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TRexit:  The Movement to Leave Traditional Prostate Biopsy “Behind”

In Australia, and to a smaller but increasing extent in the U.S., urologists are moving away from the traditional transrectal (TR) biopsy.  A much lower risk of infection is a big reason why.  

Nobody wants a prostate biopsy, but we’re stuck with it.  Literally.  Multiple times.   And for the vast majority of men (more than 2 million in Europe and North America alone), those hollow, ultra-sharp biopsy needles go right through the rectum to reach the prostate.  Unfortunately, the rectum is just chock full of bacteria, and this, in turn, means a couple of things:  the risk of infection and sometimes sepsis, and the need for antibiotics, some of them quite powerful.

Because infection can be such a serious complication, urologists have gone to great lengths to try to minimize it – particularly for men with a chronic illness such as diabetes, men with prostatitis or a urinary tract infection, or men who use a urinary catheter.  These men at higher risk often need a longer course of antibiotics, or different antibiotics.  Some options to reduce the risk of infection are to use more than one antibiotic for extra coverage, or to try to tailor the antibiotic to the specific bacteria found in a man’s rectum.

Before a TR biopsy, “we routinely swab a man’s rectum to see what bacteria he has, and we give him antibiotics based on those bacteria,” says University of Pittsburgh-Western Maryland urologist Michael Gorin, M.D.  “But despite our best intentions, sometimes these antibiotics fail to prevent an infection. Additionally, antibiotics can cause complications on their own.”

If only there were alternative.  Wait!  There is!  It’s a different way to reach the prostate:  through the perineum, the area between the scrotum and rectum; this is called transperineal biopsy.  Now, don’t get too excited:  Neither kind of prostate biopsy is ever going to be fun.  However, the perineal approach has some important advantages.  One big one: zero risk of infection!  Zip.  Nada!  “With the transperineal approach,” says Gorin, we don’t have to give any antibiotics, because instead of passing through the rectum, the needles go through an area of skin, which can be thoroughly cleansed before the procedure.”  Gorin pioneered the transperineal approach at Johns Hopkins, and is second author of an article that is shaking up the world of prostate biopsy:  “TRexit 2020: why the time to abandon transrectal prostate biopsy starts now.”

The paper’s first author, and a leading proponent of the transperineal approach, is Australian urologist Jeremy Grummet, M.B.B.S., associate professor of Urology at Monash University in Melbourne.  Grummet made a formidable argument in favor of transperineal biopsy at the American Urological Association’s annual meeting in 2017, with a PowerPoint presentation that featured, memorably, a slide of an angry poop emoji with these talking points:  “TR biopsy is dirty,” and “We use antibiotics instead of basic hygiene.”

That image was followed by a picture of a headline from Bloomberg News, about fears of an “Antibiotic Apocalypse” being stoked by antibiotic-laden chickens.  What’s happening in big agriculture, Grummet says, “is a very close analogy to what we do in hospitals.  There’s an extraordinary lack of hygiene, replaced by the use of antibiotics.  It works in the short term, but it also produces an immense amount of antibiotic resistance.”  The antibiotics often used with TR biopsies are fluoroquinolones; however, “fluoroquinolone-resistant organisms, also known as ‘Superbugs,’ have been identified in 10 to 30 percent of patients undergoing rectal swab cultures before biopsies,” Grummet notes, “and the incidence of hospitalization due to severe infections after prostate biopsy is increasing.”  A 2015 study of 455 patients in a VA hospital in Boston found that 2.4 percent of the men developed sepsis after prostate biopsy, and 90 percent had fluoroquinolone-resistant bacteria.   In addition, side effects of fluoroquinolones can be serious or potentially disabling, including depression, disorientation and agitation, tendonitis and tendon rupture, pain in the muscles and extremities, and gait disturbances.

Lack of hygiene?  But… but… don’t men do an enema before biopsy?  That cleans it, right?  Sadly, not really.  An enema flushes out poop, but it does not eradicate rectal bacteria.  It can’t.  “You can imagine, sticking a needle into a rectum, which is purpose-built for feces, absolutely crawling with bacteria.  It’s a dirty procedure; you take a clean needle, and put it through a contaminated area: that’s what a TR does every time.  You’re playing roulette with your needles; you have no idea if you’re inoculating bacteria with rectal flora into the prostate.  We try to overcome that with antibiotics.”

Going through the rectum, Grummet continues, goes against the basic surgical principle of sterile technique.  “Why do we wear gloves, why do we wash our hands?  Yet we completely turn a blind eye to that whole principle when we do a transrectal biopsy.”

What if, he says, “we could eradicate prostate biopsy sepsis?  And what if we could do it without using big-gun antibiotics on a global scale?  We can and we have.”  In a multi-center study of transperineal biopsy in Australia, Grummet and colleagues showed that of 245 consecutive men who received transperineal biopsy, there were zero readmissions for infection.  “Our series has since grown to 1,194 consecutive cases at five centers across Melbourne, with no complications and zero hospital admissions for infection.”

The actual transperineal approach, itself, is not new, notes PCF-funded investigator Edward Schaeffer, M.D., Ph.D., Chair of Urology at Northwestern University’s Feinberg School of Medicine.  “Transperineal biopsies have been around for several decades, and offer an opportunity to sample all regions of the prostate very efficiently” (more on this below).  However, there was a good reason why they weren’t popular: “The limitations of transperineal biopsies in the past were that they required general anesthesia, as they are quite painful.  Newer techniques in regional prostate blocks have enabled the use of in-office, awake, transperineal approaches.”  Using the nerve block provides more protection from pain than local anesthetic alone.

This may prove to be the big selling point for many urologists, says Grummet.  “TR biopsy has been, certainly in Australia, a well-reimbursed procedure.  You can do it in five minutes in your office.  Because transperineal biopsy traditionally required a general anesthetic, it took longer and used hospital resources and personnel.  It has been less convenient.”

Although Gorin routinely does transperineal biopsy in the outpatient setting, using a nerve block and local anesthetic, it’s a little different in Australia.  In his home state of Victoria (over 5 million people), transperineal biopsy is more commonly performed than TR biopsy,” says Grummet.  “In our practice, no one gets a TR biopsy; the transperineal procedure is common across Australia.”  However, he adds, it is still done mainly in the hospital, under general anesthesia.  “Only a few of us over here have shifted to local anesthetic.  I have done only a handful with local anesthetic, and then COVID-19 hit,” and outpatient procedures were severely limited.  Now that the country is opening up, he plans to do more transperineal biopsies with the local anesthetic and nerve block.  “With the general anesthetic, transperineal biopsy is essentially perfect.  But with the local nerve block, even if the pain relief is not perfect, if the overall greater good is to avoid infection, that is by far a bigger win than some mild discomfort.  But if it’s too painful, we shouldn’t be doing it.”

