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Talking To Your Doctor About Side Effects

Dr. Alicia Morgans is a medical oncologist at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois. She specializes in treating advanced prostate cancer and is particularly interested in addressing treatment side effects.

Prostatepedia spoke with her about cognitive impairment, stress, and prostate cancer treatment.

Have you had any patients whose stories have impacted how you approach patient care or how you think about your role?

Dr. Alicia Morgans: The most poignant in my mind right now is my grandfather who recently passed away from advanced prostate cancer. I know we have spoken about him before. His passing really brought home to me how important it is to have a good medical oncologist, and how privileged we are as medical oncologists to share in this journey with our patients and their families. He was diagnosed at a late age with prostate cancer, but throughout his entire life, he had been averse to doctors and medical care. It was challenging for our family, and for me in particular, because by that time, I was already a prostate cancer specialist. We tried to help him understand that his doctors made recommendations to help him.

During his entire treatment history, I really felt very strongly and personally how important it is to balance quality of life with length of life for men with prostate cancer and their families. Living longer doesn’t mean living better for a lot of people. It’s really important for physicians to recognize that we can’t put our own beliefs about what is most important onto someone else. We have to listen to our patients so that we hear what is most important to them. That is the thing that is most clear in my mind right now.

As my grandfather approached the end of his life, we had to make difficult decisions for him that walked a fine line between length of life and quality of life. He made decisions that some people may not make. He chose not to undergo further therapy at a certain point, even though those therapies existed, because it didn’t make sense for him given his goals and preferences. That is what I think about as being most impactful when I meet with patients.

Do you think patients are often reluctant to have those kinds of conversations with their doctors?

Dr. Morgans: Absolutely. Those are not easy conversations to have. I would say that we were lucky in my grandfather’s situation. We were lucky because I’m persistent and just kept pushing him to speak his mind and let us know what was important to him. In many conversations with patients, I find it’s really important to wait and just be quiet. Let some space fill the room so that men who may be reluctant can take that next step and answer.

As physicians, many of us are so pressed for time that we are almost pressured in the way that we ask those kinds of questions. Just letting some space sit in the room can give men an opportunity to speak. The other thing that is important to do for men with prostate cancer is engage with their caregivers and loved ones, as long as the patients feel comfortable with this interaction. Sometimes caregivers will share things that men themselves don’t feel comfortable sharing. But once it’s out, the men can open up. They feel able to continue that conversation.

I guess some patients might not know how they feel or might have a difficult time expressing how they’re feeling.

Dr. Morgans: Absolutely. No one wants to feel weak. No one wants to admit that he’s not feeling like he did 10 years ago. Optimism is a huge part of feeling well too, and for some, admitting that we don’t feel as well as we did before can stand in the way of optimism.

I think it’s important for us as physicians and as caregivers to make it clear to people that it’s okay to express those feelings. A lot of times we have ways of making those symptoms better. If you’re able to express it, maybe there’s something we can do about it.

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Genomics In The Clinic

Dr. Alicia Morgans is a medical oncologist at Vanderbilt-Ingram Cancer Center in Nashville, TN.

She specializes in treating advanced prostate cancer. She is particularly interested in addressing treatment side effects and in how men with advanced prostate cancer make treatment decisions.

Prostatepedia spoke with her recently about how genomics is—and isn’t—being used in the clinic.

Mexican Friends hanging out in CoffeeshopWhat is genomics versus genetics?

Dr. Morgans: Genetics looks at different genes that can be passed on and inherited through different generations to give you certain traits or different features, like eye or hair color. Genomics for oncology is the study of the genes that alter a cancer’s behavior or growth. It involves our understanding of what is driving a cancer’s growth in a particular person.

Are we currently using genomics for screening prostate cancer?

Dr. Morgans: We use genetics in that we think about men with a first-degree relative with prostate cancer as being at higher risk. Some organizations suggest that men with a first-degree relative should start screening for prostate cancer at an earlier age, though with the United States Preventive Services Task Force (USPSTF) recommendations, things are a little bit murky right now.

We think about people with a family history of breast and ovarian cancer who have BRCA1 and BRAC2 mutations as being an additional group who may think earlier about screening for prostate cancer.

But we’re not necessarily using genomics in the screening setting yet. We use genomics after we have screened someone and taken a biopsy. Genomics can help us predict who may have an aggressive cancer and who may have a less aggressive cancer that can be followed with surveillance instead of treated immediately with surgery or radiation.

How are we using genomics to select initial treatments?

Dr. Morgans: There are some tests that men can use at the time of prostate cancer biopsy or after a prostatectomy that help them and their doctors think about how likely their cancer is to come back, to become metastatic, or to cause them to dieof prostate cancer. Those are tests urologists most commonly use.

Some are used when men get a biopsy and some, like the Decipher test, are used on a prostatectomy specimen. GenomeDX, the company that makes Decipher, just announced a biopsy product to predict the risk of metastatic disease, as well.

There is the Prolaris test which is done on a biopsy specimen. Prolaris uses genomics to risk stratify who is likely to have their cancer come back in an aggressive form and who will have low-risk disease and not necessarily need to have surgery.

group of friends eating on the kitchen and preparing food

How do we use genomics to predict who will or will not respond to certain drugs? For example, looking at AR-V7 mutations to predict resistance to drugs like Xtandi (enzalutamide) and Zytiga (abiraterone)?

Dr. Morgans: AR-V7 testing, which would potentially help us predict who would respond to drugs like Xtandi (enzalutamide) or Zytiga (abiraterone), is not in clinical practice yet. We do not yet have a Clinical Laboratory Improvement Amendments (CLIA)-certified test that can identify AR-V7 mutations in circulating tumor cells or in prostate tissue that will tell us whether or not a patient will respond to Zytiga (abiraterone) or Xtandi (enzalutamide). At some point, a test like that will likely be commercially available.

