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How Inflammation Sparks Prostate Cancer

Believe it or not, there once was a time when the Grand Canyon was just a ditch.  Before that, it was a rough patch in the desert with a river running through it.  It took a very long time for that canyon to form, and the conditions had to be just right to allow water, blazing sun and wind to chip away through layers of fragile rock.

On a very much smaller scale, this is what happens to cause cancer when the conditions are just right.

Now, if you will:  While we’re thinking about the Grand Canyon, let’s pan the camera a few miles away. We’re near some tall pine trees, and there’s a campfire.  Some cowboys are sitting around it.  Let’s imagine that they all have white hats; they’re good guys.  (They’re also much quieter than the cowboys around the campfire in “Blazing Saddles,” so don’t go there!)

If you’ve ever sat around a fire, you know that wood sometimes pops unexpectedly and sends out sparks.  That’s exactly what happens at our little campfire, and it happens to hit one of the cowboys square on the arm.  He brushes out the sparks, then goes back to his seat.  Nothing’s really changed; he laughs it off.

Wouldn’t you know it, the fire sparks up again – right on that same poor guy.  This time, he’s a little more scorched; his shirt has a hole in it and his eyebrows got singed.  He’s also a little irritated.

It happens a few more times, and he is no longer the proverbial happy camper.  He’s moving around, no longer sitting quietly, he’s got some burns that will leave scars, and he’s angry.  His hat is so charred now that it’s almost black.  One last spark, and he’s out of there.  He leaves the campfire, saddles up his horse, and rides away, fighting mad and looking for trouble.

This little scene plays out a lot, every day, in our bodies.  There are countless campfires – like stars dotting the sky – that flare up, burn quietly, get snuffed out, and never cause harm.  The campfires are little flares of inflammation.  

Commenting on this analogy is medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation.  “The future of fighting prostate cancer,” he says, “is either to stop the sparks from flying, or to put fire retardant on the flames – or better yet, to bring in the fire retardant really early in life.  It’s all about the sparks, and what makes the sparks, and then spark interception or spark interdiction.”

Expect to Hear a Lot More About Inflammation

Inflammation is our own version of Dr. Jekyll and Mr. Hyde: When it works the way it’s supposed to – when you skin your knee or get a paper cut on your finger, for instance – inflammation is what protects your body from bacteria and germs that find their way through the open wound.  The immune system kicks in; zealous home soldiers like killer T cells spray chemicals on the intruders, puncture their armor, or even eat them whole.  You notice some redness, a little heat, maybe some swelling or even a bruise, and you know that your body is healing.  There’s a scab, new skin covering the hole or tear, and all is well. The inflammation goes away.

But what if it doesn’t go away?   Here’s where the dark side of Dr. Jekyll, his alter ego Mr. Hyde, starts to show itself.  Chronic inflammation is bad.  

“The story of inflammation is absolutely the heart of what causes prostate cancer,” says Simons.  “Inflammation lowers your defenses,” and changes the DNA.  Going back to the angry cowboy at our campfire scene: If only he had moved away from the fire, or if someone had poured a little water on the fire to cool it down and keep the flames low.  He might have had a few scars, but he would have been okay.  Instead, he began moving around, and eventually he left the campsite; if he were a prostate cell, he would have become cancerous – but still there at the site, still easily treatable.   But as he became more scorched, he became metastatic.  The continued exposure to those flames turned him from a cell sitting quietly into a metastatic cancer cell.

“We estimate that 30 percent of all cancers are caused by this kind of chemistry,” Simons adds.  The little fires hurt genes that are nature’s own tiny fire retardants, so without their subduing effect the flames burn hotter; the fires then go after the body’s normal first responders.  So the firefighters don’t stop the burning; the paramedics don’t heal the injured victims.  The inflammation draws other cells called macrophages and granulocytes to the scene; they’re supposed to be part of the body’s cleanup crew.  “Unfortunately, in cleaning up, they actually make the flames burn hotter and further damage the area.”

What causes the fires? 

One huge cause is our diet.  Fat, charred meat, processed carbohydrates, chemicals in junk food, and sugar.  Basically, what we know as the Western diet – high in meat and bad carbs, low in fruits and vegetables.   How do we know this?  Because the men in the entire world least likely to get prostate cancer are men in rural Asia, who eat the traditional Eastern diet – low in meat, high in fruits and vegetables, with hardly any processed carbs.  No soda, lots of green tea.  No fries, lots of rice.  No burgers, lots of broccoli.  But when those men come to America, their risk of getting prostate cancer goes up.  Diet matters. 

“The rural Asian diet is anti-inflammatory,” says Simons.  “It may be that these men would eventually develop prostate cancer if they lived to be 120.  But they don’t.”  If you think about our campfire analogy, maybe cells still get singed, but they’re few and far between.  That critical momentum never develops.

“We are now learning that it’s essential for men to have a healthy diet when they’re young – say, between 14 and 30.”  But men of any age can benefit from turning down the inflammation with “fire-fighting” foods.

The opposite is also true:  Obesity and one of its consequences, diabetes, make these flames burn even higher.   (In fact, this may be one reason why rural Asian men are less likely to get prostate cancer: because of their diet, they have a lower body mass index, which means less stress on their cells.) “If you are overweight or borderline diabetic, you turn on more insulin to try to control your blood sugar,” says Simons.  Insulin secretes molecules called cytokines, which – thinking of our cowboys at the campfire – are like the chuck wagon, bringing in oxygen, new blood vessels and nutrients to feed the cancer.

“Some men have more sparks flying around, and men who are overweight are in this group.  The good news is that you can reduce your insulin level with exercise,” says Simons.  “There’s a lot of evidence that just being sedentary is a terrible setup for trouble later, if you have a slightly inflamed prostate and higher insulin level.”

The prostate is particularly vulnerable to inflammation, Simons adds, because it’s just chock full of inflammatory cells called prostaglandins, most likely nature’s way of protecting the fluid that makes up semen.  So the prostate is already a tinder box.

What else makes it worse?  A big one is genetics.  Some men are born with  their own fire-starter – genes they inherited from their father or mother.  If you are of African descent, or if you have a family history of prostate cancer or cancer in general, you are at higher risk of developing prostate cancer.  That doesn’t mean that you’re bound to get it, and it may be that with cancer-fighting diet, exercise, not smoking, and plain old good luck that you will never have prostate cancer.

