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PSA Velocity:  It’s Not the Number, but What It Does!

Why did I say that no PSA number above 1, by itself, is a guarantee that you don’t have cancer?  Why do we say this in our book?

Because that’s what H. Ballentine (Bal) Carter, M.D., the great Johns Hopkins urologist and scientist, discovered.  In fact, he says:  “There is no PSA value below which you can guarantee someone they don’t have prostate cancer,” and no value that automatically means it’s cancer.  “There are men with PSAs of 20 who don’t have prostate cancer, and men with 0.5 to 1 who can have very serious prostate cancer.”

So, basically:  Your PSA number, by itself, means Jack.  What happens to it over time means everything.

This is called PSA velocity.  It is a concept pioneered in the 1990s by Carter, working with Patrick Walsh, M.D., my co-author on many books and publications, and it’s a very effective way to detect prostate cancer.  I recently interviewed Carter, who retired this summer after 32 years at The Brady Urological Institute at Johns Hopkins, for Discovery, a magazine published by the Brady.  He devoted his career to making sense of PSA, and what he has accomplished is incredible.  Among many findings, Carter also came up with median PSA numbers based on age, which we will discuss in a minute.

It’s a shame that many doctors, including even some urologists, don’t seem to grasp these simple and very effective ideas, and instead focus on the PSA number itself – an idea that was outdated 20 years ago.

I say this because I don’t know how many times I have talked to men who say:

“My doctor says I don’t need to worry about screening for prostate cancer until I’m in my 50s, and even then, it’s not really that big a deal.”

And, “My doctor says my PSA number is low, so everything’s fine, I don’t need to worry about it.”

This makes me very frustrated.  I’ve written about the travesty that happened in prostate cancer screening here, so we won’t go into that now.

Let’s get back to Bal Carter and PSA, and let’s time-travel, very briefly, to the late 1980s, when widespread screening for prostate cancer did not exist.  The discovery of PSA (prostate-specific antigen, an enzyme made by the prostate) had just made it possible, for the first time, to learn about prostate cancer from a blood test – but nobody knew what to do with PSA, or how to use it along with the rectal exam and the new use of transrectal ultrasound-guided biopsy in diagnosing prostate cancer early.

“There was controversy about even using PSA,” Carter recalls.   “There were voices saying, ‘Beware, we’re going to uncover a lot of cancers that never should have come to light.’”  And that was true.  So then came controversy over the PSA threshold:  what was the magic number that would indicate the need for a prostate biopsy?  “In retrospect, that was probably the wrong thing to be asking,” Carter says.  “There was just not a good understanding then of PSA as a continuum.”

Carter pioneered the concept of PSA velocity – the rate at which PSA rises over time.  “But that’s never been tested as a screening tool.  I honestly believe if we had not focused on a single, absolute threshold, and instead had focused on changes in PSA to alert us that someone has an aggressive cancer, in the long run we may have identified more individuals with the cancers that need to be treated, and eliminated more who don’t need to be treated.  But that will require a carefully done, prospective trial.”

Carter started looking at this years ago, in studies that would lay the foundation for PSA screening and also for safe, vigilant active surveillance as a mainstream treatment for low-risk prostate cancer.  How that came about, he says, “was really the brilliance of Pat Walsh.  When I first joined the faculty, he came to me and said, ‘What do you think would happen if we looked at changes in PSA?’  I said, ‘I think they’ll probably rise faster in people who have prostate cancer.  How can we study that?’  And he said, ‘Have you ever heard of the Baltimore Longitudinal Study of Aging (BLSA)?’”  The BLSA was conceived in 1958, when gerontologists at the Baltimore City Hospitals were trying to find a better way to study aging.  At that time, and even today, scientists would compare men and women who were in their twenties to people who were decades older.  But these scientists had a better idea:  to revisit the same person every two years, with a history and physical and blood samples that were stored.  This made it possible to look at men who had prostate disease, benign enlargement, or localized or metastatic prostate cancer – and then work backward, describing the changes in PSA, over the previous 20 to 30 years.

“I had never heard of it,” Carter continues.  “He said, ‘I know they have a large frozen serum bank, and we might be able to use some of that to look at the question: do PSA levels rise faster in men who have aggressive disease vs. men who don’t have prostate cancer?’  Sure enough, that’s the way it turned out.”

Carter’s work, Walsh says, “has changed the way prostate cancer is treated today around the world.”  Although Carter is a fine surgeon, “he has done his best not to operate on men who don’t need it.  He was a voice of reason at a time when the diagnosis and treatment of the disease underwent revolutionary changes.  With the introduction of widespread PSA testing in 1990, the diagnosis of prostate cancer reached epidemic acceleration and led to abuses fed by the greed of many fellow urologists.  Those are tough words, but there is no other way to explain it.  Bal emphasized the harm of overdiagnosis and overtreatment, proposed solutions based on improved screening practices, and developed guidelines for identifying men who should not be treated.  He began by learning about PSA.”

Using blood samples that had been collected for decades by the BLSA, Carter described how age and prostate disease influenced PSA.  “Based on his unique observations, he proposed new ways to interpret PSA levels, and specified intervals for testing that were the most informative,” says Walsh.  As Chairman of the AUA’s Guidelines Panel, Carter developed recommendations for how all urologists should screen for prostate cancer.

A Prostate Barometer

We discuss PSA in detail in chapter 4 of our book, but briefly:  PSA should never be considered a one-shot, cut-and-dried reading.  Instead, it’s like having a prostate barometer, so your doctor doesn’t have to wait for the PSA level to reach a magic number before acting.  With PSA velocity, what matters is a significant change over time, and for this to be accurate, you need to have multiple PSA measurements taken in the same laboratory, because PSA measurements can vary slightly from lab to lab.

The level of change depends on your PSA number.  For men with a PSA greater than 4, an average, consistent increase of more than 0.75 ng/ml over the course of three tests is considered significant.  Let’s say that over 18 months, your PSA went up from 4.0 to 4.6 to 5.8.  Clearly, something’s going on here.

But what if your PSA is less than 4?  Walsh says:  “Because we now realize that men with PSA levels as low as 1.0 may have cancer,” guidelines have been established for PSA velocity in these men, too:  In these men, work by Carter and colleagues suggests, any consistent increase in PSA is alarming, even an increase as small as 0.35 ng/m. a year.  They also found that many years before a man’s prostate cancer was diagnosed, when his total PSA levels (as opposed to more complex PSA readings, such as a free PSA test) were still low, a PSA velocity of greater than 0.35 ng/ml a year predicted who would later die from prostate cancer.  If you have a PSA between 1 and 4 and it is consistently rising faster than about 0.4 ng/ml a year, you should get a biopsy.

What Should My PSA Be for My Age?

Be aware:  15 percent of men with a PSA level lower than 4 have prostate cancer, and 15 percent of these men with cancer have high-grade cancer, the aggressive kind that needs to be treated.  That’s why we say in the book:  “There is no safe, absolute cutoff above a PSA level of 1.0 at which a man can rest assured that he is not at risk of harboring a high-grade cancer.  Thus, what probably is going to matter the most in the future is your PSA history.”  Get that baseline PSA level in your early 40s, or at age 40 if you have a family history of prostate cancer, of cancer in general, or if you are African American.

Then, depending on the baseline level – whether you are above or below the 50th percentile for your age – take a repeat PSA test every two to five years.  If you are in your 40s and your PSA level is greater than 0.6 ng/ml, or if you are in your 50s and your PSA is greater than 0.7, you should have your PSA measured at least every two years.  If your PSA is below this percentile, you may be able to wait as long as five years for the next test.  These are Carter’s numbers.  In another study, of a larger group of men, urologists Stacy Loeb of New York University and William Catalona of Northwestern University found the comparable numbers to be 0.7 for men in their 40s and 0.9 for men in their 50s.  

