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ED After Prostate Cancer Treatment: Old School Approach Not Good Enough

Just when everything should be getting better – you’ve been diagnosed with prostate cancer, gotten curative treatment with surgery or radiation, and now you’re looking forward to getting your life back – there’s another bump in the road: ED (erectile dysfunction). You don’t need that!

Darn it, here’s yet another “reluctant brotherhood” – a club, like that of prostate cancer, that you never wanted to join. Take heart: You’re not alone, and it’s going to get better.  But your road to success may not be a little blue pill.

Maybe you’re like a lot of men who, before treatment, envisioned themselves boldly striding forward toward recovery of potency – perhaps temporarily using Viagra, Cialis, or another pill in the class of PDE5 inhibitors as a crutch until erections returned on their own.

Unfortunately, for some men, these might as well be sugar pills. They just don’t work as promised. And instead of striding forward boldly, they find themselves making uncertain progress like the Wayfarer, a character painted by Renaissance artist Hieronymous Bosch: a poor guy just trying to get somewhere down a troubled path.

For too many men, the road back to potency is a lot more difficult, confusing, and frustrating than it has to be. This makes me mad, because I have talked to men and their families who just don’t need another health burden to deal with. It makes Johns Hopkins urologist Arthur Burnett, M.D., mad, too, and he is doing something about it.  

Burnett is a surgeon-scientist, a neuro-urologist and pioneer in the understanding of erectile dysfunction (ED). His research on the biochemical mechanisms of nitric oxide in erectile tissue contributed to the development of Viagra and other PDE5-inhibiting drugs.

Burnett is also a world-recognized authority on treating the problems in sexual function that can occur after surgery or radiation for prostate cancer – and there are several. “ED is one thing,” he says, but it’s not the only potential roadblock to sexual recovery. “Some men also develop scarring in the penis, a condition known as Peyronie’s syndrome. Some men have climacturia, where they may release a little urine during sexual stimulation or climax, so that’s problematic. There’s a whole host of things that can go wrong,” and all of these problems can be treated.

By far the most common problem after prostate cancer treatment is ED, difficulty achieving or maintaining a penile erection. The American Urological Association has just revised its guidelines on treating this. Burnett, who co-chaired the committee to change these recommendations, says they were brought about by an evolution in thinking. “Treatment should be based on shared decision-making,” he states. “Patients should have the opportunity to have a full discussion on ED with their doctor – the variety of options to treat it, the likelihood of success – and options should exclude those that may have contraindications,” that aren’t recommended in their particular case, or that probably won’t help them.

Makes sense, right? And yet, Burnett has seen thousands of patients from all over the world who have not had such a discussion with their doctor, or whose doctor has continued treatment that not only isn’t working, but never was going to work.  

The old model – the one that emerged close to two decades ago with availability of PDE5 inhibitors – had well-defined steps to follow.   “We initiated therapy along the lines of first line, second line, and third line,” explains Burnett.   The first-line treatment was the pills, “the least invasive form of therapy.”

Erection is a vascular event; it involves blood flowing into the penis, being held inside there, and then flowing back out. The nerves that are responsible for erection lie in fragile neurovascular bundles on either side of the prostate, a discovery made by my co-author on the books, Johns Hopkins surgeon Patrick Walsh, M.D., who found that if men had one or both bundles preserved during prostatectomy, it was still possible for them to recover erectile function. However, he reported that patients who were older or who had one bundle were not always successful in recovering erections, and even men who had both bundles preserved, if they had vascular problems or other health issues, were more likely to have trouble.

Burnett has spent years studying these nerves, and he has found that the surgery itself – the traction on the nerves, and the stress of having an invasive procedure – can damage them. Often they recover, but sometimes they don’t. So even if, theoretically, a man should be able to produce an erection, it’s not guaranteed.

Many men – even though their nerves have been spared – “are not likely to respond to PDE5 inhibitors,” Burnett notes. These patients, particularly men with significant vascular disease, “need to be counseled in realistic terms on their likelihood of responding to these pills, balanced with their preferences, to try to get to the most effective therapy sooner rather than later,” says Burnett.   “Vacuum pumps and injections have traditionally been second-line treatments, but perhaps that should just be put on the table up front. Even penile prosthesis surgery should be put on the table early on for patients with more severe forms of ED. If men are already struggling with erections before surgery, after radical prostatectomy, they’re going to have even more trouble, and more frustration.” In other words, if you were relying on Viagra before treatment, the pill probably isn’t going to have the same effect that it used to.

