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The Dose Transcript for October 31, 2024

Host: Dr. Brian Goldman

BRIAN GOLDMAN: Hi, I'm Dr. Brian Goldman. Welcome to The Dose. Movember is close at hand, so look out for those moustaches in support of prostate cancer research and of course testicular cancer research. Prostate cancer is the most common cancer among Canadian men, so this week we are asking: How can I protect myself or a loved one from prostate cancer? Hi, John. Welcome to The Dose.

JOHN LEWIS: Hi, Brian. Good to be here.

BRIAN GOLDMAN: So what impact do you think Movember has had on awareness of prostate cancer?

JOHN LEWIS: Well, I don't think its impact can be understated. Movember has been a global phenomenon over the past decade or so. It's not only brought awareness to men's health -- you know, men's mental health and of course our chances of getting cancer -- it has, through fundraising, has supported a ton of very valuable research into prostate cancer, testicular cancer, and men's mental health.

BRIAN GOLDMAN: Does that include your research?

JOHN LEWIS: Yeah, absolutely. So we've had a close relationship with Movember, you know, since they started. I've been growing my moustache every November, and my whole team has, you know, when they can. And absolutely, we've had several really important research studies supported by Movember.

BRIAN GOLDMAN: Which is why we have come to you and you are an internationally ranked expert. 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.

JOHN LEWIS: My name is John Lewis. I am a professor in the Department of Oncology at the University of Alberta, and I hold the Bird Dogs Chair in Translational Oncology.

BRIAN GOLDMAN: As far as cancers go, John, how dangerous is prostate cancer for men?

JOHN LEWIS: Prostate cancer is really two different diseases with two completely different outcomes. Indolent prostate cancer, which is prostate cancer that's ostensibly less dangerous, is a cancer that we often say men could die with and not of. But of course, prostate cancer can also be extremely dangerous, particularly if not caught early. And approximately 3% of all men will die of aggressive prostate cancer.

BRIAN GOLDMAN: You're the first person that I've heard who's talked about prostate cancer as being two different diseases. What's the basis for making an observation like that?

JOHN LEWIS: Depending on what numbers you look at, approximately 1 to 5, to 1 in 7 men will be diagnosed with prostate cancer in their lifetime. But to get diagnosed with prostate cancer, you typically get screened by your family doctor, you might have a high PSA test -- that's prostate-specific antigen. It's something that shouldn't be in your blood, you know, if your prostate is healthy. And then the only way to diagnose prostate cancer definitively is through a biopsy. Well, what's interesting is that in rapid autopsy studies of men, you know, 70 to 80 years old, the rate of actually positive prostate cancer is more than three-quarters. So, the vast majority of men have some prostate cancer in their prostate, you know, at some point in their lives. And so this has resulted in the diagnosis or overdiagnosis of less aggressive, indolent prostate cancer. But the issue is, is that some prostate cancers are extremely aggressive. So for prostate cancer that remains in the prostate, localized, the survival rate at five years is virtually 100%. But if that becomes metastatic or it spreads out of the prostate, it becomes a completely different and relatively untreatable disease. And the survival rate in North America goes down to about 30%. But in many other countries where treatment and screening isn't as good, this can go down, you know, 6 or 7%. So that's why I say it's two different diseases. Aggressive prostate cancer that spreads out of the prostate, you know, is a very dangerous disease and ideally is caught early.

BRIAN GOLDMAN: And you've nodded to it, but I want to amplify now this question of risk. Who is most at risk for prostate cancer? Which populations are we talking about?

JOHN LEWIS: Prostate cancer is pretty much the most commonly diagnosed cancer in men. Thirty-six per cent of all newly diagnosed cancers and 10% of all cancer deaths in men. Age is the biggest risk factor for prostate cancer. As you get older, and particularly over 50, your chance increases. If you have a family history, sort of two close relatives with prostate cancer, your chances go up pretty significantly.

BRIAN GOLDMAN: What do we know right now about who is at the greatest risk of metastatic... you know, the more serious kind of prostate cancer?

JOHN LEWIS: There are a number of socioeconomic and genetic factors. So, similar to breast cancer, where we see, for instance, BRCA1 mutations having a dramatic impact on both incidence and outcomes for breast cancer. Actually, some of these same genes are involved in prostate cancer as well. So BRCA1, for instance, has been associated with not necessarily greater incidence, but certainly worse outcomes and greater chance of metastatic disease. And of course, there are different populations that exhibit higher both incidence and aggressiveness of prostate cancer as well. Typically, the African-American population is diagnosed later and typically has more aggressive disease. As well in Canada, the Aboriginal population. There's emerging data that the Aboriginal population has somewhat increased incidence and they're generally diagnosed with a more aggressive disease.

