Prostate Seed Treatment in African American Men

This is not about prostate seed treatment, or brachytherapy, by itself.  It’s about giving a short course of hormonal therapy first, to lower testosterone in men with localized prostate cancer to make them eligible for radiation seed treatment. The idea is that a shot of Lupron or Zoladex will shrink the prostate and make it easier to cover the entire area with the seeds.

Don’t get your prostate shrunk just to get seed treatment.  There are three problems here, and one of them is huge.

One: seed treatment, also called brachytherapy, is not a better cure for localized, low-risk prostate cancer than external-beam radiation therapy or surgery. It’s just easier, because it doesn’t require an operation and recovery time, or weeks of daily radiation treatments, and men can go back to work the next day.

Two, no man should undergo hormonal therapy (also called androgen deprivation therapy) unless there is a darn good reason for it. For example, in men with high-risk disease, two to three years of hormonal therapy has been proven to save lives. In men with metastatic cancer, hormonal therapy dramatically shrinks the cancer and eases symptoms, and can be effective at keeping the cancer at bay for many years.  But we’re not talking about that right now.

If the sole justification for hormonal therapy is to accommodate one form of treatment when there are two others that have proven more successful, that’s not a very good reason. “This practice of giving three to four months of Lupron or Zoladex before seed treatment has been going on since the early 1990s,” says Anthony D’Amico, M.D., Ph.D., chief of Genitourinary Radiation Oncology at Brigham and Women’s Hospital and Dana Farber Cancer Institute. This is bad, he believes, yet many doctors do it – “despite the fact that we know that even a short course of hormonal therapy can produce irreversible breast growth and other side effects,” such as hot flashes, fatigue, decreased libido, slowing of metabolism, weight gain, cognitive impairment, “and nipple tenderness that can last up to a year; in older men it lasts longer.” (Note: The breast growth can be treated with radiation.)

And three, the huge problem: If you are an African American man, this may shorten your life span. Nobody knew this last part until D’Amico and colleagues conducted a retrospective study looking at the medical records of more than 7,000 patients. Their findings were published in the journal, Cancer. The men, all patients from the Chicago Prostate Cancer Center, all had low- or “favorable- to intermediate-risk prostate cancer, and 20 percent of them were treated with hormonal therapy to shrink the prostate before brachytherapy.

The results of their study were stunning: “We found that African American men being treated with just four months of androgen deprivation therapy were associated with a 77 percent higher risk of death than other men,” says D’Amico. “There is a very strong correlation between the short course of hormonal therapy and shortened survival. The causes of death in this situation were not related to prostate cancer, raising the question of whether a different treatment, such as surgery or external-beam radiation therapy, could easily have been done instead.”

The investigators don’t know how to explain this. D’Amico suspects that “there may be other factors intrinsic to the biology of African American men that make them more susceptible to hormonal therapy.” (This makes sense, and goes along with other research showing other key differences in prostate cancer between men of African descent and other men.)

“These findings should be considered very carefully by all men looking at treatment options for localized prostate cancer,” says D’Amico. “This doesn’t mean that men of other races are not at risk, just that African American men are at more risk. I don’t like the practice of giving hormonal therapy to men of low- or favorable- to intermediate-risk cancer, particularly in older men. It gives them more side effects for a year than they would have experienced if they had just had external-beam radiation or surgery. The metabolic side effects of hormonal therapy are not insignificant, either: it increases glucose, raises blood pressure, and some who are predisposed can get weight gain. In men who already have some of these issues, they can get worse.”

A confounding aspect of prostate cancer treatment is that what works for one man may be harmful for another. If you are an African American man getting screened for prostate cancer or already diagnosed with it, your best bet is to seek care at an academic institution or center that has expertise in personalized treatment of prostate cancer.