Other causes of sparks:  Infection.   Cigarette smoking.  Emotional stress.  Not being circumcised: several stories have shown that circumcision has a protective effect, lowering your odds of developing prostate cancer, and of dying from it.  This ties in with what we’re still just learning about the role infection plays in changing the prostate’s microenvironment, and making it more susceptible to cancer.

            Okay, then what puts out the fires?

We’re still figuring this out.  A good diet, exercise, and other flame retardants such as Vitamin D.  Dietary supplements such as turmeric seem to help, as do broccoli and tomatoes cooked in olive oil (which brings out the lycopenes).  Meditation: new research suggests that this may help calm the tiny sparks and lower the chances of cancer catching fire.

And finally, there’s a huge question mark. What else helps?  “This area of research is woefully underfunded,” says Simons. There may be a bacterial equivalent of H.pylori– the nasty bacteria found to cause stomach ulcers.   New research suggests that probiotics – “good” bacteria that change the microflora in the gut – may prove helpful in preventing cancer.  Does this mean that there are bad bacteria that do their share of causing it?  Could this be related to the link between infection and inflammation?

We don’t know.  Stay tuned.

 

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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Immunotherapy for Prostate Cancer, Part 2

Checkpoint Inhibitors

Miracle Drugs for Some, But Not Yet All

Checkpoint inhibitors have one mission: to unleash the immune system.  They wake up the sleeping T cells, and in some people with cancer, they have done this spectacularly well. But right now, they don’t help more than a fraction of patients. In other words, for every extraordinary responder – a man whose metastases in the liver and brain simply melt away, whose PSA drops from the thousands to undetectable – there are six or seven men who don’t get any better.

Doctors and scientists desperately want to change this.

A brilliant scientist and investigator named Jim Allison, with initial funding from the Prostate Cancer Foundation, was the first to discover molecules on T cells called checkpoints. He figured out that these molecules were putting T cells into an induced coma, stopping them from carrying out their mission as assassins of cancer cells, and he worked to develop the first checkpoint-inhibiting drug, ipilimumab, which has had great success in treating some cancers, particularly melanoma.  In fact, he just shared the  2018 Nobel Prize in Physiology or Medicine for this work.

Why don’t checkpoint inhibitors work better in prostate cancer? Chuck Drake, M.D., Ph.D., director of genitourinary oncology and the associate director for clinical research at the Herbert Irving Comprehensive Cancer Center at New York Presbyterian/Columbia University Medical Center, explains: “When a T cell moves into tissue, it installs a brake.” It doesn’t necessarily apply the brake; it just has one ready to go.

I wish these brakes had convenient names, like “Bob,” or “Annette.”  But they don’t; they have pesky initials and numbers, so just hang in there and power through.  This is important:  One of those brakes is a molecule called PD-1, which sits right on the surface of the T cell. “Many tumors have T cells inside them, but they’re not working, because they have PD-1 on their surface.” The T cell with the PD-1 is just sitting there. But cancer cells make sure that cell isn’t going to move by adding a molecule called PD-L1. “That’s the foot on the brake. PD-L1 binds to the PD-1 on the T cell.” Imagine a car with several unpaid parking tickets under the windshield wiper; now imagine a traffic cop coming along and putting a parking boot on the car’s front tire. That car isn’t going anywhere.

So we’ve got our superhero in a stupor, like Superman staggering around or unconscious because Lex Luthor put a big chunk of Kryptonite in the room. But wait! Checkpoint inhibitors are coming to the rescue! “If you block either PD-1 or PD-L1 with a drug, a monoclonal antibody, you can wake up the T cell, take off the boot,” T cells can come roaring in and “do what they were designed to do, which is kill specific cells, including tumor cells.” And this is happening with checkpoint inhibitors in kidney cancer, bladder cancer, melanoma, and lung cancer.

Why not so much in prostate cancer? It may have something to do with the number of mutations on the prostate cancer cell. “Some melanomas have over 500 mutations; squamous cell lung cancer can have 200 to 500 mutations; garden variety lung cancer has 150 mutations, kidney cancer has about 70,” says Drake. “But prostate cancer only has about 30 mutations.”

Basically, the more mutations a cancer cell has, the more freakish it looks to the immune system, and the easier it is to recognize as an enemy. Think about any villain in Batman – the Joker, with his green hair and white pancake makeup, for instance. The villainous disguises are really helpful to crime fighters, because they say, “This guy’s dangerous.” But prostate cancers, even the very worst ones, are more like James Bond villains; they don’t look that much different from anybody else.

Timing may be a key factor, too.   Drake recalls a study he took part in when he was at Johns Hopkins, of a PD-1 blocker called nivolumab, which has worked well in other cancers. The patients were men with late-stage prostate cancer who had been through ADT and chemotherapy. “We had zero responses in 17 patients.” He recalled some anecdotal evidence from another trial, where a man who was on enzalutamide got Provenge , “his PSA went down to nearly undetectable, and his response lasted a very long time.”

In talking with Julie Graff, the lead investigator on a recent trial where Drake was a co-investigator, “we said, why don’t we try this same thing with pembrolizumab,” another PD-1 blocker. “We wanted to have patients who initially responded to enzalutamide but were progressing, and we didn’t stop the enzalutamide, but added on the pembro. Maybe there’s something funky about tumors progressing on enzalutamide that allows the immune system to recognize them. Whatever it is, maybe it’s better to stay on the enzalutamide and just add the PD-1 blocker.”  This strategy worked in a few men who were “exceptional responders.”

This study, published in Oncotarget, showed in just a few men with the most devastating prostate cancer – cancer that has metastasized, cancer that has invaded the bones, cancer that got better for a while on hormonal therapy but came back with a vengeance when the hormonal therapy stopped working – what might actually be cures.  It’s high time!  Why shouldn’t this happen in prostate cancer, number of mutations aside?  What is it, exactly, that has been happening in those other cancers:  Tumors that should have killed people with lung cancer, melanoma, kidney or bladder cancer have melted away instead, because checkpoint inhibitors allowed the T cells to recognize the cancer that’s been growing – invisibility-cloaked in plain sight – right beside them.  The results with pembrolizumab were so dramatic, and so unexpected, that the investigators decided to publish the early results.