So, if you’re 50 and you have a PSA of 2.5, for example, and your doctor says it’s low, that doctor is wrong.  It’s actually high for 50.  It could be prostatitis, or benign prostatic enlargement (BPH).  But it could also be cancer, and you need to get it checked out.  A good next step would be to check the free PSA, with a test such as the Prostate Health Index (PSA has various forms in the blood, and these “second-tier” PSA tests can help tell whether it’s more likely to be higher because of BPH or cancer.)   The higher the free PSA, the higher the likelihood that you are free of cancer, as Carter says.  The numbers from studies vary, but one free PSA cutoff is 25 percent.  If your free PSA is higher than that, your PSA is more likely to be elevated because of BPH than it is of cancer.  If your free PSA is lower than 25, you are more likely to have cancer.

So, basically, to sum up:  You can’t just look at a PSA number and know very much at all.  It’s like looking at a Most Wanted photo and saying, “That guy looks guilty,” or “He has kind eyes!  He’s probably been framed! He’s no criminal.”  No self-respecting detective would ever try to get a warrant based on appearance.  You investigate first.  This is why you study PSA, watch what it does, and if it’s going up, check the free PSA, with a “second-tier” PSA test such as the Prostate Health Index (PHI); you also may need a biopsy.  Don’t just give it a free pass after one test because “the number’s low.”

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. You should start at age 40.  Many doctors don’t do this, so it’s up to you to ask for it.

©Janet Farrar Worthington

 

 

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Close to Home.  Again.

Why do I write so much about prostate cancer?  Because I can’t get away from it.  And now prostate cancer, never very far away, has hit close to home.  Again.

Before I tell you my story, please study this picture.  This is a picture of a miracle.  It’s not a pincushion.  It’s an MRI of a prostate, and the needle biopsy that used this MRI image to find its target – the spot of cancer in what’s ordinarily the most difficult-to-reach, out-of-the-way spot possible.  Those green needles aren’t all in there at the same time; this just shows where the needles went.  Two of them went directly into that spot of cancer.  Believe me when I tell you – as four of the most respected urologists in the U.S. have told me – this cancer would have been missed with the traditional transrectal biopsy, which uses ultrasound.  More about this in a minute.  The cancer is aggressive – Gleason 9.  But it is very small.  It is curable, the urologists all believe.  I believe it, too.

That’s my husband’s prostate.  At this very moment, we are scheduling surgery to get it taken out.

I feel like I’ve been in training for this moment for 28 years. 

That’s when prostate cancer made its first unwelcome entrance into my life – when my father-in-law, Tom, died of it at age 53.  My husband, Mark, was a medical Chief Resident at Johns Hopkins at the time, and all he could do for his dad was make sure his terrible pain was controlled.  Tom never had a chance; he had gone to see the doctor for back pain.  That turned out to be prostate cancer, which had already invaded his spine.  Tom never had a PSA screening test; nobody did back then.  That would change in a couple of years.

I worked at Hopkins, too, as the editor of the medical alumni magazine.   When Tom had been diagnosed, his doctor told him, “Don’t worry about it.  Prostate cancer is an old man’s disease – the kind you can live with for years.”  Tom died within months of his diagnosis.  I wanted to know how a 53-year-old man could die of an old man’s disease, so I decided to do a story about prostate cancer.  I set up an interview with Patrick Walsh, the head of urology at Hopkins, and we wrote a story that would change my life forever.  That sounds kind of melodramatic, but it’s true.  I have been writing about prostate cancer ever since.

Back then, I had no idea that Pat Walsh was the surgeon who invented the nerve-sparing radical prostatectomy, and that he had developed the best prostate cancer research and treatment program in the world at that time.  I wrote about Tom’s battle with cancer, and Walsh’s operation, and the research that was happening at Hopkins.  In those pre-internet days, we were inundated with requests for reprints.  Some 3,000 reprints later, we decided to write our first book.

That book was called, The Prostate: A Guide for Men and the Women Who Love Them.  We wrote it for women as well as men, because in Walsh’s experience, it was the women who got their men – fathers, husbands, brothers, sons – to the doctor.   I found this to be true:  as we were writing it, in 1992, I told both my parents that my dad should go to the doctor and get his prostate checked, and he should get this new thing called a PSA blood test.  My mom made him go and keep going every year.  He hated it, especially the rectal exam, but he went.

In 1997, when Dad was 63, his doctor felt something suspicious on his prostate – a rough patch.  “Probably prostatic calculi” (the prostate’s version of tiny gallstones), he said, but he ordered a biopsy, done by Dad’s local urologist in South Carolina.  A pathologist found prostate cancer.  My parents called me.  I called Pat Walsh about 30 seconds later.  We sent the slides to Hopkins for a second opinion, and they were read by a world-renowned urologic pathologist, Jonathan Epstein.   Two months later, Pat Walsh took out my dad’s prostate, and saved his life.  Dad had initially been diagnosed with Gleason 6 (3 + 3) disease, but – like many men – he actually turned out to have some slightly higher-grade cancer, and his pathologic stage was Gleason 3 + 4.

Note:  My dad never read my book.  My mom did, and on the eight-hour drive up I-95 to Baltimore for the surgery, she read aloud passages of the book she had highlighted.

A few years later, Mark’s grandfather, Charles, died at age 85 of complications from radiation therapy for – you guessed it, prostate cancer.  Radiation was not nearly as precise back then as it is now, and there were a lot of complications, particularly in the rectum.  Frankly, I don’t think he even needed to be treated; at his age, with heart problems, he could have done watchful waiting – the precursor to active surveillance back in the day.

A few months after that, my beloved grandfather, whom we all called Pop, died.  Of a heart attack after being put on a great big dose of estrogen – another treatment they didn’t have the hang of back then – for prostate cancer.  Like Mark’s grandfather, Pop was in his eighties, had no symptoms, and probably didn’t even need to be treated.  We know so much more now.

Patrick Walsh and I kept writing books on prostate cancer, and our first book morphed into a more cancer-focused book, Dr. Patrick Walsh’s Guide to Surviving Prostate Cancer.  Over the years, the news got better and better – particularly the chapters on advanced and metastatic prostate cancer.  When we first started, the news there was bleak.  Now, in large part due to research funded by the Prostate Cancer Foundation (PCF), for which I am proud to work as a science writer, there is more hope for treating advanced prostate cancer than ever before.  But, as my dad’s case has shown, there’s a lot to be said for early diagnosis and treatment.  Ideally, Walsh and I wrote, prostate cancer will be a blip on the radar screen – it’s caught early, it’s treated, and then it’s gone, and you get on with your life.  Many men with low-grade disease may never need treatment; they can be safely monitored for years.

When Mark reached age 40, I made sure he got his PSA tested every year.  His PSA was very low (less than 1, and then right around 1) when he was in his forties and early fifties.  Because of his family history, I told him and his doctor about getting a genetic test (which I have written about) to screen for 16 mutated genes known to be linked to aggressive cancer.  Mark took the test, and thank God, it was negative.  His PSA went up to 2, so his doctor ordered another test three months later.  It was 3.  We took another test; also 3.  I had suggested to Mark and his doctor that he get the prostate health index (PHI) test, which looks at different types of PSA.  Mark’s free PSA had dropped from 25 down to 18 – not encouraging.  As we said in our book:  free PSA of 25 and above is more likely to be free of cancer.

