Hormone Therapy TIPs

Speaker 0 00:01 <inaudible>. Speaker 1 00:03 Welcome to prostate prose. I'm dr Mark Scholz and this is my cohost, those graves. Speaker 2 00:09 Before we get into hormone therapy, which is the main topic of this episode, we wanted to quickly address a question a listener emailed us regarding our recent episode breakthroughs and radiation. He was wondering what strategies aside from space or prevent against possible side effects of radiation. He mentioned pentoxyfilen vitamin E or having a lower dose of radiation. What are your thoughts on this? Doctor Scholls Speaker 1 00:36 pentoxyfilen and vitamin E are measures or pills. That is, they can be used to help people that have already experienced radiation damage and they may help a little bit. The real trick is not to have the radiation damage in the first place and that's how space we're works at. The other ways to minimize damage are the skill of the radiation therapist. Even now with the finest machinery, it really matters who your doctor is. You get one chance to get it right. With radiation. We need to be real careful in picking who does the radiation therapy. Large reputable centers are much safer than going to a small place. Sometimes that has out outdated equipment. Speaker 2 01:17 Thank you, doctor Scholls. I'm sure that will help a lot of listeners. So onto the topic for this episode, hormone therapy, dr Scholz, in the key to prostate cancer, you refer to hormone therapy as testosterone and activating pharmaceuticals or T I. P. why did you decide to use this term instead of androgen deprivation therapy or even just calling it hormone therapy? Speaker 1 01:41 The book was designed for patients and how many patients understand what androgen is? And so I wanted to stick to words that I thought patients would understand, such as testosterone. In activating testosterone is what hormone therapy means in the prostate cancer world. Speaker 2 02:00 So hormone therapy or testosterone inactivating pharmaceuticals stop testosterone's activity or production. Why does this play into prostate cancer? Speaker 1 02:12 So prostate cancer cells come from the prostate gland itself. Most people don't know that the prostate gland in young men prior to puberty doesn't really exist. I mean, it's less than the size of your little fingers, fingernail. But when testosterone comes on at the time of puberty, the prostate grows and blossoms out. So the genetic design of the prostate and prostate cancer cells, which come from the prostate is that without testosterone, they can't flourish. Speaker 2 02:43 Testosterone makes the prostate cancer cells grow. So by cutting off the testosterone from these cells, they stop growing and the cancer would die. Speaker 1 02:53 That's exactly correct. A lot of people are under the mist apprehension or misconception that it's simply the cancer cells to sleep. And that's not true at all. In the early years when I first got exposed to Lupron, testosterone blockade, Casta ducks and these sorts of agents, we placed patients with large, uh, localized cancers on hormone therapy alone without any surgery or radiation. And we could, with sequential digital rectal exams, we could feel the tumors disappearing over a space of three to four months once they started the treatment. So testosterone seems like a really powerful anticancer drug. It's probably the most powerful anticancer drug across the spectrum of all cancers. When you look at the measurement of how effective a drug is, you look at how often people respond and you look at how long those responses last and Lupron therapy or hormone blockade or tip or whatever you call it, causes remissions and almost a hundred percent of patients in the remissions can average over 10 years long. We don't have anticancer drugs like that for other types of cancer. What are some of the misconceptions of hormone therapy? I don't know. The misconceptions are as big a problem is just the lack of awareness about how effective it is. That's one problem. The other problem is that the side effects which can be rather concerning, especially when the doctors don't know how to minimize them, uh, can be corrected oftentimes with appropriate measures. So the, the treatment itself can be quite tolerable if it's managed with expert care. Speaker 4 04:35 Consuming dairy products may increase the risk of prostate cancer research from the Mayo clinic reviewed a total of 47 studies involving more than a million people. Those are consumed dairy products. The most had a higher risk of developing prostate cancer and those who followed a plant based diet had a lower rates of developing the disease. As you lose weight and become more heart healthy, the chances that our drug is more successful for you goes up substantially. I believe that we will find out one day in prostate cancer that as men become more healthy, it either does nothing for them in terms of the prostate treatment or it will enhance it significantly, or at least it will reduce the toxicity of the treatment, which we already know for hormone therapy. You go talk to dr soles and next time you're in a consult or Alameda, he will tell you of the guy who was on hormone therapy doing Jack squat versus the guy who's taking care of himself. Speaker 4 05:32 It's a night and day difference. Night and day difference. The guy's got more energy. He's got less bone bone loss. He can tolerate hot flashes better. Everything is a little bit better. Exercise for the