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Oligometastasis in Prostate Cancer: Curable?

What if you have cancer that is confined to the prostate, with just a little tiny bit outside of it? Are you doomed? It used to be that doctors thought, “Oh, man, he’s a goner, the cancer’s spread outside the prostate.” But scientists are learning that not all out-of-the-prostate cancer is the same, and just because a spot of cancer has popped out of the prostate, doesn’t necessarily mean that it can’t still be cured.

Here’s an example of the old-school thinking: Imagine you’re lying on a chair at the dentist’s office, and the dentist says, “You’ve got a cavity, and decay is inevitable. We’ll just wait and pull all your teeth in a few years.” Like the poor gentleman in “Monty Python and the Holy Grail” who is mistakenly left for dead,” the guy in the chair is thinking, “I feel fine! I don’t want to go on the cart!”

This is pretty much the way it’s been for men were treated for localized prostate cancer with surgery or radiation who have a rising PSA.   The options have been: salvage radiation or surgery, maybe a short course of androgen deprivation therapy (ADT), a vaccine, maybe a clinical trial, and then… waiting for metastases, long-term ADT, and other forms of treatment.

But here’s some promising news:  The window of curability may be wider than anybody thought. Until very recently, the dividing line between prostate cancer that was considered curable and cancer that might not be was the prostate itself – whether the cancer was confined to the prostate or had spread beyond it to a distant site. That’s not the case anymore, says Johns Hopkins radiation oncologist Phuoc Tran, M.D., Ph.D. In the most recent (2018) edition of our book, Patrick Walsh and I wrote the section on radiation oncology with expert opinion from Tran, an innovative scientist working hard to save lives from prostate cancer.

“Clinically speaking, we prescribe treatments for men with prostate cancer as though prostate cancer presents in clear clinical states,” he says.

Think of a Venn diagram: in one circle are “men we believe to have purely localized disease, and they are curable by surgery or radiation.” In the other circle are men with metastatic disease, men who are considered “treatable but not curable with our current therapies.  In general, this old treatment paradigm says that men with localized disease benefit mostly from local therapies like surgery and radiation and very little from systemic treatment like hormones and chemotherapy.”

But Tran and Hopkins colleagues are among scientists who believe these circles intersect. New evidence suggests that in men with oligometastasis – just a few spots of cancer outside the prostate – by treating “not only the primary disease in the prostate or the pelvis, but also the few metastatic lesions, perhaps men can actually live a long time without disease progression and even be cured.” It’s the difference between being reactive – waiting for the next shoe to drop, the rise in PSA or development of symptoms – and being proactive. In other words: not just suspecting cancer is there, but knowing its precise location and going after it.

This is a dramatic and very exciting change in scientific thinking, and it’s happening because several key advances have come together all at once. PSMA PET scanning now allows bits of cancer as small as a BB to be seen – and SBRT (stereotactic body radiation therapy) or SABR (stereotactic ablative radiation) make possible precision treatment. “SBRT and SABR are highly focused radiation given in an intense fashion,” says Tran. “I tell patients it’s like spot welding—focused on a small area, very intense, and theoretically ablative, meaning it kills all the cancer in that spot.”

The Baltimore ORIOLE Trial

Can this new SABR technology plus treatment of localized cancer help men with oligometastatic cancer? “We wanted to test our idea in a rigorous way,” says Tran.  “Our Baltimore ORIOLE trial is a randomized clinical trial in patients with oligometastatic prostate cancer (defined as three or fewer metastases).” To be eligible, men must have received either surgery or radiation for the primary prostate disease, and have had no hormonal therapy for their metastatic disease. “They can have had hormonal therapy in conjunction with treatment for their primary disease,” such as a short course of androgen deprivation therapy (ADT) with external-beam radiation therapy, “but not for their metastatic disease.”

Men are randomly assigned either to receive SABR to up to three metastatic sites, or to a short observation period of three to six months – but this doesn’t mean that the men assigned to observation can’t get SABR, Tran states. “The randomization is two to one to SABR, versus a short – no longer than one- to six-month – observation period, after which they can cross over to the SABR treatment.”

