“I started doing all of this because I read about it on your blog.”  Vernon is a college professor who had radical prostatectomy eleven months ago, who contacted me to tell his story, because he hopes it will help other men. “I didn’t hear much about this at all from my surgeon.”  Vernon is black, and he had aggressive prostate cancer. “Thank goodness, it was caught early, because I was getting my PSA checked.  My father and brother had it, so I started getting checked 10 years ago, when I was 40.”

When Vernon’s cancer was found, he had robotic prostatectomy. “It was a no-brainer, because I was just 50.  But now that the cancer is gone – my PSA has been undetectable at three months, six months, and now I’m moving to every six months of follow-up blood tests – I am working hard to get the rest of my life back.  I’ve got a lot of living to do!”

It is Vernon’s nature, as he says, to do research.  So that’s what he did:  he got online and started reading everything he could about recovery of urinary continence and sexual potency after prostatectomy.  “I started taking Cialis, not just as needed but every day,” he says.  He asked his doctor for a prescription, and talked to him about taking “more than the FDA-approved dose: 20 mg a day, every day.”  His doctor said that this would be okay, since Vernon didn’t have any other health problems.  Why would Vernon want to take it every day?   “Because I read that it may help prevent loss of penile length and keep the penis vascularized” (maximize blood flow to the penis).  Has this helped?  “I’m not there yet, but I’ve definitely seen improvement over time,” he says.  “At first, I was pretty discouraged, because I had no erections right after the surgery.  Then, three to four months in, I started getting a partial erection, maybe 30-40 percent of what it was, and now it’s up to about 70 percent when I wake up in the morning.”  It still is not enough for penetration, he believes, “but it’s getting there.”

This hasn’t stopped Vernon from returning to a sex life with his wife.  “Right now, I have to use the vacuum erection device (VED) and the ring (placed at the base of the penis like a temporary mini-tourniquet, to keep the erection),” he says.  “But it works!”  He has not tried injecting his penis.  “I just don’t want to stick a needle in my penis, but I’m becoming more open to the idea.  I also don’t want to get Peyronie’s,” a condition where the penis becomes less straight when erect; this is thought to be due to scar tissue.  “I am hoping that ultimately, erections will come back on their own,” he says.  “I’m just trying to help the process along.”

Penile stretching:  “I really did not want to have shrinkage,” Vernon says.  “So, based on what Dr. Trinity Bivalacqua said in your post, and my own research, I started using a vacuum erection device (VED).  I picked one that nurse at my urologist’s recommended.  But then I also read about this British VED that uses water, that was really marketed more toward making the penis bigger, not for recovery after prostatectomy.  I like that one better; I think it does a better job of improving blood flow. Plus, you can put warm water in there, as warm as you can stand, so that has a vasodilatory (increasing blood flow) effect, as well.”

“I’m really glad I started using that as early as I did, about three weeks post op,” he continues.  “When I first started, it hurt like hell.   Everything was kind of scarred; it almost felt like I was breaking scar tissue up.  That got better within a week or so,” and he could tell the penis was beginning to stretch back to its former length.  “Then,” after further reading on the internet, “I got the Viberect,” a device “designed to help you get an erection by vibration.  I think it helps.  It seems to help more over time.  I think the important thing is just — if you think about how sex works — it’s mechanical stimulation that gets translated to the nerves.  So it makes sense that if you did something that would mechanically stimulate the nerves, you would help promote the function.  It’s kind of like using a muscle to make it stronger.  It’s not like a pleasure device; you feel like a buzzing sensation.  I just keep telling myself that I won’t be doing this forever, and when I’ve recovered, I can just have sex with my wife like always.”

In the meantime, “I have been able to have intercourse with my wife using the VED and the ring,” he reports.  “Once, I used the looser ring and it was not tight enough to keep the blood flow, so it didn’t work.  But with the tighter ring, it worked!  It was successful.

“The one thing nobody tells you,” he adds, “is the whole orgasm thing.  It’s different.  It’s not the way it used to be.  Before, it was like this buildup, and then this release. There’s none of that. It’s more like … you miss the appetizer and the main course, and go straight to dessert, but I can see how women have multiple orgasms, it seems like it’s all in the brain.  It’s kind of bypassed all the hardware down there. You don’t get that pent up feeling.  There are contractions but they’re not really doing anything,” and the climax is “dry” ejaculation, because there is no semen.   Vernon doesn’t want men to be discouraged by this:  “It’s still wonderful.  It’s just different.”