Oncologist Julie Graff, M.D., at the Knight Cancer Institute of Oregon Health & Science University, explains:   “PD-1 inhibitors on their own have not seemed to have much of an effect on prostate cancer.”  But Graff, Drake and colleagues saw two exceptions to the rule, two men with “castrate-resistant prostate cancer” (their hormonal therapy stopped working) who responded exceptionally well to immunotherapy:  their PSA went away, and their cancer appeared to be undetectable.   “We wondered whether enzalutamide, which targets the androgen receptor, might stimulate the immune system to make the PD-1 inhibitor work better.”

The team designed a study of 28 men who are taking enzalutamide but whose cancer is still progressing.  The men continued to take enzalutamide as they received four doses of  pembrolizumab. The first 10 patients were enrolled from March 2015 to January 2016.  Their ages ranged from 61 to 80, and their PSA ranged from a little over 4 ng/ml to nearly 2,503.  Here’s what happened to them:  in three men, the disease did not change; it did not get noticeably better, but it didn’t get noticeably worse, either.  Four men did not have any evidence of a benefit, and one of these men died of his cancer.  So that’s seven men; what about the other three?  Their response blew the investigators away:  Their PSA – including the man with the PSA of nearly 2,503 – dropped to the undetectable range of less than 0.1 ng/ml.  Two of these men had been on narcotics for pain, and stopped taking them.  One man’s liver metastases went away.  “These three men had a complete response,” says Graff.  “Their tumors shrank radiographically” – meaning that they couldn’t be seen in imaging – “in the lab” – their PSA falling to nearly nothing – “and clinically,” with the need for pain medication going away.  “None has had a recurrence.”

With Emmanuel Antonarakis, M.D. of Johns Hopkins, Drake is looking at ipilimumab, which blocks a different checkpoint called CTLA-4.   “It turns out that within tumors there’s another population of bad guy lymphocytes (white blood cells), called regulatory T cells. These cells have a number of ways to turn off the immune response.”  In addition to blocking CTLA 4, ipilimumab interferes with the function of these regulatory T cells. Which begs the question: “What if you help the killer T cells by blocking PD-1, and at the same time block CTLA4?”  Blocking two checkpoints at once!  “In animal models, this works brilliantly,” says Drake. “The first data with melanoma were just magical; tumors shrank in four to six weeks.” Antonarakis and Drake “took turns petitioning the drug company” to do a clinical trial in prostate cancer for several years, with no luck. Then Antonarakis and Hopkins colleague Jun Luo, Ph.D., published an important paper in the New England Journal of Medicine showing that men who have a particular variant androgen receptor, called ARV7, don’t respond to enzalutamide and abiraterone. “We said, “If we can’t try this with everybody with prostate cancer, can we at least give it to guys who have the mutation? What if we took ARV7 patients and treated them with both anti-PD-1 and –CTLA 4 (blocks CTLA-4?),” says Drake.  “Emmanuel wrote the trial,” which just finished, and was published in Oncotarget.  “That’s the first clinical trial ever to combine anti PD-1 and anti-CTLA-4 in prostate cancer. It’s very promising.”  It’s also the first study to look at a specific, very bad, form of prostate cancer.  Let’s look at that study:

Combination Immunotherapy Combats AR-V7+ Prostate Cancer:  In this Hopkins-led study of men with very aggressive prostate cancer, this combo of two immunotherapy drugs has made a significant difference – shrinking tumors partially or completely – and two of 15 men have shown exceptional responses.

Once again, no one is suggesting that these drugs would produce the same promising results in all men with aggressive prostate cancer.   But this is an exciting example of precision oncology– finding the right drug (or combination of drugs) to work for the right patient and the right cancer.  The idea is that one drug might just help a few people; but another drug might help a few different people, and if we just keep chipping away at it, eventually we’ll help everybody, one subgroup of patients at a time.

The 15 men in the study had AR-V7-positive prostate cancer; AR-V7 is an aggressive variant of the androgen receptor, first discovered at Hopkins several years ago by Jun Luo and Antonarakis (this can be diagnosed by a blood test, available at Hopkins and through a company called EPIC Sciences).  They were given a combination of ipilimumab and nivolumab.  This specific form of prostate cancer, “can lead to fatal disease in only six to nine months and has inadequate treatment options,” says Antonarakis.

Patients received treatment by IV infusion:  3 mg per kilogram of nivolumab plus 1 mg per kilogram of ipilimumab every three weeks for four doses, followed by a maintenance regimen of 3 mg per kilogram of nivolumab alone every two weeks thereafter. The patients were enrolled between December 2016 and October 2017.

Two of the 15 men (13 percent) experienced a significant drop in PSA – by at least 50 percent.  “More encouragingly,” notes Antonarakis, “one-quarter of patients achieved an objective response, meaning that their tumors shrank partially or completely with combination immunotherapy.  These responses were durable and typically lasted more than nine to twelve months.”  But here’s the most exciting part:  “At least two of these patients remain alive for more than 18 months, which is much longer than expected for patients with AR-V7+ prostate cancer.”  Which means that Antonarakis and Luo don’t even know how long the response will last, because it’s still happening.

Genetic mutations affect response, too:  The men in this study were already different from many patients with advanced prostate cancer because of their AR-V7 variant.   Were there other differences that might help predict which men will respond best to this double checkpoint inhibitor approach?  Yes:  the specific genetic mutations are very important.

“Interestingly, six of 15 patients (40 percent) harbored damaging mutations in at least one DNA-repair gene,” notes Luo.  These mutations were either germline (inherited) or somatic (mutations that just developed spontaneously as the cancer advanced).  “In these six men, we detected gene mutations of BRCA2(3 men), ATM(2 men), and ERCC4(one man).

The job of DNA repair genes is to fix mistakes that occur in the DNA as cells divide – to keep a mistake from being repeated over and over again.  “Remarkably,” notes Antonarakis, “most of the benefit from ipilimumab plus nivolumab appeared to occur in patients who had one of these gene mutations, particularly in two men with BRCA2 mutations.”  If this proves true in larger studies, “it will have profound implications for other diseases such as breast and ovarian cancers, where these genes are more frequently mutated.”  An estimated 20 percent of men with metastatic prostate cancer have mutations in BRCA2or related DNA-repair genes. “This study suggests that these gene mutations may be even more common in men with the AR-V7+ form of prostate cancer, perhaps as high as 40 percent.”