Other criteria for eligibility: small metastatic sites (less 250 cc) and a PSA doubling time of less than 15 months. “We chose less than 15 months because there are men who have biochemical failure or low-volume metastatic disease with long PSA doubling times, sometimes many years,” explains Tran. “These men probably don’t need any treatment immediately – or possibly, ever.  A PSA doubling time of less than 15 months allows us to zero in on patients for whom SABR treatment may make a difference.”

This study was funded by the Movember Foundation and the Prostate Cancer Foundation (PCF).   “The Baltimore ORIOLE trial had no preliminary data when we funded it, and without private funding, it would not have been possible. says medical oncologist Jonathan Simons, M.D., CEO of the PCF. “Generally, the federal government requires that you have one-third of the work done in advance, then they fund the other two-thirds of it. That’s a real deterrent to highly innovative projects, and this one goes after a central and potentially practice-changing question: Can these men be cured now, and be spared ADT and metastases later?”

The potential implications here are huge: “The data suggest that two-thirds of men – or perhaps even more – who progress from biochemical failure to metastatic disease progress first with oligometastatic disease,” says Tran. “The number of men who could be helped by this could be as high as 20,000 to 25,000 every year.”

Because of the possibility of long-term remission or even cure, the study has filled up fast, Tran adds. “Thus far, as expected, we have seen only minimal side-effects from the SABR, and all men continue to work and are able to resume their normal activities during the short treatment,” which generally lasts less than three weeks.  Early results “look promising.  The trial also has a number of cutting-edge genetic, blood and imaging studies associated with it that men would not have access to otherwise.”

The Baltimore ORIOLE trial is a collaborative effort involving Hopkins radiation oncologists Theodore DeWeese, Danny Song, Curt DeVille and Stephen Greco; medical oncologists Mario Eisenberger, Ken Pienta, Emmanuel Antonarakis, Michael Carducci, Sam Denmeade Channing Paller and Mark Markowski; urologists Ashley Ross and Michael Gorin; radiologists Steven Rowe and Martin Pomper; and statisticians Hao Wang from Johns Hopkins and Adam Dicker from Thomas Jefferson University.

In addition to the book, I have written about this story and much more about prostate cancer 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 you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

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Exercise and Cancer: What Your Prostate Thinks

Hey, guys: If you think exercise is just about pumping iron and getting big traps, six-pack abs and “gun show” biceps, your prostate would like to disagree.

To your prostate, how ripped or shredded you are is not nearly as important as your cardiovascular health.

Now, you may be wondering, why should the prostate even care about cardiovascular exercise? Here’s a very good reason: exercise can lower your risk of getting lethal prostate cancer, or of having cancer come back if it’s already been treated.

Epidemiologist June M. Chan, Sc.D., an expert on lifestyle and cancer, heads a research program at the University of California San Francisco that seeks fixable risk factors for prostate cancer progression – things in your lifestyle that you can change to lower your odds of dying of prostate cancer. I recently interviewed her for the Prostate Cancer Foundation’s website.

In previous work, Chan and colleagues were the first to show that vigorous exercise (such as jogging or bicycling) after diagnosis was associated with a reduced risk of prostate cancer death in men with localized disease. “We observed that three or more hours a week of vigorous activity, as opposed to less than one hour a week, was associated with an approximately 60 percent reduction in the risk of dying of prostate cancer.” Chan and colleagues observed similar results among 1,455 men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE). These findings suggest that “engaging in relatively vigorous physical activity and/or having higher cardiorespiratory fitness may protect against prostate cancer progression.”

Now, exactly why is this? That’s what Chan and colleagues are hoping to figure out. “We have a number of studies here at UCSF examining lifestyle and prostate cancer,” she says. “One trial is for men on Active Surveillance, and our main goal is to look at changes in prostate tissue.” Investigators are comparing prostate biopsy samples taken at diagnosis and again after a 16-week period in which men are randomly assigned either to continue their usual activities or to take part in a personalized exercise program that is designed to increase their cardiopulmonary fitness. The researchers also are measuring chemical processes involving circulation and metabolism, looking for specific differences in the two groups.