BRIAN GOLDMAN: Is it also fair to say that if you've got in your family history, like if your dad died of metastatic prostate cancer, that you're probably at a greater genetic risk?

JOHN LEWIS: I think that's extremely fair to say. I think the genetic component to prostate cancer is pretty well documented and quite strong. And again, the more men in your family that have had prostate cancer and particularly have had aggressive prostate cancer, that's a pretty significant risk factor.

BRIAN GOLDMAN: I gather that we judge the severity of prostate cancer by the grade of cancer and something called the Gleason score. Can you explain both to a lay audience?

JOHN LEWIS: So you generally... if you have a family history of prostate cancer, your family doctor, ideally -- if you have one -- will start suggesting getting screened in your 40s. And as I mentioned, this is a pretty simple blood test called a PSA test. If it's elevated, then you're generally recommended to have additional screening that could include an MRI or adjunctive tests. And then, of course, a biopsy. Biopsy includes, you know, a trans rectal ultrasound, and then they stick about 12 needles up between the legs into the prostate. It's not an innocuous procedure, but they take a bit of tissue out. And as you mentioned, a pathologist looks at this tissue to give it a Gleason score. So the Gleason score is basically an aggregate score that looks at, you know, how normal are the cells in this tissue. And we call it sort of differentiated, so they look like prostate cells doing their jobs. Or dedifferentiated, where they sort of become more amorphous and invasive. And so the less differentiated they are the higher the Gleason score, and the higher the risk for aggressive prostate cancer. And generally, the scores go from 1 to 5, and a Gleason Grade Group 1 is, I would say, most often non-aggressive, and Gleason Grade Group 2 and higher are sort of the levels at which you might want to look at additional tests.

BRIAN GOLDMAN: If you have an elevated PSA, are you saying that you should have a biopsy? Are there some instances in which a biopsy might not be indicated?

JOHN LEWIS: That's really one of the most important questions when it comes to diagnosing prostate cancer. PSA testing became sort of mainstream in the mid-'80s, early '90s, and as a result of starting to screen with PSA, you know, we detected a lot of advanced prostate cancers. And that really drove down the mortality rate, you know, in Canada and around the world pretty significantly. The issue with the PSA test is that while it is quite sensitive -- so it's really good at picking up a high PSA -- it's not very specific for prostate cancer. In fact, it's one of the most, unfortunately, inaccurate tests that we have in medicine, because 85% of the time you have an elevated PSA, you actually don't have prostate cancer. So there's a number of other conditions. You have benign conditions that can raise PSA and so that's really the issue. I think in the past with high PSAs we've done a lot of biopsying. Biopsy itself does not come without risk. So there's at least some risk of infection that can lead to sepsis. And of course, there's this risk of overdiagnosis of these indolent prostate cancers, and the resulting treatments that may include surgery and radiation, etc., that cause side effects, that have actually made the task force in Canada and the U.S., you know, some ten years ago, recommend against prostate cancer screening using PSA. So this has actually created an issue now where we're actually diagnosing some prostate cancers later and more aggressively. And this has actually slightly driven up the mortality rate in Canada.

BRIAN GOLDMAN: Wow. I didn't know that. What are the current screening guidelines?

JOHN LEWIS: Currently, the screening guidelines are men, over the age of 50, can ask their doctor. So it's not, it's not routinely done throughout Canada, but generally at 50, you'll have a discussion with your family physician about PSA testing. So, many men will opt to get PSA testing around when they're 50. If they have a family history, [indistinct] recommended to begin screening in your 40s, around 45. And again, our first and simplest way to screen for prostate cancer is a PSA test. But as I mentioned, because it's not specific for prostate cancer, there are other adjunctive screening tests and imaging tests like MRI that can help make that decision to biopsy.

BRIAN GOLDMAN: I gather that you've been working on a screening tool with your colleagues. What can you tell us about that?

