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The Nursing Intersection: Upregulating Quality of Life During Downregulation of the Androgen Axis

  • Authors: Victoria Sinibaldi, RN, MS, CS, CANP, CGNP; Emily A. Lemke, DNP, AGPCNP-BC, AOCNP
  • CE Released: 6/24/2020
  • Valid for credit through: 6/24/2021
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Target Audience and Goal Statement

This activity is intended for nurses and nurse practitioners.

The goal of this activity is to educate nursing professionals about current and emerging approaches with oral antiandrogen therapies in the management of locally advanced or metastatic prostate cancer to better recognize and differentiate adverse events (AEs) of therapies that target the androgen axis pathway.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • AEs associated with various therapies aimed at the androgen axis pathway in the management of prostate cancer
    • Monitoring of AEs for therapies utilized in androgen axis downregulation in prostate cancer
  • Have increased confidence regarding
    • Counseling points to empower nurses to engage in discussion with patients to optimize adherence and outcomes while on androgen axis deprivation therapies
  • Have greater competence related to
    • Mitigation of androgen axis therapy related AEs


The Annenberg Center for Health Sciences at Eisenhower requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to the Annenberg Center for Health Sciences at Eisenhower policy. The Annenberg Center for Health Sciences at Eisenhower is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of a commercial interest


  • Victoria Sinibaldi, RN, MS, CS, CANP, CGNP

    Adult & Geriatric Nurse Practitioner
    Research Associate in Oncology and Urology
    Faculty, School of Medicine
    Johns Hopkins University
    Baltimore, Maryland
    Participation by Ms Sinibaldi does not constitute or imply endorsement by the Johns Hopkins University or the Johns Hopkins Hospital and Health System.


    Disclosure: Victoria Sinibaldi, RN, MS, CS, CANP, CGNP, has disclosed the following relevant financial relationships:
    Served as a speaker or a member of a speakers bureau for: MCM Education

  • Emily A. Lemke, DNP, AGPCNP-BC, AOCNP

    Nurse Practitioner
    Medical College of Wisconsin Cancer Center
    Milwaukee, Wisconsin


    Disclosure: Emily A. Lemke, DNP, AGPCNP-BC, AOCNP, has disclosed no relevant financial relationships.

    The PIM planners and managers have nothing to disclose.

    Annenberg Center for the Health Sciences at Eisenhower staff involved in this activity have no relevant commercial relationships to disclose.


  • Davecia Ragoonath-Cameron, MS

    Medical Education Director, Medscape, LLC


    Disclosure: Davecia Ragoonath-Cameron, MS, has disclosed no relevant financial relationships.

  • Carol Smyth, MB

    Director, Content Development, Medscape, LLC


    Disclosure: Carol Smyth, MB, has disclosed no relevant financial relationships.

  • Yoji Yamaguchi, MA

    Associate Scientific Content Manager, Medscape, LLC


    Disclosure: Yoji Yamaguchi, MA, has disclosed no relevant financial relationships.

Content Reviewer

  • Robert Morris, PharmD

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Disclosure: Robert Morris, PharmD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: ViiV Healthcare
    Owns stock, stock options, or bonds from: GlaxoSmithKline

Medscape, LLC staff have disclosed that they have no relevant financial relationships.

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Jointly provided by the Annenberg Center for Health Sciences at Eisenhower and Medscape LLC in collaboration with Postgraduate Institute for Medicine

The Annenberg Center for Health Sciences at Eisenhower is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

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The Nursing Intersection: Upregulating Quality of Life During Downregulation of the Androgen Axis

Authors: Victoria Sinibaldi, RN, MS, CS, CANP, CGNP; Emily A. Lemke, DNP, AGPCNP-BC, AOCNPFaculty and Disclosures

CE Released: 6/24/2020

Valid for credit through: 6/24/2021


Activity Transcript

Victoria Sinibaldi, RN, MS, CS, CANP, CGNP: Hi. And welcome, everybody, to today's program. My name is Victoria Sinibaldi. I am a nurse practitioner, research associate, specializing in medical uro-oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital. Here with me today is my colleague Emily Lemke, who is a nurse practitioner at the Medical College of Wisconsin Cancer Center located in Milwaukee, Wisconsin.