I called Pat Walsh.  He told Mark to come to Hopkins.

We live in a small town in Arizona.  Our internist said, “at least get the biopsy done here.”

I said these words:  “Absolutely not.  You need an MRI.”

I knew this for several reasons:  I had written about it from interviews with respected urologists including Bal Carter, of Hopkins; Stacy Loeb, of New York University; and Edward (Ted) Schaeffer, of Northwestern.  And I had interviewed Rob Gray – a young guy with a young family, whose battle-scarred prostate had endured multiple ultrasound-guided biopsies, all negative, but whose PSA had continued to go up.  His doctors told him not to worry about it; Rob worried.  He would still be worrying today, except he had a fusion MRI, which combines several different ways of looking at the prostate.  Because of all his other biopsies, his prostate had developed scar tissue that masked the cancer.  The MRI found it.

That stayed with me.  Then, just weeks ago, I interviewed Hopkins urologist Michael Gorin about two things in particular.  One is multi-parametric (mp) MRI, which is similar to fusion MRI, but it’s what they call it at Hopkins.  Gorin has developed software that allows him to take the findings of mpMRI and use them as a road map to guide the biopsy.

The other thing Gorin is doing is getting to the prostate by a different approach: through the perineum.   The perineum is the area between the scrotum and the rectum.

The traditional transrectal ultrasound (TRUS) biopsy, as its name suggests, reaches the prostate through the rectum.  There are a lot of problems with the TRUS biopsy.  Because it goes through the rectum, there is a risk of infection.  There is no risk of infection from the perineum; in fact, they don’t even give antibiotics for this approach.  And, most worrisome about the transrectal approach:  it’s hard to cover the entire prostate.  This is a problem especially for African American men, who tend to develop prostate cancer in the anterior region of the prostate.  Basically, as Ted Schaeffer, an excellent surgeon and coauthor of the book, explained, if you think of a prostate as a house, the transrectal biopsy comes in from the basement.  It’s pretty good at reaching the main floor, but not that great at reaching the attic.  It’s a South to North approach.

The transperineal approach goes from West to East, and instead of a house, Mike Gorin uses the analogy of a car:  the needle comes in from the headlights to the tail lights, but it can go lower, from the front tires to the back tires, or higher, from the front windshield to the rear windshield.

Now, combine this approach with MRI, and it’s a whole new world for diagnosis.

Compared to MRI, TRUS is blind.  It’s lame.  There, I said it.  Imagine you’re playing paintball at night, and you’re trying to hit a target.  You do the best you can, but you miss a lot.   Then the other team comes in and cleans your clock – because these guys have night-vision goggles.  They can actually see what they’re trying to hit.   MRI gives the urologist night-vision goggles.

When Mark got his MRI, it showed a 6 mm lesion – a spot the size of a smallish pearl on a necklace.  There was a 70-percent chance that this would be cancer.  Gorin took that MRI and used it to guide the biopsy.  Out of 15 cores taken throughout the prostate, he took two samples from inside this spot; he had a target to hit, and he nailed it.  He is my hero.

I’m telling you this because I have learned some things that I want you to know.  In fact, like the Ancient Mariner in the very old poem by Samuel Coleridge, I feel compelled to tell you this, and I hope you will feel bound to listen.  And I hope to God that someone else will be helped by what I’ve learned, including:

Every patient needs a treatment warrior.  An advocate.  Mark is an incredibly smart doctor, but he was just as stunned at having a possible diagnosis of cancer as any other patient.  His internist wanted him to go to the local urologist for a biopsy.  Our small town is not up on all the latest technology.  We don’t have an MRI for prostate biopsies.  They don’t do the transperineal approach. Again, I am certain that if Mark had gotten the traditional TRUS biopsy, this would not have been found.  The lesion on his prostate was in the anterior region – hard to reach, especially if the doctor can’t see and doesn’t have an MRI-revealed target to try to hit.  But Mark would have done as his doctor suggested, because he was stunned and he didn’t know as much as I happen to know about prostate biopsies, because his area of expertise is digestive diseases, not prostate cancer.

The difference between ultrasound and MRI is night and day.  It’s life-changing, and life-saving.

There is no safe PSA number above 1, as Bal Carter has said for years, and as we say in Chapter 4 of our book.  My dad’s PSA was very low:  only 1.2.  And yet, he had Gleason 3 + 4 disease.  Mark’s PSA is only 3.  Please understand this point.  This may be the most important of all.  I have talked to so many men over the last nearly three decades.  So many men who were wrongly assured by their doctor – because their doctors did not know better– that “Your PSA is going up, but it’s still pretty low.  Don’t worry about it.”  If your PSA is going up, worry about it.  It may not be cancer, but you have to check.  If your doctor sees one PSA reading and judges the number by itself, that doctor is not giving you the best advice. 

            You must look at PSA velocity:  the rate of rise of PSA over time.  I will be covering this in more detail in the next post.

And finally – again, because I have written about this disease for nearly 30 years, and talked to so many men with every stage of prostate cancer – the doctors who urge men not to get tested, who tell them not to worry about it, who say there’s no benefit to getting screened for prostate cancer, that the risk of complications from biopsy are too great, that too many men are overtreated, are just plain wrong.

As urologist Stacy Loeb told me:  “A diagnosis of prostate cancer doesn’t mean you need to get treated.”  But you should be the one to make that decision; don’t let cancer make it for you.  Not all men need treatment.  Because of Mark’s family history and his Gleason score, even though the one spot of cancer is very small, we will be getting treatment.  Surgery.  I say we, because it’s both of us.  We’re a team.

Mark is worried about the main complications of surgery – temporary urinary incontinence and the risk of erectile dysfunction (ED).  Of course he is; nobody wants these complications.

I’m not.  There is a huge difference between dealing with the side effects of treatment for localized disease – cancer that is confined within the prostate, cancer that can be cured with surgery or radiation – and the side effects of treatment for advanced disease, treatment that begins with shutting down the male hormones.

The complications from surgery can be treated, and as Pat Walsh says, “Where there’s a will, there’s a way.”

“But what about incontinence?”  I don’t care.  I know that it’s almost always temporary, and if not, biofeedback is wonderful, and he can start doing the Kegel exercises now.  Absolute worst-case scenario, there’s surgery to get an artificial urinary sphincter.  We’ll deal with it.   It will be okay.

“But what about ED?”  I don’t care.  We’ll deal with it.  There are many treatments, starting with drugs.  Worst-case scenario, there’s surgery:  a prosthesic implant.  I don’t think this will happen; the cancer is nowhere near the neurovascular bundles, the nerves responsible for erection (discovered by Pat Walsh, who developed the “nerve-sparing” radical prostatectomy).  I think he will be just fine.

What matters is him being there for me, our son in high school, our son who just graduated college, and our daughter and son-in-law, who are about to have their first baby.  That’s all I care about.  Mark not being there is unthinkable.  Right now, the score in our family is prostate cancer 3 (Tom, Charles, and Pop), our family (my dad, who is about to celebrate his 84th birthday) 1.

I don’t want prostate cancer to win against our family ever again. 

When Pat Walsh called with the biopsy report, it took a second to shift from “Oh, my God,” to “Let’s roll.”  We had been praying for low-grade cancer, Gleason 3 + 3, but this high-grade; it is aggressive.  So we are now dealing with high-risk cancer.  But it is small-volume, thank God!  Because it was detected early.

“Thank God,” Walsh agreed.  “We could not have found it any earlier,” and without MRI, it wouldn’t have been found at all.  “These are the lesions we consistently missed” with TRUS biopsy.  He explained that where Mark’s tumor is, in the posterior apex of the prostate, is like the nose cone of an airplane.  It’s behind the urethra; almost impossible to reach through the rectum – but Gorin reached it through the perineum.  One more thing, Walsh said:  “It was found with a new machine that Mike Gorin has had only for a week.  This was truly a targeted MRI.”  Thank God!  Now let’s roll.

Note: This MRI is shown with Mark’s permission.  He, too, has made it his mission to help men get screened for prostate cancer, and if they have a rising PSA, to get it checked out.

Update: Apparently, the strength of the magnet in the MRI matters a lot.  The stronger the magnet, the stronger the image.  The prostate MRI magnet used for Mark is 3 Tesla.

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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The Spare Tire and Your Risk of Lethal Prostate Cancer

Note: I’m not fat shaming!  I am excited, because here is something you can do to lower your risk of dying of prostate cancer!

Fat is flammable.  There’s so much fat in bacon grease, you can use it as a fire starter.   You can also take a can of Crisco, stick a wick in it, and make an emergency candle.      

Unfortunately, the same is true for us:  excess body fat is like lighter fluid for prostate cancer.   Visceral fat, that “spare tire” around the abdomen, is even worse.  It’s not subcutaneous fat – the surface fat you can “pinch an inch” with.  It’s deep inside the belly, an evil pillow that settles over and wraps itself around our abdominal organs.

Visceral fat is the Jabba the Hutt of fat: a notorious villain in several important health problems.  Visceral fat raises your risk of heart disease, diabetes, metabolic disturbances, dementia, and in women, breast cancer.

Now, for the first time, it’s also been shown to raise your risk of getting prostate cancer – the aggressive kind that needs to be treated.  The kind of prostate cancer that kills.

Why is visceral fat so bad?  Because it’s like a blobby smokestack, polluting our bodies with its troublesome emissions.  “Visceral fat is a living, biologically active entity,” says medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation (PCF).  Like the chest-bursting alien in Ridley Scott’s iconic movie, it’s alive! And it’s up to no good.

Among other things, visceral fat messes with your hormones.  It lowers testosterone and raises estradiol, a form of estrogen.  It churns out inflammatory chemicals called cytokines, which can raise your blood pressure, affect blood clotting, and raise your risk of heart disease and stroke.  Cytokines also have a bad influence on your insulin resistance; this rising tide of glucose raises your risk of getting diabetes.

Like Charlie Brown’s friend, Pigpen, visceral fat also sheds – not dust, but fatty acids, which go right to the liver.  These fatty acids lower your good cholesterol and raise your bad cholesterol.

No one had connected visceral fat to prostate cancer until very recently.  In a study published in Cancer, which I recently covered for the PCF’s website, scientists led by Lorelei Mucci, Sc.D, of Harvard’s T.H. Chan School of Public Health, and Sarah Markt, Sc.D., now at Case Western, investigated body fat distribution and the risk of prostate cancer.  You might say that their study, of Icelandic men in the Age, Gene/Environment Susceptibility-Reykjavik Study, has shaken up the apple cart of what we understand about body fat.

Speaking of apples, visceral fat goes with the “apple” body shape.  This is bad, because the fat surrounds so many vital organs.  But what if you’re a “pear?”  If you’re a pear shape, you carry your fat lower, in the hips and thighs. This fat is usually subcutaneous fat, usually not thought to be as dangerous as visceral fat.

Guess what?  For prostate cancer, thigh fat is bad, too.  This study found that men with greater visceral abdominal fat as well as men with greater thigh subcutaneous fat are more likely to get advanced or fatal prostate cancer.  Visceral fat even raises the risk of advanced or fatal prostate cancer in men with a lower body mass index (BMI – for how to calculate yours, see below); this suggests that the location (even for a modest pot belly) is more important than the overall amount of body fat.

            Risk Goes Up with Higher BMI:  Each BMI increase of 5 was associated with a 52 percent higher risk of advanced prostate cancer, and a 56-percent higher risk of fatal prostate cancer.  Obese men – with a BMI of 30 or higher – were 2.5 times more likely to develop advanced disease, and 2.6 times more likely to die of prostate cancer.  For about every four-inch increase in waist circumference, the risks of getting advanced prostate cancer and dying of it went up significantly – by 40 percent and 45 percent, respectively.

This study may lead to important changes in medical practice.  “We are working very hard to save the lives of men who have advanced, aggressive prostate cancer, notes Simons.  “To do this, we are trying to understand in depth the genetics and consequences in the biochemistry of the disease, and are looking for ‘’druggable” targets for new classes of drugs.  Here is a risk factor for aggressive disease that can be changed!  If this applies to you, we want you to know what a difference you can make in your risk of dying of prostate cancer.”

Note:  Stress makes it harder for you to lose weight.  If you are stressed, your body makes more cortisol, and cortisol makes your body store more visceral fat.  On some ancient level, your body may be thinking:  “Oh, no, times are hard! We’re going to starve!  Better hang on to this fat!”  So, in addition to other ways to lose the fat – exercise and eating a smarter diet with fewer carbs and sugar – you might consider stress management strategies like meditation, relaxation techniques, and deep breathing.  It might help your body let go of the fat.

 

What’s My BMI? 

BMI, or body mass index, is a measure of body size – and whether you’re at a good weight for your height.  It’s pretty simple, and requires just these two things: your weight and your height.  That’s it.  You can do it yourself with this formula:  BMI = weight in pounds x 703/in2. 

Or, you can use a BMI calculator.  There are plenty of them online.  The National Heart, Lung, and Blood Institute has a BMI calculator and even a free BMI calculator app you can download.  A BMI of 18.5-24.9 is considered the healthy range; between 25.0 and 29.9 is considered overweight, and a BMI over 30 is considered obese.  Also, men with a waistline that measures 40 inches or more are more likely to have too much visceral fat.

 

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 Shockwave Therapy Work for ED?

If you’re struggling with ED, you may be wondering whether the latest miracle cure is actually a miracle cure.  You’re right to wonder.  The world of treatment for erectile dysfunction (ED) is complicated; add in emotional stuff like frustration and hope, and it can be even tougher to figure out what to do.  And here’s this new approach that’s making – well, waves.  It’s called shockwave therapy.  You may have seen ads for it on TV or the internet.

Maybe shockwave therapy deserves all the hype it’s been getting, and maybe it doesn’t:  more comprehensive research is needed, and it has not been approved by the Food and Drug Administration (FDA) as a treatment for ED. 

The good news:  shockwave therapy is noninvasive, doesn’t require pills or pumps or injections, and it doesn’t seem to cause any harm.

However:  Despite what the enthusiastic commercials and Youtube videos say, it’s not clear how well shockwave therapy works for ED.   It’s also not clear which men would benefit the most; doctors can’t give percentages of real success yet, nor can they predict how long the treatment’s effects will last.  However, “the suggestion that it works on everybody is highly questionable,” says Johns Hopkins neuro-urologist and Professor Arthur Burnett, M.D.  I have worked with Arthur Burnett for more than 25 years, at Johns Hopkins, here at VJ, on various editions of the book and most recently, as part of my work writing for the Prostate Cancer Foundation’s website.   For all that time, he has been not only a world-renowned investigator authority on the science and medicine of ED, including ED after surgery or radiation for localized prostate cancer; he’s been a voice of reason and hope for thousands of men.