JOHN LEWIS: So there are some risk factors for prostate cancer, but prostate cancer can arise without any of those risk factors in place and can be aggressive. So, in my research lab, we've been studying for about 15 years the components of prostate cancer, mostly the genetic components of prostate cancer, that drive metastatic disease. So, the most aggressive cancer that's most likely to kill men. And so our long-term goal of the lab was to try to come up with therapies that could really breed metastatic prostate cancer. But in the meantime, we realized that some of the genetic factors we had identified for aggressive prostate cancer could be used better as a screening tool. As I mentioned, because the PSA test is so poor at predicting the incidence of not only prostate cancer, but aggressive prostate cancer, and the only way to definitively diagnose the disease is through this pretty invasive biopsy, now we really need better adjunctive screening tools at that decision-making stage before the biopsy to try to make that more informed decision. So we began looking at biomarkers -- so these are proteins and genes that are present in aggressive prostate cancer and not present in indolent prostate cancer, or no cancer -- and began to build a tool that we call ClarityDX Prostate. And it's an adjunctive screening tool for prostate cancer intended as a reflex test for PSA. So if a PSA is above three nanograms per mil, the idea is that you get this adjunctive test that's very simple, that would actually increase the accuracy of PSA testing by about three times. We initially developed that test using a number of biomarkers, and then we did a prospective study with men throughout Alberta, men at Johns Hopkins University, and men at UCLA who went through their clinics. So by doing two simple biochemical tests and adding four different clinical features, we were able to improve the accuracy of PSA by three times. Which means that if we incorporated this tool into regular clinical practice as a reflex test of PSA, we could avoid up to 40% of biopsies, which was just remarkable. What was also interesting is that this MRI data is available. We can incorporate it into the algorithm and then avoid up to 50% of unnecessary biopsies. We finished that prospective pivotal study last year, and the test is now becoming available to Canadians over the past few months. And we're working with the local governments in each province basically to establish the data and make that test available to all men in Canada.

BRIAN GOLDMAN: The main symptoms of prostate cancer are urinary, so changes in urination, either interruption or difficulty emptying your bladder. Maybe painful urination, blood on urination, as well as symptoms such as pain on ejaculation, erectile dysfunction. So the symptoms are clear. But from what I gather, the vast majority of people who do have prostate cancer have no symptoms, right?

JOHN LEWIS: Yeah, that's correct. Often you can develop even aggressive prostate cancer without having any symptoms at all.

BRIAN GOLDMAN: What are the latest treatment options?

JOHN LEWIS: So traditionally, the drugs that were developed for prostate cancer all involve blocking hormone pathways. And so these drugs have dramatically improved over the past few years, blocking down the entire biosynthetic pathway of androgens, for instance, to dramatically change the course of prostate cancer. And of course, the mainstays of treatment are surgery. So again, if you have local but aggressive prostate cancer that stays in the prostate, surgery can take out the prostate and ostensibly provide a cure. So, surgery can be curative if it hasn't spread. If it has spread, it becomes more difficult. But there are many new drugs on the market that have pretty substantial impact in prolonging life. But again, for metastatic prostate cancer, there still isn't a cure. You know, I'm hopeful that immunotherapies that have had such a dramatic impact on cancers like melanoma and lung cancer, will have an impact on prostate cancer as well.

BRIAN GOLDMAN: You haven't said much about radiation. What about that?

JOHN LEWIS: Radiation, there are multiple types, but I would say two types for your listeners. There's external beam radiation, which can be very, very accurate. So they basically shine multiple beams from outside the body into the body, but focus directly on where the prostate cancer is. And also brachytherapy, which involves the insertion of radioactive seeds into the prostate where the prostate cancer is, to kill it from the inside.

BRIAN GOLDMAN: As you've said, based on your own personal risk profile and your preferences and indeed your age, a decision is going to be made as to whether you're going to treat that prostate cancer aggressively. At one end of the spectrum. At the other end of the spectrum, you're going to do something called active surveillance, like where you're just going to watch and-- you know, vigilantly, but you're not going to aggressively try to treat it. Help us navigate, you know, where people who are listening to this should place themselves in that spectrum.

JOHN LEWIS: That is the ultimate, the most important question. So, I am a big proponent of having as much health information as possible, and I think we're beginning to live in the world where we have a lot of information about how many steps we've taken, you know, what our heart rate variability is. And I believe that when it comes to vigilance for cancers like prostate cancer, more information is always better. And it's really how you use that information that's critical. Screening early for prostate cancer, I believe, is really important because there are some aggressive prostate cancers that can grow without you ever knowing. And we have interventions that can cure you or at least dramatically extend your life. So, I'm a big advocate for PSA screening. But it's really important to be able to take this information and use it appropriately to make decisions about biopsy and then treatment. And so that's why we've really focused on developing this adjunctive screening test for prostate cancer that helps men, most importantly, decide whether or not to get a biopsy rather than to get a biopsy, and to feel more comfortable about that decision. But also identify those men who probably should get a biopsy because it's much more likely to save their life down the road.