In this study, Chan is not as interested in studying the men who are already exercising a lot. “We anticipated that the biggest benefits would be observed in individuals who are relatively sedentary and who adopt moderate exercise. If men are already highly fit, they’re probably already exercising several hours a week, and we thought it would be harder to ask them to do more or spend more time, so that we could observe a relative change in fitness,” she says. “Our main goal is to increase the fitness levels gradually through a walking program in men who are at low to intermediate levels of fitness at the beginning of the study.”

The idea here is that even moderate exercise can help lower the risk of lethal prostate cancer. We’re talking about the kind of exercise that almost everyone can do. It is “purposely scaled to be relative to someone’s baseline fitness, and we are choosing men who are low- to moderate-fit,” Chan notes. Men in this study start out just by walking, and then walking faster, and then escalating – literally – to walking uphill.

The men aren’t going flat-out, like someone in a high-intensity workout. They’re just doing a little more than they could, and after they get used to that, they do a little bit more – slowly building up their fitness.

Chan speculates that the tissue samples in the exercise group will show changes in indicators of angiogenesis (cancer’s ability to build a scaffolding of blood vessels and other infrastructure so it can grow and move beyond the prostate); in inflammatory processes; in insulin and insulin-like growth factor signaling; in androgen receptor signaling pathways; and in oxidative stress mechanisms. “Biochemically, exercise could help deter metastasis of the tumor by changing the environment for the cancer” – in effect, spraying fire retardant on the tumor. Not necessarily extinguishing the flame altogether, but making it burn slower, and helping the body set up fire breaks to keep the cancer confined to its current location.

Making Prostate Cancer Fat and Happy

“Prostate cancer may be the most common cancer where exercise, used like a drug, can confer an increase in survival,” says medical oncologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation. “There is no form of treatment that has this effect, and certainly not one as beneficial to the entire body as exercise.”

It may be, Simons adds, that what exercise does – just as it improves blood flow in the arteries – is give cancer a better blood supply that keeps it happy where it is, “so the tumor has no motivation to leave.” So basically, exercise makes cancer feel like it’s at a nice hotel, with free cable TV, continental breakfast, and a pool. It’s content to stay there indefinitely, ordering room service. “When tumors are stressed” – when they’re in a bad neighborhood, in effect – “they have genes that are programmed to help them survive by getting them to crawl away to someplace that better serves their needs.”

One of those genes, Simons found in research at Johns Hopkins, not only pipes in more blood to supply the tumor; it gets rid of waste products – the cancer cells’ sewage, in effect. “When tumors try to turn on blood vessel growth to get more nutrients, they also build their own plumbing for both intake and waste disposal. Angiogenesis is not just about getting oxygen and food – glucose and protein – to the cancer. It’s getting rid of byproducts, too. That kicks off a genetic program so the cancers can relocate” – start to spread.

But giving the cancer a better blood flow might subvert the cancer’s need to boost its own blood supply. It just may be that exercise makes cancer, rather than head for the door, sit back in the recliner and reach for the remote. A contrary notion, isn’t it – that in order to turn your prostate cancer into a couch potato, your best chance is not to be one yourself?

This doesn’t mean, of course, that men who exercise are immune to prostate cancer. “There are very fit athletes who have had forms of prostate cancer that are so aggressive, so genetically mutated, that have proved fatal,” notes Simons. However, those men are at one end of the spectrum of prostate cancer. There are many thousands of men at the other end or in the middle, for whom exercise may make a real difference. “What if you have a Gleason 8 cancer, you had surgery, your PSA was undetectable, and now it’s starting to creep up. And what if you could exercise and delay its colonizing in your bones by eight or nine years, because you so shifted the chemistry in your body that the cancer cells just sat there? That’s a very abstract concept, one that’s still not widely appreciated. But if we could get even three times as many men right now exercising, we could change the overall survival of the disease.” And if scientists like Chan can figure out precisely why this is happening, it may lead to development of new treatments that could make exercise even more effective in deterring the return or spread of prostate cancer.

Is it ever too late to start to exercise? No!

In other trials, including one funded by Movember, Chan and colleagues from around the globe are studying the benefit of aerobic exercise and also strength training in men with castrate-resistant prostate cancer, to see if these interventions can help men at a later stage of cancer live longer. “There are data in men with advanced disease also suggesting that exercise may impart not only quality of life but also clinical benefits” she says.

