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Conversations With Prostate Cancer Experts


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Cognitive Impairment + Prostate Cancer

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.

What role do you think medical oncologists traditionally play in anticipating that patients might have these kinds of struggles? What role do you think the medical oncologist should play?

Dr. Alicia Morgans: That is a tricky question. I think, in general, medical oncologists have a lot of things on their plates. They’re trying to balance all of the side effects of therapy, the reason for doing a particular therapy, the complications that a therapy can cause that are medically dangerous, as well as where we go next if this treatment fails. I don’t know that they always take the time to dig deeply into questions about cognitive function, depression, or anxiety unless those things are very clear because a patient is complaining about them himself or a caregiver says it is a huge issue.

Medical oncologists have very short patient visits, especially for followups, and have many things going on that they’re trying to work through with patients. These cognitive changes are not always at the top of their list. However, it’s a critical part of our job and something that I take the time to do because of both my personal experiences and the way that I think medical oncologists should practice. That is not to say anyone else is wrong, but it is a really important part of my practice. This is something that patients are living with day to day. It’s something that needs to be addressed and can negatively impact their quality of life.

A patient’s experience of his quality of life is what really matters at the end of the day. Length of life and quality of life, to me, are both critically important. If you are not thinking clearly or you’re severely depressed or anxious—about your job, financial toxicity, or dying— you can’t live your best life. Helping optimize quality of life during treatment for cancer is a pivotal part of what we do. That being said, I don’t criticize any of my colleagues for missing discussions on this or myself when I’m having a day and running an hour and a half late, but it is something we should strive to do.

Are there ways to circumvent problems with cognitive function, or is it just a matter of identifying them early on and getting patients the help they need?

Dr. Morgans: I don’t know if there’s necessarily a way to completely avoid them, but we might, with some of the research being done, identify patient populations or individual patients who might be most susceptible to some of these side effects based on their genetics or based on the way they metabolize certain drugs.

If we can identify who may be most sensitive, we might be able to steer those men away from certain treatments and toward other treatments or delay treatment if that’s in their best interest and is a clinically reasonable choice.

Our goal is to provide men with a balance of best quality of life and longest length of life.

What we can do now is ask questions of our patients to diagnose these issues. We can ask, “How’s your mood? Are you feeling depressed? Are you feeling down?” We can figure out if they’re depressed or anxious.

If we talk to men and their caregivers about their daily life, we can treat these problems whether it is through pharmacologic therapy or counseling with a social worker, a psychologist, or a psychiatrist.

We can treat depression and anxiety.

Loss in cognitive function is a little more challenging. I have referred patients to behavioral or cognitive therapy (similar to what is recommended for patients post-stroke) to give them strategies for dealing with memory loss or thinking problems. I’ve had some success with that approach, but I would say the standard approach to managing cognitive decline is still being defined. This is the work that I am trying to do, because we still need to confirm which tools are best for measuring cognitive change, and then we need methods to prevent or reverse these issues.

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Prostate Cancer + Sexuality

Dr. Daniela Wittmann, an Assistant Professor in the University of Michigan’s Department of Urology, is a psychotherapist, educator, and researcher particularly interested in developing and testing interventions that support couples’ sexual recovery after cancer.

Prostatepedia spoke with her about the issues men with prostate cancer and their loved ones face.

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How did you come to work with cancer survivors?

Dr. Daniela Wittmann: About 35 years ago, I became a pediatric oncology social worker. That really formed my career, because I felt it was such important work. I liked working with cancer patients. I was working with people facing a significant crisis in their lives. There are many families applying their strengths to a challenging life situation and mastering it. It was very inspiring.

About 10 years ago, there was an opening in the Department of Urology at the University of Michigan. They wanted to open a prostate cancer survivorship program and they were looking for a sex therapist. I thought that would be a fascinating area to work in. I applied for and got the job and trained as a sex therapist. The rest is history. It became a passion. I now have a passion for sexual health in cancer.

Are there some issues that cancer patients face that are unique?

Dr. Wittmann: Yes. There is loss and grief. When you’re diagnosed with cancer, you worry about survival. You also worry about quality of life and what you might lose as a result of cancer treatment. That is the first issue every cancer patient faces.

The other issue that everybody faces is the impact on your family. Part of the quality of life is sexual health. I’ve learned that this is not just an issue for prostate cancer patients but for all cancer patients affected by cancer treatment in that area.

Are there some issues that breast and prostate cancer patients face that other cancer patients do not?