Going in sideways:  But wait!  There’s more!  With Johns Hopkins urologist Mohamad Allaf, M.D., Gorin developed a technique to perform MRI-guided prostate biopsy through the transperineal approach that is “not only cleaner; there’s reason to believe the transperineal approach is more accurate,” better able to sample the prostate’s anterior region – the area where cancer commonly develops in African American men.  

Besides the risk of infection, there’s another big drawback to the TR approach:  it’s hard to cover the entire prostate.  Basically, as Schaeffer explains , 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, 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.”

Is there a downside to the transperineal approach?  Although there is not any published evidence, Grummet says, “there seems to be increased scarring of the apex of the prostate in patients who have had transperineal biopsy.  That would make sense, because instead of moving the needle along the back of the prostate, which is what you do in TR biopsy, the needle in a transperineal biopsy is coming in at the apex.  I certainly haven’t seen any evidence that it actually affects the outcome of surgery.”  Another potential downside, as with TR biopsy, is of urinary retention, particularly in men with a large prostate who have more needle cores taken.  “The more cores you take, the more swelling there is.  Our published rate of retention is 2.5 percent; that is entirely reasonable.  Urinary retention is not life-threatening like sepsis is; you put a catheter in, and you take it out the next day.”  Another risk, as with the TR approach, is a “temporary, mild reduction of erectile function,” from inadvertently grazing the nerves involved in erection, “but this risk occurs in TR biopsy too.”

How can I get a transperineal biopsy?  Unless you live in Australia, or you happen to live near one of the few places in the U.S. where they are being performed, you probably can’t.  Yet.  But that is expected to change fairly soon.

Personal note here:  As I have written about earlier, a transperineal biopsy performed by Mike Gorin recently saved my husband’s life.  I am biased in favor of this approach, because several urologists have told me that because of its location in the anterior of the prostate, behind the urethra, Mark’s cancer would have been missed with a TR biopsy.  It was tiny, just 6 mm at the time of biopsy, 7 mm at the time of surgery, totally contained within the prostate, but very aggressive.  Gleason 9 cancer, diagnosed when he was just 58.  Thank God we got it out of there.   

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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How to Have Your Best Prostatectomy

Please Read This Before You Go Under the Knife.  Nobody thinks a prostatectomy will be a breeze; if anybody tells you that, take it with a big old mental grain of salt.  Even with the best surgeon in the world, there will still be some incontinence and erectile dysfunction.  But ideally, with exercises, biofeedback if necessary, and penile rehabilitation, these should be temporary, and you will be cancer-free and enjoying your life again soon.

The complications from prostatectomy ought to be minimal.   But often, they are devastating.  A bad surgeon can ruin your life.  

So please hear this advice and take it to heart:  Find the best surgeon you can.  Get it done right.

Radical prostatectomy is a very difficult operation.  It takes not only skill, but the kind of expertise you get only after being involved in a lot of procedures, first from the sidelines as a doctor in training, and then learning how to do it meticulously with the guidance of an expert surgeon.

The very best prostate surgeons specialize in the prostate.  That’s often all they do, and they do a lot of these procedures every year.  As Patrick Walsh and I said in the book, you don’t want to be part of the learning curve.

Another point:  Because there are so many bad surgeons out there, you can’t trust everything you read on the internet or from hospitals’ propaganda.

I would dearly love to weed out the bad surgeons, so they stop doing procedures they aren’t skilled enough to do.  Until that happens, well, this is your one shot at this.  Do your due diligence.  How can you find the right surgeon?  Here’s a checklist I developed and wrote about for the Prostate Cancer Foundation’s website, with the help of three experts.  Please.  Take the following things into consideration before you go under the knife:

  • Find a high-volume center that does a lot of these procedures. Often, this is an academic medical center.  An added benefit here is that if they do a lot of these, and do them well, then everyone is going to be better at helping you. The nurses know how to take care of recovering prostatectomy patients, and there is a wing or set of beds just for those men – and not also appendectomy or hysterectomy patients, whose post-op needs are very different.  How do you find a high-volume center?  Edward Schaeffer, M.D., Ph.D., Chairman of Urology at Northwestern University, says, “This can be hard, but I always refer patients to two websites that can help.”  One is the National Cancer Institute’s website, which designates “cutting-edge cancer treatments to patients in communities across the United States.”  http://www.cancer.gov/research/nci-role/cancer-centers/find And the other is a website showing National Comprehensive Cancer Network-designated cancer centers.  “NCCN Member Institutions pioneered the concept of the multidisciplinary team approach to patient care and lead the fight against cancer as they integrate programs in patient care, research, and education.”  NCCN writes the guidelines for how to screen and care for all types of cancers, including prostate cancer.  That website is:   https://www.nccn.org/patients/about/member_institutions/qualities.aspx
  • Look for a place where different specialties work together. Top centers have multidisciplinary teams – experts from different specialties including urology, radiation oncology, medical oncology, and pathology – working together on prostate cancer. Some men are perfect candidates for surgery; others might do better with radiation, and if you are one of those, you need at least to speak with a radiation oncologist before you decide on surgery. Other men need to talk to a medical oncologist, as well.  Prostate cancer is a complicated thing, and there is no “one-size-fits-all” answer for every patient.  With the multidisciplinary approach, you get the opinion of a team of experts, not just one, and the benefit is a more thorough and thoughtful approach to your treatment.
  • Ask the surgeon about results: Does he or she keep results? For how many years?  The best surgeons, like Patrick Walsh at Johns Hopkins, follow their patients for life – so they know, 25 years after the fact, whether the PSA is still undetectable, whether there was any incontinence, whether erections returned on their own or with help from medications or other treatments, etc.
  • Then double-check. “To be honest, in my experience some surgeons lie,” says urologic oncologist Trinity Bivalacqua, M.D., Ph.D., at Johns Hopkins, “and it’s hard to determine when someone is not being truthful.  The most important factor is the reputation of the institution and the department, as well as the surgeon.  One thing that helps is asking the surgeon to provide you with names of his or her patients who have agreed to speak to other patients about their experience.  This is very helpful, and will show that the surgeon has happy patients, cares enough to put this together, and knows the importance of a large support network to help a cancer patient decide what’s best for him.”
  • Are any of the surgeon’s patients willing to talk to you?  You can hear it from the “horse’s mouth” what recovery was really like.
  • How many radical prostatectomies has the surgeon done? The answer should be in the hundreds.  If it’s something like “several,” do not walk away – run!
  • Ask more than one doctor to recommend the best prostate surgeon in your area. (Note: Some doctors are in practice groups, and recommend the specialist in that group. This is why it’s good to ask different doctors in different practices.)
  • Beware of the reviews or ads on the internet. “It is unclear to me who actually goes to these sites and makes the comments,” says Schaeffer.  Maybe it’s the patients; maybe it’s a buddy of the doctor putting in a rave review to get the number of five-star listings up.  Or maybe it’s a disgruntled colleague, or a competitor hoping to drive business away from that surgeon.  Who knows?  For the most part, says urologist Stacy Loeb, M.D., M.Sc., at New York University, “Online reviews are totally unreliable, so I am hesitant to tell men to rely on them.”  Research has shown poor correlations between online reviews with outcomes, she adds, “so I am wary to recommend something that could be misinformative.  Speaking to other patients and local doctors is a much better idea.” Loeb also recommends that you check with prostate cancer support groups in your area, and ask these men about their own experience and advice on a surgeon. “The internet is full of false accusations and glamorization of surgeons and the hospital or department,” says Bivalacqua.  A lot of hospital websites, he adds, “advertise something that is often not present or real.  I know this is a sinister way of thinking about things, but it’s the reality of our society and medical profession.”
  • And finally, don’t worry about offending the doctor with questions or by getting a second opinion. You don’t get to be a surgeon without being something of a tough cookie.   People ask for second opinions all the time.  Patients ask questions all the time.  You are paying the doctor, not the other way around.  (Note: That doesn’t mean you should be rude or disrespectful; it just means you shouldn’t feel intimidated or like you are being a bad guy simply for doing your homework.)  If the situation were reversed, do you think your doctor would not make every effort to find the best possible surgeon?  It’s your prostate, it’s your recovery, it’s your life.  You don’t want to be one of those guys saying afterward, “My surgeon was not very good.”