Body Size and Prostate Cancer

Prostate cancer loves fat. Fat increases inflammation in the body, lowers insulin resistance, and just generally makes a more inviting environment for prostate cancer.

But exercise burns fat. And this, in turn, lowers your body mass index (BMI).   “Increasing evidence suggests that being overweight, either before or at the time of diagnosis with prostate cancer, is strongly associated with the risk of cancer progression and of dying from prostate cancer,” says Chan. “For example, among 2,546 men diagnosed with localized prostate cancer in the Physicians’ Health Study, a one-unit increase in BMI before cancer diagnosis was associated with about a 10-percent increase in a man’s risk of dying of prostate cancer.”

BMI calculators are available on the internet, but briefly, if you are at a healthy weight, your BMI is between 19 and 24.9 kg/m2.  In the Physicians’ Health Study, having a BMI of 30 kg/ m2 or greater “was associated with a nearly twofold increased risk of prostate cancer death,” notes Chan. Further, “a meta-analysis of six studies in prostate cancer patients reported that a 5 kg/m2 increase in BMI raised the risk of dying of prostate cancer by 20 percent, and of biochemical recurrence (having the PSA start to rise again after treatment) by 21 percent.”

 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

 

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What is Prostatitis, Anyway?

Thousands of men are diagnosed with prostatitis every year.  But guess what? Most of them don’t actually have it.

Maybe you’re one of those men, and you’ve been taking antibiotics for weeks because your doctor told you that’s what you had. How are your symptoms? Are they any better? And here’s an important question: Did your doctor get a culture to make sure there’s a bacterial infection in your prostate?  

If you got a culture of your prostatic fluid, you would know it; it’s not like swabbing your throat looking for strep or taking a simple urine test.  No, checking the fluid that is inside the prostate begins with a rectal exam.  “We push on the prostate, fluid comes out the tip of the penis, and we capture this on a slide and look at it under the microscope,” says Sarah Flury, M.D., urologist at Northwestern University, one of the world’s experts on prostatitis and one of the experts we interviewed in the newest (2018) edition of our book on prostate cancer (prostatitis is NOT prostate cancer, but because it involves the prostate, that most troublesome gland, we put it in there).

If you didn’t have a culture of your prostatic fluid, but your doctor told you that you have prostatitis and put you on a powerful antibiotic like Ciprofloxacin, then it’s no wonder if your symptoms haven’t gotten any better. (Actually, taking a long course of antibiotics could even be bad for you; keep reading.)

Imagine if you had chest pain, and you went to the hospital, and the doctor in the Emergency Room said: “Chest pain? That’s a heart attack.” But in fact, your particular chest pain is because you have acid reflux – major backup of your stomach acid into the esophagus – and it hurts so bad that your esophagus is having a spasm. What you really need is a heavy-duty acid reducer or even a proton pump inhibitor, but instead you’re getting pumped full of blood thinners and expensive medicine to dissolve a nonexistent blood clot.

This is a terrible example, but it makes the point: In medicine, you can’t assume, and you can’t put people on medication that isn’t going to help them. If you don’t actually have prostatitis that is caused by bacteria, all the antibiotics in the world aren’t going to help you, and they may cause other serious problems.

Prostatitis is a grab-bag diagnosis; a catch-all where a variety of symptoms are often chucked together when doctors “don’t know what is going on,” says Flury. Pain in the testicles? Prostatitis. Pain in the penis? Prostatitis. Pain in the bladder or rectum? You guessed it. Burning when you urinate or ejaculate? Prostatitis. It’s like the diagnostic Island of Misfit Toys from the classic TV special, “Rudolph the Red-Nosed Reindeer.”

And yet: “Bacterial Prostatitis itself is actually very rare,” says Flury.

Which begs the question, what is it? For the vast majority of men, “prostatitis” is just what the symptoms sound like: Chronic Pelvic Pain Syndrome (CPPS). But what’s causing the miserable symptoms in one man with CPPS might not be what’s causing them in another man. Everybody’s different, and you need to see a doctor who specializes in this, at a medical center where they see a lot of men with these symptoms and know how to treat them.

