Hormone therapy, or Testosterone Inactivating Pharmaceuticals, work to either stop testosterone’s production or limit testosterone’s activity in promoting prostate cancer growth. These powerful anti-cancer drugs can put men with prostate cancer in remission for years and in some cases even decades!
Discover hormone therapy treatment protocol and monitoring, get insight to hormone resistance, and learn how to counteract common side effects.
Dr. Scholz: [00:03] Welcome to PROSTATE PROS. I’m Dr. Mark Scholz and this is my cohost, Liz Graves.
Liz: [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 in Radiation.” He was wondering what strategies, aside from SpaceOAR, prevent against possible side effects of radiation. He mentioned Pentoxifylline, vitamin E, or having a lower dose of radiation. What are your thoughts on this, Dr. Scholz?
Dr. Scholz: [00:36] Pentoxifylline and vitamin E are measures or pills, that is, that can be used to help people that have already experienced radiation damage. They may help a little bit. The real trick is not to have the radiation damage in the first place and that’s how SpaceOAR works. The other way to minimize damage is 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 really careful in picking who does the radiation therapy. Large, reputable centers are much safer than going to a small place, sometimes that has outdated equipment.
Liz: [01:17] Thank you, Dr. Scholz. 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 inactivating pharmaceuticals or TIP. Why did you decide to use this term instead of androgen deprivation therapy or even just calling it hormone therapy?
Dr. Scholz: [01:41] The book was designed for patients and how many patients understand what androgen is? So, I wanted to stick to words that I thought patients would understand, such as testosterone. Inactivating testosterone is what hormone therapy means in the prostate cancer world.
Liz: [02:00] So hormone therapy, or testosterone inactivating pharmaceuticals, stop testosterone’s activity or production. Why does this play into prostate cancer?
Dr. Scholz: [02:12] 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 finger’s 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.
Liz: [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.
Dr. Scholz: [02:53] That’s exactly correct. A lot of people are under the misapprehension, or misconception, that it simply puts the cancer cells to sleep. That’s not true at all. In the early years when I first got exposed to Lupron, testosterone blockade, Casodex, and these sorts of agents, we placed patients with large, localized cancers on hormone therapy alone without any surgery or radiation. We could, with sequential digital rectal exams, feel the tumors disappearing over a space of three to four months once they started the treatment.
Liz: [03:29] Testosterone seems like a really powerful anticancer drug.
Dr. Scholz: [03:33] 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. Lupron therapy, or hormone blockade, or TIP, or whatever you call it, causes remissions in almost one hundred percent of patients. The remissions can average over ten years long. We don’t have anticancer drugs like that for other types of cancer.
Liz: [04:05] What are some of the misconceptions of hormone therapy?
Dr. Scholz: [04:08] I don’t know that the misconceptions are as big a problem as 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, can be corrected oftentimes with appropriate measures. So, the treatment itself can be quite tolerable if it’s managed with expert care.
Newscaster: [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 who consumed dairy products the most had a higher risk of developing prostate cancer. Those who followed a plant based diet had lower rates of developing the disease.
Dr. Moyad: [04:58] As you lose weight and become more heart healthy, the chances that our drug is more successful for you go 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 from hormone therapy. You go talk to Dr. Scholz the next time you’re in a consult or Almeida, he will tell you of the guy who was on hormone therapy doing jack squat versus the guy who’s taking care of himself. It’s a night and day difference, night and day difference. The guy’s got more energy. He’s got less 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 that is greater than 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 neurologists, basically came out with a statement in 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 admit it, from two clinical trials, that individuals who had a high rate of having memory loss and dementia, when they worked out regularly they stimulated a place in their brain called the hippocampus. This is the memory center. It grows like an organ, use it or lose it.
Liz: [06:40] So again, choosing your doctor is very important in this.
Dr. Scholz: [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 are all kinds of things that can arise like hot flashes, weight gain, fatigue, and weakness. These things can be addressed if the doctor engages with a patient and explains what needs to be done.
Liz: [07:03] I think in some cases men go to the doctor once every six months get a shot and they leave. How does your protocol for that vary? Should they be checking their PSAs at these appointments?