Burnett is also part of a panel for the Sexual Medicine Society of North America (SMSNA) that released a position statement in March 2019, cautioning men about shockwave therapy and other new treatments for ED that aren’t FDA-approved.  The statement also mentioned stem cell therapy, platelet-rich plasma (also called the “P shot,” or Priapus shot), and even amniotic fluid.  Without FDA approval, the SMSNA states, “the use of any novel therapy is considered off-label.”

And yet, despite the lack of definitive medical evidence supporting its use, Burnett says, shockwave therapy is “being heavily advertised, a lot of urologists are very interested in this, and it’s caught on in a big way in South America and Asia as a treatment option for ED.”  In the U.S., shockwave therapy is being offered by a growing number of urologists, particularly in Florida.

What is it, exactly?   It’s low-intensity, extracorporeal shockwave therapy (Li-ESWT), “a machine that delivers acoustic signals and a shock to tissue, much like the lithotripsy machines used to treat kidney stones.”  The idea, Burnett says, is that “you can generate a mechanical energy effect on tissues, and have a potential benefit – stimulating angiogenesis (the growth of new blood vessels) in the penis, and stimulate local chemical factors in the tissues – growth factors, paracrine signaling (cell-to-cell communication), maybe even somehow activating stem cells.”

In other areas of medicine, shockwave therapy is used to treat problems ranging from diabetic foot ulcers to heart disease.   And “for the past few years, in the world of sexual medicine, there have been some studies and literature reports presented at national meetings on the potential role of this therapy in men with ED,” says Burnett.  “There’s a lot of buzz.”

The problem:  “It’s very controversial.”  Does it work? “That’s the big question.  There may be some evidence of a short-term benefit, probably in men with mild to moderate ED.  But the treatment settings, the outcomes – it all remains investigational.”

You might not get that bit of information from the commercials on TV and the internet.  “The ads are out there.  Doctors are buying these machines, saying, ‘Plop down your $2,500, and we’ll treat you.’”

In theory, shockwave therapy is “potentially restorative,” says Burnett, in that it “might regenerate erectile tissues.”  In animal models, shockwave therapy has shown some success.  However, he notes, “there is a lack of clinical trial evidence to support its effectiveness and long-term safety” in men with ED.   No study has determined the basic parameters: energy dosage, frequency, or duration of treatment.

Who knows?  It may turn out to be great — but again, probably not for everybody.  Shockwave therapy is “potentially an exciting new therapy in the world of ED management,” Burnett continues.  “But the best patients to expect a benefit from this have not been fully well-defined. The long-term success remains uncertain. People are thinking this is some sort of fountain of youth, or magical cure to correct their ED, but that has not yet been proven.”

What about ED after prostate cancer surgery?  The men most likely to be helped by shockwave therapy after prostatectomy are also the men who are most likely to benefit from pills such as Viagra: younger men whose erectile nerves have been spared, who don’t have cardiovascular problems or other diseases, such as diabetes, that can affect either blood flow or nerve function, or both.  “Men with more severe ED, men with significant diabetic or vascular disease-related ED, men who have very poor or nonexistent responses to the pills, probably won’t benefit from it.  These men should look at other therapies – the vacuum device, penile injections, or penile prosthesis surgery.

“The real truth is that we just don’t understand who should be using this. It seems safe; there are no obvious concerns about men having complications with it.  But patients should be informed that this may not be successful, and that it’s expensive.  To say, ‘Try it, because it might work for you, even though you already had ED before your radical prostatectomy,’ creates a false hope, and that’s not good.”

Burnett and colleagues on the SMSNA concluded that until there is FDA approval, the use of shockwaves or any restorative therapies for the treatment of ED “is experimental, and should be conducted under research protocols in compliance with Institutional Review Board approval.”  Men considering such therapies should be fully informed “regarding the potential benefits and risks. Finally, the SMSNA advocates that patients involved in these clinical trials should not incur more than basic research costs for their participation.”

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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The Long, Wet Road: Conquering Incontinence After Prostatectomy

Incontinence after prostatectomy is one of the most feared complications.  The good news is that for nearly all men, it goes away.  For the very small percentage in whom it doesn’t, there is help.  This story is a very strong case in point.

In my work for the Prostate Cancer Foundation’s website,  I was lucky enough to interview JP Mac, who has had a particularly difficult struggle with incontinence after prostatectomy.  JP (real name: John P. McCann) is a novelist and an Emmy award-winning animation writer who worked for Warner Bros. and Disney.

He is also very funny.  So, when he wrote a short ebook (coming soon in paperback form) about his experience with prostate cancer – including his diagnosis in 2014 at age 61, the rush to find the right treatment and get it done before his health insurance was going to expire, his laparoscopic-robotic prostatectomy and the complications afterward, and his five-month battle to recover urinary continence after the surgery – he could legitimately have written a soap opera, or maybe even a tear-jerker; but he didn’t.

Instead, his ebook has a title that sounds like 1950s pulp fiction: They Took My Prostate: Cancer, Loss, Hope.  It’s not “Prostate Cancer Lite,” and it doesn’t minimize what he or anyone else has gone through to get back to normal after radical prostatectomy.  Far from it; in fact, his “short, hopeful essay” is a testament to what it takes to recover from this difficult but life-saving surgery: a balanced perspective, a good sense of humor, a great support system, and plain old hard work and persistence.

Here’s a message you hardly ever hear about prostate cancer, or any illness, for that matter:  It’s okay to laugh!   That doesn’t mean it’s not scary, and that it doesn’t wear you down, or that you’re not afraid you won’t ever get back to normal.

But if it’s laugh vs. cry, Mac would rather laugh.  Although no cancer is great, he says, prostate cancer is “especially seedy,” and in his case, it involved  “bloody urine, black feces, incontinence, impotence, vomiting, and various other bodily malfunctions that shouldn’t be discussed before supper.”  But he does discuss them, with the hope of helping other men and their families.  Mac knows that talking about what’s happening gives the cancer less power over your life, and helps you focus on the light at the end of the tunnel – getting your life back after the cancer is cured.

Mac is speaking out about one area, in particular, that doesn’t get talked about much: urinary incontinence.  For many men who suffer from it, in fact, there might as well be a Cone of Silence over this subject, and that’s a shame, because there is always help for urinary incontinence after radical prostatectomy.

When Mac was diagnosed with prostate cancer, his surgeon told him to buy our book, Dr. Patrick Walsh’s Guide to Surviving Prostate Cancer.  Mac did, and he referred to it a lot – especially our review of the male plumbing, which explains why at least some temporary incontinence is just about inevitable for men after radical prostatectomy.

Note: Long-term urinary incontinence is very rare after radical prostatectomy.  Results differ depending on the surgeon; also, some men have quirky anatomy — very subtle anatomical variations (not like a leg where an arm should be, or anything like that, but even tiny differences can be important in surgery, and good surgeons know this and look for such variations).  This is why, if you are considering radical prostatectomy, it is essential to find out how many of that surgeon’s patients have long-term complications.  If your surgeon doesn’t know, consider this a red flag.

The best surgeons keep track of their patients after radical prostatectomy. “In young (men in their forties, fifties, and early sixties), healthy men operated on by an experienced surgeon,” Walsh says, “about 80 percent should be wearing no pads – or at most, a security pad to catch the occasional drop – by three months after surgery, and at 12 months, 95 to 98 percent should be continent.”  Walsh considers a man continent “if he wears no pad or if he wears a pad that is dry.  “Many men continue to wear a small pad just to be safe,” he explains.  Your surgeon may have a different definition of continence, and you should find this out before surgery.  “Most men, even at three months, are not very wet.  It’s hard to believe, but urinary control does continue to improve over two years, and occasionally, even longer than that.”