Today, we will be discussing how we as nurses can increase the overall quality of life of patients undergoing therapies that suppress the androgen axis. Our program is entitled, "The Nursing Intersection: Upregulating Quality of Life During Downregulation of the Androgen Axis."

I want to start off by giving you a little update on the epidemiology of prostate cancer and give a brief overview of the current landscape of management for this disease. Prostate cancer is the most common non-skin cancer diagnosed in men in the United States. Approximately 191,930 new cases are expected to be diagnosed this year. The sad news is, that in spite of the advances in diagnosis and treatment, prostate cancer continues to be the second leading cause of cancer-related death in men in the United States. And it is estimated that approximately 33,330 deaths will occur this year. This is a pretty significant number.

Prostate cancer progresses along a continuum, but this progress is unpredictable. In many men, slow growth of cancer cells allows for monitoring or active surveillance. In others, rapidly progressing disease requires intervention.

This slide shows a clinical state model, one similar to the one that Dr Howard Scher, from Memorial Sloan Kettering, published and described about 20 years ago in The Journal of Urology. Each clinical state is based on the extent of disease, the presence or absence of radiographical metastasis, prior and current treatments, and serum testosterone levels. Each state shows a clinically significant time point and a decision point that helps providers in the management of the disease. Unfortunately, we still do not know the complete biology and history of prostate cancer, so the morbidity and mortalities from the disease continues.

What is so exciting for prostate cancer is that within the past 10 years, since the discovery of docetaxel in 2004, we have had FDA approval of 9 new drugs and 13 different indications for the management of prostate cancer. The new drugs include 4 AR-targeted therapies, abiraterone, enzalutamide, apalutamide, darolutamide. We have immunotherapy, sipuleucel-T, an alpha emitter radium-223, chemotherapy cabazitaxel, and more recently, the discovery of 2 PARP inhibitors olaparib and rucaparib, both FDA approved within 5 days of each other. It is such an exciting time. Today's program will only focus on drugs that target the androgen axis.

Androgen deprivation has been around a long time. In fact, it dates back to the 1940s when Huggins and Hodges discovered that when a man's testosterone production dropped, his prostate cancer stopped growing. This was accomplished by orchiectomy, surgical removal of the testicles. Reduction and suppression of male hormone axis has been the gold standard of care for prostate cancer for over 50 years.

LHRH agonists and antagonists both target LHRH hormone and lower the amount of testosterone made by the testicles. And while this worked for a while, it soon became evident that LHRH therapy alone was insufficient to manage patients with advanced prostate cancer. Researchers went back to screening novel agents and in the ensuing years, first generation anti-androgens followed by second generation anti-androgens were discovered. Anti-androgens blocked the androgen receptor and cut off the supply of hormones needed for tumor growth.

Now, I would like to turn the discussion over to Emily, who will discuss LHRH agonists and antagonists.

Emily A. Lemke, DNP, AGPCNP-BC, AOCNP: So as Vickie previously mentioned, prostate cancer is a hormonally-driven disease. So therefore, having your testosterone at a castrate level is the backbone of therapy for these patients with prostate cancer. And how this is accomplished medically, and when I say medically, I mean with medications as opposed to having an orchiectomy or removal of the testicles, is with LHRH agonists and antagonists.

So, almost half of men with prostate cancer will receive androgen deprivation therapy at some point in their treatment trajectory. And this is used both in the curative intent setting, where patients get it in conjunction with radiation as well as in the advanced or metastatic setting. And overall, this is generally pretty well tolerated.

So having testosterone at castrate levels is the backbone of therapy. And doing this with the LHRH agonists is how we accomplish this. This slide here shows the mechanistic approach. So LHRH agonists work by suppressing the luteinizing hormone productions, and therefore the synthesis of testosterone androgen. So at initial dose, there can be a flare due to a surge of LH before these levels start to fall. And so more simplistically, this is a mechanism where basically the anterior pituitary tells the testicles to stop making testosterone.

