse cardiac events [MACE], given that in a randomized trial, the HERO trialopens in a new tab or window, patients with prior MACE had significantly fewer risk of non-fatal MI [myocardial infarction] or stroke.

Mangels: You actually read my mind. I was going to ask you about not only cardiovascular monitoring, but also diabetes monitoring, for example.

Wee: Absolutely. This can cause metabolic issues including weight gain, diabetes, etc., and this is where we need to partner with our primary care colleagues as well. These patients, sometimes the perception is if a patient has cancer, that's the only thing that matters, but in an ideal situation, these patients can live for years. So we do need to watch these other comorbidities and make sure we're managing them effectively to mitigate any adverse effects, especially when it comes to ASCVD [atherosclerotic cardiovascular disease] risk.

Mangels: I want to ask you in particular about older patients. I'm assuming a part of your practice is dealing with older patients with prostate cancer and particularly metastatic. They're underrepresented in clinical trials, so we don't have a ton of information about what works best and how it works. Does a patient's age and frailty and life expectancy figure into your treatment decision-making?

Wee: The life expectancy and frailty certainly does. The age sometimes could be a surrogate of that, but there are people that are 90 years old that look very vibrant, and so I don't use the age as an absolute cutoff by any means. I still try to do a doublet if possible. I'd be probably more hesitant for someone that's not as healthy to do a triplet with chemotherapy in those situations, but certainly you can have a lower threshold to reduce intensity of treatment.

One thing is if a patient let's say is on androgen deprivation plus an ARPI and you're wondering what's causing the side effect. Sometimes I'll just stop the ARPI for a few weeks and see if it gets better. If it gets better, you could reconsider going at a lower dose.

Mangels: Sure. When you're dealing with these older patients before you're making a treatment decision, are you typically ordering a geriatric assessment or a health assessment in general?

Wee: Yeah. I think this is one area where all of us could do better with the geriatric assessment and trying to ensure polypharmacy. There are a lot of competing medical issues that some patients can get when they're older.

That's one of the challenges I find is we have to watch the bone density, we have to watch lipids, we have to watch diabetes. And if you do too much at the first visit, sometimes the patient, all they hear is cancer and they kind of block out the rest.

So as my practice has evolved, I've put some of these survivorship things off to the second or third visit, knowing that we'll come back to them because they need to be addressed and they're important, but they don't immediately need to be addressed when a patient has so much on their mind, understandably.

Mangels: Thanks so much for your insights, Dr. Wee. And thank you for joining us on Beyond Diagnosis, where we explore not just what physicians know, but how to effectively and compassionately share that knowledge with patients. See you next time.