For example, in some men the cause of pain or tenderness in the scrotum or lower back is actually the pelvic floor muscles in spasm– like a hard muscle knot in the neck or back, except it’s close to the rectum. “There’s treatment for it,” says Flury, “specialized physical therapy, where they do a pressure point release.” Other men have bladder symptoms that are related to interstitial cystitis, which is the “irritable bowel” of the bladder, with muscle spasms. Some men with frequent or burning urination get better with Flomax or another drug in the category of “alpha blocker.” These drugs relax the muscles in the prostate and bladder and help relieve symptoms. Some men get better by changing their diet – because for them, spicy foods seem to set off the symptoms. Men who have difficulty or pain when urinating are often helped by biofeedback and physical therapy.

“Chronic pelvic pain is the broadest diagnosis,” says Flury. “It’s the base of the pyramid. Prostatitis is one of the diagnoses that can cause pelvic pain – not the other way around. Prostatitis is completely misunderstood and misused as a diagnosis. There are many different causes, and it is incredibly rare that it’s actually a bacterial infection in the prostate.”

So, if you have these symptoms, or if you’ve been told that you have prostatitis, what should you do?   “First, know that you’re not alone,” says Flury. “You have something real, but it’s quite possible that you’ve been given the wrong terminology for your diagnosis. CPPS is a heterogeneous syndrome; it’s not a specific disease, and ‘one size fits all’ doesn’t work. It’s a framework, and men have different symptoms within that framework: urinary symptoms, psychosocial symptoms like depression, muscular problems, neurological symptoms, organ-specific problems – in the penis, or testicles, or bladder, or prostate. All those things fit into CPPS.”

Flury is troubled by the number of men who have come to see her after another doctor told them, “You have prostatitis. Try these antibiotics for six weeks and see how you feel.” It’s not that easy. “People treated for six weeks on Cipro, without a diagnosis of infection? It’s terrible. You have to take a history. There may be 10 different causes for these symptoms, and 20 possible treatments.” Many of these men never even had a culture to confirm the diagnosis; they just got put on antibiotics.

It is worth it, Flury adds, to go to a center of excellence. She recommends that you start with this link: http://www.mappnetwork.org. There is a network of centers across the country, where physicians and scientists are doing research on the entire spectrum of CPPS. Even if you don’t want to participate in a clinical trial, physicians at those centers know how to figure out what’s actually causing your symptoms, and plan the treatment accordingly. “CPPS is a common condition, but many traditional therapies fail,” she says. Undoubtedly, that’s because the wrong thing is being treated. Find a doctor who can figure out what you really have. If you’ve been given a diagnosis of prostatitis, the first thing to do is to make sure you actually have it. If you have an infection, you need antibiotics, but if you don’t, you don’t need antibiotics. Many more men have CPPS than prostatitis.”

            Antibiotics: There Are Risks

Some people have the idea that – because in the 1940s when they first came out, these truly were miracle drugs – everything’s better with antibiotics. But here’s why it’s not good to be put on six weeks of a powerful antibiotic if you don’t really need it:

In July 2016, the FDA issued a warning to doctors. It advised restricting the use of fluoroquinolone antibiotics for certain uncomplicated infections – because the “serious side effects … generally outweigh the benefits for patients.” People with some conditions – such as sinusitis, bronchitis, and a simple urinary tract infection – have other options; there are lots of antibiotics that treat those problems. However, men with acute or chronic bacterial prostatitis don’t have as many other choices, so for them, the risks of fluoroquinolones are probably worth it.

But you sure don’t want to be taking these drugs if you don’t need them – and if you haven’t even had a proper culture to determine if you even have an infection.

“An FDA safety review has shown that fluoroquinolones, when used systemically… are associated with disabling and potentially permanent serious side effects that can occur together. These side effects can involve the tendons, muscles, joints, nerves, and central nervous system.” Some of these side effects include “tendon, joint and muscle pain, a ‘pins and needles’ tingling or pricking sensation, confusion, and hallucinations. Patients should talk with your health care professional if you have any questions or concerns.”

  

What if You Actually Do Have Bacterial Prostatitis?

No getting around it: if you do have bacteria-caused prostatitis, you need to take antibiotics for six weeks.