Dr. Scholz: [07:16] Yeah. Typically when we start someone on TIP, we check them monthly for a few months. The PSA should plummet about ninety percent in the first month. That’s an average response. The PSA should drop to undetectable levels within four or five months. You want to ensure that it’s working. Of course, as I already mentioned, you want to talk to people about how to reduce any potential side effects.
Liz: [07:41] Can you define what an undetectable PSA is?
Dr. Scholz: [07:45] I use the threshold of a PSA that’s less than 0.1. There are assays that go lower, but that’s a good place to generalize. Studies show that the men who can get their PSA down to less than 0.1 have much better long-term outcomes.
Liz: [08:04] How long should the PSA remain undetectable?
Dr. Scholz: [08:08] The PSA should stay 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.
Liz: [08:24] We’ll talk about hormone resistance in a little bit. I’ve read that TIP isn’t curable. What does that mean?
Dr. Scholz: [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 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 again and the PSA will start to rise. I’ve only had a couple patients that went into complete remissions that never recurred in my whole career, so we don’t look for TIP to cure people, but it’s amazingly powerful at regressing the disease and controlling the disease.
Liz: [09:14] I’ve seen at Prostate Oncology Specialists that hormone therapy and other therapies such as radiation are used at the same time.
Dr. Scholz: [09:23] Yeah, as I mentioned, the hormone therapy by itself is great at inducing a remission but doesn’t completely cure every last cancer cell. That’s where the radiation comes in. So the radiation can come in and completely sterilize the residual cancer cells and help men actually get cured so that the disease never returns.
Liz: [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.
Dr. Scholz: [09:58] Yeah, that’s correct. The combination is good because usually the spots that are outside the prostate, at least at early stages, tend to be tiny. Of course, 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.
Liz: [10:26] You can combine hormone therapy with radiation or surgery, but you can also combine 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?
Dr. Scholz: [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 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 wasn’t the case. What was happening was the cancer cells were learning how to make their own testosterone chemically, internally inside the cancer cell. 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. 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 Erleada, Nubeqa, or Xtandi 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 from the get-go: Gleason 8, 9, 10, PSAs that are very high. 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 Erleada, Nubeqa, or Xtandi to the Lupron to enhance cure rates further.
Liz: [12:15] How do you tell if someone is resistant to hormones?
Dr. Scholz: [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 PSAs and very high Gleason scores. 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.
Liz: [12:55] Would you start these second generation drugs at the first sign of resistance?
Dr. Scholz: [13:00] Absolutely. Sometimes there are a few steps you have to go through to re-stage 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.
Liz: [13:20] Are there any symptoms of being resistant to hormones?
Dr. Scholz: [13:24] No, not directly. I suppose after an extended period of time, if the cancer is just allowed to run amuck and PSAs rise up into the hundreds, people can start to get symptoms from the cancer itself. For the most part it’s purely a lab abnormality, a sequential rise in PSA.
Liz: [13:44] So when 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.
Dr. Scholz: [13:55] Yeah, I say 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. All the doctors had been telling them they’re probably going to die within a couple of years. Well, they went into complete remissions with undetectable PSAs. So of course they’ve been extremely grateful through the years. They no longer come in every month; they come in every three or four months to get their PSAs. But now after 20 years of treatment we’re expecting they’re going to continue to do well for a long, long time.
Liz: [14:37] So, when you say these men have been on hormone therapy for 20 years and are remission, what does that look like? Are they getting hormone therapy every day? Is this a monthly thing?
Dr. Scholz: [14:48] The most commonly used agent, called Lupron, 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. Oftentimes our patients that are stable with undetectable PSAs will come in and see us every three months, get a PSA and get an additional shot. There are other supportive methods, of course, that we’ll probably be getting into as this podcast unfolds.
Liz: [15:17] You mentioned several second-generation hormones. Is one better than the next?
Dr. Scholz: [15:23] There’s actually four products. I’ll just name them quickly Zytiga, Erleada, Xtandi, and Nubeqa. Two of them, Nubeqa and Erleada, have only been 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. Zytiga for example, requires the use of a little bit of cortisone, a medicine called prednisone. People have to monitor to make sure there’s no irritation of the liver or problems with potassium. Xtandi has been associated with little higher incidence of fatigue. Erleada seems to cause skin rashes a little more frequently. Nubeqa 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.
