Tag Archive for: testosterone

What Are Current Prostate Cancer Treatment Options?

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What Are Current Prostate Cancer Treatment Options? from Patient Empowerment Network on Vimeo.

What treatment options are available for prostate cancer patients? Expert Dr. Channing Paller shares an overview of prostate cancer treatment options including surgery, radiation, combination therapies, hormonal therapies, and the PEACE-1 clinical trial.

Dr. Channing Paller is Director of Prostate Cancer Clinical Research at Johns Hopkins Medicine. Learn more about Dr. Paller.

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Transcript:

Katherine:

What are other options that are available now, for patients? 

Dr. Paller:

For curative intent, the main two treatment options are surgery, radiation. Many people for very localized disease are trying other therapies, such as cryotherapy, and more focal therapies. But really, for curative, the standard is surgery or radiation. And as it gets more advanced, circling back to advanced prostate cancer, we are learning that combination therapy is better. So, adding pills like abiraterone, adding systemic therapies, help patients do better. 

So, there’s a big, long list of therapies upfront that we use for metastatic hormone-sensitive prostate cancer. There’s abiraterone, there is apalutamide (Erleada), there’s enzalutamide, and now, darolutamide (Nubeqa).  

And in fact, in fit patients that can tolerate chemotherapy for metastatic high-volume prostate cancer patients, we always recommend triple therapy, either with abiraterone, docetaxel, and ADT, or with darolutamide, docetaxel, and ADT, and these patients really seem to do better for longer. The other thing I would add is the PEACE-1 trial, which looked at abiraterone and docetaxel, found that patients would do best by adding growth factor support. And so, that is recommended. 

The other thing I want to point out to patients is, I know we’re all eager to get started when we find out we have a diagnosis of metastatic prostate cancer, but sometimes, these therapies are quite tough on the system when you have a lot of cancer in your body, and my recommendation to everybody is, one thing at a time. 

So, start the hormone therapy and wait at least 30 days, and in fact, in the PEACE-1 trial, they waited 45 days, right? That allows the testosterone levels to fall, it allows you to adjust to the side effects of hormone deprivation therapy, and it allows your body to be ready for the next line of therapy. And you can add the ADT to second line, such as abiraterone or daro during that time, but not adding the chemo all at once, that really makes a difference. 

I find, unfortunately, when patients and their providers don’t follow those strict criteria, as they did in the trial, meaning they start chemo and abiraterone and ADT on day one, the levels of chemotherapy get higher in the bloodstream because testosterone regulates that, and we’ve published on that before. And they end up with terrible side effects from the chemotherapy, such as neutropenic fever, which means you end up in the hospital with a bloodstream infection and a fever, and more neuropathy, meaning numbness and tingling in your hands and feet. 

And so, I really caution people to spread those therapies out over the first 90 days, and you’ll do better in terms of side effects, and just as well in terms of overall survival. 

Katherine:

Where does hormonal therapy fit into the treatment options, and have there been any advances in hormonal therapy? 

Dr. Paller:

Yes. So, hormonal therapy is the mainstay of how we take care of prostate cancer patients, whether we do this with surgical castration, which is not done very often anymore, or we do it with an LHRH agonist, or we do it with an LHRH antagonist. So, that means that we can do it with medicines that block the signaling, but that tells your body to produce testosterone in various ways. What’s really neat is we’ve made advances, that there are now oral options for some of these therapies. 

In particular, there’s a new therapy called Orgovyx, or relugolix, that is an oral LHRH antagonist that locks testosterone and allows us to stop prostate cancer growth. In addition, there are a variety of LHRH agonists that can be given as subcutaneous shots. 

Low Testosterone in Cancer or Transplant Survivors

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I was one of the authors (out of more than 50) of a review article on male specific late effects in stem cell transplant patients [1]. The article looked at many late effects in male transplant survivor. This post is a summary on one late effect, hypogonadism (that is low testosterone) as well as my opinion about the recommendations on screening for low testosterone.

We do not know much about low testosterone in cancer survivors or transplant survivors. There is a significant increase in the incidence of low testosterone but the size of the increase in transplant survivors is not well understood. Symptoms related to low testosterone include: “loss of body hair, small testes, and ED (Erectile Dysfunction)”. Other symptoms that may be signs of low testosterone but may be signs of other problems include: “loss of libido, anemia, fatigue, lack of motivation, reduced muscle mass, and increased fat mass” (I don’t really know what “lack of motivation” means). The article recommends: “testing and consideration of hormone replacement therapy based on symptoms”. This is similar to what has been recommended in the past [2].

