How long can I live with advanced prostate cancer?
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This is a CBC Podcast. Hi, I'm Dr. Brian Goldman. Welcome to The Dose. When Joe Biden announced recently that he'd been diagnosed with advanced prostate cancer that spread to the bone, it raised lots of questions. Like, why wasn't the condition spotted sooner? And what might the prognosis be for the former U.S. President? So this week we're asking, how long can I live without a dose?

with advanced prostate cancer. Hi, Lawrence, welcome to The Dose. Thank you. How much do you think the Biden news has upped the call volume to doctors about PSA testing? Good question. My guess would be that, yes, it's really sparked a lot of interest.

And you're the expert, which is why we've come to you. But before we begin our conversation, can you give us a hi, my name is, tell us what you do and where you do it. I'm Dr. Lawrence Klotz. I'm a urologic oncologist at Sunnybrook Health Sciences Center. I'm a professor in the Department of Surgery at the University of Toronto. And I'm the chair of prostate cancer research at Sunnybrook.

And that's exactly why we've come to you with all of these good questions that I'm sure a lot of people have. So let's begin by asking you, what does it mean when we hear that someone has advanced prostate cancer? How is it defined? The term advanced prostate cancer is actually not one that we use so much in the field because we make a key distinction between localized prostate cancer or

which would be considered by and large non-advanced, and metastatic prostate cancer. The word metastasis means that the cancer has spread. In the case of prostate cancer, usually that means it's spread to the lymph nodes or the bones. Prostate cancer is a bone-seeking cancer.

So the word advanced usually refers to metastatic, but it can also refer to patients who have what is called locally advanced cancer, meaning the cancer has grown extensively in the area of the prostate. And therefore, the word is a little bit ambiguous. And as clinicians, we try to avoid it. But in general, it means disease that has spread and

And I guess the other key point is that most patients with advanced or metastatic prostate cancer would not be considered curable. The disease can be controlled, often for a long time, but a cure is generally not in the cards.

Do we know why prostate cancer, when it is advanced, when it metastasizes, is a bone-seeking cancer? There's not an easy answer to that. It's easier to describe the phenomenon than to understand the basis for it.

But there are certain cancers, the other really common one is breast cancer, that are bone-seeking. In other words, the majority of the time when it spreads, it spreads to the bones. It has to do with the interaction between prostate cancer cells and the cells that exist in bone marrow, which stimulate each other to grow and progress.

So it's not that the cancers don't land in other organs, they do, but it's a bit of what you could call the seed and the soil phenomenon. So for a variety of molecular reasons, the soil of bone marrow is

stimulates the seed of the prostate cancer cells to grow. So how do you formally diagnose advanced prostate cancer? There's really two scenarios. You could call it the synchronous and the asynchronous scenario. So in this case with President Biden, as far as we know, and I just want to emphasize that there really is a dearth of

of facts about what is going on with him at this point. So it's to some degree a matter of speculation, but some patients present with bone metastasis. They have no prior diagnosis and they show up often in the emergency department complaining of back pain. In the worst case scenario, they have a big spinal cord metastasis that's actually compressing their spinal cord. It can even present with leg weakness.

Prior to the PSA era, about half of patients diagnosed with prostate cancer were diagnosed that way. They present with back pain or with leg weakness or something to suggest that they've got some very abnormal thing going on. Then they would go on and have a bone scan. And there's a very characteristic appearance of metastasis.

on bone scan that allows a radiologist to say, this looks like metastatic prostate cancer rather than arthritis or other changes. The second scenario, the asynchronous scenario, which is much more common now,

is that the patient is diagnosed with prostate cancer, usually because of an elevated PSA, treated and followed. And then over time, it looks like the disease wasn't cured by treatment. It comes back.