mental health benefits is what's so profound. Do you know something happened this year? This is greater than on this entire meeting, which nobody cares about because it's not a big story. The American Academy of neurology this year in their clinical guidelines when they're teaching future neurologists and current neurologist basically came out with their statement and their 2018 guidelines that nobody picked up on. Oh, by the way, if you're high risk for having dementia and you exercise a couple of days a week, it will probably reduce your chances of getting dementia. What? We don't have a single drug that does that. They had to finally come out and admitted from two clinical trials that individuals that had a high rate of having memory loss and dementia when they worked out regularly, that stimulated a place in their brain called the hippocampus, which is the memory center. It grows like in Oregon, use it or lose it. Speaker 2 06:40 So again, she was in. Your doctor's very important in this. Speaker 1 06:44 The doctors need to be listening to the patients and meeting with them on a regular basis when they're having hormonal blockade. There's all kinds of things that can arise like hot flashes, weight gain, fatigue and weakness, and these things. Can be addressed if the doctor engages with a patient and explains what needs to be done. Speaker 2 07:03 I think in some cases men go into the doctor once every six months get a shot and they leave. How does your protocol for that vary? Should they be checking their is at these appointments? Speaker 1 07:16 Yeah. Typically when we start someone on tip, we check them monthly for a few months. The PSA should plum it about 90% in the first month. That's an average response and the PSA should drop to undetectable levels within four or five months. You want to ensure that it's working. And of course, as I already mentioned, you want to talk to people about how to reduce any potential side effects. Speaker 2 07:41 Can you define what an undetectable PSA is? Speaker 1 07:45 I use the threshold of a PSA that's less than 0.1. Uh, there are assets that go lower, but that's a good place to generalize and studies show that the men, they can get their PSA down to less than 0.1 have much better longterm outcomes. Speaker 2 08:04 How long should the PSA remain undetectable? Speaker 1 08:08 The PSA should stay, uh, undetectable. As long as the treatment is continued. In the case where PSA starts to rise, while men are still on hormonal therapy, a change of therapy is essential. That's called hormone resistance. Speaker 2 08:24 We'll talk about hormone resistance in a little bit. I've read that tip isn't curable. What does that mean? Speaker 1 08:31 The treatment, as I mentioned, is so effective. It's really remarkable, but it does not have the power to eradicate every last cancer cell. So if men take a holiday when they're responding there and their PSA is less than 0.1, the testosterone will come back and the cancer, the tiny amount that remains will start to grow and then the PSA will start to rise. I've only had a couple patients that were, they went into complete remissions that never recurred in my whole career, so we don't look for a tip to cure people, but it's amazingly powerful regressing the disease and controlling the disease. Speaker 2 09:14 I've seen that prostate and cology specialists that hormone therapy and other therapies such as radiation are used at the same time. Speaker 1 09:23 Yeah, as I mentioned, the hormone therapy by itself is great. It inducing a remission but doesn't completely cure that. Every last cancer cell, that's where the radiation comes in. So the radiation can come in and completely sterilize that the residual cancer cells and help men actually get cured so that the disease never returns. Speaker 2 09:48 Hormone therapy is a whole body treatment. So it's targeting cancer throughout the body while something like surgery or radiation just targets the prostate gland. Speaker 1 09:58 Yeah, that's correct. And the uh, the combination is good because usually the spots that are outside the prostate, at least at early stages tend to be tiny. And of course those, some of those that are small enough might be curable with hormone treatment. Also, new radiation treatments now are capable of going outside the prostate and treating lymph nodes in the surrounding areas as well. So there's a lot of synergy between hormone treatment and radiation treatment. Speaker 2 10:26 So you can combine hormone therapy with radiation or surgery, but you can also combined one type of hormone therapy with another type of hormone therapy. Can we talk a little bit about what types of hormone therapy there are? Speaker 1 10:40 Yeah. So the biggest discovery in the last 10 years or so has been what we've termed second generation hormone treatments. Earlier when we mentioned the possibility after a number of years of developing hormone resistance in the old days, we thought that hormone resistance was a result of the cancer cells learning how to grow without any testosterone. Subsequent studies, however, demonstrated that that wasn't the case. What was happening, the cancer cells were learning how to make their own testosterone chemically, internally inside the cancer cell, and so once that was realized, the pharmaceutical industry designed medicines to block the activity of testosterone inside the cancer cell. These are what we call second generation hormone medicines, so