What about incontinence?  “Everybody said, do Kegels, do Kegels,” Vernon says.  “The problem there is, I felt I could not sense the anterior part of the pelvic floor, the part I could contract.  I could feel it contract in the back, toward the anus, and the middle, toward the scrotum. I could not feel the front.  Then I read that men who lack sensation in the proximal urethra are the ones who have more trouble with incontinence.  So I thought, how can I contract something I can’t feel?”  Once again, Vernon turned to the internet, “and sure enough, there were devices marketed for male urinary incontinence that involve patches and electrical stimulation — basically a TENS unit.  I thought, if that can do what I can’t and it wasn’t too expensive, then why not?  So I bought it from England.”  This particular unit “comes with two options.  One is an electrode you put in at the anus with some lubricant, and the other are patches, and to get the anterior part, you basically put a patch just above the penis in the front and behind the scrotum in the back, or the patch above the penis in the front and the rectal probe.  The device has programs for urge, stress, or mixed, so I used the one for stress incontinence.”  The key seems to be in repeated use, he adds.  “If I don’t do it for a while, I will use the rectal probe, but ordinarily, I can just use the perineal patch and the suprapubic patch.  If I keep doing it, it works, and I hardly have any drips.  If I use it regularly, I am able to do a Kegel in the front, but if I don’t do it, I lose the sensation there, and I have to start back up again.”

Vernon has his eye on the prize of a cancer-free life that one day, will be pretty much back to normal.  “I’m optimistic.  It’s just slow.  From what I’ve read, nothing’s able to speed up the recovery.  I’m just trying to stack the deck in my favor. On the other hand, I feel like I’m young and I’m lucky.  I had aggressive cancer, and it was caught early!  Thank God!  I want to live!  I feel like I’ve been given the gift of life. I just want all of my life back.”

In sharing his story, Vernon hopes that if you are facing prostatectomy, you will be inspired to be proactive about your own recovery, so you can get your life back, too.  Note:  This is just one man’s approach.  Talk to your doctor about the best approach for you.  That said, if you’re not getting the answers you need, do your own research.  Many medical centers have experts on sexual health and urinary incontinence.  This is their job.  Please don’t be stoic and just wait for it to get better on your own.

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

 

If, as we have seen, inflammation can lead to prostate cancer, could anti-inflammatory agents help protect against it?

The jury’s still out.  However:  Johns Hopkins epidemiologist Elizabeth Platz, Sc.D., has been intrigued by this possibility for many years.  She is senior author of a new study on the use of aspirin and statins, published in Cancer Prevention Research.  The study, of men in the placebo arm of the Prostate Cancer Prevention Trial, doesn’t answer this question once and for all – but adds more weight to the idea that, for lowering the risk of developing potentially fatal prostate cancer, fighting inflammation is a good thing.

Evidence from observational studies has suggested that when taken regularly over time, aspirin may lower the risk of prostate cancer.  These drugs block enzymes that play a key role in the body’s inflammatory response.  Other studies have linked long-term use of statins, prescription drugs that are used to lower cholesterol but that also are anti-inflammatory, to a lower risk of advanced and metastatic prostate cancer.

In this most recent study, the investigators looked for inflammation markers in benign prostate tissue samples.  “We compared the use aspirin and statins with the presence and extent of inflammation in the prostate tissue,” says Platz.  They also looked at prostate biopsy slides for the presence of certain immune cells that are involved in inflammation.

“Of 357 men, 61 percent reported aspirin use, and 32 percent reported statin use,” Platz continues.  “Aspirin users were more likely to have low FoxP3, a T regulatory cell marker, and statin users were more likely to have a low CD68, a macrophage marker.”  “Our results suggest these medications may alter the immune environment of the prostate. A next step is to determine whether these immune alterations may underlie the epidemiologic observations that taking an aspirin or statin may protect against getting advanced prostate cancer, and dying from it.”

Prostate Cancer Loves Fats          

Here’s some more recent research out of Johns Hopkins, a neat bit of  basic science that may help explain the findings of Platz’s recent study:  “Our work is mechanistic,” says investigator Marikki Laiho, M.D., Ph.D., director of the Division of Molecular Radiation Sciences, “and provides insight into how the tumor microenvironment senses the excess load of the lipids.  Diet and statins obviously relate to the amount and regulation of the lipids, and have shown those clear correlations to prostate cancer.  However, we need to understand why to be able to correct the problem. Our work provides at least one explanation how the lipids fuel cancer. One part of the work was just to feed the prostate cancer cells with cholesterol, which made them more invasive.”

It turns out that even on a cellular level, prostate cancer gravitates to its own kind of junk food – the tiny version of deep-fried Oreos with a side of chili cheese fries.  Laiho and colleagues have just figured out how the body enables prostate cancer’s terrible diet.