Dr. Wittmann: Yes. For most men, prostate cancer is a highly survivable disease. Quality of life becomes a huge topic.

Not so long ago, we analyzed long-term survivorship data in Michigan and found that the three top issues concerning prostate cancer patients were: fear of recurrence, the impact on their families and partners; and the management of long-term side effects. Of those long-term side effects, sexual function was the most problematic.

Do you think that caregiver issues come up more in the prostate cancer world than in other cancers?

Dr. Wittmann: No, they are fairly similar and come up in the same way.

The complication for prostate cancer patients is that the role of the cancer caregiver intersects with the role of a sexual partner. Sometimes, it’s difficult for caregivers to navigate this complex role. For the most part, partners really don’t have anyone to talk to about this. It’s an intimate area of life. People don’t necessarily talk to their friends and relatives about it.

Providers, generally speaking, don’t address it. It becomes an area of sorrow, sadness, and helplessness for partners. Although many partners are good at problem solving and many couples work it out, there are also many who don’t find a solution.

How do you work with prostate cancer patients and caregivers?

Dr. Wittmann: At the University of Michigan our program is designed to address both men and their partners. You can’t really address the men alone because their partners are very involved. Men want them to be involved; the partners want to be involved.

We start with a preoperative education where men who are about to be treated for prostate cancer and their partners come in for a two-hour seminar. Our multidisciplinary team presents information about surgery outcomes, side effects, and rehabilitation. We have a discussion at the end. We have anywhere between 15-25 couples and some single men in the audience.

After surgery, the men and their partners are invited to talk with a nurse practitioner. They get a physical and an evaluation of their functional recovery. Then they talk to me about the support that they need to maintain sexual intimacy as they’re recovering erectile function.

Some are followed on an as-needed basis. Others are followed every few months.

It is really difficult for men and couples to gauge if their own recovery is typical. We can give them some perspective and problem solve together. A small proportion of men asked for more intensive follow-up. Some have preexisting issues either in the emotional or sexual relationship that I can address with sex therapy. A few men are followed individually.

Do you have any thoughts or any advice for men who don’t have access to a program like this?

Dr. Wittmann: Yes. There are some resources that are potentially helpful. The American Association of Sexuality Educators, Counselors, and Therapists is an organization of people trained as sex therapists. They list good sex therapists on their website with a map of the United States. You can click on it and find a sex therapist in your local area.

Malecare has resources for heterosexual and homosexual men with prostate cancer.

If you’re in a cancer center, there may be a social worker who can work with you, or a nurse who has some knowledge about sexual health. Many nurse practitioners are quite well versed.

Any last thoughts for patients?

Dr. Wittmann: People can sometimes get very upset, sad, anxious, and even depressed about these issues, so finding a mental health provider in your area can really help. Some can also help solve problems with sexual health or find qualified providers who can, so definitely reach out.

Don’t feel that this is something you should solve on your own. There are resources out there. If your immediate physician, nurse, or nurse practitioner doesn’t know them, maybe a mental health provider will. Then, go online to find the resources that I just mentioned; these are good, vetted resources.

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Fear + Prostate Cancer

Ms. Nina Priebe is a social worker at the Cedars-Sinai Cancer Center in Los Angeles, California. She works with prostate cancer patients and their caregivers to manage some of the emotions sparked by the cancer journey.

Prostatepedia spoke with her about stress, depression, and prostate cancer.

Are there common themes that come up in your work with cancer patients? Are some specific to prostate cancer?

Ms. Nina Priebe: All cancer patients deal with the shock and disbelief of their diagnosis. They also go through feelings of lack of control, identity issues, sometimes role changes, changes in their family, and changes in communication.

Many things in their lives often have to be rearranged in terms of priorities. Side effects can have all kinds of impacts, both on emotions and psychological body image.

Many people have kind of an existential crisis: What does this mean? How did this happen? Why did this happen to me now? They’re meaning-making. They’re trying to make meaning of what happened. The caregiver experience parallels it in many ways.

In prostate cancer, men experience issues related to erectile dysfunction and incontinence. Some experience mood swings from the treatment. They may cry for no apparent reason whereas, in the past, they may have had a good sense of control over their emotions. That’s confusing and can be very overwhelming.

How does the caregiver experience parallel some of the issues that prostate cancer patients may find themselves facing that, say, caregivers of pancreatic cancer might not?

Ms. Priebe: A caregiver is anyone who helps. That help can range from practical kinds of help to emotional support. But the caregiver is also shocked by the diagnosis. Sometimes there were no symptoms. It was just a check-up. They too can have some denial or just some shocking disbelief.