In 2016, some 23 years after my bone marrow transplant (BMT) I was diagnosed with low testosterone. I had finally asked one of my doctors to get tested and my testosterone level was 192 (my free testosterone was also low, and this is useful for the doctors, but I won’t mention it anymore). The normal level of testosterone is between 300 and 1000 nanograms per deciliter (ng/dL). [3] While I had symptoms, low libido, loss of muscle mass and fatigue primarily, no doctor had asked about those symptoms, and I had not thought about them as more than getting old.

I started on testosterone replacement, and it has made a huge difference. The biggest difference in my mind is less fatigue. One of the more common side effects of testosterone replacement is it can raise your red blood count (I like to call this an “effect”). Since a year or two after my transplant, my hemoglobin was on the low side (typically 12-13, normal for men is 13.2-16.6) and my hematocrit was generally between 37 and 40% (normal for men is 38.3-48.6%) [4]. A few years ago, at my annual exam my hematocrit was close to 35%. I went to see an oncologist (the oncologist who treated me is no longer seeing patients in the office). A whole bunch of tests were run, but not a testosterone test and nothing abnormal other than my red blood values was found. After starting testosterone replacement, my hematocrit is 43-45% and my hemoglobin is 14-15. The biggest change for me is that I have far less fatigue presumably because I have more red blood cells.

Testosterone levels naturally decrease with age. The folklore is that the testosterone level decreases about 1% per year from age 30 or so. [5] Other sources say from age 20. I believe this means that if you level is 800 at age 30 (there seems to be little data for a “normal” level at different ages), it will go down about 8 units per year (1% of 800). So, at age 80, the level would be around 400 (if this actually means a decrease of 1% of the current level every year, it will go down to about 480 at age 80). If the level was 600 at age 30, then it would be about 300 at age 80 (or around the low end of the normal range, which I imagine is about the average level for 80-year-old men). What if a 30-year-old had a testosterone level of 800 and then was diagnosed with AML and had chemotherapy and a transplant? Perhaps 2 years post-transplant is now 500, which is normal. There seems to be no data on testosterone levels in long term transplant survivors. However, if this goes down 8 units a year (this seems to be as good a guess as any), then after 25 years the level would be 320 and after 30 years it would 280, which is less than the 80-year-old man without cancer. It is important to state that there appears is no data to support or refute this scenario. Still my belief is that this is essentially what happened to me. My guess is that quite a few male transplant survivors have a testosterone level in the normal range 1 or 2 years post-transplant (although most will not have it tested) but will eventually have hypogonadism and likely not realize it.

While there is a lot we do not know about testosterone levels in transplant survivors (or for that matter healthy men), there is one thing we do know. “The majority of health care professionals do not address [sexual dysfunction]” [1]. In my mind this calls into question the recommendation to test testosterone levels “based on symptoms”. Most doctors do not seem to ask about symptoms specific to low testosterone and the other symptoms are non-specific. It seems to me that not testing testosterone levels at say 1 or 2 years post-transplant is likely causing harm to some male long term survivors. A better guideline would be to routinely test 1 or 2 years post-transplant and then again if symptoms warrant.

The BMT Infonet as part of their Celebrating a Second Chance at Life Symposium had a really good workshop on Sexual Concerns in Men after Transplantation by John Mulhall MD, from Memorial Sloan Kettering Cancer Center. You will have to register before viewing the replay of this workshop. While it covered other topics, there was a lot of information about low testosterone 

Contact Art Flatau, flataua@acm.org

Bibliography

[1] Phelan, R et. al., “Male-Specific Late Effects in Adult Hematopoietic Cell Transplantation Recipients: A Systematic Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complica,” Transplantation and Cellular Therapy, 2021.

[2] Navneet, Majhail S.; et. al., “Recommended Screening and Preventive Practices for Long-Term Survivors after Hematopoietic Cell Transplantation,” Biology of Blood and Marrow Transplantation, vol. 18, no. 3, pp. 348 – 371, 2012.