One more really important point that I hope you will consider: many men who are diagnosed with one Gleason score actually have higher-grade cancer found after surgery, when a pathologist examines the entire gland. The needle biopsy just samples a tiny percentage of the prostate, and in black men, cancer tends to develop in a different part of the prostate than it does in white and Asian men. Edward Schaeffer, M.D., Ph.D., chairman of urology at Northwestern, recommends that African American patients get an MRI if prostate cancer is suspected. This can help pinpoint areas of cancer that a needle biopsy might have missed, and your doctor may recommend surgery or external-beam radiation therapy instead of seed treatment.

The take-home message here, D’Amico states, is this: “Do not get hormonal therapy unless it has been proven to increase prostate cancer cure rates and prolong your survival. This does not fall into that category: There is no evidence that hormonal therapy followed by seed treatment increases the chance of cure compared to other treatments.” Worse, “it possibly exposes African American men to unnecessary danger, because there are other treatments that have the same cure rate but without this risk. Until we know from further study what is causing this risk and with whom, I would be very cautious about hormonal therapy use just to get seed treatment, or patients accepting it.”

You can read more stories like this (written by me) on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it. If you are African American or have a family history of prostate cancer, you are at higher risk of developing it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

 

 

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Testosterone Replacement Does Not Raise Prostate Cancer Risk

Is your doctor squeamish about testosterone replacement?  Many are; in fact, to many doctors, the idea of testosterone replacement has ranked right up there with playing with fire. They worry that men will get burned – that increasing a man’s testosterone will make him more susceptible to prostate cancer. They worry about this because the mainstay of treatment for advanced prostate cancer is to do just the opposite – to shut down testosterone, and cut off the supply of male hormones to cancer cells.

But there’s good and surprising news: Boosting low testosterone doesn’t seem to raise the risk. In fact, it significantly reduces a man’s risk of getting aggressive prostate cancer.

Before we get carried away and say, “Extra testosterone for every man!” and run around tossing out gel patches, pills, and shots, we need to talk about what this actually means.

Let’s look at the study, recently published in the Journal of Clinical Oncology. In an international effort, scientists from New York University and Sweden analyzed the health records of more than 250,000 men on several health care registries in Sweden, including the National Prostate Cancer Register. There were 38,570 men who developed prostate cancer between 2009 and 2012, and 284 of them were on testosterone replacement therapy (TRT) before they were diagnosed. The investigators compared those men with 192,838 men who did not have prostate cancer, 1,378 of whom were on TRT.

What they found completely up-ended their hypothesis that giving replacement testosterone might be risky. “We found no relationship between the use of testosterone and the development of prostate cancer as a whole,” urologist Stacy Loeb, M.D., the study’s first author, told me when I interviewed her for the Prostate Cancer Foundation’s website, pcf.org. Even better, “we found that long-term use (more than a year) of TRT is associated with a much lower risk of aggressive cancer – a 50 percent lower risk.”

Testosterone actually lowers prostate cancer risk? Well, it does for the men who don’t have enough of it to start with. The men in Sweden who were on TRT, the investigators believe, actually need to be on it, and are prescribed it by their doctor. That’s not always the case in the U.S., where it’s common to see TV ads telling men that if they’re tired and have a low sex drive, they may have “Low T,” and offering prescription help.

So what we’re talking about here are men with below-normal testosterone who take medicine to get their testosterone level back up to normal range. “There are some interesting tie-ins to this,” says Loeb. Previous studies have shown higher rates of high-grade prostate cancer in men who don’t produce enough testosterone, “so it’s definitely a possibility that restoring the testosterone to the normal range could prevent this from happening. ”

In the study, researchers noticed an initial bump of men diagnosed with prostate cancer soon after they started TRT. However, these were low-risk cancers (easily treatable; in fact, many low-risk cancers can safely be treated with active surveillance), and Loeb believes the reason they were diagnosed at all was most likely because the men had received prostate cancer screening when they started the TRT.

How do you know if you have low testosterone? The symptoms, just as the TV ads claim, include fatigue, low libido, and decreasing muscle mass. “But a man should never just start taking a testosterone supplement just because he has those symptoms, because a lot of other diseases can mimic low testosterone,” notes Loeb. And if you have erectile dysfunction (ED): “You’re better off taking a medication such as Viagra, Levitra or Cialis. A lot of men come to the doctor thinking they want to be on testosterone. They’ve seen the direct-to-consumer advertising, and they just want it. But that doesn’t mean it’s the right solution for them.”