“I see patients in my clinic who might best have been fast-tracked to a penile prosthesis early.” Burnett even sees men who had “non nerve-sparing” surgery – that is, both neurovascular bundles were removed (which is the right thing to do if cancer has reached these nerves) – who have been “done a disservice,” by being offered medicine that is simply not going to work for them. “Oral therapy depends on a necessary degree of intact nerve function,” Burnett explains. In other words, the pills augment what the nerves are already trying to do. “Their doctor says, ‘Let’s just try PDE5 inhibitors,’ but there are no nerves for penile erection. They start the first-line therapy. Then it’s, ‘Let’s wait another six months; keep trying.’” And that is not acceptable, in Burnett’s opinion. “We have to understand how these different therapies work, think about the clinical presentation of the patient, the variables that may impact his erectile physiology.”

Just having “all guys get first-line treatment, no matter what, and seeing how they do, then ‘maybe we’ll consider vacuum pumps and see how that goes for several months, and if it doesn’t work, we’ll consider injections’ – that’s not good enough. “It’s a much more practical model we’re evolving, one that’s focused on the patient’s desires and what is most likely to be effective.”

Make no mistake, Burnett adds, “if the patient has undergone a good-quality nerve-sparing radical prostatectomy, we should give his nerves the opportunity to recover function,” and not just jump to the third-line treatment, the penile prosthesis, right away. Nerves can continue to recover and erections can continue to improve even as long as four years after surgery. But that doesn’t mean a man should just stoically wait to resume his sex life until the day he achieves a decent erection, either. Maybe try a PDE5 inhibitor and a vacuum erection device, for instance.

Why do so many doctors insist on starting with the pills? Maybe they don’t take the time to find out how well the man’s erections were before surgery; maybe they don’t take heart disease or other health problems (again, some illnesses can hinder blood flow to the penis) into consideration – or maybe, as Burnett suspects, “they think, ‘the pills don’t have much of a negative impact,’ even though the patient will be frustrated for months.” Or maybe “they think, ‘More invasive therapies carry risks. Let’s see how he does,’ and they don’t consider that his sexual dysfunction can have a real impact on his health and wellbeing.” Too many doctors, he adds, “just pat ‘em on the back and say, ‘Things will be fine; you’ll be all right.’”

            But months and months of an unrestored sex life can be demoralizing, Burnett continues. “That’s why I think it’s more humane and appropriate to proceed with effective management of patients – not just treating ED by recipe. If somebody really is not predisposed to do well with PDE5 inhibitors, why push that on him?”

Similarly, injections work very well for some men, but not for others; men who have a large belly or who have poor hand-eye coordination, for instance, have difficulty. Other men simply “don’t feel that doing a needle injection is something that appeals to them. Why would we tell a man that’s all he’s got, instead of referring him to a penile prosthetic surgeon?”

Vacuum erection devices also have their pros and cons. “On the pro side, it’s noninvasive, and it’s fully under the control of the patient,” says Burnett. “But on the downside, it’s cumbersome and mechanical, it involves trying to draw blood into the penis, there’s a constriction band, it feels cold, and it can feel unnatural. Just put it on the table, and try to figure out what will work for one patient at a time – not some rote approach.”

Most men who get a penile prosthesis are happy with the result, says Burnett. “The erection feels natural, and they wonder why they didn’t get it sooner.” Why don’t more men with severe ED choose this option? “Part of it depends on how we in the medical community have presented it to patients.” Many of Burnett’s patients come to him after years of feeling frustrated with the first- and second-line treatments. “All too often, I hear patients say, ‘My internist said never get a penile implant; they get infected, and mechanically they don’t work.’ That’s unfortunate that this is what they’re being told.” In the 1970s and 1980s, penile prosthetics were not as reliable and were more prone to malfunction, but they have vastly improved since then.  

“Just like every other option, the prosthesis has its pros and cons. There is a 1 percent infection risk with prosthetic devices.” Burnett notes that doctors who are “infrequent implanters” tend to have higher infection rates, while “for expert surgeons, high-volume implanters, the infection rate is very low.” Burnett implants 80 or more penile prostheses a year, and “if I see an infection even once a year, it’s very rare.”

Patrick Walsh has told his patients for years, “if there’s a will, there’s a way,” and if they want to have a sex life after surgery, they can. Burnett, Walsh’s longtime colleague, adds to that message of hope from the doctor’s standpoint: “Never give up on a man who wants to preserve and restore his opportunity to be intimate with his partner.   We should try to explore options to help him achieve that.”