Liz: [16:08] You mentioned Erleada 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 and what that means in terms of treatment?
Dr. Scholz: [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 force 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. Castration-sensitive and castration-resistant 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.
Liz: [17:31] 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.”
Dr. Scholz: [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. 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.
Liz: [18:06] So when men are responding to treatment, I’ve heard they can take a holiday even though they have cancer?
Dr. Scholz: [18:12] Yeah, it doesn’t seem rational. The studies 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 cancer is sensitive to the hormone treatment. What they’ve shown is that you can allow testosterone to come back, PSA will start to rise, but if it doesn’t go too far, say up to around five or something like that, that almost certainly the disease will respond when the hormone treatment is reinitiated. So, 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.
Liz: [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.
Dr. Scholz: [19:08] Yeah, that’s a good point. The psychology of living with this disease is fascinating. Many people feel like they’ve had a really big brush with death being told they have cancer. 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.
Liz: [19:46] Testosterone levels. Is this also something you test throughout treatment?
Dr. Scholz: [19:51] At least initially, you want to confirm that the Lupron is lowering the testosterone down to very low levels. 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. They could be off Lupron indefinitely and a year or two later their testosterone will still be very low.
Liz: [20:19] So are any newly diagnosed patients choosing hormone therapy over say surgery?
Dr. Scholz: [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 remission with hormone therapy and watch it. This would be more practical, especially in the intermediate-risk patients. In high-risk patients, the studies show that long-term survival is improved by getting a combination of hormone treatment plus radiation.
Liz: [21:13] One of the positives about hormone therapy is that once you’re off it and your testosterone is back up, the side effects reverse. Can we talk a little bit about the side effects that might present with hormone therapy?
Dr. Scholz: [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. That can happen very quickly when people go on treatment. 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. Someone can be doing 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. Testosterone helps not only build muscle but preserve muscle. 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.
Liz: [22:12] If someone’s starting their exercise training, what should their diet look like? Should there be any changes in that?
Dr. Scholz: [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 tend to push our patients more towards a plant-based diet. The idea 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.
Liz: [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 long after they’re finished with therapy can they expect the side effects to go away?
Dr. Scholz: [22:58] In terms of weight training, the side effects are almost eliminated, that 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. 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.
Liz: [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?
Dr. Scholz: [23:56] Yeah, I’m glad you brought that up. In my opinion, the simple answer is no, it’s not valid. 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, their memory recovers and that’s not dementia. Dementia is a progressive, irreversible process. 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. There is clearly some memory decremental decline for people that are taking these medicines, but it’s not permanent.
Liz: [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.
Dr. Scholz: [24:52] Absolutely true. Another issue that comes up is, does Lupron, and agents such as these, cause heart attacks? 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. 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, it’s a secondary effect of the weight gain that can happen in people that aren’t careful.
Liz: [25:30] Does the weight training help men prevent the osteoporosis that these drugs might cause?
Dr. Scholz: [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, Xgeva. It’s very important for men to have their bone density measured. That requires a scan, a bone density scan or a DEXA scan, that should be done every two years in men that are on this type of treatment.
Liz: [26:01] Preventing side effects is a big deal. Check out our blog at prostateoncology.com to find the methods for minimizing these problems. We have a couple shout-outs to give. The first is we wanted to say thank you to the Us TOO San Antonio West Prostate Cancer Support Group, led by Dr. Joseph Harrison Jr. for hosting Dr. Scholz recently. If you’re in the San Antonio area, you should look them up. We also want to thank Karen Jagoda from the Empowered Patient Podcast for having Dr. Scholz on her show.
Karen Jagoda: [26:33] Just wondering, have you seen any progress in treating other cancers without using surgery as the first option?
Liz: [26:41] It’s a really great episode and you can check it out on empoweredpatientradio.com
Dr. Scholz: [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, and 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. 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.
Liz: [27:37] The great thing about podcasts is that you can share with friends and you can listen while you’re getting your weight training in.
Dr. Scholz: [27:42] Thanks so much for listening.