Psychological Effects From ADT a Growing Challenge in Prostate Cancer

Heather Jim, MD

Androgen-deprivation therapy (ADT) can be associated with significant psychological effects in patients with prostate cancer.

Additionally, these side effects—which include depression, Alzheimer disease, and coronary disease—are often underreported by patients, according to Heather Jim, MD.

“It is really important for the clinician to let [patients] know that a lot of men experience this. Let’s get them help and try to help them feel better,” said Jim, who discussed these significant events in her lecture at the 2016 OncLive State of the Science Summit on Genitourinary Cancers.

OncLive: What are the side effects associated with testosterone-lowering drugs?

Why is depression an important side effect to address?

What about concentration?

In an interview with OncLive during the meeting, Jim, an associate member in the Health Outcomes and Behavioral Department at Moffitt Cancer Center, further described the psychological impacts of testosterone-lowering drugs for patients with prostate cancer—and what oncologists should do to help.Jim: Testosterone-lowering drugs are associated with a whole constellation of side effects that include depression, cognitive impairment, fatigue, loss of muscle mass, and inflammation, as well as cardiovascular disease and cardiovascular mortality.It is really quite astonishing, because we have done some research at Moffitt Cancer Center that suggests that after about 6 months on ADT, 40% of patients are experiencing clinically significant depressive symptoms, which is really a huge number. It is important to treat depression not only to help patients feel better, but because depression is associated with increased mortality in patients with prostate cancer.Concentration is an interesting one because there are data that suggest that ADT is associated with increased cognitive impairment over time, and particularly increased problems in visual motor skills, which is the ability to mentally represent 3-dimensional shapes in your mind and then translate that into fine motor skills—such as copying a task or creating building blocks.

In clinical practice, you must hear about “chemo brain” often. Is there a relationship between that and ADT?

What about muscle mass exercise in coronary disease?

We do neuropsychological testing with these patients and what we find is that, at least in our study, about 50% of men experience cognitive impairment after 1 year on ADT. There has also been data from other groups to suggest that ADT is associated with an increased risk of Alzheimer disease. Men who have been treated with ADT for at least 12 months have doubled their risk of Alzheimer disease.Yes. It is interesting because it’s not really clear how much of cognitive impairment is due to the cancer itself versus due to therapy. We know, for example, that even patients who have been treated with chemotherapy or ADT show cognitive deficits before they even receive that treatment. Is it due to the fact that there may be some sort of systemic inflammation? We are not sure—even before there is any kind of treatment.Testosterone, of course, is associated with increased muscle mass. When you eliminate testosterone from the body using ADT, then patients start to lose muscle mass. This doesn’t only include upper body strength such as grip strength, but also lower body strength as well—such as strength in their legs. Perhaps it is not surprising that patients who are treated with ADT also experience significant fatigue that increases over the first 12 months.

Alzheimer disease is included as a side effect, as well?

What we actually found is that the increases in fatigue in these patients are associated with inflammation increases in circulating inflammatory cytokines. That may be one of the mechanisms by which ADT causes fatigue.The data are really kind of intriguing about that. As you know, there is no cure for Alzheimer disease or no real way to prevent it. At this point, it is something that just needs to be monitored in these patients.

There are things that patients can do who maybe are experiencing cognitive impairment, but not dementia. It is a less severe form of cognitive impairment. For example, they can learn kind of compensatory behavioral strategies to help sort of remember things, such as putting their keys in the same place every time. It can help normalize some of these cognitive deficits as a result of cancer treatment.

Then, there are data in other populations—such as healthy older adults—that suggest that exercise may have beneficial effects on cognition. Those are things that patients can try, as well. There is no real downside to exercising and no real side effects.

Are there challenges with men reporting these side effects?

Why should physicians focus on these side effects?

There is better imaging that makes it easier to diagnose Alzheimer at an earlier stage now. Again, it is one of those situations where you may have that diagnosis and, certainly, there are drugs that can slow cognitive decline in people with Alzheimer disease. As of now, there’s no real cure for it.One of my messages today is that you really have to ask these men about some of the specific side effects that they might be experiencing, because we know that patients with cancer in general tend to underreport some of the side effects that they have. This is particularly common in older men who might feel some stigma associated with depression and cognitive impairment, or these types of things.There are a couple reasons. First of all, depression is associated with increased mortality in patients with prostate cancer. However, depression in patients with other cancers is associated with reduced treatment adherence. To the extent that you treat and improve this depression, there is the chance that you may be able to keep patients on treatment for longer and, potentially, also positively impact their survival.

In some ways, the physician or clinician, is the first point of contact. They need to be the one asking about these things, so that if a patient says, “Yes, I’m feeling kind of blue,” or, “Yes, I’m having cognitive problems,” they can refer those patients out to get additional help from specialists who can address those particular issues.