There’s one other important message here: Watch out for shysters. “Don’t waste your time or money with over-the-counter treatments or supplements,” says Burnett. They don’t work. Also, be very suspicious of high-cost experimental treatments. “The Sexual Medicine Society has taken a stand about some of this, and in our new ED guidelines for the AUA, we make it very clear that some things are investigational and require further evidence to show that they work.” These include shock wave therapy, stem cells, and platelet-enriched plasma injected into the penis. “Guys are being told, we’ll give you a couple of shots, and you’ll be fine. They pay out of pocket – $10,000 for as yet unproven therapy. It’s reprehensible, people out there trying to exploit these men. It is really terrible.”

It’s particularly terrible when there are medically proven approaches that Medicare and insurance will pay for that can actually restore a man’s sex life.

 

How Common Is ED After Surgery or Radiation?

 

Answering this question is more difficult than you might think, for two reasons: First, every surgeon and radiation oncologist has different results, based on expertise and the number of times the doctor has performed the procedure. So that’s one variable. The other variable is huge – and that’s your personal health. Start with the SHIM score, which is based on a few simple questions. You must be honest here. No one else will see these answers but you and your doctor.

After surgery: “In general,” explains Burnett, “erections are temporarily lost in many men who have a radical prostatectomy. Even with nerve-sparing, the nerves can be traumatized.   It takes a while for these nerves to recover. Although men may have some sporadic erections, it is very common for men not to be able to have consistent erections during the first nine to 12 months after surgery, without help.”

In men who are able to be sexually active without the help of a PDE5 inhibitor before nerve-sparing surgery, the potency rate after surgery gets better over time. “The potency rate at six months is different than at 12 months, and it’s even better at 24 months,” says Burnett. “Most men who had nerve-sparing surgery are going to recover erections in the second year.” Over the long term, he continues, “probably 80 to 90 percent of men who have pre-operative erections have the potential to recover erections without PDE5 inhibitors – if they have no other co-morbidities.”

This is the key. Co-morbidities are other health problems that could affect blood flow – particularly, blood flow to the penis. Major risk factors for not recovering erections, even if you have nerve-sparing surgery, include being a cigarette smoker (cigarettes are vasoconstrictors; they cause your blood vessels to contract); having diabetes, and having cardiovascular disease. There are other conditions and medicines that can affect erections, as well; this is why you need to have an honest discussion with your doctor about your current health and sexual function before treatment.

What about after radiation treatment? It’s kind of the opposite situation. “Unlike surgery, where you have a major loss and then you recover, with radiation you’re pretty much fine and then many men tend to lose erectile function over time,” says Burnett. For these men, PDE5 inhibitors may help. “As many as 50 percent of men who undergo radiation experience a general decline after two or three years – but for the first two to three years, men do not experience any true erection impairment.” Unless, of course, they were already having problems before treatment. The honest SHIM score is important here, too, and so is the discussion of any risk factors that you may already have with your doctor.

Note: None of this means that sex is impossible after you have surgery or radiation treatment for prostate cancer. If you want it, you can absolutely have it, Burnett says – but you may need more than PDE5 inhibitors, especially if you are already experiencing some ED before treatment.

False expectations are cruel. “Patients need to recognize if they aren’t the optimal guy to fully recover potency after surgery without any help,” says Burnett.   “Today, I had a 56-year-old professional athlete in my office, who had a perfect SHIM score and stage T1c cancer.” This man is highly likely to have full recovery of erections after surgery, because his cancer is minimal, and his cardiovascular system is in great shape.

But another man with that same stage of cancer who is diabetic and a smoker might not have such an easy recovery of potency.   That man can still have a full and wonderful sex life, Burnett says, but it might require a penile prosthesis. Knowing this before treatment could spare that man months of frustration.

 

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, Gut Bacteria, and Your Poop

What does your poop reveal about your gut bacteria (called the gut “microbiome”), and what does this have to do with your immune system’s ability to fight off cancer? Just how important is this gut flora, or bacteria, anyway?

Let’s look at the last question first. How important is your gut bacteria? It’s very important to your whole body: your brain, your heart, your immune system – and, although no one has proven it yet, we suspect that it is also very important to your prostate. Being able to empower the gut bacteria – to increase certain “good” bacteria that, in turn, will help the immune system do a better job of fighting off disease – may soon help people with some types of cancer respond better to immunotherapy.

Recently, scientists studying colon cancer found that certain bacteria are found in half of all colon tumors and when the cancer spreads, the bacteria spread right along with them. In another study, scientists found that two different forms of bacteria work together, like fertilizer, to help colon cancers grow. In still other work, scientists studying melanoma found that the presence of certain gut bacteria can change how cancer patients respond to immunotherapy.

I have written about understanding and tapping the power of the gut bacteria here, and here, as it relates to irritable bowel and depression. But cancer! This article mainly applies to prostate cancer, but the implications are rich for many types of cancer.

