Risk Factors in Advanced Prostate Cancer

Stephen Freedland, MD: We’ve been hearing about cardiovascular events for a long time in prostate cancer, but as we’re getting better at keeping these men alive, and not dying of their prostate cancer, we are seeing an increased risk of cardiovascular events. We know that men with cardiovascular disease are more likely to develop prostate cancer. This is a group of men who walk in the door and are at a higher risk of having cardiovascular disease and developing cardiovascular events: MI [acute myocardial infarction], stroke, or heart failure. We need to be careful with these men and thoughtful in terms of treating them with ADT [androgen deprivation therapy]. There is overwhelming observational data that androgen deprivation therapy, at least via GNRH agonist, which is what’s largely been done for the last several decades, does increase the risk of cardiovascular events.

When we think about the comorbidities we’re looking for, a lot of men will have hypertension, and that is a cardiovascular risk factor. In some of the data sets I’ve looked at, upward of 70% to 80% of men with advanced prostate cancer will have hypertension. Obesity is another cardiovascular risk factor, it’s about one-third of the men we see. We try to do clinical trials of statins; however, they’re tough to do because so many men are already on statins to begin with. If you lump some of those together, you end up with a metabolic syndrome. Many men will have diabetes as well. Certainly, if they’ve had a cardiovascular event, an MI, they’ve had stents placed, they’re on anticoagulants for the stents, or they’ve had a stroke, those men are at particularly high risk of developing another cardiovascular event from the ADT. We need to be cognizant of that. This is not to say that we should avoid ADT, but we should use it carefully. Does this patient really need hormonal therapy in the first place? If yes, they have metastatic disease, or symptomatic—in certain circumstances we’ll know it has tremendous benefits. We have to be thinking, what can we do to reduce the risk of having new cardiovascular events in these patients?

One thing I spend a lot of time talking with my patients about is lifestyle interventions: getting exercise and losing weight. Invariably the question is, what’s the best way to lose weight? When I talk to different dietitians and experts in the field, there’s only 1 thing they can all agree on: that simple sugars are bad—cookies, cakes, candies, and soda. That’s what I focus on, which is trying to eliminate the simple sugars. Within that, if patients are interested in a vegan, Mediterranean, or ketogenic diet, I’m happy to work with them. But I make sure they’re aware that diet is important, but exercise—particularly vigorous weight-bearing exercise—is important in terms of reducing osteoporosis.

Moving on from lifestyle, is there anything we can do drug-wise to try to reduce those risks? There are some exciting data with a new oral GNRH antagonist, relugolix. In a randomized trial, a secondary outcome was a reduced risk of MACE [major adverse cardiovascular event]. It wasn’t the primary outcome of the study. It’s consistent with some of the older data we saw with degarelix, but that was never the primary outcome of a study. There are increasing data that this may be a class effect of the GNRH antagonist. At this point, we don’t know that for sure, but it does seem quite promising.

Almost everyone is hypertensive, needs to lose a little weight, and has some high lipids. But the strong risk factors would be if they’ve had a MACE event before, they’ve had stents, they’ve had a CABG [coronary artery bypass grafting], they’re on blood thinners because of the stents they have, or they’ve had a stroke or TIA [transient ischemic attack]. With those patients, we have to be thoughtful and say, “They need hormonal therapy, but is putting them on an agonist the right answer?” I’m not here to say yes or no, but it’s something we need to pause to think about. What is the way that I’m going to protect this patient from getting into trouble with this prostate cancer, and also how am I going to prevent him from getting in trouble with his heart?

What’s amazing is that if you look at men with prostate cancer, not necessarily the men getting ADT who are a little more advanced, but in general, men diagnosed with prostate cancer are more likely to die of heart disease than prostate cancer. The patient is diagnosed with cancer, yet they’re more likely to die of heart disease. Heart disease is the No. 1 killer of men in general, so we’ve always got to be thinking heart-healthy. We’ve learned that there’s the suggestion that relugolix, particularly GNRH antagonists, may be more heart-healthy.

Transcript Edited for Clarity

*Dr Freedland receives consulting honorarium from Astellas, Pfizer, Janssen, Clovis, Merck, AstraZeneca, Sanofi, Bayer, and Myovant. He is a speaker for AstraZeneca and Sanofi.