Acute Bacterial Prostatitis. If you have this, you know it, because it’s debilitating – so much so, that you are probably reading this in the hospital. You most likely also have a fever, chills, and extreme pain. This is not the time to be a macho man and suffer through it. You need immediate treatment. Go to the doctor or, after hours, an emergency center.   This is very important: If you have acute bacterial prostatitis and you don’t get help right away, you could develop a life-threatening infection in the blood (called sepsis), or not be able to urinate (urinary retention, which requires a temporary catheter), or develop an abscess within the prostate (an infected area of pus under pressure; as you can imagine, this is very painful).

“Acute bacterial prostatitis is an infection that can have very severe symptoms,” says New York University urologist Stacy Loeb, M.D. “It requires immediate treatment with antibiotics. It is also one of the potential risks of a prostate biopsy: this is why all men who undergo a prostate biopsy require antibiotics before and after to reduce the risk of a symptomatic urinary tract infection – and acute bacterial prostatitis is really an acute urinary tract infection. In fact, recent studies show that acute prostatitis after a biopsy can be more severe than other cases.”

The good news is that once you start taking antibiotics – usually in the category called fluoroquinolones; an example is Ciprofloxacin – you will start to feel better fairly quickly. The thing is, you will need to stay on antibiotics much longer than you might expect. If you just take a course of antibiotics for a week to 10 days and then stop, and even a tiny amount of infection remains in the prostate, guess what? It is likely that the prostatitis will come back – this time as a chronic infection, which is harder to get rid of.   If you have an episode of acute bacterial prostatitis, then, you should stay on antibiotics for about six weeks. Be steadfast with the antibiotics and wipe it out the first time. You don’t want to go through this ever again if you can help it.

Chronic Bacterial Prostatitis. This is rare. Here, too, the treatment is antibiotics. The “chronic” part is that this form of prostatitis can come back every so often for years if an episode of acute bacterial prostatitis is not adequately treated the first time. The treatment is the same: six weeks of antibiotics.

More about prostatitis 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.”  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

 

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Do Statins Prevent Lethal Prostate Cancer?

Statins are toying with prostate cancer scientists.

Study after study hints at a tantalizing connection between taking these cholesterol-lowering drugs and protection from getting lethal prostate cancer.

But an actual magic pill guaranteed to do this just keeps hovering just over the horizon, like the Goodyear Blimp, taunting scientists and oncologists who would love to have something to give to men and say, “Here, take this every day, and you won’t get aggressive prostate cancer.” Or, “This will lower your chances of having your prostate cancer come back after treatment.” Or. “This will help you stay on active surveillance and not develop a higher grade of cancer that needs treatment.”

The link between statins and all these scenarios hasn’t been definitively proven yet. On the other hand, it won’t go away, either.

The problem is, there’s a big difference between suspecting that statins might have a protective effect against aggressive prostate cancer and being willing to go out on a limb and recommend that all men start taking them.

So far, not a single scientist is prepared to do that.

And still, statins won’t go away. What is it about these drugs, anyway? Is it the fact that statins lower cholesterol, and that this in itself somehow changes the body’s susceptibility to prostate cancer? Or is it some other biochemical action of these drugs?

Nobody’s entirely sure about that, either. Meanwhile, here statins sit, blowing raspberries and waggling their ears at scientists trying to find the answers.

The latest study to tease prostate cancer scientists comes from Denmark: scientists looked at nationwide Danish registries and identified 31,790 men who were diagnosed with prostate cancer from 1998 to 2011; of these, 7,365 died of the disease.   (Note: the study does not describe how these men were treated, nor whether they were diagnosed by regular screening. Also, there are more and better treatments for prostate cancer now than there were back then – so don’t get distracted by these numbers; that’s not the point of this article.) Then they looked to see which of these men had also taken statin drugs, and how these men fared compared to the men who had not taken them. In secondary analyses, they looked at the use of statins before prostate cancer diagnosis, and at one year or five years after diagnosis. They concluded that men who took statins after diagnosis were less likely to die from prostate cancer. “However,” the scientists reported, “it remains to be established whether this association is causal.”

Yeah.  In an accompanying editorial in the Journal of Clinical Oncology, Harvard epidemiologist Lorelei Mucci, Sc.D., M.P.H., and Memorial Sloan Kettering oncologist Philip Kantoff, M.D., note that “cholesterol is a precursor of androgens (male hormones) and…can act by reducing androgen bioavailability, thereby limiting tumor growth.” In other words, cholesterol feeds androgens, which in turn, feed a prostate tumor.