Caregivers should be part of the treatment team. Because they’re not the patient, sometimes they put aside their own needs, which isn’t good in the long run. Some of them have their own medical problems, or they have the demands of elderly parents, young children, or special needs children, and the changing roles that may occur.

A typical change is that a man who always took care of the finances does not have time now because he’s in treatment or doesn’t have the energy. Role changes may occur and then change back again, but the caregiver balances his or her own work with caregiving.

Some issues that come up for prostate cancer patients and caregivers are related to stress and fear.

What role do you think fear plays?

Ms. Priebe: Fear changes, depending on the process. At the time of diagnosis, depending on the man’s history, fear can play a large role. My fiancé’s father had died of prostate cancer, so he was initially very fearful of death.

After that, the primary focus of his fears related to impotence. But my focus as a caregiver was on his survival.

You’re gathering information, going for second and even third opinions. I think the fear can be about making the right treatment decisions. Sometimes you have two and three differing opinions about what to do.

After treatment, there are fears about recovery for both the patient and the caregiver. Following that, people fear the cancer will come back. And then there is the anxiety around scans and blood tests every year or every six months.

Do you think the fact that there’s a fair amount of controversy over how to best treat prostate cancer adds to that sense of fear?

Ms. Priebe: Absolutely. In his case, my fiancé regrets his decision, but that’s because he had some adverse effects some years later. We see in hindsight. We didn’t know. He made the best decision he could at the time given what we knew.

What do you say to men and their caregivers? Do you have any advice about coping strategies or ways to deal with these emotions?

Ms. Priebe: As much as both of them can, I strongly advise them to maintain some part of a routine in their lives. I tell them to practice relaxation, which means different things for different people. There are all kinds of relaxation techniques, including hypnotherapy. But distraction, inducing relaxation as much as possible, and keeping some part of a routine are most important.

I have lots of patients who’ve gotten into adult coloring books. I have people that use guided imagery, which many of us use here at the Cedars-Sinai Cancer Center. Those kinds of things are very important.

What about support groups? Do you find them useful for men and caregivers?

Ms. Priebe: Some men who don’t have a good support system find it really useful. It varies. We have them, but many men just want to go on with their lives and they don’t want to focus on what they’ve been through with a group.

What about caregiver support groups?

Ms. Priebe: I think they end up being useful. People think that when they join a support group, they have to stay indefinitely. Sometimes, it might just be a certain stressful time in the process. Finding out that their feelings are normal—that other people have felt that way—can just be the reassurance needed to feel that they’re really okay.

What should patients and caregivers be aware of as they go into treatment or monitor themselves for recurrence?

Ms. Priebe: Being as generous with yourself as possible and allowing yourself to mourn are important. Until you mourn, you can’t go on to see: What did this bring to my life that might be positive? Have I now decided that different things are important to me? Whether something as simple as getting up and watching the sunrise or as complicated as a relationship that needed some repair, allowing yourself to mourn is the first step in being able to improve, adjust, and accept whatever has occurred.

You can’t really deal with anything until you acknowledge that you’re mourning.

Ms. Priebe: That’s right. You lost something. You grieve.


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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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Anxiety, Depression + Prostate Cancer

Mr. Chuck Strand is the CEO of Us TOO International Prostate Cancer Education and Support Network. He discusses the anxiety and depression often associated with prostate cancer.

A cancer diagnosis of any type triggers a wide range of initial reactions and emotions. While in some instances it might provide a sense of resolution, a more typical response may include sadness, loss, fear, guilt, stigmatization, embarrassment, anger, or disappointment.

Many aspects of living with a prostate cancer diagnosis can be sources of anxiety and depression— everything from anticipating the next PSA (prostate-specific antigen) blood test results to dealing with the post-treatment impact of common side effects like incontinence and erectile dysfunction (ED).

Unfortunately, men and their partners are not always fully informed about the likely side effects when selecting a treatment. In addition to managing the anxiety resulting from ED and/ or incontinence, an unexpected decrease in a man’s sexual virility can lead to a sense of betrayal or reduced trust in his medical provider or in the medical community in general. Recognizing and learning to cope with anxiety and depression can be critically important for effectively managing life with prostate cancer.

In a recent collaborative survey conducted by Us TOO International and CancerCare, 94 percent of men who were diagnosed with prostate cancer indicated that experiencing anxiety and/or depression is to be expected. Anxiety and depression can interfere with a person’s day-today activities, responsibilities, and relationships and can impact not only the person with cancer, but also the caregiver. Helping family members manage their distress may have a beneficial effect on the distress level of the person with cancer.