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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Beyond PSA: “Second-Line” Tests for Prostate Cancer

Maybe you’re in your 50s, and your PSA is 3.  Maybe you’re in your 60s, and it’s 4.  Maybe you’re in your 40s, and it’s 2.  And maybe, unfortunately, your family doctor seems in no hurry to do anything about it, saying something complacent like, “Your PSA looks good,” or “the government guidelines don’t really recommend screening for prostate cancer, so we probably don’t even need to check it every year.”  Or, “You’ve got some enlargement of the prostate.  That’s probably what it is.”  Or, “It’s still pretty low.  Let’s just watch and see what it does.”

This makes me want to scream!  Right now I want to scream anyway, and cry.  I’m thinking a lot about one of the world’s nicest guys, whom I wrote about here, who was diagnosed at age 45, after many trips to the doctor for urinary problems, back pain, and other symptoms that should have raised red flags — especially because this man is Black, and automatically at higher risk for developing aggressive prostate cancer — but didn’t.  When he was diagnosed, his PSA was in the 200s, and the cancer was widely metastatic.  His wife, an amazing advocate and warrior for her husband, told me this week that he has now entered hospice care.  He should have started getting his PSA tested at age 40.  How different might his life be right now if his cancer had been diagnosed while it was confined to the prostate?  He was in and out of doctors’ offices for years, and nobody even looked at his PSA.

Dear Readers, I talk to a lot of men with prostate cancer.  Some of them have actually been diagnosed.  

Let’s just think about that for a minute.  So I’m going to tell you what I tell them.

Screening starts with the PSA test, and then it can escalate:  In our book, we talk about the great work by Johns Hopkins urologist Bal Carter, M.D., which I’ve also written about here, on PSA velocity.  Carter and my co-author, legendary Johns Hopkins urologist Patrick Walsh, M.D., were very troubled by a study showing that 15 percent of men with a PSA lower than 4 have cancer, and 15 percent of these men with cancer have high-grade cancer.  That’s because there is no safe, absolute cutoff above a PSA level of 1.0 where a man can rest assured that he is not harboring a high-grade prostate cancer that needs to be treated.  There’s just no guarantee.

The PSA number itself is not as important as what that number does over time, how fast it changes; this is PSA velocity.  But there are some numbers for men younger than 60 that are helpful as reference points: that is, whether you are above or below the 50th percentile for your age.  If you’re below the 50th percentile for your age, you may not need to take a PSA test every year — although, frankly, men, it’s a simple blood test, and if you’re getting your cholesterol checked, then what the heck?  Your blood is there at the lab anyway!  Get the PSA checked!  But if you’re above the 50th percentile for your age, you should have your PSA measured at least every two years during your 40s, and every year from age 50 on.  Men in their 40s who have a PSA level greater than 0.6 ng/ml are in this group, as are men in their 50s who have a PSA greater than 0.7.  Those are Carter’s numbers; in a large study, urologists Stacy Loeb, M.D., of New York University and the Manhattan Veterans Affairs (see below) and William Catalona, M.D., of Northwestern University, found the comparable numbers to be slightly higher, 0.7 for men in their 40s and 0.9 for men in their 50s.  What about men older than 60?  One study showed that 2.6 was a good PSA cutoff point.  This is still a lot lower number than many doctors seem to be troubled by.

Maybe it’s because they don’t want to put a man through a prostate biopsy if it’s not necessary.  Well, sure, that makes sense.  But what many family doctors don’t seem to realize is that times have changed!  Good news:  You don’t have to move directly to having needles stuck in your prostate!  It’s not the Monopoly bad-case-scenario of “Do not pass Go, do not collect $200!”  There is a next step!  It’s a “second-line” test:  a blood or urine test that can provide other layers of information beyond the basic PSA test.  There are several good ones out there.  Which one do you need?  Well, as Marlon Brando said in the classic 1953 movie, The Wild One:  “Whadya got?”

There’s no shortage of options!  There are blood tests that provide more nuanced information than the basic PSA test, plus urine tests and even, if you’ve already had a biopsy, molecular biomarker tests, which aren’t done on body fluids but on tissue samples.  These tests can be helpful, not only in diagnosing cancer, but in risk stratification – predicting which cancer is more likely to be aggressive, and which cancer is less likely to need immediate treatment.