Statins act on this pathway, but they also act in some other, cholesterol-independent ways that affect prostate tumors. “Given the multiplicity of possible mechanisms by which statins might work,” the editorial said, “it would be of clinical interest to know whether nonstatin lipid-lowering drugs have the same effect as statins on prostate cancer mortality.

“Taken together, the data from (this and other statin studies) point toward a substantial salutary effect associated with statins, with hazard ratios (a way to measure the effect of a treatment) comparable to many of the more toxic and more expensive agents that now are used for advanced prostate cancer.” And now here comes the uncertainty: With studies like this, the editorial continues, “there is a risk that systematic error… may explain the observed associations.” In other words, are there complicating factors that could be messing up how these results are viewed?

Almost certainly there are, says Johns Hopkins epidemiologist Elizabeth Platz, Sc.D., M.P.H. “You can’t rule out bias in these studies. Even though the investigators tried to take other factors into account, when you look at the patients who were taking a statin and those who were not, they’re very different people. So I worry about saying to all men, ‘Take a statin just because you have prostate cancer and want to be able to do something.’”

That said, “I think there actually is something in statins that protects against prostate cancer. But until we can rule out confounding factors, I can’t say that men should take a statin even if they don’t have a cardiovascular need.”

On the other hand, she adds, if you’re already taking a statin because a doctor has put you on one to help prevent a heart attack or stroke, you may also get some bonus protection against lethal prostate cancer.

Why shouldn’t you just start taking a statin? Because these drugs can have complications, including inflammatory arthritis, muscle weakness, and inflammation of the colon. “If you take a huge group of men who don’t have prostate cancer,” says Platz, “or men who have survived prostate cancer but who have a risk of it coming back, you certainly would not want to tell them to take a statin to prevent lethal prostate cancer, because you would cause a ton of side effects.”

Just about every drug has side effects – even aspirin, which many people take as a preventive measure against stroke, heart disease, and colon cancer. But aspirin also raises the risk of gastrointestinal bleeding, among other things. So there’s a balance: is it better to run a slight risk of a GI bleed and lower your risk of having a stroke?

“Everyone wants to do a trial to prove that statins work,” says Platz. But that’s a lot easier said than done. “So many men are already taking a statin. It wouldn’t be ethical to take them off of that medicine to get them into a trial. We also need more basic science to understand the mechanisms of statins, and the mechanisms of the side effects, too.” At some point, she believes, someone will do a big clinical trial that will answer the question of statins as adjuvant therapy or prevention for prostate cancer once and for all – but it’s going to be really hard. “You might have two guys who look just the same, but one will have a different inflammatory milieu than the other; one will be more pre-diabetic.”

Here’s the kicker: No drug, ever, has proven to be as effective at protecting against prostate cancer and pre-mature death in general as having a healthy weight and being physically active. “If you want to reduce your risk of lethal prostate cancer while increasing your well-being, improve your diet and increase your activity level. Improving your diet is good for reducing your heart attack risk, too. It’s good for your overall health. “

Men who have diabetes are not more likely to get prostate cancer, but they are more likely to die of it if they do get it, “probably due to some very complex pathways that may have to do with glucose itself, or insulin, or the inflammatory environment that seems to result in diabetes,” continues Platz. “So another important thing for men to think about, if they are at risk, pre-diabetic, or diabetic, is to get their blood sugar under control, improve their diet, and exercise to put on lean mass,” and get rid of excess body fat.

There are no shortcuts here. There is no magic bullet. And in Platz’s opinion, shortcuts may not be the way to go, anyway. “If you take a pill, you’re messing with the system. There are going to be side effects, and it’s not holistic. Changing your diet and lifestyle will benefit many aspects of your health, including your mental wellbeing. You’ll feel better if you lose weight and exercise.”

 

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

 

 

 

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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.”

In addition to the book, I have written about this story and much more about prostate cancer 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 you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

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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.”

In addition to the book, I have written about this story and much more about prostate cancer 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 you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

 

 

 

 

 

 

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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.

 

In addition to the book, I have written about this story and much more about prostate cancer 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 you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

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