So LHRH antagonists on the other hand, they bind to the gonadotropin-releasing hormone receptors on the pituitary gonadotropic-producing cells, which reduce the release of LH and FSH and testosterone, but they don't cause the initial release of LH, and so therefore, there's no flare phenomenon with these drugs.

So this table summarizes the list of approved LHRH agonists and antagonists, which, with the mechanism of action described as we went through on the previous slide. In general, LHRH agonists are more commonly used due to their more convenient dosing schedule. However, in patients who might have a high burden of disease, where that initial flare of testosterone could cause pain or urinary obstruction, using the antagonists or degarelix is sometimes chosen for the first few doses to eliminate that risk of flare.

And I just want to note that both the agonists and the antagonists are equally as effective in patients with prostate cancer.

So the next few slides are going to focus on androgen and anti-androgen inhibitors which are utilized in patients with advanced and metastatic prostate cancer. So this graphic summarizes how androgen receptors work at the cellular level. So flutamide, bicalutamide, nilutamide, enzalutamide, apalutamide and darolutamide, they all work by inhibiting the androgen receptor, but enzalutamide, apalutamide, and darolutamide, they go a step further and they inhibit that androgen receptor-binding ability at the DNA level. And so, simplistically, these are just the more potent anti-androgen.

Now this graph that explains the mechanism of action of abiraterone, and it's a bit more complicated. So, the agent abiraterone prevents testosterone production by inhibiting the CYP17A1 enzyme, which is a rate-limiting enzyme implicated in androgen biosynthesis that is created primarily by the testicles, but it's also within the adrenal glands and the prostate cancer itself. So when we block this enzyme, we prevent the conversion of pregnenolone and progesterone into testosterone precursors, such as DHEA and androstenedione.

So this mechanism of action establishes a more complete inhibition of circulating testosterone. And abiraterone is unique in that it's able to block the adrenal glands and the prosthetic testosterone production, whereas other agents only block the production at the level of the testicles. So this is just a nice summary slide for your reference that goes through these mechanisms of action that we previously discussed. Just to note on darolutamide, in addition to competitively binding with the androgen receptor, this is a fancier third-generation anti-androgen. And its potency is not affected by this F876LAR mutation, that's considered critical for resistance to enzalutamide and apalutamide. So it's just a little different than those other newer anti-androgen.

All right, so now I will turn it back to Vickie.

Ms Sinibaldi: So within expanding therapeutic armamentarium for our patients with prostate cancer, it becomes really important for us as nurses to know what drugs are available for the various clinical disease states, what the doses and dosing schedules are and the routes of administration. So let's start off with our frontline LHRH agonists and antagonists. As Emily mentioned in our earlier slides, there are different LHRH agonists, but the 2 most commonly used are leuprolide and goserelin. Leuprolide is given as either an intramuscular or subcutaneous injection. It depends on the brand. Leuprolide comes as a 1-month, 3-month, 4-month, or 6-month injection. This makes it an ideal drug to use.

What varies with these drugs is patient-provider preference, dosing schedule, the route of administration and cost. In my practice, we generally give the every-3-month preparation, as this is how we often like to follow our patients. In patients that we feel we do not need to see so often, we'll give the every-6-months depot injection and continue with our every 3 month follow up visits, through tele-video visits. Remember, it has the same efficacy. The IM injection is preferably given in the buttock, subcutaneous injections are generally given in the stomach, but can burn. So this could be a preference in terms of your patient deciding which medication he would like to have.

Goserelin is another LHRH agonist. It comes as a 1- or 3-month preparation. It is an implant and it's given subcutaneously in the stomach. As Emily mentioned earlier, these agonists can cause a tumor flare resulting in a transient worsening of the tumor symptoms during the first few weeks of treatment. So you need to be aware of your patient's overall disease status. Tumor flare could result in full blown ureteral obstruction and spinal cord compression.

Degarelix is an LHRH antagonist, and when given will result in a rapid decline in the testosterone production. This medication is given subcutaneously, the initial dosing is 240 mg given as 2 injections of 120 mg each. This is then followed by a maintenance dose of 80 mg administered every 28 days. Patient compliance with treatment is important with this medication, as it only comes in the every-1-month preparation.