The PSA continues to rise and eventually on staging tests, which include a bone scan and a CT scan, they are found to have spread of the disease. So we don't really know in President Biden's case whether he was the common asynchronous type, whether this diagnosis was made years ago and we just don't know about it, or whether he was one of these now much less common types.

synchronous cases where everything is diagnosed at the same time. So I assume in his case, if this wasn't a prior diagnosis, it's

He had some symptoms. They did the bone scan. They saw the typical pattern of bone metastasis. And then he had a PSA. I don't know what it was, but presumably it was quite high. And then they generally confirm that with a biopsy. Since we're going far out on a limb, patients can say, I don't want the testing. And he might have said, I don't want you to keep doing the PSA. 100% correct. Now, the other factors that come into this are phallic

family history, for example. And I don't know if there is a family history of prostate or cancer in the Biden males or breast cancer in the women's side of the family. If there is a family history, then that does certainly increase the risk significantly. But look, every guideline recommends, given that there are pros and cons of screening, that patients make their own decision. Now, I do think

the pendulum has shifted in favor of PSA screening over the last 10 years. The Canadian guideline was published in 2014, the Canadian Task Force on the Public Health Exam. So it hasn't been revisited in Canada in 11 or 12 years.

And it's a negative guideline, but really the world has changed. The whole approach has changed. The tests we do are different. The way the biopsy is done is different and much safer. So there is a general consensus amongst, I would say, knowledgeable people in the field that PSA testing has real value as long as it's done correctly.

appropriately, meaning many fewer biopsies than we used to do, imaging before biopsy, don't test

older people without a lot of caution or a very strong indication. So if it's done wisely, then I think it has a lot to be said for it. Of course, in this case, we don't know if he'd been tested, whether he would have been diagnosed earlier. Probably he would have been, whether this current scenario would have been prevented.

is another, really it's an unanswerable question. - When you mentioned the Canadian Task Force guidelines, you called them negative guidelines, and I think you mean that it's a guideline that basically discouraged ongoing screening beyond a certain age. - Not just beyond a certain age. The Canadian guideline basically discourages anyone

from getting PSA screening. There are scenarios, for example, patients who are at very high risk because of their family history or race, where it's a little more equivocal. But by and large, for the average person, the current guideline, which again, was formulated about 12 or 13 years ago and published about 11 years ago, is negative.

Now, it's largely disregarded because I think many family physicians follow the literature and the literature is very clear that this test has value if it's used appropriately.

But it's created a lot of confusion and there's certainly many family doctors, and I don't blame them, who say, well, our national guidelines says don't do it and I'm going to comply with that. So both family doctors and patients have a lot of confusion and uncertainty in this area.

From what you've said, advanced prostate cancer can sneak up on patients. And how much does regular PSA testing prevent that? So the way I think about this is what I call the metaphor of the barnyard.

You have a barnyard and the animals leaving the barnyard is the equivalent of metastasis. And there's basically three animals in the barnyard. You have turtles who are destined to wander around inside the barnyard indefinitely.

And the turtles are the equivalent of what's now called grade group 1 prostate cancer, the low-grade, very indolent prostate cancer that develops with age in most men and really poses no threat to the patient. One of the major advances in the last two decades was a widespread acknowledgement that these low-grade cancers develop

not only don't need to be treated, but shouldn't be treated. And that's been very widely adopted now in Canada. At the other end of the spectrum, you have the birds and the birds fly away at the first opportunity. Maybe Joe Biden has a bird. So a bird is a type of cancer that's so aggressive that very early on in its development, before it can be possibly tested by a screening test, it's already metastatic.

We know there are birds, but they are few and far between in the prostate cancer area. And again, maybe that's what President Biden had. But far more common is the rabbits.

And the rabbits jump around inside the barnyard and then they jump out. And the rabbits are where you have benefit of screening because you detect a rabbit before it's metastasized, you cure it, you have prevented metastasis. And we have a great deal of evidence that a substantial proportion of prostate cancers are rabbits. The two largest groups are the turtles, which pose no threat,

the rabbits, which are curable and which have a benefit of early detection. The birds are always going to be there. There's always going to be the aggressive cancers that no matter how intensively you screen, they are going to spread. But they are rare. So the scenario, the one scenario regarding President Biden that he had this disease, which was undetectable, and then suddenly, boom, explosive progression to metastasis and

Very unlikely. Not unheard of, but very unlikely. So again, the screening benefits patients if they have a rabbit. And the estimate is overall about half or two-thirds of patients have cancers that have a metastatic potential. Hi, everyone. I'm David Duchovny.