Helping us navigate these options is New York urologist Stacy Loeb, whom I recently interviewed for the Prostate Cancer Foundation.  “First and foremost,” Loeb says, “if a patient has an elevated PSA, the thing to do is to repeat the PSA test at the same lab.  It may feel like backtracking, but step one is to confirm that it even is elevated.”  This is why using the same lab as you’ve used in previous PSA tests is important; what might seem to be a rising PSA might just be a normal fluctuation between labs using different equipment.

However, Loeb adds, “many urologists will order the repeat test as a Free and Total PSA blood test,” because this test is inexpensive and readily available, and because it provides some additional information.   “Free PSA measures whatever PSA in the blood that is not bound to proteins.  The higher percentage of PSA that is free, the more likely you are to be free from cancer.”  This test provides context:  If the percentage of free PSA is higher than 25, then the elevated PSA is more likely to be caused by BPH, benign enlargement of the prostate.  If it’s lower than 25 percent, this doesn’t automatically mean that there’s cancer, but it does raise the likelihood that cancer may be present.

“It’s also important to rule out other causes of an elevated PSA.”  Having prostatitis can raise your PSA; so can having a urinary tract infection.  So can having sex within three days before getting your blood test, because sexual activity stimulates the prostate, which then can release more PSA into the blood.  Similarly – a big oops here for the doctor! – getting your blood drawn after the rectal exam, which stimulates the prostate and shoots PSA out into the blood stream, can make your PSA level temporarily higher.

And then there’s MRI.   “In our practice,” says Loeb, “we’re getting MRIs as the next step for patients who have an elevated PSA.  If the MRI shows a suspicious lesion, we recommend a targeted biopsy.  If the MRI is not suspicious, but we’re still worried because of the patient’s PSA and clinical picture, in that context, a biomarker test could potentially give the extra data point that could help us proceed with a biopsy anyway.  What’s nice about MRI is that it shows us suspicious areas – so in addition to providing information on the risk that significant cancer is present, it also gives us some information on where to look.  The data are very clear that performing targeted biopsies based on MRI findings is a superior strategy to only performing biopsies that sample various locations all around the prostate,” in which cancer is easy to miss.  Note:  The power of the magnet in MRI makes a difference; the stronger the magnet, the better the picture and the more the doctor can see.  You want a 3 Tesla (3T) MRI, not 1.5.

Now, about those other blood tests:  In addition to the free PSA test, here are two more that include free and total PSA, but look for other factors, as well:

PHI (Prostate Health Index):  PHI not only helps determine if cancer is present; it also can predict the likelihood of finding high-grade cancer on a prostate biopsy.  “PHI also predicts the likelihood of progression during active surveillance,” says Loeb, who with Catalona reviewed the effectiveness of PHI for the journal Urology.   “PHI is a simple and inexpensive blood test that can be used not only for biopsy decisions, but for risk stratification and treatment decision-making.” In a Johns Hopkins-led study, PHI outperformed PSA in predicting prostate cancer in general, but proved especially helpful in finding clinically significant (higher Gleason grade) cancer.  It was even better when combined with MRI; in the study, no men who had a PHI score lower than 27 and a PI-RADS of 3 or lower had clinically significant cancer.  For men who went on to have prostatectomy, a higher PHI score was associated with a higher Gleason grade of cancer and pathologic stage.   PHI also provided discernment, reduced the number of men who needed biopsies without overlooking clinically significant cancer.

4K score:  This blood test combines four prostate-specific biomarkers (three forms of PSA and also human kallikrein 2, a protein made by cells lining the prostate), plus clinical factors including age, to assess a man’s likelihood of having high-grade prostate cancer found at biopsy.  Studies at UCSF, reported in the Journal of Urology, evaluated 4K score and a prostate MRI scan, both for their ability to detect high-grade prostate cancer and to help patients avoid unnecessary biopsies.   “Both of these tests can predict the risk of finding a clinically significant prostate cancer,” cancer that needs to be treated. They found that MRI was a more able predictor of high-grade prostate cancer than the 4K score – however, MRI was not sensitive enough to detect all high-grade prostate cancer, “and 4K testing alone could be sufficient as the initial tool to select patients who may benefit from a biopsy.”  But even better, they found, was combining 4K and MRI:  “Using higher 4K cut points such as greater than 15, combined with MRI… allows for more avoided unnecessary biopsies with minimal missed high-grade prostate cancer cases.”

Loeb adds:  “About 12 percent of the time, MRI can miss something.  So, if we still suspect that cancer may be hiding, that’s a good case for using a biomarker test” like PHI or 4K.  “With a biomarker test and MRI combined, the chance of missing a significant cancer is exceedingly low.”

Urine tests:  One urine test, EPI, is done using a fresh-catch urine specimen.  This test can help predict clinically significant prostate cancer in men who have not yet had a biopsy.  Another, the PCA3 test, is done after “a vigorous rectal exam,” says Loeb.  It looks for mRNA levels of a marker, called prostate cancer gene 3, to help rule out other causes of an elevated PSA test, such as BPH or prostatitis.  “It’s FDA approved for use in men who have had a negative biopsy.”  Then there’s Select MDx, which measures mRNA levels of two biomarkers commonly expressed in prostate cancer, and MiPS, developed at the University of Michigan, which combines PSA with two biomarkers for prostate cancer.  “More head-to-head data is needed comparing all of the different blood and urine markers to find out which is best in different patient scenarios,” says Loeb.

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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Cancer’s Sweet Tooth

Cancer loves sugar, and sugar really loves cancer.  Isn’t that sweet?  Actually, no, it’s more like a match made in hell – because sugar (glucose) makes many types of cancer grow faster.

Scientists have long known that cancers soak up glucose like a sponge; in fact, German physiologist Otto Warburg, who found that tumors extract glucose at a rate 20 to 50 times higher than do normal cells, won the 1931 Nobel Prize for for his research on metabolism.  Lew Cantley told me that.  Cantley, Ph.D., is a world-renowned scientist and Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.  I recently interviewed him for the Prostate Cancer Foundation’s website, pcf.org.

Cantley has spent much of his career studying the interplay between sugar and cancer.  His studies suggest that it’s not so much the amount of glucose in your bloodstream that helps promote cancer, as it is the level of insulin, the hormone made by the pancreas that controls glucose.  Insulin helps turn glucose into immediate energy, and also helps your body pack it away for longer-term storage.  Briefly, when you eat, your blood sugar goes up; this causes your pancreas to say, “Hey! We need to make more insulin!”  Insulin, like Paul Revere, then travels rapidly throughout the land, telling the cells to let the glucose in, either to be used right away or saved in muscles, fat cells, and the liver.