However, Loeb adds: “Don’t be afraid to supplement your testosterone if it’s low. There are certainly risks to having a low testosterone level for years; it can affect your cardiovascular system and your musculoskeletal health.” And this new study suggests that raising that testosterone level back up to where it should be may even reduce your risk of getting aggressive prostate cancer.

This research has raised new questions, including:

What about men with low testosterone who have been treated for prostate cancer and are presumably cured? Is it safe for them to go back on testosterone? “Our study did not include men who already had a diagnosis of prostate cancer. These men should be evaluated on a case-by-case basis,” says Loeb.

Why do low levels of testosterone lead to aggressive prostate cancer in some men? And could restoring normal levels of testosterone mitigate this risk? “We have a lot more work to do to understand the implications of these findings.”

You can read more stories like this (written by me) on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

 

 

 

 

 

 

 

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Does ADT Raise Your Risk of Alzheimer’s?

Part Four of Four

It’s challenging enough that you need to be on androgen deprivation therapy (ADT) in the first place.   Now, in addition to prostate cancer, you have to worry about the risk of dementia?

Some studies have shown an increased risk for Alzheimer’s disease, and cognitive impairment and depression are known problems that can go along with ADT. We’ll come back to those in a moment.

There is some reassuring news: a new study, the largest of its kind, published in the Journal of Clinical Oncology, suggests that your risk for Alzheimer’s disease does not go up with ADT.   The study was led by Clement Joseph McDonald, M.D., of the National Institutes of Health. It involves a massive database: the medical records of men with advanced prostate cancer – more than 1.2 million of them, age 67 and older, enrolled in Medicare.

Between 2001 and 2014, 35 percent of these men were treated with ADT (either through drugs such as Lupron or with surgical castration). Of these men, about 9 percent developed Alzheimer’s disease, nearly 19 percent developed dementia, and about a third died without developing either condition.

Now, here’s where it gets a little complicated: the unadjusted rates for dementia in men who were on ADT were slightly higher than for the men not on ADT – nearly 39 percent compared to nearly 33 percent. But when McDonald and colleagues accounted for factors such as other cancer treatment, other health conditions, and age, they found that the risk of Alzheimer’s was not significantly higher in the men on ADT. In fact, it was even slightly lower, but this “possibly was attributable to the high death rate.” In fact, the average time of follow-up was about five and a half years.

If you’re reading this and you think, “Oh, no, they didn’t live very long, and that’s why they didn’t get dementia,” well, you may be right. But treatment for advanced cancer is getting better all the time, and it’s not clear from this study whether these men went on to have second-line treatment, such as abiraterone, enzalutamide, taxotere, or any of the immunotherapy drugs currently being tested in clinical trials across the country.

So take heart: New and better treatments are here, and what happened to these men does not define what’s going to happen to you.

But here’s where the grain of salt comes in: Some of these men did develop dementia. So even if it wasn’t technically Alzheimer’s, the name of the problem doesn’t really matter if you’re the one who’s got it. What do we make of this?

As we’ve discussed before, ADT can cause metabolic syndrome: it can raise your blood pressure, your blood sugar level, your cholesterol and triglycerides, and it’s very easy to gain weight – particularly right in the belly, which raises your risk for diabetes, heart attack, and stroke. You need to burn more calories than you’ve ever had to in your life just to lose a pound. That doesn’t mean it can’t be done – it can. You just have to work harder. But you can do this, and it helps if you don’t eat a lot of carbs.

If you are on ADT, you also need to do your best to help out your cardiovascular system with exercise. It doesn’t have to be anything more strenuous than walking; just keep that blood flowing and the heart pumping, and what’s good for the heart is good for the brain. Which means, you can help prevent cognitive damage by staying active. Many men with ADT also have temporary depression. This also is improved by exercise – but if you need it, medication can help these symptoms, too.