Join me on my podcast, Fail Better, where we use failure as a lens to reflect on the past and analyze the current moment. I speak with makers and performers like Rob Lowe, Rosie O'Donnell, and Kenya Barris, as well as thinkers like Kara Swisher and Nate Silver, to understand how both personal setbacks and larger forces impact our world. Listen to Fail Better wherever you get your podcasts.

That is the clearest explanation of the value of PSA testing that I have ever heard. And I want to thank you for it. Joe Biden, apparently in the information that's been released, has a Gleason score of nine. How does that fit in? The Gleason scoring system is out of 10. We've actually moved away from that because the lowest Gleason score is a six.

Six out of 10 is the low-grade cancer that doesn't pose a threat to patients that we now manage conservatively. But patients here, they're a six out of 10, and they think they're 60% of the way to the grave, which is a complete misconception. So we now move to what's called grade grouping cancer.

And essentially Gleason score nine is now called a five out of five. So this is the, we hardly ever see Gleason,

Gleason score of 10, but 9 and 10 are now called grade group 5. That is the highest grade. Those are aggressive cancers. They're usually, frankly, lethal cancers, very common for them to spread, even if they're the asynchronous type, meaning that you first diagnose when they're apparently localized, you treat them,

still the majority of these patients will show up with spread of disease down the line. So it's not at all surprising, given that he has metastatic disease, that it's high grade. So what are some of the options for treating prostate cancer diagnosed at a later stage?

This whole area has just been on fire for the last 10 or 15 years. We have a whole slew of new drugs, all of which have been shown in prospective randomized trials to prolong survival. So the landscape has changed dramatically. 20 years ago, the only treatment was hormone therapy.

which I'll come back to in a second, and one chemotherapy agent which didn't improve survival.

Now we've got at least 10 or 12 agents of different types. So the basis for treating prostate cancer for now about 80 years has been what is called hormone therapy or androgen deprivation therapy, ADT. And the principle is that if you take away the male hormone testosterone, this is the signal that cancer cells need to grow.

to survive. If you take away the male hormone, then the cancer cells regress. And this was discovered by a guy named Charles Huggins, who was actually a Canadian from Halifax, but he did his work in Chicago, won the Nobel Prize for this at the time, which was the early 1940s. This was really perhaps the first effective systemic therapy for cancer, which is why it was thought to be so important.

The problem with hormone therapy, which I'm sure, by the way, President Biden is on now if he wasn't already on it,

is that there's pathways that are induced by the hormone therapy that result in some of the cells surviving. So while 99.9% of the cells die off, you have a small subpopulation that survive, and they eventually become predominant. And that is called hormone resistance. And the cells then survive and grow despite survival.

the lack of testosterone in the patient. By the way, the ADT is achieved usually with drugs called LHRH agonists or antagonists that result in complete suppression of testosterone production. So you start with the hormone therapy. Then the second major advance has been a class of drugs called antigen receptor pathway inhibitors or ARPIs.

And these are an augment of the ADT of the hormone therapy, and they result in significant prolongation of survival by really targeting the androgen receptor pathway, which stimulates prostate cancer growth more effectively. So that's the second major area of progress, and that began around 10 or 15 years ago.

We also, around the same time, have chemotherapy agents, a class of drugs called taxols. The commonest one is docetaxol that also is a traditional chemotherapy agent but prolongs survival.

The next advance, more recently, again, the last five years, has been two areas. One is a class of drugs called PARP inhibitors that target a survival pathway and work most powerfully in men who have a mutation in the DNA repair pathway that

can be occasionally in every cell in their body called a germline mutation, but more commonly develops over time in the cancer and allows the cancer to survive.

And then fourth is a class of drugs called theranostics, which is a targeted radiation agent. So you have what's called a radionucleotide, a radioactive molecule of which the one that's most widely used is lutetium that emits radiation that is tagged to a targeting molecule that targets prostate cancer cells called PSMA.

So that combined molecule delivers the radiation directly to the prostate cancer cells.