So what about anti-androgens? Remember prostate cancer can be looked at as growing along a continuum. Patients first treated with LHRH agonists or antagonists will in most cases experience a rapid PSA decline and even show improvement in symptoms. Many show radiographical improvement in scans. But historically, after about 18 to 24 months, these patients go on to developing progression of their disease and they will often need other treatments. The great thing about these drugs is that they are all oral agents. The first-generation anti-androgens include bicalutamide, flutamide, and nilandron. As Emily mentioned earlier, these drugs work by attaching to the androgen receptor. Many physicians use combining ADT with an LHRH preparation plus an anti-androgen to offer patients a more effective treatment than castrate therapy alone.

Flutamide capsules are indicated for the use in combination with LHRH agonists for the management of locally advanced disease, stage B disease and stage D disease, that's metastatic disease. Bicalutamide, they're 50 mg tablets indicated for the use in combination with an LHRH preparation, and it is used for patients with metastatic disease. Nilandron tablets are indicated for use in combination with surgical castration. That means orchiectomy for the treatment of metastatic prostate cancer.

So, it was definitely great for us, during the late 1980s and 1990s, because we had 3 drugs that we could actually use in patients who had progression of their disease. They all possess the same core mechanism of action.

So moving along to our second-generation AR-targeted therapies, a better understanding of the antigen receptor signaling pathway, and mechanisms of resistance to castration over the past decade led to this discovery of novel androgen receptor-targeting agents. And the first to come along was abiraterone. Abiraterone was initially and originally FDA-approved for metastatic, castration-resistant prostate cancer, but later moved up in our landscape and can be used to manage metastatic, high-risk castration sensitive disease. This drug comes as a tablet of either 250 mg or 500 mg. The daily dose is 1000 mg a day on an empty stomach.

Taking this medication with food will in increase the amount of medication that gets absorbed by your body 5- to 7-fold. And this definitely means an increase in the risk of side effects such as high blood pressure, water retention, hypokalemia, muscle weakness, and possibly cardiac dysfunction.

Now let's move on. Following the FDA approval of abiraterone, we had the approval of 3 more second generation anti-androgens, enzalutamide, apalutamide and darolutamide. All are taken orally at the doses seen on this slide, but have different indications. Enzalutamide for metastatic, castration-resistant prostate cancer and non-metastatic, castration-resistant prostate cancer. Apalutamide for non-metastatic, castration-resistant prostate cancer and metastatic, castrate-sensitive prostate cancer. Darolutamide for non-metastatic, castration-resistant prostate cancer.

Clinical trials showed that these drugs roughly double the time that it takes for cancers to start spreading to the bones and other sides of the body from less than 18 months to 3 years or more. So now you can see why these drugs were so exciting to actually have on the market. And while studies comparing which of these 3 drugs is better, and which offers the best efficacy and better side effects, those studies are right now nonexistent.

So what happens is, physicians will go and talk to their patients about the available treatment, the potential side effects, and they will share, in the decision, as to which medication will suit them the best. The new anti-androgen generation has a higher affinity for the androgen receptor and optimizes androgen blockade effect. Now I'll turn it over to Emily.

Dr Lemke: OK, so now we're going to go through some of the important drug-drug interactions that apply to these medications. So first, here we have LHRH agonists and antagonists. And as you can see from this table, because it doesn't impact the CYP450 system, there's really very few interactions. So, I personally have never come across any clinically significant drug interactions with any of these medications for my patients.

So this table lists the possible interactions. And as with all of these medications, running a drug interaction search on whatever system your institution uses for this is important. It's also a really good opportunity to collaborate with your pharmacist colleagues to help clarify if there's anything we need to be aware of.

Of these first-generation, anti-androgen, bicalutamide is the most commonly used in my practice. And so it's just important to highlight from this slide the risk of interactions with anticoagulation therapies as well as phenytoin, those are the ones we run into most commonly.

Next, we have the drug-drug interaction with abiraterone, enzalutamide, apalutamide, and darolutamide. And again, I can't stress this enough, collaborating with your pharmacist at the initiation of therapy to determine what possible drug interactions might be present as well as collaborating with the prescribing provider of the said medication that might be causing an interaction is key. So just to note here, abiraterone -- common drug interaction we see is with beta blockers.