The study also showed that the combination of nivolumab plus ipilimumab was safe and tolerable in men with AR-V7+ advanced prostate cancer.  “We did see some important side effects including colitis, pneumonitis and hepatitis – all caused by an over-activated immune system. These side effects were managed with prompt administration of steroids, which often resulted in reversal of these conditions.”

Encouraged by these preliminary findings, Antonarakis and his team are now expanding the study to include more patients.  This larger study is currently open to enrollment (https://clinicaltrials.gov/ct2/show/NCT02601014?cond=NCT02601014&rank=1), and is actively seeking participants.  If you are interested, please call Mrs. Rana Sullivan at (410) 614-6337.

So where do we go from here? Medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation, quotes Winston Churchill: “Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.” In other words, it’s just getting good. “We are learning so much about the immune system.”

There may be a dozen or more potential checkpoints to block. “We only have drugs for about half, and we have a lot more being investigated.” It may be that for the T cells to eradicate prostate cancer, it will require one or more checkpoint inhibitors, plus one or more vaccines. “When we’ve really got a checkpoint inhibitor that allows these T cells to wake up, PSAs will fall, tumors will melt away. When one of these works, man does it work!”

Immunotherapy-induced changes in how we kill cancer are happening so fast, it’s hard to keep up. In lung cancer, for instance, 30 percent of patients now get a checkpoint inhibitor, nivolumumab, before they get chemotherapy, and about half don’t even need standard chemotherapy.   “We don’t even know what some of the antigens are,” says Simons. “We’ve got to make this work for every patient.”

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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Immunotherapy for Prostate Cancer, Part 1

You’ve got a lot of antibodies floating around in your blood – to every cold or virus you’ve ever had, plus all the antibodies your body has made after you got a shot to prevent the flu, measles, mumps, chicken pox, or tetanus, etc.

If results of a clinical trial are as promising as scientists believe they will be, we may soon be entering an era where every man diagnosed with prostate cancer gets a combined vaccine to help his body fight it off.

The idea is to “harness the tremendous power of the immune system to augment what your body has done your whole life, which is fight off infections,” says medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation. “Prostate cancers grow because the immune system misses them, or mistakes them for something normal instead of a foreign invader.”

It’s all about the flags: The immune system uses a very effective communication system that’s a lot like semaphore – using handheld flags to send messages, spelling out words by changing the position of the flags. Cells that hoist the “friend,” or “self,” flags get to sail freely; the immune system leaves them alone.   But enemy invaders – viruses, infectious bacteria and other harmful pathogens – announce their nefarious intentions by flying the body’s version of the Jolly Roger, the skull and crossbones: the flag that screams, “foreign!” or “enemy!” These flags are called antigens.

Unfortunately, prostate cancer cells often trick the body by waving a false flag. They get safe passage; the threat is unrecognized by the immune system.

The goal of all immunotherapy – vaccines and checkpoint inhibitors – is to teach the immune system to recognize cancer as the enemy: to rip off the false flag and show cancer’s true evil colors. It’s similar to unmasking the creepy reptilian aliens in “V,” if you remember the TV miniseries from the 1980s.

It’s also like a toddler’s shape sorter: What’s happening in immunotherapy research right now is incredibly complicated, intimidatingly dense and confusing to understand, even for doctors. If you were to pick up an immunotherapy journal and skim through it, you might think somebody had gotten the “caps lock” stuck on the typewriter, because just about any article you might read is chock full of words like PD1 and GM-CSF and CTLA4.

Don’t let the jargon throw you. We’re going to try to cut through all the alphabet soup for you because you need to know this stuff: immunotherapy is going to be increasingly important in prostate cancer. One day, it may even be the way we cure advanced prostate cancer.

Basically, what scientists are trying to do here is very simple – something your kids, grandkids, or maybe even you learned to do at a very early age: match the target with the right block.

Yes, immunotherapy has a lot in common with a toddler’s shape sorter; except instead of finding the right place for the star, crescent moon, triangle or oval blocks, scientists are finding drugs that target extremely tiny points of vulnerability in the body’s immune system. They’re finding the chinks in our armor, and filling them very precisely to help us not only withstand the attack of cancer, but launch a counterstrike.  Level one of immunotherapy here is a prostate cancer vaccine.

Provenge: Provenge (also known as sipuleucel-T) is the only immunotherapy that has been approved by the Food and Drug Administration for prostate cancer. It is usually given to men who have early metastasis after they have been on androgen deprivation therapy (ADT). (This is called castrate-resistant prostate cancer, or CRPC.)

“The vaccine is made from a man’s own cells,” says physician-scientist Charles G. Drake, M.D., Ph.D. In addition to being a renowned expert on immunotherapy, Chuck Drake is the director of genitourinary oncology and an associate director for clinical research at the Herbert Irving Comprehensive Cancer Center at New York Presbyterian/Columbia University Medical Center.

The immune cells are collected in a process called leukapheresis – blood goes out through a needle in one arm, some white blood cells, platelets and red blood cells are taken out, and the rest of the blood is pumped back into the other arm. Then, those cells are put in a culture with an engineered protein that links prostatic acid phosphatase (PAP) with what Drake calls a “special sauce” that activates the immune system. PAP is an enzyme that, like PSA, is made by prostate cells. That special sauce – think of Miracle Gro for plants, or maybe baking soda to activate the yeast in bread dough – is designed to kick-start the immune cells: it’s called GM-CSF (granulocyte-macrophage colony-stimulating factor).

In multiple clinical studies, Provenge has been shown to increase average survival by a few months – but don’t just look at those statistics. Provenge might be able to achieve much more than that if given earlier, in men with a “lower tumor volume” (in other words, not a lot of cancer) or less aggressive disease. It also might achieve a kind of synergy or extra momentum if it’s combined with other treatments.

“It’s a good start,” in the sense that the Mercury and Gemini space programs prepared the way for the Apollo rockets, says Simons; before astronauts walked on the moon, pioneers like John Glenn had to escape gravity and orbit the Earth. “You can’t have immunotherapy unless your body can see the foreign flags. Provenge is about using GM-CSF,” which Simons pioneered as a young faculty member at Johns Hopkins, “to activate the dendritic cells to educate the immune system. The vaccine is actually against a flag that prostate cancer cells fly: PAP.” Other vaccines in the works recognize other flags such as PSA and PSMA (a molecule on the surface of prostate cells).

In men with metastatic cancer, Provenge is able to slow down cancer, but not stop it. “This is a big clue that we could do more in at least 30 to 40 percent of patients if we had something better than the Mercury program,” says Simons. “It’s great to extend life, but what we want to do is eradicate the cancer.” That said, Provenge is “exceptionally safe,” with “the fewest side effects of anything we give to prostate cancer patients. There’s no nausea, no vomiting; you may feel like you’ve got the flu, but most of the time men don’t even feel that.”

Give it sooner? If Provenge works better when a man is healthier in general, then why not give it before there’s any evidence of metastasis? Maybe after surgery or radiation in a man who is otherwise healthy, except that his PSA is going up? “We agree with that idea so much, we started a trial” involving about 60 patients, says Chuck Drake. “Men with a rapidly rising PSA after surgery or radiation were randomized to get either a year of ADT with vaccine starting about month after the ADT began; or the vaccine first, followed by a year of ADT. Men got a better immune response when they got the vaccine first, and then the ADT.”  This was just a small study, Drake notes, and a larger randomized trial is needed. “But our trial helped us figure out the right order – the vaccine first, and then the ADT – and that you could do it safely. A few of the men who got both the vaccine and ADT recovered their testosterone, but never got their PSA back. They have done very well.”

Like so many scientists and physicians working to help men with prostate cancer, Drake hates the side effects that go along with ADT and hopes one day that we’ll find an effective way to treat advanced cancer without taking away the male hormones. For now, he would be happy to put men on ADT for the briefest amount of time necessary, along with immunotherapy, to get their cancer into remission, perhaps continuing with “maintenance immunotherapy, potentially forever.”

However, because the main goal is to cure the cancer and save the man’s life, Drake is also looking at a different group – men who have doubled down on hormonal therapy, who are still on ADT but who have added an androgen receptor-targeting drug such as enzalutamide or apalutamide.

Other vaccines that target other flags: Other vaccines are in the works. One is based on a modified version of listeria (a bad kind of bacteria that, in its unaltered state, can give you food poisoning). Another, called PROSTVAC-VF (also called PSA-TRICOM), developed with PCF funding, uses a modified smallpox virus as its means of entry into the body and targets any cell that makes PSA. “There’s no good cell in your body making PSA once you have prostate cancer,” says Simons. “If we could get your T cells to recognize and destroy everything that makes PSA, you’d be cancer free.”

PROSTVAC is being tested along with GM-CSF in a worldwide clinical trial called the Prospect Trial, involving 1,200 men with metastatic CRPC from about 200 centers. It’s designed to test whether early treatment with this vaccine improves survival. Investigators are waiting for the results, and if it performs as well as they expect, then men could start getting this vaccine in addition to Provenge. “These vaccines are so safe,” explains Simons, “that you could get more than one. When you get the hepatitis vaccine, you’re really getting four vaccines in one. You can get multiple antigens, or flags. The whooping cough vaccine has seven flags in it, and it works a lot better than if you just got one. We will be combining these prostate cancer vaccines down the road if each one shows a benefit. The great promise of all these vaccines is, if you can figure out all of the antigens you need, you might be able to vaccinate right after surgery or radiation,” and one day, men might not need ADT, or they could delay it for many years.

If the PROSTVAC trial is successful, Simons believes, “every man with prostate cancer should get vaccinated, and should get GM-CSF. Antigen-specific immunotherapy is already curing the most fatal form of lymphomas, because scientists perfected the way to make a T cell kill off that antigen. Now lymphoma is a disease where they just give a little chemo to beat down the numbers of cancer cells, and then they activate the T cells and they destroy the cancer.”

Still another vaccine, called GVAX, is being tested by Drake and Antonarakis in men with high-risk prostate cancer undergoing surgery. Here, men are getting either a short course of ADT alone, or GVAX vaccination followed by a short course of ADT. The benefit here is that a pathologist can examine the surgically removed prostate to see whether the immune system has been activated – whether there’s evidence that the immune cells have begun to attack the cancer.

Combining vaccines and checkpoint inhibitors: In another clinical trial, Doug McNeel, M.D., Ph.D., at the University of Wisconsin, is testing a combination of a vaccine called MVI-816 that, like Provenge, targets PAP, plus a checkpoint inhibitor (see below). This particular checkpoint inhibitor, called pembrolizumab, blocks PD-1, and in early data, the combination looks encouraging: PSA levels have dropped and some men’s tumors have shrunk. The idea here is to educate the T cells – to fly the Jolly Roger on the cancer cells – and then unleash the T cells to attack them. “Immune checkpoints are natural compounds that cells make to protect themselves, and they’re the reason why we aren’t just rejected by our mothers when we’re conceived,” says Drake, “because babies in the womb are half ‘foreign’ with the father’s DNA. Once a killer T cell starts attacking something that it thinks is foreign, it won’t stop unless brakes are put on it. Checkpoint inhibitors basically take the brakes off T cells; that’s their job. Checkpoint inhibitors release the hounds.”

Can the immune system go from oblivious pacifism to DEFCON 1, with alarms sounding and the military being deployed? And if the military – the immune system’s enemy-killing T cells, or antibodies made by B cells – gets involved, is it enough to stop the cancer?

The key is to alter the balance, says Drake. “For a lot of tumors, there’s an ongoing battle with the immune system. The immune system smacks the tumor down, the tumor gets around it.”

The ultimate goal of immunotherapy is to tip the balance toward the immune system. To unleash the hounds.

 

Who’s Who in the Immune System: A Primer for You!

Making sense of some very complicated stuff only a few scientists truly understand: A guide to the immune system for the rest of us

                

Let’s think of the immune system as a Broadway musical. The star of the show is the T cell (actually, there are a bunch of different types of T cells, but let’s just focus on the Killer T cell, not to be confused with the “natural killer” cell; see below).

Killer T cells: These cells live up to their name: they’re precision assassins. When they are on their “A game,” they are merciless, and nothing, not even cancer, stands a chance. Killer T cells have a large and growing fan club:  “They’re my personal favorite cell in the world,” says Drake. “They’re incredible. They can go anywhere, and kill any other cell if it has the right target,” or flag.  “T cells are amazing,” agrees Simons. “They can move out of the bloodstream and go in the bone marrow, the lungs, the liver, and start attacking cancer wherever it is. They have little sensors on their surface that can recognize viruses you haven’t even been affected with yet – just because they’re foreign.”