So we've had the ADT for 80 years, the last 10 or 15 years, the ARPIs, the PARP inhibitors and the theranostics as well as chemotherapy. So now the challenge is how do you use these? Which do you start with? How do you sequence them? Do you use them in combination? So we're at the point now where these drugs are being used in different combinations at different stages and

Each one of these has been shown to prolong survival. So whereas, say, 15 years ago, the average patient with metastatic prostate cancer would live about three years, now the survival is more like five to six years. And there's big ranges around that estimate. So you have some patients who may live 10 or 15 years despite having metastatic disease. And unfortunately, you have others who

where the disease progresses very rapidly despite of all these new therapeutic advances, and the patient can sometimes die within a year. For comparison's sake and for the sake of perspective, though, for people who are listening to this,

not a high percentage of people diagnosed with advanced prostate cancer are going to belong to the same category as Biden. That's true. There's a number of predictors that allow you to stratify the patient's risk of having an aggressive course or a more responsive course. One of them is the grade group. His is the worst. Most patients don't have that.

And when the grade group is grade group two, three, or four, uh,

far more common and generally less aggressive, less fast moving. And the second is the extent of the cancer. So does the patient have a handful of metastasis? Nowadays, we increasingly use what's called metastasis directed therapy, meaning you zap with radiation if there's one or two or three solitary areas of spread versus very widespread disease where

that kind of approach obviously isn't going to achieve anything. The third very powerful predictor is what happens to the PSA after a course of treatment. So if indeed PSA

He has recently been diagnosed and only recently started treatment. It will be very informative in terms of his prognosis to learn what his PSA has done after a period of six months or so of this therapy. And we may learn that or we may not. Who knows?

Well, maybe a bit of a mixed picture, but more hopeful than I think a lot of people might have believed or understood, especially hearing the news about Joe Biden. We hope he lives a long time with his disease. And Dr. Lawrence Klotz, I want to thank you for coming on The Dose to talk about advanced prostate cancer. Pleasure. Thank you for the opportunity. Dr. Lawrence Klotz is the Chief of Urology at Sunnybrook Health Sciences Centre in Toronto and a professor at the University of Toronto. He

Here's a dose of smart advice. Advanced prostate cancer, also known as metastatic or stage four prostate cancer, means that the cancer has spread beyond the prostate gland to the surrounding lymph glands and beyond. Prostate cancers most commonly metastasize to the bones and lymph nodes. To a lesser extent, they can also spread to the liver, the lungs and the brain.

The Gleason score is a system that has been fairly commonly used to indicate how aggressively the cancer is likely to grow and spread. More recently, the grade grouping on a scale of 1 through 5 gives a more accurate prognosis. There are several reasons why advanced prostate cancers may go undetected. The originating cancer might be small and hard to spot. The cancer may not appear on MRIs and other kinds of diagnostic imaging.

A biopsy sample may not contain the cancer. Since early prostate cancers often don't cause symptoms, there may be no reason for patients to check back with their doctor. Prostate-specific antigen or PSA testing can be used to monitor patients. An elevated PSA test does not tell you for certain whether or not you have advanced prostate cancer. However, the trend of a rising PSA test over weeks or months may indicate that a cancer has become advanced and therefore potentially deadly.

Prostate cancer screening was once considered controversial because it led to overdiagnosis, over-testing and adverse effects of prostate biopsies. With more accurate testing these days, doctors are getting better at picking out patients at risk of advanced cancers and biopsies and other test methods have fewer side effects.

Generally speaking, advanced prostate cancer is not considered curable. But newer treatments are helping improve quality of life and are prolonging survival. These treatments include androgen deprivation therapy, androgen receptor pathway inhibitors, cancer chemotherapy, and theranostics, which uses PET scans to target cancer cells with radiation therapy.

These new approaches are prolonging the lives of people with advanced prostate cancer. If you have topics you'd like discussed or questions answered, our email address is thedoseatcbc.ca. If you liked this episode, please give us a rating and review wherever you listen. This edition of The Dose was produced by Brandi Weichle and Samir Chhabra. Our senior producer is Colleen Ross. The Dose wants you to be better informed about your health. If you're looking for medical advice, see your healthcare provider. I'm Dr. Brian Goldman. Until your next dose.

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