Why does a tumor suck up more glucose?  “The main reason,” says Cantley, “is that insulin can turn on the glucose transporters (proteins on cell membranes that carry glucose into cells), similar to those in the liver, muscle and fat.  The presence of those glucose transporters on tumor cells is in part regulated by insulin.  That’s why I keep focusing on the insulin.”

Cantley began studying the insulin receptor in the 1980s, when he was on the faculty at Harvard University.  A few years later, after moving to Tufts University, he discovered an enzyme called phosphoinositide-3-kinase (PI3K); PI3K signals cells that insulin is present; the cells, in turn, open the valve that lets in sugar.  Normally, PI3K does good and vital work, helping cells survive, grow and proliferate.  But sometimes it goes awry; in Type II diabetes, this PI3K pathway becomes sluggish, cells don’t respond appropriately to insulin and become insulin-resistant.  But in cancer, even in someone who’s insulin-resistant, PI3K does its job too well; glucose floods in, tumor cells feast on sugar and grow faster.  “What we now know is that mutations in the PI3K pathway make tumor cells hyperactive in response to insulin.”

In many cancers – sugar-loving cancers; not all cancers are addicted to sugar, but many are – PI3K is like a power switch that drives growth.  “PI3K is the most frequently mutated cancer-promoting gene in humans,” says Cantley.  It may be involved in as many as 80 percent of cancers, including breast cancer, bladder cancer, and certain brain tumors.

What about prostate cancer?  Well, one of the most common genetic events in prostate cancer is the loss of a gene called PTEN; cancer just knocks this gene out.  “PTEN makes an enzyme that reverses what PI3K does.  PI3K makes a lipid, and PTEN destroys that lipid; you have to have a balance between those two enzymes to keep growth under control.  But in prostate cancer, and in breast cancer , the loss of PTEN activates production of this lipid that drives cell growth.

“This tells us we probably should try to keep insulin levels as low as possible if we have cancer, to try to keep the tumor from growing.   If we can keep the diet under control, or exercise to keep glucose levels and insulin levels low, we have a much better chance of slower growth of the tumor.  Our research would also argue that pharmacological intervention would be more effective if we keep insulin levels low.”

Even better:  Keep insulin levels as low as possible anyway, whether you have cancer or not.  “This is a powerful potential cancer-prevention mechanism,” says Howard Soule, Ph.D., Executive Vice President and Chief Science Officer for the PCF.  “Reducing processed sugar may turn out to be even more important for cancer prevention than treatment.”

Can we learn to use cancer’s sweet tooth as a weapon against it?  Cantley’s research has already led to the development of several PI3K-inhibiting drugs: idelalisib, approved by the FDA in 2014 for treatment of lymphoma and leukemia and alpelisib, approved in 2019 for treating breast cancers with mutations in PI3K.  But Cantley also believes that changing the diet – to one low in sugar, but also low in other carbohydrates, which can cause blood sugar to spike – can make cancer-fighting treatments work even better.  In a landmark 2018 paper published in Nature, Cantley and colleagues showed in mice that by severely restricting carbohydrates “and keeping the insulin level low, tumors would respond much more dramatically to drugs that are already approved to treat them.  Tumors we had never been able to shrink in mice, we could shrink with a low-glucose diet.

“That’s my obsession now, to get that message out there.  Endocrinologists tell patients to exercise more and eat less sugar to keep diabetes under control, but for me, it’s even more critical to keep insulin levels low in order to get better outcomes for cancer patients.”  Cantley’s research suggests that “if you have a mutation in the PI3K pathway that causes cancer, and you’re eating a lot of simple carbohydrates, every time your insulin goes up, it’s making the tumor grow.”

How can this knowledge help slow the growth of prostate cancer?  Here’s one example:  “For prostate cancer patients with low Gleason scores who are on active surveillance, it makes perfect sense to pay a lot of attention to what you eat.  Try to keep your consumption of sugary drinks as low as possible.  Keeping sugar down is the best thing you can possibly do.”  It used to be, Cantley notes, Japanese men hardly ever got prostate cancer.  “But second-generation Japanese Americans have prostate cancer in similar rates to Caucasians.  It’s clearly lifestyle,” the Western diet.  “The truth probably is that some Japanese men in their 90s had some level of prostate cancer, but didn’t consume enough sugar for the cancer to advance.”

Here’s another:  If you are on ADT for metastatic prostate cancer, you are more likely to gain weight, and also to develop insulin resistance.  One way to fight this is by limiting your sugar and simple-to-digest carbs.  Bonus: keeping insulin down may also help slow down the cancer.  Watch out for protein drinks, too; many are loaded with sugar.

What about the ketogenic diet?  It’s low in carbs and high in fats.  “I’m not preaching the ketogenic diet; I don’t eat it myself,” says Cantley, who says he weighs the same now as he did in high school.  “I eat what my grandparents ate:  a healthy diet, lots of raw vegetables, some animal fat, healthy vegetable fats, an intermediate amount of protein.  I don’t avoid fats, but I prefer olive oil on salads, and healthy fats from fish and avocado,” instead of loading up on butter and cheese.  “I eat more protein than the ketogenic diet would recommend, and I do occasionally eat rice and pasta.”

But here’s the kicker:  “The one thing I’m fanatic about is not drinking anything with sugar:  no orange juice, no apple juice, no soda.  I’ll eat an orange, but I won’t grind it up and drink it.”  Sugar in liquid form is rapidly digested, which results in “glucose peaks, followed by insulin peaks.”

What about alcohol?  “A dry martini is probably safer than wine; there’s not much sugar in there.”  However, Cantley adds, “I do drink wine, but as low in sugar as possible.”

Exercise is a great way to divert sugar into someplace safe:  the muscles.  “Muscle is where you store a lot of sugar in your body.  If you drink a sugary drink after exercising, your insulin goes up, and you drive all that glucose into your muscle.  Whether you’re exercising at the time you drink a sugary drink, or you just put on muscle from exercise in general, there’s still a benefit: insulin won’t spike.”   However, exercise doesn’t make it safer to drink a lot of sugary drinks, because…

Sugary drinks are bad.  It’s not just sodas; sweet teas and coffee drinks have more sugar than you may realize.  Even sports drinks are loaded with sugar.  In 2019, Cantley and colleagues published another landmark paper in Science, involving mice with polyposis syndrome (mice genetically predisposed to developing polyps in the colon).  They demonstrated that sugary drinks can dramatically drive the growth of intestinal polyps.  “We gave mice high-fructose corn syrup, and their polyps grew two to three times faster.”  Fructose is a different sugar from glucose, and although “fructose is not consumed by tumors, it goes straight to the liver and turns into fat.  Fructose makes you fat.  But the other issue is that intestinal epithelial cells can directly consume fructose.  We think this explains why there has been a doubling to tripling rate of colorectal cancer in young adults.”