The culprit is a lipid-regulating protein called CAVIN1, the scientists reported in the journal, Molecular Cancer Research.  In lab studies, when CAVIN1 was removed from cells in and around the prostate tumor, the fatty acid that was in those cells spilled into the tumor’s microenvironment.   The effect on prostate cancer cells was dramatic:  the cancer cells soaked up the lipids, which then acted as turbo fuel to make the cancer spread more aggressively.

“In every prostate cancer cell line we tested,” says research fellow Jin-Yih Low, Ph.D., the study’s first author, “tumor cells universally had an appetite for the lipids, using them to strengthen the protective membrane around the cell, synthesize proteins and make testosterone to support and fuel the cancer’s growth.  The tumor cells then behaved more aggressively, exhibiting invasive and metastatic behavior.  Just having access to the lipids gave the tumor cells more power; the tumor’s behavior changed.”

But wait!  There’s more:  nearby cells changed, too.  Deprived of their lipids, normal stromal cells started to churn out inflammatory molecules, adding fuel of their own to the fire. 

Laiho’s team then confirmed their findings in mouse models, comparing tumors with and without CAVIN1 in the stromal cells.  In the mice, Laiho says, “although the presence or absence of CAVIN1 did not affect the speed of tumor growth, lack of CAVIN1 definitely caused the cancer to spread.  All of the mice with tumors that lacked CAVIN1 had a twofold to fivefold increase in metastasis.  The tumors also had a fortyfold to hundredfold increase in lipids and inflammatory cells.”

The investigators were surprised at these results, Laiho adds.  “We suspected CAVIN1 was important, but we didn’t realize how important.  The tumor’s microenvironment matters, and the amount of lipids matters a lot.”  Just changing the level of lipids “created a situation of rampant metastasis.”

What could come from this research?  One possibility is development of a new biomarker:  a loss of CAVIN1 in local or locally advanced cancer, for example, could signal a higher risk of metastasis.  The next step is to understand more about the inflammatory process in the tumor’s microenvironment.  “We want to understand why the inflammation brings in macrophages, immune cells that further exacerbate the inflammatory process, instead of T cells, which should attack the cancer.”  The more scientists know about how inflammation does its nasty work to inflame cancer, the closer we are to finding a way to stop 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

Why does it matter if you eat right and exercise?  Everybody knows the answer; in fact, we’ve all heard it so many times, it’s easy to tune it out:  diet and exercise are good for you.  Duh!  Who’s going to argue with that? Having a healthy lifestyle is right up there with world peace as a worthy goal!

Bear with me here:  With a topic such as this, I know I’m either preaching to the choir – people who are already exercising and eating a pretty good diet – or I run the risk of turning off the people I really want to hear this message, by seeming to preach at all: people who might think, “Go ahead, tell me what to do.  I really enjoy that.  Micromanage my life.  Maybe you’d like to come over and look at my closet and tell me what shirt to wear today.”

Okay, fine!  I’m not here to tell you what to do.  But I am going to try really hard to tell you why you might want to do certain things, and how good diet and exercise – or the lack thereof – can affect prostate cancer.

Please pardon the long set-up, but let’s begin with some facts, with plenty of links for further reading:

If you exercise, you are less likely to have cancer return after treatment, less likely to get metastatic prostate cancer and die of it.  What does exercise do?  A lot of good things for your vascular system, which, in turn, can help slow down prostate cancer metastasis.  But you know what it also does?  It helps you lose weight.

And it just so happens, men who lose weight are less likely to die of prostate cancer.

And sugar can make cancers grow faster.

And men who stop smoking are less likely to have cancer come back after treatment, and less likely to die of prostate cancer.

Exercise also helps control stress, and the stress hormone, cortisol, affects adrenal receptors, and can play a role in making cancer grow and spread faster.

Now, here’s why all this matters so much:  smoking, not exercising, quaffing sugary drinks, eating processed, fatty foods, and being overweight all contribute to inflammation.

I’m going to be writing a lot about inflammation in the next few posts, because it is becoming increasingly evident that inflammation can lead to cancer – and it’s quite possible that if we can prevent inflammation, we may prevent or at least slow down cancer.

What Inflammation Does

In a landmark study, Karen Sfanos, Ph.D., and scientists at Johns Hopkins have shown for the first time that bacterial infection can cause prostate cancer.  The study was led by Sfanos and her former graduate student, Eva Shrestha, Ph.D., in collaboration with Angelo De Marzo, M.D., Ph.D., Jonathan Coulter, Ph.D., and colleagues.  Infection? That’s not the same as inflammation!  True… but bear with me.