those medicines are used in two settings. One is if the standard tip, something such as Lupron for example, stops working, you can then add medicines like or Lita new Becca or Extendi and get another remission. The other way these new second generation medicines are being used is in men that look like they have particularly dangerous cancers. The get go Gleason eight nine 10 PSA is that are very high and people are concerned that a percentage of people won't be controlled with just standard Lupron or radiation and so more doctors now are starting to add a second generation hormone medicine like or Lita new Becca or extending to the Lupron to enhance cure rates further. Speaker 2 12:15 How do you tell if someone is resistant to hormones Speaker 1 12:20 if they haven't had any previous treatment? It's a little bit of guesswork. We just know that resistance is a little more common in men that have very high PSA and very high Gleason scores, but if someone has been on Lupron for example, and they've been taking it for four or five or six months and the PSA has not dropped to less than 0.1 that's certainly a sign of resistance. Another sign of resistance is people that have been taking Lupron for a long time and now their PSA is rising instead of dropping. Both of those are indications of resistance to tip. Speaker 2 12:55 Would you start these second generation drugs at the first sign of resistance? Speaker 1 13:00 Absolutely. Sometimes there's a few steps you have to go through to restage patients with scans, but the second generation drugs are well tolerated and effective. The other options that are used for that kind of a problem tend to have more side effects and the response rates aren't as high. Speaker 2 13:20 Are there any symptoms of being resistant to hormones? Speaker 1 13:24 No, not directly. Uh, I suppose after an extended period of time, if the cancer is just allowed to run a muck and PSS, uh, rise up into the hundreds, people can start to get symptoms from the cancer itself. But for the most part it's purely a lab abnormality, a sequential rise in PSA. Speaker 2 13:44 So went on hormone therapy. Patients should be monitoring their PSA monthly to make sure they're not becoming resistant and to make sure the hormone therapy is still working. Speaker 1 13:55 Yeah, I see. That's a good rule of thumb, especially when people are getting started. We do have patients that have been on hormone treatment for years. I have a couple of patients in the practice that started their hormone therapy over 20 years ago. They went on Lupron, quite frightened. They had metastatic bone disease. And they thought that all the doctors had been telling them they're probably going to die within a couple of years, and they went into complete remissions with undetectable PSA. So of course they've been extremely grateful through the years, so they no longer come in every month. They come in every three or four months to get their PSA. But now after 20 years of treatment, of course we're expecting they're going to continue to do well for a long, long time. Speaker 2 14:37 So when you say these men have been on hormone therapy for 20 years and an RN remission, what does that look like? Are they getting hormone therapy every day? Is this a monthly thing? Speaker 1 14:48 So the most commonly used agent called is an injection that can be given at varying time periods. The company markets a product that can be given once a month, once every three months, every four months, and every six months. And oftentimes our patients that are stable with undetectable PSA is we'll come in and see us every three months, get a PSA and get an additional shot. There's other supportive methods of course that we'll probably be getting into as this podcast unfolds. Speaker 2 15:17 You mentioned several second generation hormones. Is one better than the next? Speaker 1 15:23 There's actually four products. I'll just damn them quickly say Tega or Lita XTANDI a new backup, two of them new Beck enter later only on the market now for a year, a couple of years and we're just learning about them. The medicines all tend to be equally effective but they do have slightly different side effects. Zay Tega for example, requires the use of a little bit of cortisol and a medicine called prednisone and people have to monitor to make sure there's no irritation of the liver or problems with potassium. Extendi has been associated with little higher incidents of fatigue or Lita seems to cause a skin rashes a little more frequently. Neubecker is very new. We're not familiar with it yet. The hope is that it may have the least side effects of all, but that is yet to be proved. Speaker 2 16:08 You mentioned or Lita and this was FDA approved a couple years ago for metastatic castration resistant prostate cancer, but this was actually recently approved for hormone sensitive prostate cancer. Can you talk a little bit about that, what that means in terms of treatment? Speaker 1 16:25 The world of pharmaceutical coverage, because these medicines are quite expensive, has been broken down into artificial subcategories to help the insurance companies control their costs, so they forced the pharmaceutical companies to do a clinical trial at every stage along the way. As men develop more progressive prostate cancer, it's kind of ridiculous because we know that if these medicines work at one stage, they'll work at all the stages, but to get coverage and these medicines can cost an awful