 

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

 

 

ADT and Cognitive Impairment

Part Three of Four

Does ADT cause cognitive impairment? This question seems simple, but really, it’s more like opening a medical can of worms. So let’s ask a different question. Do men on ADT get cognitive impairment? Yes, some do. But many don’t. It is hard to pin down definitive facts here – like, how many men get it? What’s the risk at one year, two years, five years, and ten years?

Nobody knows the exact statistics, and there are several reasons why.

  • There are probably many more men on ADT with cognitive impairment than we know about. But they don’t spend enough time with their doctors, at 5- and 10-minute follow-up visits to renew their Lupron prescription, for their mental status to be evaluated. Cognitive impairment doesn’t always show up in casual conversation.
  • Scientists looking to answer this question aren’t using standardized criteria. For example, does hormonal therapy mean only ADT, or ADT plus another drug, like enzalutamide? Also, are we talking about actual Alzheimer’s disease here, or just an inability to find the right word quickly on a crossword puzzle?

Well, what about men who are actually showing signs of cognitive impairment? That’s not much easier; there are still more questions:

  • Would they have gotten it anyway?
  • Did they start ADT with some risk factors for dementia already on board?
  • If they are showing signs of dementia, is it because when they got on ADT they stopped exercising, gained weight, and experienced depression – and could one of those those factors actually be the tipping point?

I recently interviewed medical oncologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation (PCF), and medical oncologist Alicia Morgans, M.D., of Northwestern University, about ADT for the PCF’s website.  “We have reached a crossroads, and in some ways, it’s actually a sign of progress,” notes Simons. Long, long ago, heart disease wasn’t a big health problem – because people died of other things, like accidents and infections, and diseases that we now get routinely vaccinated for. Diabetes wasn’t a huge risk for many people; sugar wasn’t widely available, there was no such thing as soda, obesity was rare, and people were more physically active. Prostate cancer wasn’t that big a deal, either, because most men didn’t live long enough to get it.  “Not too long ago, men with metastatic cancer died within months or a few years of their diagnosis. Today, men with metastatic prostate cancer are living long enough to develop other problems, and doctors – who previously had just been focused on keeping these patients alive – are trying to figure out how best to keep them alive and well.”

What we have here is an issue of survivorship – living with metastatic prostate cancer, and dealing with the side effects and challenges of treatment.   Medical oncologist Alicia Morgans, M.D., M.P.H., of Northwestern University, is a pioneer in studying survivorship. Cognitive issues have not been much studied in prostate cancer, and scientists are playing catch-up. “It’s not fair for us just to look at the benefits of treatment anymore,” she says, “now that we are starting to understanding the risks better.”

One easy place to start is to make sure that all men who are put on ADT really need it.   Next, men on ADT need better follow-up to monitor their cognitive function.   Morgans believes cognitive impairment in men on ADT is “underreported, underappreciated, and underdiagnosed.” In a PCF-funded study, Morgans’ patients are taking brief neuropsychological tests; the tests look for changes in verbal memory, visual memory, attention, and executive function. She hopes to develop reliable tests that can be done online – tests that could be given to many more patients in clinical trials, so that investigators can get an idea of the scope of the problem.

Family and friends can help: Someone who is having cognitive impairment may not be aware of changes, or may not be able to articulate them well. But his family and friends can help bring worrisome symptoms to the doctor’s attention.

Layers of medication: One of Morgans’ patients, a 76-year-old man, had been doing fine on Lupron for years. But when his PSA started to rise, Morgans added abiraterone, and then enzalutamide. For this man, enzalutamide might have been the tipping point, “one thing on top of another thing, on top of another thing. He was experiencing confusion and forgetfulness,” she says. The man, a minister, was not able to write or deliver sermons anymore. “We decided, despite the fall in his PSA, to stop the enzalutamide.” Four weeks later, his cognitive function had improved, and “he continues to give sermons today.”