Could treating the bacteria help prevent cancer, make it less likely to spread, or make immunotherapy more effective against it? I recently interviewed Johns Hopkins scientist Karen Sfanos, Ph.D., whose work is shedding light on the role bacteria play in cancer – particularly, in prostate cancer – for the Prostate Cancer Foundation (PCF), which has invested $1 million in research to help explain the gut microbiome’s role in metastatic prostate cancer.  Call it a “gut feeling.”

Eight Pounds of Your Body Is Just Bacteria

Here’s something to consider about the megapopulation of bacteria in your gut: A lot of us have been exposed to bad bacteria, but these bugs don’t kill us. In our large intestine, we have about eight pounds or so of trillions of bacteria; in fact, we have more bacteria than cells in our bodies. Some of them are good, and some of them are not so good.

But some people die from bacterial infections in the gut; what happens to make them more susceptible? Dysbiosis: an imbalance, where the bad bacteria take over. For example: say you have an upper respiratory infection, and you get antibiotics. Antibiotics wipe out bacteria. They don’t distinguish between good and bad species; they just kill ‘em all. The good bacteria are collateral damage, and sometimes this scorched-earth result creates an opportunity for very bad bacteria to thrive in your gut. What’s going to fix that, more antibiotics? Maybe, but not always. In fact, when you wipe out the gut flora with antibiotics, an even worse form of bacteria – something nasty like C. difficile, for instance – can take over.

Again, what does this have to do with cancer? Here we go: If antibiotics fail, the most effective way to cure intractable C.difficile is with a fecal transplant: basically, taking the poop of someone who does not have C. difficile, who has a healthy gut microbiome, and inserting it in your colon. It’s gross, but it can also save someone from chronic, miserable illness.

Karen Sfanos is one of a few pioneering cancer researchers wondering if the same principle could apply to treating prostate cancer.   With colleagues at Hopkins and Thomas Jefferson, she is looking at gut bacteria – a heck of a lot of it, in at least a thousand patients undergoing various treatments for advanced prostate cancer. As principal investigator of the PCF grant, Sfanos is stockpiling gut bacteria and building a microbiome specimen repository that will serve as an international database for research.

Sfanos, a molecular microbiologist, has long been interested in the relationship between bacteria and prostate cancer; in fact, she is among a growing number of scientists who are proving that urine is not (as scientists supposed for decades) sterile, and was the first to describe the urinary microbiome in men with and without prostate cancer. Bacteria in the urinary microbiome may shed light on the presence of microbes that can cause prostate infections, including some that are sexually transmitted infections. These microbes may produce no symptoms but may lead to chronic inflammation – and this, in turn, may cause prostate cancer in some men.

Meanwhile, a few studies looking at other forms of cancer “started to indicate that the gut microbiome could have an influence on treatment response,” Sfanos says, “and that really got us thinking about whether the gut microbiome could influence how well men respond to prostate cancer treatment.”

In studies with medical oncologist Julie Graff, M.D., of Oregon Health & Science University, Sfanos has been working to see if there is a difference in the gut microbiome of men with widely metastatic prostate cancer who have responded dramatically well to the checkpoint-inhibiting immunotherapy drug, pembrolizumab.

Originally, Graff and colleagues suspected that the men in their studies who were exceptional responders to this drug had cancers with “microsatellite instability” (they had tumors with many genetic mutations) – which made the cancer cells stand out and be more easily recognizable as enemies to the immune system. And this is undoubtedly true, but it’s not the whole story.

In Graff’s initial small study, published in Oncotarget, three men out of 10 had dramatic responses: their metastatic tumors in the liver, brain, and elsewhere disappeared, and their PSA levels plunged. Tumor tissue from two of these men was available for further analysis and, indeed, one of the men’s tumors had microsatellite instability. But the other man’s tumor did not. The number of tumor mutations, explains Sfanos, “cannot fully explain those responses to immunotherapy,” in Graff’s and other studies. “People who do not have that phenotype are still having dramatic responses.”

For these men, “the gut microbiome could be contributing in several ways. If the immune system is blocked from recognizing the tumors,” because the cancer uses sneaky tricks and devious disguises to hide itself from the body’s roving immune system soldiers that would kill it, “the right mix of bacteria could help stimulate the immune system – and combining that with the immune checkpoint inhibitor might drive a robust anti-tumor immune response. So that could explain what’s happening in patients who do have this high mutational burden.”

What about the other people with various forms of cancer who do have microsatellite instability – the weird-looking, multi-mutated tumors that the immune system can see and say, “Hey, that’s not supposed to be here!” Why do only some of them respond well to immunotherapy? The gut may be helping them, too.   Is it diet? Do these people just eat better, and thus have a healthier gut microbiome?