lot of money. You have to meet certain basic criteria and castration sensitive castration resistance are just subtypes of prostate cancer that are sort of artificial separations to help satisfy the insurance companies that they're not paying for an expensive medicine that doesn't quite fit the criteria. For example, metastatic castration resistant prostate cancer just means that they have some spots of cancer that are detectable on a scan. That's what metastatic means. Castration resistant stands for someone that's been on Lupron and it has stopped working. In other words, the PSA has been rising, Speaker 2 17:31 so it sounds like what you're saying is that doctors can be a little more flexible with these medications. They're what the FDA calls off label medications. Speaker 1 17:41 The medicines are going to be effective against all stages of prostate cancer. Some people of course have very mild types of prostate cancer and using a strong second generation hormonal agent would be unjustified. It'd be overkill, but we do know that certain types of prostate cancer can be life threatening and to withhold these medicines simply because they don't fit some pharmaceutical criteria is irresponsible. Speaker 2 18:06 So when men are responding to treatment, I've heard they can take a holiday even though they have cancer. Speaker 1 18:12 Yeah, it's doesn't seem rational. And the studies at to evaluate that possibility are actually quite conclusive. It is safe to take a holiday from hormone treatment if the PSA has been undetectable, which proves of course, that the cancers sensitive to the hormone treatment. What they've shown is that you can allow testosterone to comeback. PSA will start to rise and but if it doesn't go too far, say up in to around five or something like that, that almost certainly the disease will respond when the hormone treatment is reinitiated so then men get to have a better quality of life, enjoy a period of time having normal testosterone levels, but it does not engender any hormone resistance and it does not shorten survival times. Speaker 2 18:59 Are people ever resistant to taking a holiday? It seems like if a treatment was working, you'd kind of just want it to keep working. Speaker 1 19:08 Yeah, that's a good point because the psychology of living with this disease is fascinating and many people feel like they've had a really big brush with death being told they have cancer and of course they're greatly relieved when their hormone treatment gets their PSA to undetectable levels and they're in what we call a complete remission. That peace of mind sometimes outweighs the advantages of getting testosterone back. Certain individuals, especially those that tolerate the hormone treatment well, may prefer for quality of life psychologically to stay on treatment and keep their PSA undetectable Speaker 2 19:46 testosterone levels. Is this also something you test throughout treatment? Speaker 1 19:51 At least initially, you want to confirm that the Lupron is lowering the testosterone down to very low levels. And of course when hormone treatment is stopped, there's a variable recovery time. Some people will have their testosterone come back within a month or two elderly men say in their eighties sometimes never recover their testosterone, so they could be off Lupron. And definitely in a year or two later their testosterone was still be very low. Speaker 2 20:19 So are any newly diagnosed patients choosing hormone therapy over say surgery? Speaker 1 20:25 A small minority do outside the United States? Actually, it's fairly popular. It's an inexpensive way to control the disease. In the United States. Over the last 10 15 years, radiation treatments have become so much less toxic and radiation has the advantage of curing the disease, whereas the hormone treatment merely controls the disease. So when looking at all the pros and cons of these different options, most men are leaning towards doing radiation and getting rid of it. But the option does exist to simply, you know, go into a remission with hormone therapy and watch it. This would be more practical, especially in the intermediate risk patients, the high risk patients, the studies show that longterm survival is improved by getting a combination of hormone treatment plus radiation. Speaker 2 21:13 One of the positives about hormone therapy is that once you're offered and your testosterone is backup, the side effects reverse. Can we talk a little bit about the side effects that might present with hormone therapy? Speaker 1 21:25 Yeah, that's really important because a lot of them can be prevented if you know what you're doing. The biggest of course is loss of muscle and that can happen very quickly when people go on treatment. So we always counsel patients to get a trainer or get signed up at the gym, start weight training three days a week, and to be faithful and consistent so someone can be do everything they're told for three or four months, they're feeling great, their muscles are normal and they take a two week holiday and they can lose a huge amount of muscle right away. So testosterone helps not only build muscle but preserve muscle. So men that commit to doing weight training on a regular basis will eliminate a lot of the muscle loss, which is the cause of most of the fatigue that you hear talked about that's associated with hormone treatments. Speaker 2 22:12 So if someone's starting their exercise training, what should their diet look