However:   Cancer knows how to snake-charm these cells, to put them into a trance, or a straitjacket, or to put the “boot” on their tires so they can’t go anywhere – pick your metaphor, but the bottom line is that cancer temporarily takes the T cells out of commission. Cancer cells secrete a substance that puts T cells to sleep – but don’t kill them – on a large scale. If you’re a James Bond fan, think of that scene in “Goldfinger,” when planes fly over Fort Knox and cropdust entire platoons – soldiers with loaded guns at the ready – with gas that makes them drop instantly. Or that moment in “Sleeping Beauty” when the entire kingdom plunges into a 100-year slumber, waiting for the handsome prince to come save the day. One of prostate cancer’s first official functions is to deactivate the T cells with molecules that act as brakes, or checkpoints.

Checkpoint inhibitors are like the handsome prince: they allow the kingdom of T cells to wake up. There are several checkpoints, or sleeping potions. One is PD-1. Another is CTLA-4. In their proper role, checkpoints are good. “Nature doesn’t want a T cell to kill off your kidney or gastrointestinal tract,” says Simons. In an autoimmune disease, for instance, T cells are misdirected; they mistake good and decent cells for the enemy, and destroy tissue. When someone gets an organ transplant, unless the immune system is suppressed, the body will reject the foreign organ. “The reason transplants are rejected is that T cells realize that these cells are foreign, and within days or even hours destroy every last one.” Thus, the body’s checkpoints. “Nature is very sophisticated about keeping T cells from going crazy. T cells that make a mistake can be fatal.”

But cancers that successfully keep T cells from doing their job can be fatal, too, and cancer cells co-opt checkpoints so successfully that there can be a T cell sitting right next to a cancer cell and the T cell does nothing, because the cancer is sending a signal saying, “I’m normal, don’t kill me.”

Checkpoints such as PD-1 are tiny molecules sitting on individual T cells. And incredibly, there are several drugs that can deactivate them. Pembrolizumab and Nivolumab target PD-1. A drug called ipilimumab targets CTLA-4. For each checkpoint – and it’s still not clear exactly how many there are – potentially, there is some way to block it, and the Prostate Cancer Foundation is actively funding this research.

From what we know right now, it seems that a minority of men with prostate cancer respond to PD-1 blocking drugs. Only a few men with prostate cancer respond to ipilimumab. Scientists aren’t sure why. But maybe the men with prostate cancer who don’t respond to those drugs will respond to different checkpoint inhibitors.

Now, back to that Broadway musical: There don’t seem to be any bit players in the immune system. Yes, T cells are the stars, but there are plenty of potential stars waiting in the wings. These include:

Natural Killers. These sound like something Quintin Tarentino would write about, but really, they’re foot soldiers, under the command of the T cells. “T cells don’t fight alone; they bring reinforcements,” says Simons. “Natural killer cells poke a big hole in a cancer cell or a virus, but they need direction. They need to be told where the fight is. But they’re really good at killing.” Checkpoint inhibitors aimed at helping unleash natural killer cells are being developed.

Macrophages. When cancer cells die, there’s carnage. Macrophages are early responders to the crime scene, and they chew up the debris. GM-CSF activates macrophages. Physician-scientist Pam Sharma, M.D., Ph.D., of MD Anderson Cancer Center, suspects that some types of prostate cancer may be more susceptible to immunotherapy drugs that activate the macrophages, rather than, or in addition to, the T cells. But macrophages aren’t just scavengers. “They do something very important: they put cancer cell flags on the surface of cancer cells,” explains Simons, “so they’re like educator garbage men.” T cells eventually reproduce, and then die. Their offspring cells need macrophages to show them the ropes – so they can find the flag and kill whatever is flying it.

Some cancers have more macrophages than T cells. Some of these macrophages are counter-productive: not only do they not help, they may also secrete substances that make the tumors grow more quickly.

Mast cells. These are immune cells involved in the allergic response. What do they have to do with prostate cancer? Apparently something, because scientist Karen Sfanos, Ph.D., at Johns Hopkins, and colleagues just discovered that men who have more mast cells are less likely to have a recurrence of prostate cancer after radical prostatectomy.

Dendritic cells: These are the cells that stand in the wings and give the T cells stage directions, pointing out which flags are for “self” and which are for “foreign.” They encourage the T cells that target foreign invaders to get out there and do their thing – multiply, attack, kill!

B cells. If T cells are the stars, B cells are the co-stars. They make Y-shaped antibodies, which grab onto the flags on a cancer cell. Antibodies attract the macrophages to come and clear away the debris. B cells are like a Neighborhood Watch on steroids. Think of the nosy neighbor on “Bewitched,” Mrs. Gladys Kravitz, watching for suspicious activity through her binoculars, spying in the bushes, or peeping through the window. Now imagine Mrs. Kravitz on steroids – as a drone, maybe – flying around the body looking for anything that’s not supposed to be there. They don’t do the actual killing of the enemy cells, but they aim the laser at it so the T cells can see it.

“B cells are the least studied immune cells in cancer, but they’re incredibly promising,” notes Simons. “Prostate cancer generally shuts them down with checkpoints, too. But we think we have identified a checkpoint inhibitor for them, as well. It would be a very good thing to have prostate cancer cells making antibodies.” As a matter of fact, Drake’s team published a paper showing that if men taking Provenge make more and better antibodies, they seem to live longer.

Vista. “Vista may be a major switch” that really puts T cells to sleep, Simons explains. If checkpoints like PD-1 put a T cell into a trance, Vista might put it into a deep sleep – think of Juliet faking her own death in Shakespeare’s play, sleeping so deeply that her heart barely pumped and her lungs barely breathed. When cancers make Vista, T cells are exceptionally sleepy. A drug that blocks Vista might make those cells be exceptionally wide awake. An anti-Vista drug “just went into clinical trials for prostate cancer.” It might take a cocktail of antidotes – anti-PD-1, anti CTLA4, anti-Vista – to allow T cells to achieve maximum killing potential against prostate cancer.

Helper T cells. We weren’t going to talk about other T cells, but these cells help the B cells that make antibodies to do their jobs.