Consuming sugar in liquid form is worse than having that same amount of sugar in solid form.  Cantley explains:  “If you eat an apple, it takes a long time to get to the colon.  By the time it gets there, all that sugar has leached out.  But if you have that same amount of sugar in a drink, that watery sugar gets to the colon pretty quickly.  That’s independent of the insulin elevation (discussed above), and it’s another scary reason why young people should avoid drinking sugary drinks, no matter how much you exercise.  You may be a champion marathon runner, but if you’re drinking sugary drinks all the time to keep up your energy, this is a real warning that you should pay attention to.”

Now, back to prostate cancer:  Would taking a PI3K-inhibitor help slow cancer’s growth?  As is often the case with prostate cancer, it’s not that simple.  It turns out that there are two different kinds of PI3K, an alpha and a beta form that can contribute to prostate cancer.  “When prostate cancer loses PTEN, it uses PI3K alpha and beta form redundantly to drive the tumor.”  This means that a drug that targets only the alpha form probably won’t be as effective in prostate cancer as in other forms of cancer, where only the alpha form of PI3K is involved.

However, “our preclinical findings are overwhelmingly supportive, and the retrospective data in patients strongly suggests” that one day, in addition to surgery, radiation, hormonal therapy or other treatments for prostate cancer, patients will be prescribed a precision diet to make the treatment more successful.  “The more we learn about cancer metabolism, we are understanding that cancers are addicted to particular things.  For many cancers, that thing is sugar.”

In addition to the book, I have written 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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COVID-19 and Male Hormones: What’s the Connection?

Why has the COVID-19 virus killed many more men than women?  What does the virus have to do with male hormones?  Well, quite a lot, it turns out, and a lot of what scientists now know about this male hormone (androgen)-virus interaction comes from scientists studying prostate cancer.  Scientists whose research happens to have been funded by the Prostate Cancer Foundation (PCF).

Suddenly, the genetics of prostate cancer have also become the key to finding new treatments for this terrible coronavirus.  I write for the PCF’s website, so I’ve been lucky enough to learn about some of this research from the scientists first-hand.

It all has to do with genes and proteins:  That’s how the virus sneaks into the nose, throat and lungs, and does its evil work; how it enters the cells in the airway and starts reproducing like crazy, causing the cells to burst open.  The explosion of respiratory cells causes terrible inflammation, swelling, and congestion.  Worse, oxygen can’t get into the bloodstream.  This devastation can result in a ventilator in the ICU, or in death.

Think of this nasty virus as a con man who looks normal – like Fred MacMurray as Steve Douglas, the beloved dad in “My Three Sons.”  He seems benign, and he walks right into your house through your front door.  But oh, no! It’s actually Fred MacMurray as Walter Neff, the murderous insurance salesman in the iconic film noir, Double Indemnity!  By the time you realize he’s a bad guy, it’s too late! You’re in trouble.

COVID-19 does the same thing.  It attaches itself to a certain receptor called ACE2, which then tells cells, “This guy’s legit.  Let him in.”  ACE2 is the doorknob; that’s how the virus enters cells in the nose, airway and lung.

What does this have to do with prostate cancer?  The specific gene that makes it possible for the virus to grab onto ACE2 and keep entering and killing respiratory cells is called TMPRSS2.  PCF-funded scientists have studied this gene extensively in prostate cancer since 1988.  They know, from 32 years of research, what controls the TMPRSS2 gene that unlocks the receptor that lets in the virus:  androgens (male hormones).  TMPRSS2 is an androgen receptor-controlled gene.  

            Scientists believe they can stop the virus’s attack on the body by targeting TMPRSS2.

“In about half of all prostate cancer patients, TMPRSS2 is involved in a genetic event that can drive prostate cancer,” PCF-funded investigator Matthew Rettig, M.D., told me in a recent interview.  Rettig is a medical oncologist at UCLA and Chief of Hematology and Oncology at the VA Greater Los Angeles Healthcare System.  “The gene is tightly regulated by male hormones in prostate cancer.”  Male hormones, primarily testosterone, activate the androgen receptor and cause more TMRPRSS2 to be available on the surface of cells for the virus to enter.  “The question is, does TMPRSS2 in lung tissue behave in the same fashion as it does in prostate tissue?  We have good, correlative evidence that it does.

One way to do it is to shut down testosterone for a few weeks (being tested in TMPRSS2-targeted clinical trials discussed here, midway down the article).  “It turns out that if you suppress male hormones, that will suppress the production of the receptor,” Rettig says.  Basically, explains medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the PCF, “if you suppress male hormones, you reduce the total number of door handles the SARS virus can use to enter.”  Imagine evil, Double Indemnity Fred MacMurray, trying to get into the car where he commits the murder; there were no power door locks, so as he gets to each door, you push the lock down:  one, two, three, four!  You locked him out!

“Conversely,” says Rettig, “if you add male hormones to lung tissue, it will increase the expression of the receptor.  There is a lot of molecular/biochemical/scientific evidence that supports this concept: that the receptor for the virus is regulated in at least a similar manner in lung tissue as it is in prostate cancer tissue.”

Rettig continues:  “It is not a stretch for someone doing prostate cancer research to immediately see this connection and say, ‘Why don’t we temporarily suppress male hormones,” with available, FDA-approved drugs, “in male patients who are suffering from COVID-19, to see if we can immediately ameliorate the severity of the illness?’”

Don’t women have at least a small amount of testosterone?  “Yes,” notes Simons, “but while thousands of women have been infected, men are still more likely to become infected and die from COVID-19.”  Rettig adds:  “A striking study just reported that a huge proportion of women test positive who have no symptoms.  We think they actually may be protected by a combination of low androgens and high estrogen.  Work done by some of our colleagues at Columbia suggests that female hormones – estrogen and estrodiol – actually suppress the expression of the receptor.”  Then why not give estrogen to men?  “It does seem to suppress the receptor, but when it’s first given, in the first few hours,” there’s a temporary backlash, “a transient rise in the expression of the receptor that could make the disease more severe.”