The bacterial culprit found in this study belongs to the family Enterobacteriaceae, which includes E. coli. Better known as a nasty gastrointestinal bug, E. coli causes inflammation in the urinary tract and is a known cause of bacterial prostatitis.  As the scientists discovered, colibactin, a genotoxin produced by some strains of E. coli, can also instigate a series of unfortunate events in the prostate.  Bacterial infection leads to acute and chronic inflammation, which can lead to the development of a lesion in the prostate called proliferative inflammatory atrophy (PIA), first described by pathologist De Marzo, oncologist William (Bill) Nelson, M.D., Ph.D., and other Johns Hopkins scientists; it can also cause DNA damage. The presence of colibactin is even more ominous, because it can directly lead to double-stranded DNA breakage. 

Sfanos suspects that this combination leads, in turn, to another development:  fusion of two genes, TMPRSS2 and ERG, that normally should remain separate, but in this case get abnormally spliced together.  Now, it may be that by themselves, TMPRSS2 and ERG are like Robert Leroy Parker and Harry Alonzo Longabaugh:  put them together, and they became Butch Cassidy and the Sundance Kid, and together, they got into much worse trouble than either one managed alone.  This TMPRSS2/ERG fusion – found in as many as half of all prostate cancers – is thought be an early event leading to the development of prostate cancer.

“We found evidence in human tissues (from prostatectomy specimens) that bacterial infections are initiating the TMPRSS2/ERG fusion,” says Sfanos.  “We don’t think this is the only way bacterial infections contribute to cause prostate cancer.  But in this particular study, the way we looked at it was by tracking the presence of these TMPRSS2/ERG fusions.”

It is entirely possible, notes De Marzo, “that other types of mutations or events could also be caused by bacterial infections or inflammation.  But looking at these fusions gave us ‘smoking gun’ evidence that bacterial infection was the initiating event.”  Sfanos adds that “the colibactin-producing bacteria, TMPRSS2/ERG fusions, PIA, and tiny buds of cancer were all there, in the same place at the same time, a snapshot of prostate cancer being born.”  The team’s early findings are available online in BioRxiv, a scientific data-sharing website, and a manuscript for publication is undergoing peer review.

Bacterial infection is a known cause of other cancers.  H. pylori, for example, is a well-established cause of stomach cancer.  “We believe that many different types of microorganisms, certain types of sexually transmitted infections (STIs), and other infections in the prostate can certainly cause the same chain of events,” says Sfanos.

How did the bacteria get into the prostate?  They could have come from the urethra.  “These bacteria are good crawlers,” Sfanos says.  De Marzo recalls what the late Don Coffey, Ph.D., the longtime director of the Brady’s scientific labs, used to say: “The urethra is like the Holland Tunnel for bacteria.”

Note:  These tiny cancers are not the cancers that were biopsied and that led to the diagnosis of prostate cancer; they’re too young even to achieve a Gleason grade.  They’re just baby sites of cancer cropping up, in addition to the more mature cancer that was already there.  Prostate cancer is multifocal:  in most men with prostate cancer, several sites of cancer develop at the same time.  But because of the unique molecular tools used in this study – looking for TMPRSS2/ERG fusions and “ERG-positive PIA” – Sfanos, De Marzo and colleagues were able to catch the formation of these invasive cancers in real time.  “This might start to explain the multifocal nature of prostate cancer,” says Sfanos. “There might be multiple infections or other inflammatory events that occur throughout a man’s lifetime.”

Sfanos suspects that the men whose tissue was used for this study “likely all had undiagnosed infections.”  These findings may lead to development of a new test, using urine or prostatic fluid, to look for colibactin or markers of inflammation in the prostate.  Future studies may look at urine samples along with prostate tissue for such markers, and  new imaging technology may one day be able to detect inflammation, as well.

For more than 20 years, De Marzo and Sfanos, with Brady scientists Bill Nelson, Srinivasan Yegnasubramanin, M.D. Ph.D., Elizabeth Platz, Sc.D., and William Isaacs, Ph.D., have studied inflammation as a risk factor for prostate cancer, particularly looking at PIA.  Sfanos “has also been the major champion of infection” as a risk factor, De Marzo says.  Now, these two paths of investigation have come together.

Could dietary changes make a difference?  “Bill Nelson showed years ago that loss of expression of the GSTP1 gene rendered prostate cells more susceptible to DNA damage caused by a chemical compound that is found in charred meat,” says De Marzo.  “Infection plus a bad diet might make this worse, and then combine that with the underlying genetics.  There might be multiple culprits, a constellation of things over years.”  We’re going to look more at diet in future posts.

Coming up next:  Could anti-inflammatory drugs help?

 

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