[3] Icahn School of Medicine at Mount Sinai, “Testosterone,” [Online]. Available: https://www.mountsinai.org/health-library/tests/testosterone

[4] Mayo Clinic, “Complete Blood Count,” [Online]. Available: https://www.mayoclinic.org/tests-procedures/complete-blood-count/about/pac-20384919

[5] Mayo Clinic, “Testosterone therapy: Potential benefits and risks as you age,” [Online]. Available: https://www.mayoclinic.org/healthy-lifestyle/sexual-health/in-depth/testosterone-therapy/art-20045728

[6] WebMd, “Is Testosterone Replacement Therapy Right for You?,” [Online]. Available: https://www.webmd.com/men/guide/testosterone-replacement-therapy-is-it-right-for-you

Why Patients Should Speak Up About WM Symptoms and Side Effects

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Why Patients Should Speak Up About WM Symptoms and Side Effects from Patient Empowerment Network on Vimeo.

Is Waldenström macroglobulinemia (WM) causing fatigue? Dr. Jorge Castillo shares why WM patients should share any symptoms and side effects they experience with their healthcare team.

Dr. Jorge Castillo is Clinical Director at the Bing Center for Waldenström Macroglobulinemia Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School. Learn more about Dr. Castillo, here.

See More From The Pro-Active Waldenström Macroglobulinemia Patient Toolkit

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Transcript:

Katherine:                  

Fatigue seems to be very common among Waldenstrom’s patients. Here’s a question that we received before the program. Kasey asks, “Why do I feel so tired all the time? Is there anything that can be done about it?

Dr. Castillo:               

That’s a great question, and as I said before and basically kind of summarizing what I put together, I mean, there are many patients why a symptom with Waldenstrom’s could be fatigued. One of them is they could be anemic. The other one, they could have some hyperviscosity symptoms causing some fatigue, maybe some inflammation in the body because of the Waldenstrom’s, but maybe there are other reasons why patients can be fatigued.

And if you go out there in the streets and you start asking people, “Are you tired?” 80 percent of Americans are going to be tired. I’m not trying to minimize the symptoms of the patients. What I’m trying to say is we need to be very careful at understanding what the relation of the fatigue is with the disease. We need to be convinced that there is a relation there.

If that happened in my clinic – for example, a patient comes to see me, and they are fatigued; their hemoglobin is 14, which is normal; their IgM is about 1,000, which is not supposed to cause hyperviscosity. So, I do not know really in that context if the Waldenstrom’s is driving the fatigue or not.

Katherine:                  

Or if it’s something else.

Dr. Castillo:               

Exactly. So, we need to make sure that the patient doesn’t have any iron deficiency, that the patient doesn’t have any thyroid problems, that the testosterone problems are okay, that there’s no sleep disturbances, that there’s no depression. So, there’s so many different other things that we need to make sure are not there before we mount into that. Because if someone is fatigued with a hemoglobin of 8, which is very low, with my treatments, if I make that 8 14, I know the fatigue is going to get better. But if the patient is fatigued with a hemoglobin of 14, which I am not going to improve with my treatments, then how confident do I feel that I’m going to improve the patient’s quality of life with a potentially dangerous treatment?

So, we talked about already secondary leukemias, neuropathy, other problems that the patient can have with the treatments or because of the treatments.

So, we need to balance that out and understand that the potential benefit has to be higher than the potential risk, and that’s why the personalization comes into play. So, fatigue is a big issue, and we try to take a very systematic approach about that, you know, ruling out other conditions, making sure that we understand its relation with the disease before recommending treatment just for fatigue.

Katherine:                  

Yeah. This is one side effect that is so important for patients to share with their healthcare team, right?

Dr. Castillo:               

Oh, absolutely.

Katherine:                  

So that their healthcare team can know how to treat them.

Dr. Castillo:               

That’s right. And again, there are so many interventions that are not medications that could be done in these type of situations, right? Meditation, mindfulness. There are so many other approaches to try to help in these type of situations, changing a little bit sometimes the perspective, trying to be a little bit more on the positive thinking, right?

So, there are so many different ways outside of pharmacological approaches that we can use to try to improve our patients’ quality of life.

Katherine:                  

Yeah. Knowing that one has an incurable disease can be very stressful, right? Knowing that you have to live with this.

Dr. Castillo:               

That’s absolutely correct, and again, what I’ve seen happening in some of my patients is every little thing that happens to them, they do not know if it’s because of the disease or not.

Katherine:                  

Oh, yeah.

Dr. Castillo:               

“So, I have a twitch there. Oh, it’s due to Waldenstrom’s. Do I need to be treated because of that twitch?” And that, I understand it. Well, I try to understand it. I’m not in that same situation, so I cannot understand it completely. But I try to understand how if you don’t trust your body anymore, right? I mean, you have a disease, and you don’t trust your body anymore, then how you trust all these little symptoms here and there?

So, in my conversations with my patients, I discuss these things openly and that you’re going to have a lot of different symptoms here and there. Most of them probably are not going to be related to the disease, but if some of them are concerning enough to you in terms of your activities, in terms of eating, drinking, sleeping, social life, sexual life, you know, working life, then let me know, and then we will be happy to investigate those because anything can happen to anybody.

So, you can have other problems. Waldenstrom’s doesn’t protect you from anything, so, and it’s always important to discuss this with patients and pay attention to the patients, not dismiss their symptoms, think about them with them, talk about them with the patients to try to understand how these are affecting them.

What Are Some Hereditary Factors Impacting Prostate Cancer Patients?

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What Are Some Hereditary Factors Impacting Prostate Cancer Patients? from Patient Empowerment Network on Vimeo.

Along with aging, hereditary factors also contribute to prostate cancer incidence. Expert Dr. Leanne Burnham details some of the hereditary factors, their mechanism of action, and some treatments under study in prostate cancer clinical trials for African American men.

See More From the Prostate Cancer TelemEDucation Empowerment Resource Center

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Transcript:

Dr. Leanne Burnham

So, cancer is a disease of aging, and cancer is a hereditary disease for a lot of different kinds of cancers, not all, but for a lot of them. And so prostate cancer is one of those that we know for sure that there are some genetic variations that are passed down from our parents that would make men either predisposed or not to get prostate cancer and also would predispose them to get aggressive prostate cancer.

And so, for example, if you have a father, an uncle, grandfather, if you have family members that have had prostate cancer, and beyond that, if you had women in your family that have had breast cancer, then that increases your chance as a man to get prostate cancer and to get it even younger than other races would. And so certain things that we look at in the lab and in the clinic at City of Hope are really trying to understand what those hereditary factors are, and then how you can target them with drug treatments specifically.

So, for example, we have a clinical trial that a team of us developed, and we are looking at the ability of something called PARP inhibitor not to get too technical with you, but PARP inhibitors, if you want to Google it, they are at the forefront of prostate cancer treatments right now, and especially a few running in clinical trials. And so there is a hereditary disposition, there is a mutation on the BRCA gene that leads to PARP inhibitors benefiting any person that would have that BRCA mutation.

What we’re doing in our clinical trial is we are using a PARP inhibitor called talazoparib (Talzenna), and we are not only providing that to patients that have the spark commutation, but we are extending it to patients that may not have that mutation, and the reason for is because, and I definitely don’t want to get crazy technical, but the reason for it in a nutshell, as we know in cancer there is an interaction between PARP inhibition and androgen receptor function and reaction to treatments. And so, you may have heard of androgen and androgen receptor when it comes to prostate cancer, it’s really the fancy way of saying testosterone, and prostate cancer needs testosterone, or it needs androgen and androgen receptor to function and to grow. And so, what we want to see in this clinical trial is if we target, if we use PARP inhibitors in combination with hormone therapy that’s targeting androgen production androgen receptor, will we see better treatment and better response to the drugs in those patients. And the extra cool part to me is we know that there are variations in DNA segments that affect androgen receptor function in African American men. And so, for a specific mechanism that I won’t dive into, it involves trinucleotide repeats and link, segments links and all this, but because of these variations and androgen receptor in African American men that we know was associated with their ancestry and what they’ve inherited in their own DNA, this drug should work better in African American men. And we will be able to tease that out in this clinical trial. So, it’s an opportunity for African American men who have prostate cancer who have not developed castration resistance yet, but who do have metastatic prostate cancer so, at that point, there is not a cure, right, and so you can go to your physician, and you can get a standard of care therapy, or you may want to consider this clinical trial where you would receive standard care therapy. And then also, as I said before this VIP access to this new drug, this PARP inhibitor that we think may improve outcomes in men.