But don’t lose hope, he adds:  “For many men, the recovery of urinary control is a slow process. The most important thing you can do is not get discouraged.  If your doctor told you there is only a 2 percent chance that you will have a long-term, serious problem with urinary control, believe it.  This means there’s a 98-percent chance that you’ll be back to normal someday, even if nobody can say exactly when.”

From Three Sphincters to One

Why is urinary control an issue after surgical removal of the prostate?  Normally, Walsh says, men have not one, not two, but three separate anatomical structures to control urine.  There is a sphincter in the bladder neck, one in the prostate itself, and then there’s the external sphincter (also called the striated sphincter), below the prostate. Radical prostatectomy knocks out two of these, leaving only the external sphincter to do the work of three.

Because of the other two sphincters, in most men this external sphincter is never tested or even used much; there is no way to know before radical prostatectomy how strong it really is.  Also, like every other muscle, this sphincter loses its tone with age.  A complicating factor is that older men are more likely to have some benign enlargement of the prostate (BPH), too. This could make the bladder thicker and more muscular – and much more powerful than a sphincter that may not have been that effective to begin with.

Mac didn’t really think about this in a lot of detail until his catheter came out after the surgery.  “A nurse handed me a thick cotton pad to put in my underwear.” Mac’s urologist “warned me that the urine was coming, as surely as a Cambodian rice farmer predicting the monsoon. Little could be done, he explained, until I underwent physical therapy. There I’d learn exercises to strengthen the underused muscles of my external sphincter.”

Mac was so happy to have the catheter out that he thought the worst was over.  Cotton pad in place, he made an appointment to come back in three weeks, and took his wife out for breakfast.  “Rising an hour later after three cups of coffee,” he gushed urine “as if putting out a fire in a wastebasket.”  It turns out that the worst was just beginning.  “Basically, the bladder holds urine until a series of reflexes causes a bathroom urge.  Bladder and sphincters then receive a message from the brain to check flow until an appropriate time. When you’re incontinent, any time is just dandy.  You can experience stress incontinence with activities that suddenly increase pressure inside the abdomen, like lifting or standing. Then there’s urge incontinence, which is a sudden uncontrollable need to leak.  Finally, there’s overflow incontinence when you can’t sense if the bladder was filling.  I had all three.”

Suddenly, Mac’s new normal was a life with absolutely no bladder control.  “Movements gross and subtle, lying on my back, it didn’t matter. Everything ended in a demoralizing urine surge. I really needed that physical therapist. But our new insurance had other ideas.”

While he “moped around home like the Incredible Surging Man,” his wife, Joy, spent hours on the phone wrangling with the old and new insurance companies, whose bureaucracies were “sharp as a paper cut,” Mac comments. Meanwhile, he experimented with leakage protection:  “I tried packing my regular underwear with cotton pads. That idea cratered in less than a day. Not only were ‘man diapers’ necessary, but they required cotton pads inside as well. I was soaking through three pads a day minimum. Each morning, I’d wake up drenched, smelling like an interstate washroom.”

Days passed until, Joy finally convinced the insurance company that “we were, indeed, customers and had paid for a specific plan.” Then, the insurance company insisted that the physical therapist wasn’t covered by the plan.  Mac was desperate; his urologist’s office staff stepped in to wrangle with the insurance and finally got the go-ahead for the physical therapist. While all this was happening, “I lived the life of the urine free spirit.  Avoiding coffee or soda mattered little. No internal spigot staunched the constant flow.”  Mac got sick of smelling urine, of feeling that he was “marinating in pee.”

Three or more times a night, he says, “I’d awaken with man diapers soaked and pressure on my bladder. Sitting up, I’d whiz into a hand urinal, change, clean myself, then lie back down and hope for a little sleep before the next voiding.”

At last, Mac could see a physical therapist.  Mac drove to the appointment – his first time behind the wheel since the operation – hopped out of the car, and soaked himself again.  Then he met Eva, his physical therapist, who used biofeedback to help him identify the right muscles to use.

“She hooked my perineal and abdominal muscles to a laptop via adhesive pads, and for the next hour, gave instruction in finding, then clenching and unclenching my striated sphincter in order to control urination. On the computer screen, I could monitor my efforts. A moving graph alerted me when I targeted the correct muscles.”  Mac learned how to do Kegels – clench-and-release exercises to strengthen the pelvic floor muscles below the bladder.

“I found biofeedback to be of great value,” and for Mac, it helped him start to regain bladder control.  “I know a guy who underwent the same radical robotic prostatectomy,” he says.  “Afterwards, his urologist tossed him a few sheets of diagrammed Kegel exercises and said ‘Vaya con Dios.’ No one told my friend you could overdo these exercises. While other factors may’ve been in play, his continence recovery turned out to be longer and messier than mine. Maybe a little biofeedback could’ve improved his condition quicker.”

Eva gave Mac daily exercises with frequency and duration goals.  She also encouraged him to walk daily.  Psychologically, the Kegels were important,” he notes.  “I lived with a constant dribble that could transform into a flood. Eva’s exercises provided me concrete specific actions. She also warned me against overtraining that could fatigue the striated sphincter, rendering it too tired to work.”

Five days later, at his next PT session, “I saw progress.”  For the first time, he could stand up without urinating.  Next, he learned to anticipate the “go” urge – and not wait until he felt pressure in his bladder.  “I could then reach the toilet with something left in the bladder.”  Mac discovered that, in order to stand up without putting excess pressure on his bladder, he had to walk bent over, “like Groucho Marx.” At first, he could go maybe three or steps without a surge.

Joy noticed improvement before Mac did; so did his urologist, who told him, “a lot of the discomfort you’re feeling now will pass. Once you strengthen the striated sphincter, your bladder urges will stabilize.”

There was some good news:  Two months after surgery, Mac’s PSA was undetectable.  His cancer was gone!  And finally, after much hard work, his bladder control began to return.  “With persistence, I sensed how to locate and activate my new bladder-control muscles.  Eva suggested I aim to eliminate jug peeing (with the handheld urinal at night) and excessive bathroom visits.  Using the striated sphincter, I should school the bladder, aiming for fewer, but more productive, bathroom trips. In the meantime, I discovered a cost-effective method of cutting down on cotton pads out in public. By inserting several sheets of double-ply toilet paper into my man diaper, I caught the wild leaks. Just toss and replace the tissue. It was easier than finding a stall and swapping out cotton pads.”

Then, for two nights in a row, he only urinated once. By mid-November, nearly two months after his surgery, “I’d slept an entire night without awakening to pee.  In the morning, I loped ape-like to the bathroom and urinated. Just after Thanksgiving, I stopped wearing man diapers and returned to underwear, albeit with a cotton pad and toilet paper inside.”

For Christmas, Mac and Joy flew to the Pacific Northwest to visit his sister.  Traveling was “an adventurous time, with me unable to cross forty feet of airport concourse without running into a washroom jackknifed over.  I grew to be an expert at identifying tile patterns.”

But even his “odd potty walk” would not last forever. By March 2015, “ I could check flow and walk upright to the bathroom.  My newly discovered striated sphincter knew the routine and exceeded expectations.  I’d finally turned a corner.”

It might not seem like it now, if you’re going through the worst of what Mac endured, but remember: only about 2 percent of men have long-term incontinence after radical prostatectomy, and if you’re in that percentage, there is still hope. Talk to your urologist about biofeedback, which made all the difference for Mac.  Other options include collagen injections, a mesh sling to help take some of the pressure off of the sphincter, and for severe incontinence, an artificial urinary sphincter.