like? Should there be any changes in that? Speaker 1 22:19 Well, you've got sort of competing issues here. The bodybuilders of course load up on protein, but we know that prostate cancer can feed on protein, so we're tending to push our patients more towards a plant based diet. The idea it with weight training is not to try and become like Arnold Schwarzenegger, but just to keep the normal amount of muscles that most people have had all their lives. Speaker 2 22:43 I know you usually urge patients to start weight training before therapy starts. When can patients expect side effects to present and how far? How long after they're finished with therapy? Can they expect the side effects to go away? Speaker 1 22:58 In terms of the weight training, the uh, the side effects are almost eliminated. <inaudible> being fatigue. Other problems like hot flashes usually take a month or two to show up and then depending on a patient's age, say in a 65 year old, you're looking at about a three to five month recovery period and if the testosterone gets back to normal in three or four months, people will start feeling pretty normal within a month or two. Another important point about diet is that when people are on testosterone blockade, their metabolism slows down and they put on weight much more easily. So that's another advantage of the plant based diet is that the caloric density is a lot less than your average American diet and it's easier to keep your weight under control, which is a big struggle for some patients who are taking this treatment. Speaker 2 23:45 I've recently seen in the news a lot about dementia and its connection to hormone therapy. Is this something that's valid? Speaker 1 23:56 Yeah, I'm glad you brought that up because it's, in my opinion, the simple answer is no, it's not valid. But what they're observing in these rather poorly designed trials is that if you take testosterone away from elderly men, their memories aren't quite as good. But if you stop the treatment, they're memory recovers and that's not dementia. Dementia is a progressive, irreversible process, but these studies have not been designed well enough to make a distinction between people that have short term reversible memory issues while on treatment and the people that have the true type of Alzheimer's disease where they get progressively worse no matter what you do. And uh, there is clearly some memory detrimental decline for people that are taking these medicines, but it's not permanent. Speaker 2 24:42 I also wanted to mention that testosterone does decrease while you age. So just for general men's health, you should be watching over your diet and exercising. Speaker 1 24:52 Absolutely true. Another issue that comes up is does Lupron and agents such as these cause heart attacks and large studies? Again, some not very well designed have shown that for men on hormone therapy there is a slightly higher incidence of heart attacks, but it's also been shown as I mentioned already, that men put on a lot of weight. Sometimes their blood pressures go up and that will indeed put people at greater risk for heart attacks. So it's not a direct effect of the medicine incident. Secondary effect of the weight gain that can happen and people that aren't careful Speaker 2 25:30 as the weight training help men prevent the osteoporosis that these drugs might cause. Speaker 1 25:35 Yeah, it's an issue that you can lose calcium from your bones when your testosterone levels drop and the weight training does help. The other thing that helps are certain medications such as Fosamax, Prolia, IX, Jeeva, and it's very important for men to have their bone density measured and that requires a scan, a bone density scan or a DEXA scan and that should be done every two years in men that are on this type of treatment. Speaker 2 26:01 Preventing side effects is a big deal. Check out our [email protected] to find the methods for minimizing these problems. We have a couple shout outs to give. Uh, the first as we wanted to say thank you to the us to San Antonio West prostate cancer support group, led by Dr. Joseph Harrison jr for hosting dr Shoals recently. If you're in the San Antonio area, you should look them up. We also want to thank Karen Jagoda from the unpowered patient podcast for having dr Scholls on her show. I was wondering, have you seen any progress in treating other cancers without using surgery as the first option? It's a really great episode and you can check it out on empowered patient radio.com. Speaker 1 26:47 I'm so glad we've had a chance to talk about tip hormone therapy, androgen deprivation, whatever you want to call it. The treatment is very effective for men with prostate cancer, but being a powerful treatment, you need to know how to use it, when to use it, how to minimize side effects. We've only provided a brief introduction here, but it's important to be aware of what these medicines can accomplish. So I hope we've been able to communicate that hormone therapy is a very effective treatment for prostate cancer, but people who are in this type of therapy need to know how to avoid all the side effects. The most crucial one in my mind is weight training, regular exercise to keep the muscles strong. Second most important is diet to keep your weight under control. Speaker 2 27:37 The great thing about podcasts, you can share with friends and you can listen while you're getting your weight training in. Speaker 1 27:42 Thanks so much for listening.