BRIAN GOLDMAN: But there is a subgroup of individuals who might be listening to this right now. Perhaps they're in their 80s and they're in otherwise good health. Let's just say they don't have a strong family history, they don't come from an ethnic background that puts them at risk. Might active surveillance and just watchful waiting be a reasonable approach for them?

JOHN LEWIS: Yeah. So if you get your PSA tested and it's high, maybe you get an adjunctive screening test that says you're unlikely to have aggressive prostate cancer, surveillance is the way to go. So this is-- active surveillance is making a conscious choice not to get aggressive treatment at the time, but just to keep watching, maybe get a PSA test every year, to see if that number is changing. And having, you know, a regular conversation with your physician to be able to make that decision to keep watching, keep waiting, or to see if there is a cancer that's potentially advancing and it might need some treatment.

BRIAN GOLDMAN: Finally, then, what can men do to reduce their risk of developing prostate cancer?

JOHN LEWIS: There's no way to completely prevent prostate cancer, unfortunately. But you can significantly reduce your risk by basically adopting healthy habits. So, maintaining a healthy weight. So being overweight or obese is definitely linked to an increase in risk, both of getting prostate cancer and having aggressive prostate cancer. Regular exercise is critical. You know, at least 150 minutes of moderate intensity exercise per week is recommended. Eating a healthy diet. And what this means for you may be different, but generally a low-fat diet, rich in fruits and vegetables and whole grains. And of course, most importantly, limiting processed and ultra processed foods. Limiting alcohol. Any links between drinking alcohol and better outcomes have pretty much been dispelled at this point. Stopping smoking is a clear one and, of course, getting a regular prostate screening.

BRIAN GOLDMAN: Well, John Lewis, we asked the question, what can I do about my risk of prostate cancer, and you answered all of our questions. Thank you so much for appearing on The Dose.

JOHN LEWIS: Real pleasure to be here, Brian. Thank you.

BRIAN GOLDMAN: John Lewis is a professor and Bird Dogs Chair in Translational Oncology at the University of Alberta. Here's your dose of smart advice: Prostate cancer, which originates in the prostate gland, is the leading cancer among men. Roughly one in eight Canadian men will develop prostate cancer over their lifetime. Most cases are diagnosed among men aged 50 and older. In most men, prostate cancer is slow growing. In a small percentage, the disease metastasizes fairly quickly and eventually causes death. Knowing which type of cancer you have is the challenge. But there are several risk factors. One is having a family history of prostate cancer. Ethnic background is another risk factor. Rates of metastatic prostate cancer are higher among African-American and Indigenous men. Obesity is another risk factor. Other suspected but not proven risk factors include tobacco use, elevated testosterone levels, pesticide and other chemical exposures, and certain diets. Having an enlarged prostate does not increase your risk. Prostate cancer is usually silent in its early stages. Symptoms include more frequent and more urgent urination, straining to pee, reduced or interrupted urine stream, trouble emptying the bladder, painful urination, dribbling, and blood in the urine or semen. Other symptoms include erectile dysfunction and painful ejaculation. Because prostate cancer metastasizes to the pelvis and spine, symptoms may include back and hip pain. There are two widely available tests to help detect prostate cancer early. PSA, or prostate-specific antigen, is a blood test. An elevated PSA level means you may have prostate cancer and need further testing. The cost of PSA testing may or may not be covered by your provincial or territorial health system or your insurance. A digital rectal exam, or DRE, using a gloved finger, is done by your health-care provider to feel the prostate for abnormal lumps. Men at average risk of prostate cancer should consider testing beginning at age 50. African-American and Indigenous men and those with a family history should consider testing beginning at age 45. A biopsy of the prostate is needed to confirm the diagnosis. Further testing may be needed to see if the cancer has metastasized. Not every prostate cancer requires treatment. Because these cancers often grow slowly, in many cases it can be monitored, with treatment recommended if the cancer is growing. Newer screening tests will hopefully identify patients who should have a biopsy -- and if positive, more aggressive treatment -- and those who can safely watch and wait. If you have topics you'd like discussed or questions answered, our email address is thedose@cbc.ca. If you like this episode, please give us a rating and review wherever you get your podcasts. This edition of The Dose was produced by Sameer 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 health-care provider. I'm Dr. Brian Goldman. Until your next dose.

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How can I protect myself from prostate cancer? - Transcript

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