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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Block SRCs, Kill Prostate Cancer?

This is part of On the Horizon:  a series written with the sole purpose of sharing hope:  showing you some of the new treatments that are being developed to fight cancer that has defied everything else.  Because I write for the Prostate Cancer Foundation’s website, I get to interview scientists developing highly promising treatments that aren’t widely available yet, but they’re in the works.  Salma Kaochar, of Baylor College of Medicine, is one of these scientists.

How do you stop a runaway train?  Take a few seconds and think about it; feel free to draw from any runaway-themed movies you might have seen.

Well, you could go after the track: rip it up: a train can’t go very far without a track.  Get rid of its fuel:  this was an idea in “Air Force One,” where Harrison Ford dumped jet fuel in mid-air.  Slow it down:  in “Unstoppable,” Denzel Washington and Chris Pine tried to halt a runaway by pulling it from behind with another engine. This didn’t work for very long; next, they tried to engage the brakes – first on the individual cars, and then on the main engine.  Blow it up: If you didn’t really care about innocent bystanders or collateral damage, you could just take a rocket-powered grenade or heat-seeking missile and try to destroy the runaway engine… if you happened to have such a weapon, if you knew how to use it – and if, of course, this weapon actually works like you hope it will.

Metastatic prostate cancer is like a runaway train. Every day, scientists are getting closer to stopping it, with a drug or treatment that targets one of cancer’s weak spots.  Cut off its fuel:  That’s the reason for ADT (androgen deprivation therapy), shutting down testosterone and other androgens (male hormones) that drive the cancer; and also for androgen receptor-blockers, drugs like abiraterone and enzalutamide.  Hinder its ability to grow:  that’s the purpose of chemotherapy, and of drugs that target angiogenesis – like the tracks for the train, there are pathways cancer needs before it can get rolling.  But these types of drugs often don’t work for long.

Wouldn’t it be nice to target several of these ideas at once?  Not an either-or situation, but a “this mechanism and this one, too, and also this one.” 

That has been the dream.  What could be even better?  A drug that would not mess with the male hormones; something that would enable men to keep their testosterone and prevent the side effects of ADT.

We may have found one.  It’s preliminary, and probably two years away from clinical trials, but Salma Kaochar, Ph.D., Nicholas Mitsiades, M.D., Ph.D., and colleagues at Baylor College of Medicine seem to have found a promising new strategy that rips up the track, and dumps the jet fuel, and turns on the brakes – and causes, at least in mice, no collateral damage. 

It shortstops prostate cancer at the protein level and at the same time, turns up the immune system – in a way unlike any form of immunotherapy currently available– and doesn’t affect testosterone at all.

“We are developing a first-in-field approach to target the previously undruggable family of cancer-promoting genes for the treatment of both androgen receptor-dependent and androgen receptor-independent castrate-resistant prostate cancer (CRPC),” says Kaochar.  She presented her findings at the 2018 Scientific Retreat of the Prostate Cancer Foundation.

What is this secret weapon, and how does it work?  If we continue with our movie analogies – and pardon me for doing so, but otherwise this stuff is hard to explain – then it’s like that scene in “Raiders of the Lost Ark,” where Indiana Jones, faced with a fearsome, sword-wielding assailant, pulls out a pistol and shoots him.  He doesn’t try to out-fence a master swordsman.   He changes the game.

Kaochar and colleagues have found a potential game-changer, a target that no one has ever tried in cancer before: p160 SRCs, or “steroid receptor coactivators.”  These are “master regulators of transcription factor (key proteins) activity necessary for cancer cell proliferation, survival, metabolism, cell motility, invasion and metastasis,” she explains.  “In prostate cancer, they are required for the function of the androgen receptor and its variants.”

Transcription factors are proteins that act as a key to turn on a gene – just like a key in the ignition of a car.  Except here, if you have more keys, you can make the engine go faster.   “In CRPC, there is frequent overactivation of p160 SRCs,” Kaochar continues. “This results in increased androgen receptor activity, faster growth of the prostate cancer cell (more powerful and determined cancer cells), resistance to therapy, and bad outcomes.  Increased levels of these SRCs are associated with very poor prognosis.  SRCs are also important for the energy homeostasis (energy balance) in prostate cancer.”

The most deadly prostate cancers are addicted to SRCs.  They’re like crack for cancer. 

But guess what?  “SRCs can be reprogrammed.  They can be suppressed.”  And this can happen in localized tumors as well as in metastatic cancer.  Theoretically, there is no point in cancer at which this couldn’t start to work.  “Our goal is to find something to hit cancer at that late stage, where there’s absolutely no other treatment, where it’s all over, everywhere.”

In mice, Kaochar and colleagues are using “pulses” of treatment, not one continuous treatment.  Each pulse shuts down all the machinery cancer needs to grow, and also energizes the body’s immune system to fight the cancer.

Overactivation of SRCs appears to be extremely common in prostate cancer, and in other forms of cancer, as well.  So far, in laboratory tests using various types of aggressive, hormone- and chemotherapy-resistant prostate cancer cells (because men with prostate cancer don’t all have the same genetic mutations), 100 percent of prostate cancer cell lines tested in a dish have tested positive (see below) as being driven by SRC.

“These p160 SRC molecules are important in many cancers,” Kaochar says, “including uveal melanoma,” a particularly nasty form of melanoma that attacks the eye. “Uveal melanoma is a hormone-independent cancer, and it is heavily addicted to these molecules.”  Not only is uveal melanoma deadly; it is an “orphan disease,” rare, and lacking big financial support for research.  Kaochar’s research, funded by the Prostate Cancer Foundation, may lead to the first effective treatment for this disease, too.

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Could Controlling Metastatic Cancer Really Be Just a Matter of Tweaking?

If you’re a certain age – old enough to remember life before digital TVs – you probably know a lot about the fine art of tweaking.  If your picture was fuzzy, there were lots of ways to fiddle with the TV to try to fine-tune it.  There was the antenna, of course; actually, there were two, one up on the roof, and the rabbit ears on the TV set itself.  Then there were the knobs:  color, contrast, brightness, horizontal and vertical control.  It took a lot of trial and error, but tweaking was the key to a better picture.

Could controlling cancer be anywhere near that simple?  Well, in practice, it’s a heck of a lot more difficult, but the idea may be that simple:  tweaking the cancer cells, and also fine-tuning the normal cells.

Salma Kaochar and colleagues at Baylor are really developing several things at once: One is a sophisticated test to see if a man’s prostate cancer – and, quite possibly, anyone’s melanoma, breast cancer, pancreatic cancer, glioblastoma, ovarian cancer, etc. – is controlled by SRCs, which do various biological things, ranging from housekeeping chores like DNA repair, to controlling the metabolism, to controlling various proteins and driving cancer cell growth.  She is working on a simple test that works like a stoplight:  green means positive, yellow means maybe, and red means no. But the thing is, cancer might test red today, but as it continues to mutate and become more dangerous, it might test green in a few months. 

So far, 100 percent of the various prostate cancer and other cancer cell lines Kaochar has tested – in RNA sequencing and tests of more than 1,000 different genes – have come back green.  “More than 92 percent of the genome is coded by SRCs,” says Kaochar. “In prostate cancer and breast cancer, we have seen the same thing, and we believe it’s true in multiple different cancers.”