The stress and anxiety associated with a prostate cancer diagnosis can be significant enough to influence a man on active surveillance to opt for treatment earlier than necessary, resulting in what is often referred to as over-treatment.

Treatment decisions must address whatever aspect of disease management is a priority for each man, after he has sufficient information on all treatment options, possible or probable side effects, and management of side effects.

One man’s priority could be to do everything he can to minimize the possibility that prostate cancer will metastasize, while another man’s priority could be to do everything possible to maintain and maximize his quality of life. It is important for a man to recognize that once diagnosed with prostate cancer, the disease will unfortunately be a perpetual issue of concern and a potential source of anxiety due to ongoing monitoring of PSA test results at a minimum, regardless of the course of action he takes. While active surveillance can be emotionally exhausting, over-treatment can result in decreased quality of life with ED, incontinence, and the potential emotional and psychological impact of having second thoughts about his treatment choice.

Symptoms of Anxiety and Depression

Anxiety and depression not only affect the quality of a man’s life, but can also keep the body’s immune system from functioning at its full capacity. Additionally, it can have a negative impact on adherence to treatment regimens. Therefore, it’s important to recognize these conditions and attempt to address them accordingly.

Anxiety is a feeling of nervousness, fear, apprehension, and worrying—typically about an imminent event or something with an uncertain outcome. Symptoms include: feelings of fatigue or weakness, sweating (for no reason), chest pains, headaches, gastrointestinal problems, or inability to rest.

Depression is a feeling of severe despondency and dejection. Symptoms include: sleeping more or less (as compared with regular sleeping habits), loss of interest in daily activities, an unusual increase or decrease in energy, changes in appetite (eating either more or less as compared with regular eating habits), increased irritability or impatience, or difficulty concentrating.

Action Items to Help

Take action rather than passively accepting anxiety and depression as a given. Begin by acknowledging the very real relationship between anxiety, depression, and prostate cancer. Take stock of your own emotions. Talk to your doctor about your concerns. Make sure your diet is heart-healthy/prostate-healthy. Exercise even if you do not feel like it. Especially if you do not feel like it! Exercise releases endorphins and neurotransmitters that promote relaxation and eliminate excess cortisol, a hormone released during stress and associated with anxiety. Get mindful and try to incorporate yoga, meditation, acupuncture, or other holistic practices into your life. These lift the body, mind, and spirit. Try to keep a positive attitude when possible, but understand that ups and downs are normal and expected during prostate cancer treatment.

If appropriate, your doctor might be able to provide a referral to a counselor who can help. Some common techniques to effectively manage anxiety include talk therapy (especially Cognitive Behavioral Therapy [CBT]) and antianxiety medications. Depression can be managed though lifestyle changes to establish more connections and support, psychotherapy (including Cognitive Behavioral Therapy), pharmacological treatment and, in advanced situations, Electroconvulsive Therapy (ECT).

Reach Out!

If you are dealing with prostate cancer and experiencing anxiety and/or depression, know that you’re not alone. Educational resources and support services are available to help cope with anxiety and/or depression.

Many men with prostate cancer and their wives/partners have dealt with anxiety and depression. It can be helpful to attend an Us TOO prostate cancer support group to share experiences and gather information and strength from those who have successfully managed these challenges.

To find an Us TOO prostate cancer support group near you, visit www.ustoo.org/Support-Group-Near-You, call 800-808-7866, or email ustoo@ustoo.org.

To join a prostate cancer support group via telephone, visit www.ancan.org/support-calls.

For individual counseling on anxiety or depression by telephone and online group counseling, contact CancerCare at 800-813-4673 or www.cancercare.org.


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Living A Normal Life After Prostate Cancer

Dr. Stephen Freedland is a urologist at Cedars-Sinai in Los Angeles, California and the Director of the Center for Integrated Research in Cancer and Lifestyle, Co-director of the Cancer Genetics and Prevention Program and Associate Director for Faculty Development at the Samuel Oschin Comprehensive Cancer Institute.

Dr. Freedland treats the whole patient and not just a man’s prostate cancer.

He frames this month’s conversations about stress, depression, and prostate cancer.

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Historically, the goal was to cure cancer. We don’t really cure other major medical problems like heart disease, diabetes, high blood pressure, or high cholesterol: we manage them. Cancer, in general, and prostate cancer, in particular, are becoming chronic diseases. Occasionally, we need to do something more aggressive, but we really just need a management strategy so that people can live normal, healthy lives even after being diagnosed with cancer.