We also tend to run into issues with enzalutamide and apalutamide with DOAC, statin and hypertension medication. And sometimes the fix is as easy as just changing to a different agent. For example, if you're using an ACE inhibitor instead of the calcium channel blocker. But other times it can be more complicated, and you have to have a risk-benefit ratio discussion with the patient, with the prescribing provider of the problem drug and with the oncology team.

So for example, is the patient's cardiac history more likely to be immediately life-threatening, with a discontinuation of a beta blocker as compared to their prostate cancer? These are the types of discussions we have to have.

All right, so similar to drug-drug interactions, understanding and knowing patients' comorbidities also need to be considered when starting any of these oral anti-androgens. So for example, if a patient has diabetes and they are being started on abiraterone and prednisone, we know that the prednisone has the potential to raise their blood sugars. Kind of similar with blood pressure, many of the oral anti-androgens can raise blood pressure, and so sometimes we even have to adjust their current blood pressure medications on therapy. And again, this requires collaboration with the primary care provider or cardiologist who had initially started them on antihypertensive therapy. So establishing the potential for drug interactions and the impact on chronic diseases is something that needs to be a regular part of patient teaching and education prior to starting any of these therapies.

All right, I'm going to hand it back to Vickie now.

Ms Sinibaldi: There are certain factors that we need to take into consideration when choosing the ideal treatment for our patients. One important factor is the extent of disease. Does your patient have castrate-sensitive or castrate-resistant disease? Castrate-resistant prostate cancer is defined as biochemical disease recurrence, or progression despite castrate levels of testosterone, and this is generally a serum testosterone of less than 50. Does your patient have non metastatic, that's the M zero patient? That is, despite treatment, their PSA continues to rise without overt disease on scans.

And is your patient symptomatic or asymptomatic? Are we dealing with low volume disease or high volume disease? High volume disease is usually defined as the presence of visceral metastasis, and greater than or equal to 4 bone metastases with at least 1 outside of the vertebral column and pelvis. And what is their PSA-doubling time? Is it slow? Is it rapid? This chart here shows the various disease states and the drugs that are approved for the use and treatment in that particular state.

The treatment of prostate cancer originally focused on managing metastatic disease, followed by castrate resistant disease. Then we had the invention of the PSA, and biochemical failure created a new clinical state. It soon became evident that if we gave some of these agents at an earlier time, we could achieve a better outcome. So we did studies and we ended up with another state, the metastatic, castration-sensitive state, and then moved on, most recently, to the non-metastatic, castration-resistant state.

Knowing the history of prior therapies is also very important. Has the patient had prior hormonal therapy? If so, how many prior hormonal therapies? Studies do show that when patients fail 1 therapy, there's still a chance that they can respond to another therapy. So it's important to know what kind of response they had to the prior hormonal therapy. And this is very helpful for you to decide whether or not you should continue with the hormonal therapy. And what kind of side effects did they experience? This may have a great impact on your patient as to whether or not he's going to say, "Yes, I will accept another maneuver." Other important factors to consider are overall performance status, comorbidities. What are his current medications? Does he have allergies to certain medications? And definitely checking the labs.

We need to take caution when giving certain drugs -- some people have had seizures while taking apalutamide. The chance of seizure may be raised if you have certain blood brain vessel problems, take other drugs that may raise the chance of seizures, or if you have ever had a seizure, brain injury, or stroke. When thinking of using abiraterone, we need to keep in mind that the risk of endocrine side effects may be increased. There's also the risk of developing severe hepatic toxicity. So you actually need to evaluate your patient fully from head to toe to determine whether or not this is the right medication for them.

With enzalutamide, the major reported event that's most bothersome was fatigue, significant baseline cancer-related fatigue may get worse, causing a significant decrease in overall quality of life. With LHRH agonists, as well as antagonists, you need to keep in mind that this is not benign therapy, and you will need to monitor your patients closely, especially in your real elderly patients with significant fall or fracture history.