For this man, the key to cognitive issues seemed to be enzalutamide. For another man, it could be something different. It could be a different kind of domino effect – the higher risk of diabetes and cardiovascular disease, for instance; maybe these other health problems, in turn, affect the vitality of the brain. “There may be subclinical strokes or cerebrovascular disease that we don’t know about,” Morgans says.

Loss of estrogen? Morgans suspects that a change in cognitive function might also have something to do with a man’s estrogen levels. Women aren’t the only ones who make estrogen; men make it, too, at lower levels. But ADT causes men to have “very low levels of estrogens, lower than postmenopausal women have.”  In studies of women with breast cancer, she points out, “low estrogen levels on their own can be associated with cognitive decline. It’s not ‘chemo brain,’ it’s something different.”

Men with prostate cancer don’t need to have low estrogen levels in order for their cancer to be treated; it just happens as a byproduct. Normally, men need some level of testosterone in order to make estrogens. “Estrogen doesn’t have to fall for us to treat prostate cancer, but it does fall with the method we use – we know testosterone drops to a place it’s never been since puberty.” Would giving some type of estrogen along with the ADT be helpful? No one knows.

Depression is a risk factor for dementia; big changes in sleep habits can also be a risk factor. It may be that addressing each of these separately – with an antidepressant, with exercise, and with melatonin to help with sleeping – could help keep the brain working better.

What about changes in the way ADT is given? Intermittent therapy may be an option. This could mean giving ADT, stopping it for a few months, and then starting back up again. “When men go off ADT, their testosterone comes back, they feel better, think better, their executive function is better – their ability to do a crossword puzzle, or find a synonym, or find the word they’re searching for – and they feel more like themselves again.” Another approach, as investigator Samuel Denmeade is testing at Johns Hopkins, is “bipolar” hormonal therapy: alternating ADT with its polar opposite – high-dose testosterone.

Could “brain exercise” help? Maybe. Crossword puzzles and mind-challenging games may indeed act as mental push-ups and sit-ups, says Simons.

The ultimate goal for treatment, scientists and doctors agree, is to find a way around ADT altogether, or to change it somehow so that the prostate cancer is affected, but the brain is not. Until then, it’s up to doctors to use ADT wisely, only when it is medically appropriate. “Using hormonal therapy has to be more than just a reflex, like giving people penicillin for a head cold,” Simons states. “The PCF, in fact, is actively funding research for other ways to treat metastatic cancer that don’t involve hormones at all.”

It’s also up to you, too, to make sure you start ADT only if and when you need it. If you are at intermediate- to high-risk of recurrence, or if you have a rising PSA but no evidence of metastatic disease and your doctor wants to put you on ADT, get a second opinion. You may also be eligible for a clinical trial of a different kind of therapy that does not affect your hormones, including treatment for oligometastasis — SBRT radiation to a few spots of cancer in your bones, or surgery to remove cancer that is just in one lymph node.

If you do have metastatic disease, right now ADT is the standard of care, and it could put your cancer into remission for many years. There is a lot you can do to help mitigate the side effects – which, in turn, may help protect your brain.

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More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

 

ADT and Metabolic Syndrome

Part Two of Four

Metabolic syndrome includes an unholy cluster of bad things that can lead to a heart attack or stroke. Elevated blood pressure; unhealthy levels of blood sugar, cholesterol, and triglycerides; and abdominal fat – a big jelly donut of visceral fat, also known as “heart attack fat,” right around your belly, a cardiac spare tire. A big gut equals a bigger risk for diabetes, heart attack and stroke.  All of this is magnified with ADT, androgen deprivation therapy for prostate cancer.

Maybe you already have some of these risk factors; maybe you’ve already had a heart attack, or you’ve got diabetes. If you need ADT, you need it.

But hear these words: You will need to fight what it’s doing to do to the rest of your body, even as it saves you from your prostate cancer.

You will need to get mad at it. Work hard to take back your life – work doubly hard, because not only will it try to turn you into a tub of butter, but you might get mildly depressed. Your brain will tell you that you’re too tired to exercise. It’s deceiving you. You must not listen to it. Exercise anyway.