In cancer cells in a dish, “SRC 160 looks like a real vulnerability,” says Kaochar.  Jonathan Simons, M.D., medical oncologist and molecular biologist, and CEO of the Prostate Cancer Foundation, which has funded this work, describes it as “hitting the carotid artery.  If it works, it would be a stopper.”

But, “the more we learn, the more complicated the story gets,” Kaochar cautions.  “It’s exciting to have something that does so many things and has so much promise.  But at the same time, we have to carefully examine everything, and make sure there is no toxic effect.  That’s the spectrum where we’re really focused right now.”

Because this is first-in-field – a whole new class of drug – it will require a lot more testing before it can be tried in humans. Starting with cell cultures, then mice, then rats, then larger mammals.  “We just don’t know what their off-tumor effect,” on normal cells that are just minding their own business, “would be.”

Kaochar’s idea is that this drug would tweak the body: turn down SRC function in cancer – slowing down cancer cell growth, and also shutting down the cancer’s drive to metastasize – but also turn up the immune system at the same time, so the body can fight off the cancer.

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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Regular Guy, Exceptional Responder

I’ve said it before, because this is what some of the finest researchers in prostate cancer have told me:  The goal for aggressive prostate cancer is to find out which genes are involved and treat with gene-specific medicine — ideally, even preventing the need for androgen deprivation therapy (ADT).  We’re not there yet, but some men are blazing the trail for the future.  Chris Seelye is one of them.  He just happens to have a mutation in a particular gene, BRCA2, that just happens to respond particularly well to platinum-based chemotherapy: a drug called carboplatin, given in combination with another chemotherapy drug, docetaxel.  Chris is an exceptional responder to this treatment.

The very best part of my work, including the writing I do for the Prostate Cancer Foundation, is getting to talk to men like Chris:  men who are beating the odds dramatically.  Men who weren’t expected to make it, who are, in fact, thriving because of treatments that didn’t exist a few years ago.

Not very long ago, the future looked pretty bleak for Chris.  At just 62, this professional photographer from Washington State thought he had maybe a year to live.   “I was facing a terminal illness and was reaching the time where I had to start making decisions,” he says.  Decisions like, “Do I continue pursuing my love of photography, or is it time to start selling equipment and cutting back and sitting on the couch dreaming of the days when I could do those things?”

Then Chris, a U.S. Navy Veteran who served in the Vietnam era, joined a clinical study.  His oncologist, Bruce Montgomery, M.D., is leading it at the Veterans Affairs (VA) Puget Sound Health Care System as part of a new partnership  between the VA and the Prostate Cancer Foundation.  Montgomery, who is also on the faculty at the University of Washington School of Medicine, Fred Hutchinson Cancer Center, and the Seattle Cancer Care Alliance, thought Chris might do well in this study because of the genetic makeup of his metastatic cancer.

He did not anticipate that Chris would go into complete remission,  because he had “metastatic, castrate-resistant prostate cancer,” Montgomery says, “the kind that kills men.  As part of the VA-PCF collaboration, we did deep (genetic) sequencing of his cancer and we found that he has a mutation in his BRCA2 gene.  Because we knew he had this, we got him in this study.  His PSA has gone from over 200 to 1.  The scans he had initially, which showed metastatic disease, are now essentially normal.  He’s had a complete radiographic response.”  In other words, scans are not able to find cancer in Chris Seelye.

What Helped Chris?  A Chemo Combo

Men in this study receive carboplatin (not a standard drug in the treatment of prostate cancer) along with docetaxel.  Small data sets from Montgomery’s group and others predicted an 80-percent likelihood of response to this treatment if a patient has a tumor with BRCA2, and those responses are likely to be “exceptional” – significant and long-lasting. On the other hand, the expected response to docetaxel alone (the standard chemotherapy Chris would otherwise have received) is 25 percent or less.

Exceptional responses are what ongologists wish for desperately but, too often, do not see in men with metastatic prostate cancer. “It’s hard to actually put into words, to be honest with you,” says Montgomery.  “We all, every day, hope for a miracle.  And this is as close to a miracle as we get right now.”

PCF funding helped develop gene-targeted therapy– a whole new way to approach cancer. Recent research, also funded by PCF, found that people with many different kinds of cancer share mutations in genes like BRCA1 and BRCA2, which are often linked to breast and ovarian cancer. This means that a drug that helps a woman with breast cancer who has a defective BRCA gene will also help a man with prostate cancer who has the same bad gene.  It’s treating the gene, not just treating the specific organ that has cancer.

“Not Going to Let Myself Get Depressed.”

 Chris joined the Navy when he turned 18, did a four-year hitch at the Naval Air Station in Alameda, California, was honorably discharged as a 3rd-class Petty Officer, went to school on the GI Bill to “learn about things I didn’t know,” and has spent his career doing mainly industrial, technical, and nature photography, plus professional printing and publishing.  “I learned of my prostate cancer in 2014,” he says, “after a year of working with my primary caregiver to diagnose a set of (urinary) symptoms.”  When he finally took a PSA test, it was “through the roof,” and a biopsy diagnosed high-grade cancer.

Although some men might go through “a period of denial, saying ‘why me,’ I never really had that,” Chris says.  “I knew that keeping a good attitude was paramount to successful treatment, so I refused to let myself get depressed, and even to this day, I have not gone down that road.  I just couldn’t get myself to make it worse.”  It helped him, Chris adds, early on when a doctor explained, “We’re not treating your cancer, we’re not curing your cancer.  We are managing.  That was very helpful in terms of my acceptance, not getting this false hope of, ‘maybe I’m the one, the first person to ever beat a terminal cancer.’”

And yet, here he is, the exceptional responder.  Chris is still getting used to the term.

At first, “my expectations were that realistically, this is my best last chance.  I was either going to be dead within a year or this was going to present a better alternative.  So far, the results have been pretty stellar.”  But Chris is cautious when he talks about the future. “I would phrase it that I have optimism, as opposed to hope.  I know that still, we’re not talking about cure, we’re talking about management – but I’m optimistic.  I had an expected expiration date.  Now, with participating in this study, that’s taken away.  I don’t see an expiration date any more– or if there is one, it’s years out, as opposed to months out.”

Although he’s not ready to call this combination therapy a life-saver, “it certainly is a life-extender.  I’m highly optimistic that this quite likely is going to keep me going long enough for the next round of treatments that are in the research phase now.”  One day, he believes, his doctors won’t be talking about a terminal illness anymore, but a chronic one.  “I’ll take chronic over terminal any day.”

If you have just been diagnosed with, or are battling prostate cancer, Chris has this advice for you:  “Don’t just hope, but know that new treatments are coming online practically as we speak.  Newly diagnosed patients actually have better treatment options than I had just three years ago.”  And if you have not been diagnosed with prostate cancer but are having urinary symptoms:  “Get the PSA test.  I was 59 when I was diagnosed.  Had a PSA been done when I was 55, maybe the outcome might have been different early on.”

And, if you can, participate in a clinical trial:   “It’s a life changer.  With this study, new questions are being asked and investigated. It happens that I have this specific genetic defect.  This alliance between the VA and the PCF looking at exactly that question has allowed me to participate in a study and my prognosis is very different than it was. I would strongly encourage the VA to participate in every cancer study that they can get their hands on, particularly as we’re moving away from  management to actual treatments” for metastatic cancer.  “I happen to be one of the very early patients who actually has optimism that in my course of treatment, we’re going to actually achieve the transition from terminal illness to chronic illness.”

For now, as for selling his beloved photography equipment: “That’s off the table!  I’m looking forward to the winter of (photographing) migratory birding season; that’s going to start up in less than a month. I’m ready to go and I’m ready to keep going.”

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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