Now I will turn over to Emily who will discuss common adverse events.

Dr Lemke: All right, so overall, these therapies are pretty well tolerated. However, there are some important adverse events which the patient should be aware of and that need to be monitored by the oncology team. Testosterone is a key piece of bone and muscle health, and so therefore, when we take away that testosterone or make it at castrate levels, there can be risk of bone density and muscle mass loss. Many patients experience hot flashes, and I described these as similar to what menopausal women experience.

Almost all men on ADT will experience sexual dysfunction, and this usually in the form of erectile dysfunction and loss of libido. And this can be pretty catastrophic for some patients. And so I therefore think it's very important to set expectations at the beginning of therapy. Metabolic syndrome can occur, fatigue is common, anemia can be seen, and occasionally patients might experience some emotional and cognitive changes, but these are less common.

So this slide discusses the claim of cardiovascular disease and how it's impacted by LHRH agonists and antagonists. And so, this claim is largely made from observational studies as opposed to randomized control trials. And so, overall the risk-benefit ratio of ADT and the possible risk of cardiovascular disease really leans in favor of proceeding with androgen deprivation therapy. As listed here, the possible explanation that ADT and cardiovascular disease can be linked is with metabolic syndrome. And this is a bit of a "chicken or the egg" concept here. Because we know that prostate cancer is one of the 10 cancers linked to obesity, so many of these patients have pre-existing, metabolically linked comorbidities.

And lastly, there is a pooled analysis of 6 randomized controlled trials that compare degarelix to leuprolides, and they did show that degarelix is associated with a lower risk of cardiac events. So, in patients who have significant cardiovascular disease, sometimes we do consider using degarelix as opposed to leuprolides, which tends to be the more commonly used LHRH agonist.

This slide nicely summarizes the most common adverse events associated with the novel anti-androgen. A few I would like to highlight are as follows, and we will dive into management strategies for these a little bit later in the presentation. All these drugs can cause fatigue. In fact the majority of cancer treatments and cancer itself can cause fatigue, so this isn't surprising. Furthermore, patients on any of these medications will also be on an LHRH agonist or antagonist which can cause hot flashes too. So those 2 side effects of fatigue and hot flashes are not surprising.

Just to highlight a few from each medication of what I see more commonly, with abiraterone, it's important to pay attention to hypertension and edema. Apalutamide, rash is more of a unique finding there, hypertension again and some diarrhea. Darolutamide can have some pain, and again a rash. And then enzalutamide can have more significant fatigue than is seen with the other medications, and then some weakness and decreased muscle strength. And then if patients tend to be more prone to constipation or diarrhea, 1 of those 2 usually can be seen. And then lastly, like the others, hypertension.

And any patient getting abiraterone, we like to monitor labs at regular intervals. And these intervals are the same for all of the oral anti-androgens. So we usually check lab, blood pressure, and a clinic visit at 2 weeks after starting the medication, 4 weeks after that, and then 6 weeks after that, assuming that the patient is doing well. Once the patient has been on these meds for about 3 months and they have stable lab and blood pressure, we will monitor them about every 6 to 12 weeks depending on their tolerability. And like I said, this schedule can be applied to all patients on the novel anti-androgen. So specifically with abiraterone, we like to get a comprehensive metabolic profile (CMP) and a complete blood count (CBC) at every visit. I also encourage these patients to check their blood pressure at home and report if it is consistently greater than 140 over 90.

And as previously mentioned, because these patients are on prednisone as well, the blood glucose can be impacted. So it's important if they have diabetes, to be keeping a closer eye on that. And it's important to know who's on the patient's team as far as other subspecialties and their primary care provider. Because sometimes when issues arise, we do need to coordinate with them.

Enzalutamide, similar to abiraterone, patients will have a CBC and a CMP checked at every visit along with the blood pressure monitoring. One specific enzalutamide side effect to note is the fatigue or memory issues or sometimes it's described as "brain fog" by patients, this is more commonly seen in patients on enzalutamide. And most patients with prostate cancer are over 65, so this can be a difficult side effect to tease out and know if that is truly drug related or age related. So this is where having a geriatric specialist you can refer to is very helpful.

And looking at apalutamide, again, similar to enzalutamide and abiraterone, we like to check a CBC and a CMP. As well as with apalutamide, check thyroid function at regular intervals. Lipid channels can also be checked, but usually we do this less frequently than the CMP, CBC, and thyroid function. Rashes can be a classic apalutamide side effect, so it's important to see these patients and assess them for any potential rash, and it usually presents as a maculopapular rash. And then in the case of significant hypertension, thyroid dysfunction or a refractory rash, that's when we are coordinating with our specialists.

A special note on apalutamide is that, in patients with baseline cardiac comorbidities, we need to maximize their medical management and make sure that that is nice and tucked before starting apalutamide and continue to closely monitor that. And perhaps most importantly is, avoid prescribing this in patients who have a history of seizures. And if any seizure develops while on drug, you need to discontinue the apalutamide immediately and involve neurology.

OK, in darolutamide like the others, it's going to require monitoring with CBCs and CMP as well as blood pressure. And again, it's like a broken record here, if the blood pressure is getting worse, or if there's a refractory rash, that's when we are going to involve our specialists in cardiology or dermatology.

Generally, liver function test (LFT) issues are managed by holding the medication and restarting at a lower dose. But if they don't resolve, occasionally we do have to refer to hepatology as well.

All right, I'm going to hand it back over to Vickie.

Ms Sinibaldi: OK. So let's dive in to management strategies and practical recommendations a little bit further. How can we manage fatigue? It may seem counterintuitive, but researchers say, expending energy by engaging in regular exercise may pay off in the long run. So I recommend that my patients exercise routinely. Exercise will boost the endorphins and make your patient feel energized. It will also raise the oxygen levels in the blood. The best exercises are aerobic exercises. Stretching and strengthening exercises are also important.

Adapting a healthy diet is wonderful. Your body runs off what you feed it. Besides what you eat, it's when you eat it that can also have a great impact on your energy level. Did you ever notice how you feel sluggish after a big lunch or dinner? This is because your body is using its energy to digest that big meal instead of powering the rest of your body. So the easiest way to avoid the post-meal coma is to eat several smaller potion meals throughout the day. Your diet should consist of lots of vegetables and fruits and low in fats, carbs, and sugar.

You also need to keep in mind that we may need to modify treatment strategy in cases where severe or unmanageable fatigue occur. You want to encourage the providers that you work with to modify the treatment strategy if fatigue becomes unbearable to your patient. I think that many patients need to be aware of the potential for weight gain and muscle atrophy. That not only comes along with aging, but also comes with a decrease in testosterone. The potential for weight gain and the difficulty of losing it once you have gained it is such an important factor to point out to your patients. Maintaining a healthy diet, at times recommending a nutritionist or dietician, incorporating routine exercise, as I discussed previously, are all part of controlling weight gain and muscle loss.

Fluid retention and edema can be seen in patients receiving hormonal therapy. You need to be aware of symptoms such as wheezing, chest pain, chest tightness, swelling, weight gain. And how can we manage this? You can tell your patients that whenever they're sitting or lying down, use pillows or cushions to raise their feet above the level of their heart. You can instruct them to modify their diet, to eliminate salt. Restaurant foods, fast foods, are full of salt. Wearing compression stockings can also help your patients. You need to encourage them to keep walking, to wiggle their toes and ankles often. But at times these interventions don't help, and your patient may need a diuretic.

Elderly patients receiving androgen therapy are at risk for falls and fractures. Hormonal therapy increases the risk for osteopenia and osteoporosis. Therefore, it's very important for us as nurses to evaluate bone health, fracture risk prior to hormonal therapy and throughout the course of treatment. Lifestyle interventions are important particularly with regard to exercise. So as you're going to hear, a recurring intervention is diet and exercise. A healthy lifestyle. No smoking and limit alcohol consumption.

We also like to encourage our patients on a hormonal therapy to take calcium and vitamin D supplements. And in some patients, we would like to administer a bisphosphonate such as zoledronic acid or denosumab, to help decrease the risk of skeletal-related events.

Men receiving androgen deprivation therapy may at risk for cognitive impairments. But keep in mind that like prostate cancer, cognitive dysfunction increases with age. Cognitive impairment can erode quality of life and put patients at risk for significant, long-term consequences. So what is really important with regard to managing cognitive impairment is, for early detection, you want to ensure physical safety, you want to instruct your patient that they should continue exercising, get enough sleep, and relax.

Now I'll turn over to Emily.

Dr Lemke: OK. So managing the rash is something that we want to make sure the patients understand at the beginning, that this is a risk. And so, if they do start to notice a rash, make sure that they let us know. And usually these are managed with oral antihistamines, and in more severe cases, systemic corticosteroids. Usually we'll try some topical steroids first before going to the systemic corticosteroids.

Metabolic changes, when you lose your muscle and bone mass, sometimes you can have increased fat, and then some of these medications do impact the lipid channel. And so, making sure that we're monitoring these, we're coordinating with their primary care provider, and then watching specifically for signs of mineralocorticoid excess such as hypertension, low potassium, fluid retention, and any cardiovascular events.

So cardiovascular events, as we've touched on quite a bit in this presentation, is something that we need to be really aware of at base line and throughout treatment. And so, making sure patients are keeping track of their blood pressure and taking all of their medications that are medically managing any of their cardiovascular comorbidities is really important. And obviously we know that exercise and dietary modification can help reduce the risk of cardiovascular adverse events.

So diarrhea, this is my "bread and butter" it seems like. And so, Imodium®, or loperamide, is usually our go-to for helping with this. And so I tell patients to use that as needed as it's generally prescribed on the bottle. You don't want to exceed 8 tabs in 24 hours. But one thing that is my tried-and-true is also psyllium fiber; this is what is in Metamucil®. And so what you want to tell patients to do is to take this with a small amount of water or none at all and mix it into their food if they're having issues with diarrhea, because that can really help gel the stool together.

Increasing fiber is also another nice option. That, if patients want to try something more holistic.

Hot flashes are very common. About 80% of men have them. And if you want to treat them with a more conservative approach, you can tell them to avoid potential triggers such spicy food, alcohol, and caffeine. If we need to do medication management, usually the first one is venlafaxine, and if that doesn't work then I would move to gabapentin.

Then sexual dysfunction, and this impacts almost everybody who are receiving hormone therapy. And manifests as decreased sexual desire and erectile dysfunction. And so this is one that's really hard to manage but setting expectations prior to starting therapy and really suggesting that couples look for other ways to maintain their relationship intimacy.

Bone health, Vickie touched on this a bit, and so I will just clarify that you want to make sure you're doing routine DEXA scans at base line, and then every 2 years, as well as taking vitamin D and calcium supplementation. And if patients do have osteopenia and osteoporosis, we usually do treat them with a bisphosphonate. Exercise with weight bearing and resistance exercises is also important.

So, most of the treatments included in this talk are overall well tolerated, and hopefully we've provided you with some management strategies if side effects do show up. But they've really provided a paradigm shift in the management of advanced prostate cancer. So setting expectations at the onset of treatment usually makes this therapy go smoothly. Because when patients have an idea of what to expect, it's a lot less distressing when it happens. These are usually life-long therapies for these patients, and so really keeping their lifestyle in mind when you're choosing their LHRH agonists or antagonist dosing is important. And then this is something I'm very passionate about, is looking at treatment by extra big life events. Because we give these patients these medications to keep them alive for as long as they can and the point of that is, of course so they can enjoy their life. And so, patients have a daughter's wedding coming up, or an anniversary, giving them a week or 2 off here and there so that they can enjoy those events without having to worry about any side effect profile is really important.

As we move forward in the scientific arena with prostate cancer, the things we're starting to look at is sequencing of treatment, both with these oral agents we've discussed and IV chemotherapies. And as with all oncology care right now, molecular profiling is really the Holy Grail. And if we can use that as the driver of treatment selection, that is really the ideal for all cancer. And so that research is ongoing.

And then I would just like to remind everybody to make sure and answer the postactivity assessment questions so that you can receive credit. And Vickie and I thank you all for attending this today.

This transcript has been edited for style and clarity.

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