This begs another question, and the answer has changed since I first interviewed Rettig a few weeks ago.  I asked him:  If shutting down the male hormones can stop the virus from invading the lungs, are men who are on androgen deprivation therapy (ADT) for prostate cancer protected?  He said, “Nobody knows yet.”  And that was true.  But since that time, another PCF-funded study of men with prostate cancer in Italy found that men who were on ADT were four times less likely to be infected with the coronavirus than men who were not on ADT, and five times less likely to die.  You can read about that here. And another approach, also being tested in clinical trials, involves a drug used in Japan to treat pancreatitis.  It is also a TMPRSS2-blocker.

It is amazing that in a matter of weeks, scientists have learned so much about this virus, including good potential avenues for treating 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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Whack-a-Mole and Prostate Cancer

Oligometastasis:  Good News from the ORIOLE Study

To the growing and hopeful list of strategies for attacking prostate cancer, let us add this approach:  Whack-a-Mole.

That’s how Johns Hopkins radiation oncologist Phuoc Tran, M.D., Ph.D., describes it to his patients.  The actual scientific name for this highly sophisticated strategy is stereotactic ablative radiotherapy (SABR, highly focused, intense doses of radiation), for men with oligometastasis – up to three small bits of cancer that have broken away from the main prostate tumor and started to grow elsewhere.

Previously, I wrote on Vital Jake and also on the Prostate Cancer Foundation’s website, about the Baltimore ORIOLE study, led by Tran, who also contributed greatly to our book.  Tran was enrolling patients in a small study to see if men with oligometastasis would benefit from SABR in addition to treatment of their primary tumor.

His strategy was a new one – part of a general rethinking of what represents curable prostate cancer.  The boundary used to be very clear:  prostate cancer was either confined to the prostate or prostate bed, or it wasn’t.   Like a light switch with no dimmer, there was no in-between:  a man with only one metastasis was believed to face the same fate, eventually, as a man with widespread metastases.  It was just a matter of time.

But Tran believed that the lines of prostate cancer were not so clear-cut as scientists had assumed; that instead of two circles – localized and metastatic cancer – that didn’t connect, we might be dealing with a Venn diagram, with oligometastasis as the critical area where the two circles overlap.  “It may be that the window of curability is wider than we thought,” he said last year, and we all hoped that he was right.

Tran and colleagues at Johns Hopkins, Stanford, and Thomas Jefferson University recently published results of the ORIOLE Phase 2 clinical trial in JAMA Oncology.  The results are promising:  54 men with oligometastasis were randomly assigned either to treatment with SABR or to observation.  To detect and keep track of the oligometastases, the study used PSMA-PET scanning, which uses a small molecule linked to PSMA (prostate-specific membrane antigen, found on the surface of prostate cancer cells) as a radioactive tracer.  This PSMA-targeting tracer can highlight areas of cancer as small as a BB – much smaller than can be seen on regular PET or CT imaging.  “PSMA-PET allows us to treat lesions we otherwise couldn’t see,” Tran explains.  “A CT or bone scan would miss those lesions, and patients would presumably not do as well.”

At six months, 61 percent of the men in the observation group progressed – compared to only 19 percent of the men who received SABR.  “We also saw a significantly decreased risk of new metastatic lesions using PSMA PET-CT” says Tran.  “The men in the SABR group did considerably better.  This is a definite signal that we can perhaps modify metastatic disease.”

This was a Phase 2 study, and “we need larger Phase 3 trials,” he says.  “But this is very positive, and we hope that in the future, we will be able to change the course of metastatic disease in some men.” 

Some interesting points here:  First, Tran and colleagues hope that “complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT).”  The key question, Tran says, is, “can we alter the natural history of metastatic prostate cancer with metastasis-directed therapy (MDT)?”  They don’t know the answer yet.  Most men with oligometastatic disease who get these spots of cancer zapped don’t experience a complete drop in PSA.  This, Tran says, suggests that “residual micrometastases are present but undetectable.” Does SABR simply reset the clock – does it keep pushing the snooze button?  Or, as the scientists hope, does it make the cancer less likely to form new metastases?

Bad Pioneers on a Bad Journey:  Tran and other scientists theorize that the spread of cancer is a story of colonization.  A few pioneers set forth on a journey to a new land.  At first, it’s touch-and-go; their survival is tenuous.  Just think of the early colonists in the U.S., from England, France, or Spain.  Until they took root in the new land, these nascent colonies were frail:  they needed reinforcements from their mother countries – medicine, weapons, tools, food – and “eventually they did survive.”  So it may be with the seeds of cancer; either the cancer cells themselves, or their messages (in the form of genetic and chemical telegrams) are dispatched to the primary tumor, the mother country.  If the mother country is no more – if it has been eradicated by surgery or radiation – then small cancer outposts might get similar support from visiting each other.  But if those outposts are destroyed by SABR, even if there are a few cancer cells remaining in the tissue or bloodstream, it doesn’t matter:  the environment is too hostile, and the numbers are too few for new colonies to survive – “or, if they did, it would take much longer.”

“It’s like Whack-a-Mole”:  In the ORIOLE trial, Tran and colleagues looked for circulating tumor DNA (ctDNA), and identified certain gene signatures that can tell if a man is more likely to respond to SABR.  “Patients who don’t have these mutations responded very well,” he says.  They also have learned from this and other research that men with oligometastasis fall into three basic groups.  “Some men do really well after one course of SABR,” with no recurrence of cancer.  A second group of men have a small recurrence.  “Another site pops up; a microscopic metastasis that we couldn’t see before establishes itself into a macroscopic metastasis.  It’s a limited return of cancer and it responds to another round of SABR.”  Then some men, after a few months, have multiple new areas of cancer.  “For these men, the SABR doesn’t control the disease at all.”

Imagine a green lawn, with one or two dandelions, Tran tells his patients:  “You can pluck those two or three weeds, and wait and see.  Sometimes you get lucky; sometimes another weed or two pops up, and you pluck them.  It’s like Whack-a-Mole.  You can do that for a while,” with repeated SABR treatments.  As the scientists reported:  “If a single round of MDT arrests the progression of some, but not all, lesions, subsequent rounds of MDT might salvage the remaining disease, until what remains is inadequate to support a metastatic phenotype.” Basically, for some men, a treatment strategy might be to keep knocking the cancer down until, like a prizefighter who’s taken one too many blows to the head, it can’t get back up.  Imagine:  punch-drunk prostate cancer that may still be staggering around, but can’t raise a fist.  Wouldn’t that be nice!