Here’s what you’re up against: Normally, if a man wants to lose a pound, he needs to burn 3,500 calories. A man on ADT who wants to lose that same pound needs to burn 4,500 calories. He’s slogging upstream with ankle weights. His metabolism is slower, his sugar metabolism is messed up, his blood pressure may be higher, and for many reasons, he probably feels like crap. Maybe he stops taking care of himself.   This is the worst thing he can do.

You need to be aware of this, because it might not be on your doctor’s radar.

Just as important, you need to enlist your family and friends, NOT ONLY to help push you to exercise and eat right – cut way down on the carbs and sugar, especially – but to tell you if you seem depressed, because depression might have snuck up on you, and you might not have noticed it.

I recently interviewed medical oncologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation, and medical oncologist Alicia Morgans, M.D., of Northwestern University, about ADT for the Prostate Cancer Foundation’s website.

All of these things can be fought, both doctors say. However, “if you just go back to the urologist or oncologist for a 5-minute appointment and another Lupron shot, you are probably not getting the monitoring you need,” says Simons. Depression may not show up in a brief doctor’s visit. Even if the scale shows that you’ve put on weight, your doctor might say, “Well, that’s common with ADT.”

Years ago, when doctors first started using ADT, “men didn’t live that long,” Morgans notes. “Now, men are living for years or even decades on ADT, and if that stops working, there are other drugs that can help, and exciting new types of drugs showing amazing results for some men in clinical trials.” This is very good news; however, the downside is that doctors might just think, “hey, it’s great, he’s still alive and his PSA is not moving up.”

But we know that weight gain is not only a common side effect of ADT; it’s bad. It’s also something you can help prevent. You need to exercise, with cardio (walking, swimming, riding a bike, aerobics, jogging, etc.,) plus weights for strength. These can be light weights; you don’t need to turn into Arnold Schwarzenegger and bench-press a Volkswagon Beetle or anything like that. You just need to keep your muscles working. Exercise will help with depression, with the cardiac risks, and with the risk to your brain. As University of Colorado radiation oncologist E. David Crawford, M.D., recently put it, “What’s heart healthy is usually prostate-cancer healthy… I’ve got a number of (patients on ADT) who are in great shape and they’re tolerating [treatment] quite well. These are the people who are out there, who continue to lift weights, they continue to exercise, they watch their diet.”

The metabolic syndrome that ADT causes may be a major reason – nobody knows for certain yet – why some men who are on ADT have cognitive impairment.

Coming up next:  ADT and cognitive impairment.

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

ADT and Prostate Cancer: Who Really Needs It?

Part One of Four

The only people who really like androgen  deprivation therapy (also called ADT, or hormonal therapy) are the drug companies that make billions of dollars a year selling the drugs.   Doctors don’t like it, and men don’t like being on these drugs.  So why do it?   There are few specific situations when ADT therapy is the right thing to do. These are the most common:

* Intermediate-risk men who are given six months of ADT plus external-beam radiation;

 * High-risk men who are getting radiation therapy. This is a finite course of ADT, and this combination – two or three years of ADT plus external-beam radiation – has been proven to cure cancer in many men.

* Men with metastatic prostate cancer. ADT can make a big difference in these men, in relieving their symptoms and dramatically improving their quality of life. It can also extend life – some men have been on ADT for 20 years and are still going strong.

Who should not get ADT? Anybody else with prostate cancer. If you just have a rising PSA after radiation therapy or radical prostatectomy, that is not a good enough reason for a doctor to put you on ADT. If your doctor wants to put you on ADT to “shrink your prostate” before brachytherapy, that’s not a good enough reason.

ADT has never been shown to extend life if it’s given too soon, as opposed to taking it when you need it. Johns Hopkins urologist Patrick Walsh, M.D., with whom I have written several books on prostate cancer, has been saying this for many years.