IDO: Indolamine amase (IDO) is the reason your mother’s body didn’t reject you in the womb. It’s a gene made in the placenta. Cancer cells stole the recipe; they make it, too, to keep your body from rejecting them.

 

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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Living in Prostate Limbo

Ask Rob Gray* to talk about how prostate cancer came into his life, and he has the best possible response: “I prefer to talk about how it came out of my life.”

For nearly a decade, among other tests and procedures, Rob underwent 17 PSA tests, five PCA3 tests, and nine MRIs. He endured five prostate biopsies, some of them saturation biopsies, that made him feel like a human pincushion.   He remained steadfast in prostate limbo – when doctors couldn’t find cancer, but they couldn’t rule it out, either, because of some abnormalities in his MRIs and biopsies. Because he kept looking for answers when it would have been so easy to assume everything’s okay and leave it alone for a few years, Rob is cancer-free today.

He is only 49 years old – the age when many men just start to think about prostate cancer.

Rob’s ordeal started back when he was in his thirties. When he asked for a PSA test, his family doctor thought he was worrying too much: “We don’t traditionally order that test until you’re 50,” he told Rob. Note: The National Comprehensive Cancer Network recommends that men start getting screened for prostate cancer in their forties, and at age 40 if they have a family history of the disease. But Rob didn’t have a strong family history of prostate cancer, just a slight one. His grandfather developed it in his eighties, and wasn’t even treated for it because he had other significant health problems.

All Rob had at first was a minor urinary problem and the need to know why it was happening, which led him to read about possible causes, which led him to the prostate, which led him to the PSA test.

He also had a heck of a lot of persistence and maybe was even a bit of a pain in the medical butt because he wouldn’t just let it go. Thank goodness he didn’t. He is cancer-free because of his tenacity.

Over a remarkable nine-year gauntlet, Rob basically did hyper-vigilant active surveillance before the disease was ever diagnosed. He and his doctors followed his prostate, as best they could, in real time. He had so many biopsies that scar tissue developed in his prostate, which made it more difficult to interpret the abnormal MRI results, and if it weren’t for technology that recently became available, an MRI-guided fusion biopsy, his cancer still might not have been found.

When it was finally diagnosed, and when his prostate was removed – with more difficulty than it should have been for a man his age because of all that scar tissue – his Gleason grade turned out to be a 7 (3+4), higher than the Gleason 3 + 3 score found on his biopsy.

And here’s the really amazing part: During this time, Rob developed a strong family history of prostate cancer which did not exist before he began his active surveillance, the kind that should make most doctors take notice and say, “You need to be screened early for prostate cancer.” His father developed it at age 70, and a few years later, so did his maternal cousin, at age 56. In just a few years, he went from having hardly any family history to having three men (and maybe four, if Rob himself developed it) in the family with prostate cancer. It is very important to tell your doctor when your family history changes for exactly this reason: it should upgrade your risk, and you should be followed more closely.

Prostate Purgatory

It all started in 2005 with a drip; actually, a few drips after urination from time to time. “It wasn’t substantial,” he says, “but it was enough to raise an eyebrow for any guy,” particularly an active, otherwise healthy, 38-year-old man. “It started to weigh on me so much, so that I would need to be conscious about what I would wear.” Rob started reading up on his symptoms, trying to figure out what could be the cause.

In 2008, at his yearly physical, Rob asked his family doctor for a PSA test. “It came back at 1.6,” higher than it should have been.   The doctor said, “’I thought you would have been below 1.0. This may be something we want to explore,’” and referred Rob to a local urologist. His urologist in Connecticut performed several diagnostic tests for urinary problems, including a Uroflow test, a renal ultrasound, and a cystourethroscopy, in which a lighted tube is threated through the penis to examine the urethra. This was his least favorite, says Rob, of all the tests he’s had. “It was like Alien Autopsy,” he laughs. “I’d never experienced anything in my life like that, and it was just the beginning of the barbaric things I had to experience!”

And so it began. Five months later, in March 2009, the next PSA test came back with 1.9 and a rectal exam detected some swelling of the prostate, which the urologist suspected was prostatitis.   Rob had his first biopsy that same month, and three of the 12 samples showed high-grade PIN (prostatic intraepithelial neoplasm); this pathological finding is not cancer, but it’s not normal, either. In fact, where high-grade PIN is found, cancer is often lurking nearby – except the needle didn’t find it.

The next two PSAs were 1.9 and 1.8, taking us to 2010, and at this point, Rob decided to go to an academic medical center with expertise in treating prostate cancer. “I’ve been known to research things ad nauseam and then research them again to validate my original findings,” he says. “I thought, ‘if there’s any possibility that something’s developing, I have got to find who’s the best in this field.’” He sought a second opinion on his biopsy slides at Columbia University in New York; the results were confirmed.

The next few years saw more PSA tests, with the results ranging from a high of 2.3 down to 1.36. Ash Tewari, M.D., now Director of Urology at Mount Sinai, ordered Rob’s first PCA3 test. PCA3, like PSA, is a blood test and it is not a replacement for PSA, but an adjunct to it. The PCA3 test is more cancer-specific; the lower the score, the lower the odds of a positive biopsy. In Rob’s case, however, the PCA3 was not the crystal ball he’d hoped for; the first result was a false score of 58.8; the second was 18.3, the third was 18.7, and the fourth was 12.4. Another PSA test showed a free PSA ratio of 27 percent – again, not terribly helpful in Rob’s case. Generally, in men with a PSA lower than 4, a free PSA greater than 25 percent is more likely related to benign enlargement of the prostate, or BPH.

Rob had his first of nine MRIs – three of them endorectal – in 2010 before moving to the 3T MRI. It was not until he had a fusion biopsy conducted by urologist Ardeshir Rastinehad, M.D., at Mount Sinai – in which the needle biopsy is guided by MRI and ultrasound combined – done in June 2017, that cancer was finally detected – just a little, low-grade, Gleason 6. Rob had his prostate removed by urologist Ketan Badani, M.D., director of robotic surgery at Mount Sinai. His surgical margins were negative – no cancer was left behind. His nerve bundles were preserved. When the pathologist examined the prostate specimen after surgery, Rob’s cancer turned out to be of a slightly higher grade, Gleason 7 (3 + 4) – a finding that “validated my decision to have the surgery,” Rob notes.