That probably won’t work in every man, Tran says.  “Unfortunately, sometimes there will be a whole bunch of seeds all at once, and at that point, you need weed killer all over the lawn,” or systemic therapy.  However, SABR plus ADT, androgen-blocking drugs, or chemo might one day provide “the multipronged attack required to cure this disease.”

Looking ahead:  In a follow-up trial, called RAVENS, men with oligomestatic prostate cancer are randomly given either SABR alone, or SABR plus radium-223 (Xofigo).  “What we have seen in the men in that second group – the ones who have more isolated spots of cancer popping up – is, they’re not recurring where they received the SABR, but in areas that were microscopic, and commonly in the bone.”  Radium-223 targets cancer in bone.  “It releases a radioactive particle that is very toxic but is so focused that it only kills in a radius of two-three cell depths.  It’s ideal for microscopic disease.”

More and larger studies are needed, but in the future, Tran envisions, men with oligometastasis will require more vigilant monitoring, and ideally, regular follow-up PSMA-PET scanning.  “This has the potential to be practice-changing.  We are very excited by our results, and by the potential to modulate the course of metastatic prostate 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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The Other Survivors

When it comes to disrupting your life, prostate cancer cuts quite the swath.   We don’t know exactly how big this trail of disruption is.  We don’t know how bad it is, either.

Let’s start with the numbers.  In the U.S. alone, there are more than 3 million men out there who are prostate cancer survivors.  Although we can speculate, we don’t know exactly what these guys are going through; everybody’s experience is different.  It doesn’t help, either, that many men are reluctant to discuss the side effects of treatment.

But these men are just the tip of the iceberg.  An estimated 73 percent of men aged 65 to 80 are married or have partners, says New York University urologist Stacy Loeb, M.D.  “It’s safe to say that if there are more than 3 million prostate cancer survivors and approximately three-fourths of them are partnered, that’s a lot of people who are being affected by this disease.”

And hardly anybody knows what these wives and partners are experiencing; in part, because hardly anybody has asked them.  Loeb and colleagues are hoping to shine some light on these other survivors.  Loeb was first author of a study recently published in the Journal of Sexual Medicine, called, “A Call to Arms: Increasing our Understanding of the Impact of Prostate Cancer on the Sexual Health of Partners.”  I recently interviewed her for the Prostate Cancer Foundation’s website.

Loeb and colleagues found that sexual disruption for these couples often starts with biopsy!  “One of the potential effects of sampling the prostate with needles is blood in the semen, which can be off-putting to both patients and their partners.  It usually doesn’t last more than a few weeks, and it’s not medically dangerous. “However, seeing blood can certainly be disruptive of the sexual encounter – so even from the process of diagnosing prostate cancer, there can be an impact on sexual health for the couple.  There is controversy over whether biopsies – or repeated biopsies – are associated with erectile dysfunction (ED).”  Some evidence suggests that undergoing multiple biopsies can cause scar tissue to develop in the nerves responsible for erection, but the medical literature is “a bit conflicting, Loeb says.  It’s also difficult to study, because many men getting multiple prostate biopsies are also getting older, and have other health conditions that can affect sexual health.

And that’s just diagnosis of prostate cancer.  “All forms of prostate cancer treatment can have a potential impact on sexual health,” says Loeb.   For example:  “With surgery, the greatest insult to the body is at the beginning, and then function can gradually recover over time.  With radiation, ED can take several years to develop.”  But what about the men – and there are thousands each year – whose cancer requires more than one form of treatment?

“Surveys from both the U.S. and the UK show that many men who undergo various forms of prostate cancer treatment have sexual complaints,” says Loeb.  “However, many of them are not getting any treatment for their ED or other issues.  This really has a huge impact for the partner.  ED is one of many possible sexual consequences.  Penile curvature (Peyronie’s disease) is another.  There’s the potential for penile shortening (note: use of a vacuum erection device to stretch the penis can help prevent this) and there are issues with libido.” Men who have had prostatectomy may also struggle with urinary incontinence, and some may experience sexual incontinence (leaking urine during sex).  “There are changes in orgasm after prostate cancer treatment, as well,” Loeb adds.

Men who undergo short- or long-term androgen deprivation therapy (ADT) experience a loss of libido and complications including gynecomastia (breast swelling; this can be treated with radiation).  Does this affect their partners?  Of course!  But by how much, nobody knows.  The doctor visits are typically “focused on the patient,” says Loeb.  “There’s a significant unmet need for greater support for partners.”

Many prostate cancer treatment centers offer their patients help with penile rehabilitation for recovery of sexual function.  “In some practices, there is a different urologist, nurse practitioner, or physician assistant who manages sexual health issues than the urologist who did the surgery, whose main expertise is in cancer control.”  The good news is that sexual medicine subspecialists can provide a lot of help.  The not-so-good news is that many men don’t take advantage of what these experts can offer.  There’s still a lot of stigma.  In the study, Loeb and colleagues found that a significant number of patients were not seeking help with sexual recovery.  Shame or unwillingness to discuss sexual issues may account for some of the reluctance; another barrier may be financial.  “Some of the treatments are very expensive.”  For example, erection-assisting drugs can be expensive, and many insurance plans don’t offer reimbursement for a VED (although the Veterans Administration does cover VEDs).

The other not-so-good news is that “there’s a lot of work to be done with the partners, defining their experience and the unmet needs that they have, and finding ways to provide additional support to them.”

In one way, these survivorship issues are a good sign – they’re happening because more men with localized disease are being cured of prostate cancer, and more men with cancer that has escaped the prostate are living for many years, says Loeb.  “But what comes with that is having a large pool of survivors who are living for years with the impact of the disease.  This impact does not only affect the patients, but also the people around them.”  In the study, some of the partners described “problems with relationship dynamics,” arguments or the opposite: isolation.  “They feel they can’t discuss it with their partner.”  Some describe making changes, like using a certain type of condom to deal with sexual incontinence.  “In some cases, there’s a real feeling of grief; people feel cut off from their partner, and they can’t discuss some of the sexual issues easily. There really is a great need for more research in this area, and help for the partners of prostate cancer patients.” Many of the partners, by the way, may be having sexual health issues of their own, including going through menopause.

So:  Men, be kind to your partners.  They’ve been through a lot with you.  Even though it’s not in their bodies, it’s their cancer, too.  

All of this said, I just want to add a personal note:  As the wife of a prostate cancer survivor, I‘m just so happy, and so very grateful, that the cancer is gone!  This doesn’t mean the recovery hasn’t been a drag; it has.  But that weight of fear that felt so crippling, for me at least, was much worse.  

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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