Why not just start ADT? At least it’s doing something, rather than sitting around waiting for the cancer to spread. Well, that sounds good. Please refer to the previous paragraph, and read that first sentence again. Now, if you have a rising PSA, there are other things you can do that may help a lot. These include:

  • Salvage surgery or radiation, if your doctor thinks the cancer is still confined to the “prostate bed,” the area around the prostate.   (Note: In this case, if you get salvage radiation, your radiation oncologist may want to put you on a limited course of ADT, which is one of the two specific acceptable situations for ADT; see above.)
  • Immunotherapy; a vaccine such as Provenge, designed to boost your body’s ability to fight off the cancer.
  • Early chemotherapy.
  • A clinical trial testing a promising new drug.
  • Treatment for oligometastasis. Cancer may only be in a lymph node or in a few spots in the bone, and doctors are now treating this. It may still be possible to cure your cancer. I will be writing more about this in future posts.

Don’t get me wrong: I’m not hating on ADT. If you need it, you need it. But it’s not just like taking a vitamin supplement or getting a flu shot. There are serious side effects with long-term ADT – things that testosterone normally helps protect you from – including thinning of bones, loss of muscle mass, weight gain, loss of libido, hot flashes, mood changes, depression and the risk of cognitive impairment.

Coming up next:  ADT and metabolic syndrome, and how to fight it.

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.

 

 

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Gene-Targeted Treatment for Prostate Cancer

In a matter of weeks, Mark Meerschaert went from being an athlete to someone who could barely walk; metastatic prostate cancer had come from nowhere and spread like wildfire throughout his body.

A highly respected mathematics professor and researcher – the kind who fills up the blackboard in his classroom with labyrinthine calculations to answer questions of probability, statistics, physics and the like – he did what he does best: looked at the numbers. Men with widespread prostate cancer that is not responding very well to standard-of-care treatment don’t live very long.

So then Mark did what I hope everyone with a challenging diagnosis will do: He became his own advocate. He did some research and found a different doctor, Heather Cheng, M.D., Ph.D., a medical oncologist at the Seattle Cancer Care Alliance, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center. She also started the world’s first prostate cancer genetics clinic.

It turns out that Mark has a mutated gene that runs in his family. It’s called BRCA2, and when it is not working as it should, it’s more notorious for increasing the risk of breast and ovarian cancer; recently, scientists discovered that it increases the risk of prostate cancer, too.

Because of Mark’s bad copy of BRCA2, Cheng immediately focused on this gene and suggested a very different type of treatment – off-label use of a drug called olaparib, currently approved by the FDA to treat ovarian cancer. Olaparib is a PARP inhibitor; basically, it blocks a protein that cancer cells need to repair themselves, and has worked especially well in people with defects in the BRCA2 gene. Olaparib and other PARP inhibitors such as rucaparib and niraparib are currently being studied in clinical trials for prostate cancer patients.

I want to pause here just for a moment to make two points. First, among the many very smart things Cheng did was to get genetic sequencing of tissue from Mark’s metastatic cancer.   This is because cancer can change over time. We’ll talk more about this in a minute, but if you have metastatic cancer, there may be different mutated genes than in the younger cancer that was originally diagnosed from the needle biopsy of your prostate. This matters because there may be a new medicine that works well with your particular mutated gene or genes. The other really important point is that, because these new drugs are so specific, they don’t work for everybody. One drug might only help a small percentage of men. But another new drug might help a different small percentage, and a third new drug might target still another small percentage – and you might fit into one of those groups. So take heart! There are entirely new drugs being developed.

“She said, ‘Let’s try something else,’” Mark recalls. Cheng told him that the medicine may take a few months to kick in fully. “I started olaparib in October of 2016. At the end of 2016, we did a bone scan, and saw that there was cancer all over the place: my ribs, hips, legs – I can’t remember all the places – some lymph nodes. One day, I walked my dog, and I had to sit down,” right in the middle of the walk, “and rest for 20 minutes.”   That fall, Mark – on the faculty in the Department of Statistics and Probability at Michigan State University in East Lansing – organized a conference.   He was the moderator, and was supposed to stand up for five minutes between talks and moderate discussions. “I couldn’t stand up for five minutes.”