There are clinical trials that are attempting to use the presence or absence of AR-V7 to either enroll people, risk stratify them, or statistically stratify them in the analysis, but it is not a commercially-available and clinically-used test at this point.

Do you think that is the path genomics will take in the future?

Dr. Morgans: We would love to have a test that could tell us which drugs will work for a particular patient’s cancer and which drugs won’t. We don’t have those tests now, but if and when that information becomes available to clinicians, it will dramatically impact how we treat prostate cancer.

Do you think genomics will change how we design clinical trials?

Dr. Morgans: It already has to some extent. There are clinical trials that focus around certain mutations or alterations. There are studies that include only patients with AR-V7. There are PARP inhibitor studies that use the presence or absence of DNA repair defects to include or exclude patients. These advances in our understanding of genomics are definitely being integrated into clinical trial design.

If those clinical trials demonstrate a benefit, it will be another step forward for genomics. Genomics will then have to be incorporated into our practice over time.

Young man carrying his bicycle

So it’s just a matter of time before we demonstrate genomics’ usefulness and then it will quickly become integrated into patient care?

Dr. Morgans: I don’t know how quickly, but we’re trying. Changing practices in medicine doesn’t always move quickly enough for many of us for important safety reasons in place to protect patients. I would say that genomics has already demonstrated utility. Now we need to finish the clinical trials to really prove that it has a role in clinical practice to help men live longer and better lives. If the studies don’t show this, it won’t be integrated into patient care. I think we are all hopeful that genomics will provide meaningful direction for clinicians as we choose among treatments for men with prostate cancer.

To this point, there is a great New England Journal of Medicine paper by Dr. Joaquin Mateo and colleagues that performed biopsies on men with advanced disease who had had one or two lines of chemotherapy. (See Prostatepedia June 2016 for a conversation with Dr. Mateo about that study.)

The men in the study underwent biopsies and were then treated with Lynparza (olaparib), which is a PARP inhibitor. Those men who had DNA repair defect mutations appeared to have a very high response rate to Lynparza (olaparib) by the criteria included in that study.

I would say that genomics is already demonstrating the possibility of effectiveness. It just needs to be demonstrated on a larger scale. Mateo’s study only included 50 or so people, not hundreds, as we would have in a definitive, practice changing study. But early signs of clinical utility are definitely there.

Photo beautiful couple in winter forest

Couldn’t a medical oncologist take that study by Dr. Mateo and his colleagues and apply the same principles to his or her own patient?

Dr. Morgans: Medical oncologists are doing that, but sometimes we’re limited by insurance. I have patients on Lynparza (olaparib) right now, and we are hopeful that all will go well. We commonly use genomic testing to look at mutations in patients’ prostate cancers, but whether or not an insurance company will pay for us to use an off-label treatment is another question.

It’s easier in a clinical trial setting, because pharmaceutical companies pay for the cost of the drug. It can be more challenging if you’re not in a clinical trial setting.

Are those drugs very expensive?

Dr. Morgans: One of my patients paid out-of-pocket for a week for Lynparza (olaparib), and I believe it was in the thousands.

What about genomic tests? Are they expensive?

Dr. Morgans: That varies by state, by medical institution, and by patient insurance. I have not had trouble getting genomic testing for my patients.

What if a patient has already been treated years ago. Is the biopsy tissue usually preserved or does a patient have to request it?

Dr. Morgans: The patient doesn’t have to request it if a biopsy or surgery was already done. The patient can talk to his doctor or his family could talk to his doctor and say, “We want to have genomic testing.” The doctor just has to request the test and identify the tissue sample that should be used. Sometimes the patient has preserved samples. If that patient has had a prostatectomy, for example, there may be a recently preserved sample that could be sent.

However, I would say the most useful genomic testing is done on a metastatic site at the time that a patient is progressing after first line treatment. The reason is that over time, after being treated with multiple medications, prostate cancers acquire new mutations that allow them to become resistant to different treatments.

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If you sample the initial prostate tumor, you may find a set of mutations that don’t include the ones currently driving that cancer and allowing it to get around the treatments used at that particular time. If there is a way for patients to undergo a biopsy of a metastatic site, that tissue would give them a clearer picture of the mutational or genomic profile of his cancer at that time. There can also be some difference, or heterogeneity, between the genomic profile of different metastatic sites. The genomic profile of one metastatic site may not be exactly the same as another metastatic site. There are stronger driver mutations that we think really help that cancer grow and spread and are driving the growth of that cancer. We hope those mutations would be the same across different metastatic sites, but different sites do acquire different mutations. That has been demonstrated in multiple studies at this point.

If you get multiple biopsies over a number of years, should you have all of those tissue samples tested?

Dr. Morgans: You could. But I don’t know how many times an individual insurance company will pay for genomic testing. I have had some patients tested multiple times, usually separated by at least a year to two years because they were on one therapy and then another. These are not inexpensive tests. Sometimes an insurance company may say, “We just won’t pay for that.” But I have not had a problem getting a genomic test at least once for patients.

Is there anything else patients should know about genomics?

Dr. Morgans: Genomics is where we’re going. Being able to predict who will respond to which treatment is our goal. We want to prevent people from being exposed to treatments that aren’t going to help them and stop them from wasting time on therapies that are not going to help them to live longer and better lives.

I would say that, right now, while genomic testing is happening in the clinic, sometimes it takes a patient asking, “Can I have genomic testing on my tissue?” If you are really interested in getting cutting edge prostate cancer treatments, at least understanding which mutations are present in your personal cancer is the place to start.