With this shift from quantity of life to quality of life comes an opportunity for us to have conversations about how prostate cancer and its treatments affect daily life. People are now younger at diagnosis than ever before. They’re still active. They’re still working. They’re still productive members of their families and of society.

How do we help them maintain that while providing the best cancer care? The challenge is how to marry those two. It’s not enough to focus on Gleason score, PSA, and stage. The focus is on the patient. On the person. It’s not just about the numbers.

I applaud Prostatepedia for delving into this subject matter with some very engaging conversations with some of the world leaders on the topic. I work very closely with Dr. Arash Asher at Cedars-Sinai Medical Center. We focus now on nutrition, exercise, and psychosocial health. It’s really spectacular to see. Men are able to maintain much of their quality of life and sometimes feel better than ever.

At the same time, we’re realizing that what works for one patient will not necessarily work for another. There is no shortcut to sitting down with a patient, understanding his needs, goals, and desires, and then working together to come up with a care plan that manages his cancer and his side effects. We want to keep you psychologically strong and able to fight your cancer–but also to live your lives.

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Prostate Cancer Vaccines

Dr. Douglas McNeel is a Professor in the Department of Medicine at the University of Wisconsin-Madison and Director of Solid Tumor Immunology Research within the UW Carbone Cancer Center. Dr. McNeel focuses on prostate immunology and the development of antitumor vaccines as a form of prostate cancer treatment.

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Can you give us an overview of vaccines for prostate cancer: which are available now and which are still in development?

Dr. McNeel: If a person has prostate cancer, he usually has surgery or radiation therapy to remove the cancer. These initial therapies cure a majority of patients, but about a third of the time, the disease comes back or resurfaces. We can usually detect the recurrence at a very early stage with a PSA blood test.

Our original thought was that the point of recurrence is the time to intervene, to create a tissue-rejection response.

You can’t really do without a normal kidney. The same is true of the liver.

But you can do fine without a prostate. So if we can create a rejection response to remove any prostate tissue, whether it’s cancer or not, that would be okay.

That was our original thought. The idea with vaccines is to teach the host to generate an immune response that will recognize and destroy cancer cells. But this is a challenge to treat existing tumors with vaccines. With infectious disease vaccines—what we normally think of when we talk about vaccines—we get an immune response that then protects you later on. We call them prophylactic vaccines. But we don’t treat active infections with vaccines. We treat them with therapies that target the bug directly or infuse in an immune system like an adoptive therapy approach.

With cancer, we see the same kinds of hurdles. What we know from animal models is that there are a number of cancer vaccines that can protect animals from cancer, but to get the best response against existing cancers, you have to start when tumors are small and barely detectable. That has been a challenge in pushing those vaccines into human trials.

We’re also learning that when you generate an immune response by means of a vaccination, the cancer can put up a big barrier very quickly to fight against it. Our thought process on vaccines is currently in the midst of changing given that kind of information.

A number of cancer vaccines have been studied over the years. Most of the effort has not produced anything, because we have been looking at vaccines alone, usually in patients with more advanced cancers.

There has been one exception. Provenge (sipuleucel-T), which is a vaccine targeting a protein called prostatic acid phosphatase, was approved in 2010. In this approach, patients have blood removed and their antigen presenting cells are spun out. Then the target of the vaccine, this prostatic acid phosphatase protein fused to an immune-modulating drug, is put together in the lab in the culture dish. The education of the immune system akes place in the lab, if you will. Those cells are then shipped back and infused back into the patient two or three days later. That process is cumbersome, but the approach was shown to be effective.

One large trial led to its FDA-approval. But there were other supportive Phase III trials showing that people who got the vaccine versus those who got a placebo vaccine did better and lived longer. It was a challenge rolling out Provenge (sipuleucel-T) because we don’t see PSA declines with it. We also don’t see changes in the tumors on scans, but we know that men with advanced prostate cancer, in general, live longer if they get that treatment.

Prostvac is an approach that has been in Phase III trials up until recently. Unfortunately, the Phase III trial was deemed to not have met its primary endpoint in September 2017. It did not show that people lived longer. It’s unclear if Prostvac will be developed or not.

Prostvac is a viral vaccine. There is one virus that encodes PSA and then a separate virus. People are immunized with one virus coding the PSA and then boosted with the separate virus. The idea is to use viral vaccines to focus the immune response on the target protein PSA.

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