He used a cane, then a walker, then a wheelchair. He took a leave of absence from his job. Now he is looking forward to going to work. “The great thing is,” starting early in 2017, “I just slowly started to feel better and better,” he says. “At some point, I said, ‘Maybe I can go for a walk again. I had a little numbness in my foot, but I said, ‘I’m going to keep walking,’ so I did. I walk my dog every day, a couple of miles. Now even the numbness is gone.

“In the last six months, I’ve gone from shockingly, disastrously ill to feeling – I’m still cautious, still waiting for the other shoe to drop; nobody knows how long this is going to work,” Mark told me when I interviewed him for the Prostate Cancer Foundation’s website, pcf.org. “There’s no data on people like me. Now I feel great.”

Unexpected Family History

Mark is one of the pioneers of gene-targeted treatment for prostate cancer – medicine that, as Cheng explains, “is tailored to the weakness of his cancer resulting from a specific gene mistake in that cancer, rather than just treating it the same as all prostate cancers.” In other words, treating the gene, not the cancer.

“I knew that I was BRCA2 positive before I was diagnosed with prostate cancer,” he says; after his brother was diagnosed with breast cancer, several members of Mark’s family got genetic testing. But he never expected to get prostate cancer. In fact, although Mark had gotten a PSA test every year, he had stopped. “My doctor said, ‘We don’t need to do PSAs.’ For two years I didn’t get a PSA.”

Mark believes the policy of not screening men – which recently was revised – because of a fear of overtreatment is misguided. “A PSA costs almost nothing. To me it’s a misreading of the statistics,” somehow saying it’s worse for some men to get unnecessary biopsies than for other men to miss their shot at an early cancer diagnosis.

In 2013, Mark developed some urinary symptoms and went to see a urologist. Cancer was found.  Around this time, he received some bombshell news: “My dad had prostate cancer. But I never knew that until after I was diagnosed. Had I known, I would have kept PSA screening.” Mark’s father had been treated for prostate cancer when Mark was away in college, and his parents never said a word. “I’m a big fan of sharing knowledge with your family, even though it might be a little embarrassing. You might not feel comfortable talking to your kids about things like impotence, but they really need to know.”

Mark underwent external-beam radiation therapy and a two-year course of androgen deprivation therapy (ADT), which ended in March 2016. “By July of 2016, something just felt a little off. I went to see a urologist. He said, ‘I don’t think it’s anything to worry about, I saw something kind of weird, so I sent it off for a biopsy.’ It came back as high-grade cancer,” Gleason 9. The prostate cancer had come back with a vengeance.

Genetic tumor sequencing: When Mark went to the Seattle Cancer Care Alliance, “they got the tissue from last July and sequenced it.” As Cheng suspected, the genetic makeup of the cancer in Mark’s first prostate biopsy in 2013 was not the same as the tissue removed in 2016, after the cancer had time to mutate and become more dangerous. “They found out that I have the BRCA2 mutation in one of the two copies in my germline, but in the metastatic cancer cells, it was mutated in both copies.

“Dr. Cheng said, ‘Your cancer is very aggressive, but that might work in your favor going the other way.’ That turned out to be absolutely correct. It got bad really fast, and it got better really fast.” He is still taking the olaparib. “I guess I’ll keep taking it as long as it works.   The question is, what happens next?

“I’m very interested in things like the five-year survival rate for people like me. Nobody knows. They’ve only been using this since 2015, and the studies were on ovarian cancer.”

So there are no guarantees. However, Mark says, “I can deal with that. I do feel like this is something pretty remarkable. My God, what if this had happened five years ago?”

More of this story and much more about prostate cancer are on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.” The PCF is funding the research that is going to cure this disease, and they have a new movement called MANy Versus Cancer that aims to crowd-fund the cure, and also empower men to find out their risks and determine the best treatment. As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

Regular disclaimer: This is a blog. It is not an encyclopedia article or a research paper published in a peer-reviewed journal. If a relevant publication is involved in the story, I mention it. Otherwise, don’t look for a lot of citations, especially if I’m quoting from a medical professional.