“Literally, the first thing out of my mouth when I woke up in recovery from surgery was, ‘Was it contained?’ I was still groggy, and I must have asked my wife that question a dozen times. She was at my bedside when I awoke, and she said that it was – with a smile that said more than you could imagine for me and my family. I knew it had taken longer than it should have, based on when I went into surgery and the time estimated to wake up in recovery, which contributed to my concern. But this delay turned out to be because of the extra time it took to work around and cut away the buildup of scar tissue from all the biopsies. “There was so much scar tissue that it also contributed to the abnormal MRI results, which led to the increased number of biopsies. If I hadn’t had the fusion biopsy, it might not have been found. I would be living with it in me undetected and with a false sense of security – the thought of which is truly unsettling for me.”

We just fast-forwarded through years of worry, of waiting, of inconclusive tests – none of which Rob probably would have gotten if his pesky PSA had been where it should have been. As the volatility in his PSA persisted, so did Rob’s mission to stay ahead of anything that might have been developing.

In the meantime, because Rob and his wife didn’t have children during the early days of his ordeal, he banked his sperm just in case he ended up with prostate cancer. “Here I was, still young, and I didn’t know what tomorrow was going to bring. I had this sense of urgency to be prepared for the worst.” He even duplicated PSA tests with different doctors just to double-check; or as Rob puts it, “stress-test the results against one another.” A recent family photo, taken outside, shows Rob, his lovely wife and three beautiful young children, all looking healthy and happy.

Why was he so worried? Because of his dad and his cousin. Both developed prostate cancer. In tests in 2011, his dad’s PSA showed up as 10.3 and 7.56 – both numbers much higher than they should have been for a 70-year-old man. By this point, Rob knew the drill, and he plugged his father into the best system he could, with the same doctors he had come to know so well. An MRI and two biopsies later, Rob’s dad was diagnosed with Gleason 6 prostate cancer. He had a prostatectomy in 2013. In 2016, Rob’s cousin had a PSA of 8.9, was diagnosed with Gleason 9 disease, and once again, Rob’s experience helped him show his cousin the path forward; he, too, had a prostatectomy.

There are several take-home messages here:

  • It’s up to you. Many doctors don’t order PSA screening during a routine physical, especially in men who don’t have a family history of the disease or in men younger than 50. If you’re age 40 or over, you should get a baseline PSA test, and then get it checked regularly afterwards. It’s easy: if you’re getting your blood checked anyway for cholesterol, lipids, etc., adding PSA to the list of things to be looked at is just a matter of your doctor checking a box on the lab form.

  • Do what you need to do. Rob really needed to know what was going on. At one point, his family suggested that he “was becoming a bit of a PSA junkie,” Rob recalls, and he asked himself: “Am I actually losing my mind? Am I looking for a problem?” But when his father and cousin were diagnosed with prostate cancer, “suddenly everyone in the family realized this was genetic” and appreciated Rob’s efforts.

  • Find doctors you have confidence in, and go to the best place you can. Many studies have shown that if you get treated for a disease – any disease – at a large-volume hospital where they treat a lot of people with this same problem, you will do better. Your cancer will be less likely to return, and you are less likely to have complications from treatment because they are really good at treating it there.

  • PSA fluctuates. There are many reasons why; if you have an infection in your prostate, engage in some form of intense physical activity, or have intercourse one to three days before your blood is drawn it could result in a higher PSA than normal. BPH and prostatitis can also drive up the PSA level.

  • Be prepared, or as Rob says, “Stay in front of the 8 ball.” Rob not only banked sperm ahead of time just in case he had his prostate removed; he researched various forms of treatment and – very important – got himself in the best possible shape for surgery. During the almost two months between his conclusive biopsy and prostatectomy, “I worked out every day as if I was training for a marathon,” he said. “I never missed a day at the gym. So when it was game time, aka the surgery, I was going to be in the best possible shape I could be and ultimately recover faster. In fact, just two hours after I was in my hospital bed post-surgery, I was up and walking laps around the unit in the hospital while some men were literally unable to get out of bed for a day or two because of their physical condition going into surgery.”

  • Take care of your family. “I have a brother, and three young sons, ages six, four, and two. God willing, nothing will happen to them,” but Rob will be on guard, making sure they get regular PSA screenings. He also made his sister aware that her risk of breast cancer may be higher, too, “once I started reading about the correlation between breast and prostate cancer I recommended that both she and my brother take the germline test. ”

  • Help your friends. Rob didn’t tell many friends before surgery that he had been diagnosed with prostate cancer. “I didn’t want it to become a ‘Woe is me’ situation and I certainly didn’t want to expend any energy fielding dozens of phone calls asking how I was doing, even though I know it was because they genuinely cared. I just needed to focus on preparing for the surgery and the recovery process.” He also told his wife, “I want to be the guy you can confidently point to regardless of where we are after you overhear somebody saying, ‘I’m scared, my husband is scared; he’s just been diagnosed with prostate cancer.’ It’s at that very moment you can say, ‘See that guy over there? Go talk to him. He had his prostate out X months ago and you would never know it.’ That’s the value I can take away from this recent journey: an experience I can share with others who find themselves in a similar situation.

“I was fortunate enough to dodge a bullet, and I want to – I feel obligated to – pay it forward. Any chance I can get to alleviate the fear that is most often fueled by uncertainty is something I want to offer. The anxiety that people are living with because they simply don’t know what to expect, where to start, or better yet, the incredible resources that are available to them as long as you know where to look;; the playbook, if you will. I did the Kegel exercises religiously as prescribed before and after surgery, which led to my getting off the pads after just two months, Sexual function is also fine, which was a welcome surprise.”

  • Reach out. Rob, who couldn’t let it go during the search for prostate cancer, isn’t about to let go now; in fact, he hopes that other men will be helped by his story. “This disease affects one in eight men over a lifetime – and more specifically, my grandfather, my father, my cousin, and me.   When I talk to friends who don’t know what a PSA test is, it proves there needs to be an even louder rally call and greater effort to educate and increase awareness around prostate cancer – so that like me, others can stay ahead of it, make the right decisions, and live long, healthy lives after detection and surgery.”

*Name has been changed, at Rob’s request, to protect his privacy.  The names of the doctors in this story have not been changed.

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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