“Certainly, diet does have a profound influence on the composition of your gut flora,” says Sfanos. To understand more, it’s time to look at your poop – or rather, at the poop of men with advanced prostate cancer who are contributing to this repository – in a very high-tech way. With each fecal sample, Sfanos and colleagues extract all of the bacterial DNA and RNA. They’re generating “microbiome profiles” that include bacteria, viruses, fungi, and protozoa. Then, they are correlating the gut flora with the treatment the men are receiving – and hoping to find answers to so many questions.

“I am extremely interested in the interplay between bacteria and circulating hormones,” says Sfanos. Does ADT – androgen-deprivation therapy, which deprives prostate cancer of the androgens, or male hormones, that nourish it – change the makeup of bacteria in the gut? “It’s an underappreciated relationship: they influence each other. The gut bacteria influence the circulating androgen levels, and vice versa. They’re talking to each other.”

In one ongoing study, “we looked at the gut flora of men across the prostate cancer spectrum,” Sfanos notes – men without prostate cancer, men with localized prostate cancer, men with recurrent prostate cancer, and men with metastatic prostate cancer. “We were really interested in determining if there are differences based on what treatments the men were being given. Oral anti-androgens, including abiraterone and enzalutamide, “may directly interact with the gut flora. We found that these men in our study had measurable differences in the composition of their gut flora. Something specific is going on in the men taking oral anti-androgens.” In further analyses, Sfanos and colleagues found that in men taking these drugs, “there are bacteria capable of hormone biosynthesis in the gut: microbes able to synthesize and metabolize precursors that can be hormones. This could potentially influence treatment response.” In other words, some gut bacteria can synthesize androgens that “could maybe even continue to nourish the tumor. We are very actively studying this right now.”

The gut flora, she adds, are “absolutely linked” to some of the other health problems that can accompany ADT, particularly metabolic syndrome. “This is very understudied in men with prostate cancer.” (Sfanos’s most recent work is currently in press, to be published soon in Nature’s journal, Prostate Cancer and Prostatic Diseases. In the meantime, here’s a link to a related study she did.

What might this research lead to? How could it help men with advanced prostate cancer fight their disease? Here’s one example Sfanos can envision. “Let’s say we discover a species of bacteria that’s capable of metabolizing an androgen,” a nasty bug that could counteract the effects of abiraterone by whipping up its own homemade batch of male hormones. “If depriving men of androgens leads to an outgrowth of some bacteria that can make their own androgen, we could check for them in a patient’s stool sample and try to get rid of them.”

Boosting the immune system: The epithelial barrier, the thin lining of the intestinal wall, is a virtual Checkpoint Charlie for immune system activity. This is a gateway with “a massive amount of immune cells on one side, and bacteria on the other side,” Sfanos notes. “Several studies have shown that certain species of bacteria are overrepresented in the gastrointestinal tract of people who respond to immunotherapy.” One research group has focused on a group of bacteria called Ruminococcaceae, and another is studying a microbe called Akkermansia muciniphila. Either of these, or both, may turn out to be very important. “The idea is that if, for whatever reason, the presence of these microbes is essential to generate a response to immunotherapy, you would want to introduce these bacteria,” in a fecal transplant or perhaps in the form of a targeted prebiotic or probiotic.

There probably won’t turn out to be one “magic bullet” form of bacteria, which is why a fecal transplant might be helpful. It is an intriguing idea: taking the gut bacteria from someone who responds extremely well to immunotherapy, and transplanting that – in poop form – into the colon of someone whose gut bacteria is not as beefed up for cancer-fighting. Would this stimulate the immune system so that it would knock out the cancer? Could it turn flabby, couch potato bacteria into ripped, mighty, cancer-fighting bacteria? And could this beefed-up bacteria help put your cancer into remission?

It’s early days yet. But if the bacteria within our bodies can shape how our immune system functions, if it can help determine how we respond to cancer treatment – or even whether we get cancer at all – then understanding the very complicated interplay between gut bacteria and cancer could be a game-changer.

“Historically, many prostate cancer biobanks have not included fecal samples,” says Sfanos. This means that nobody has correlated the other markers for how prostate cancer develops or progresses – PSA, Gleason score, genetic mutations, or clinical outcomes – with what’s happening in the gut.

Thanks to Sfanos and colleagues, that’s not the case anymore. 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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Oligometastasis in Prostate Cancer: Curable?

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

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

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

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

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

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

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

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

The Baltimore ORIOLE Trial

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

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

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

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

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

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

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

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington