Prostate Cancer and Genomic Testing
April 05, 2021April 4, 2021
Yale Cancer Center
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- 00:00Support for Yale Cancer Answers
- 00:02comes from AstraZeneca, dedicated
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- 00:07hope for people living with cancer.
- 00:10More information at astrazeneca-us.com.
- 00:14Welcome to Yale Cancer
- 00:15Answers with your host
- 00:17Doctor Anees Chagpar. Yale Cancer
- 00:19Answers features the latest
- 00:20information on cancer care by
- 00:22welcoming oncologists and specialists
- 00:24who are on the forefront of the
- 00:26battle to fight cancer. This week,
- 00:28it's a conversation about prostate
- 00:30cancer with Doctor Michael Leapman.
- 00:32Doctor Leapman is assistant professor of
- 00:34urology at the Yale School of Medicine,
- 00:36where Doctor Chagpar is a
- 00:38professor of surgical oncology.
- 00:41Michael, maybe we can start off by
- 00:43laying the groundwork and giving us
- 00:46a bit of a landscape of prostate cancer.
- 00:49How common is it? How lethal is it?
- 00:51Who gets it? Why should we care
- 00:54about this disease?
- 00:55Prostate cancer is something
- 00:57that I think is always on our minds.
- 01:00We hear a lot about it on the news.
- 01:03It is the most commonly diagnosed non
- 01:05skin cancer in men and over 230,000
- 01:07American men are expected to be
- 01:09diagnosed with prostate cancer next year.
- 01:12And it's also the second leading
- 01:14cause of cancer death in men,
- 01:16and so that imbalance between how common
- 01:18it is and the risk of death from prostate
- 01:21cancer is really quite interesting,
- 01:23because the majority of men who are
- 01:25diagnosed with prostate cancer will
- 01:27not have a very aggressive cancer.
- 01:29But then again,
- 01:30there is a lot of aggressive prostate
- 01:32cancer that requires treatment,
- 01:34and so figuring out that balance,
- 01:36figuring out where one lives
- 01:38on that spectrum is really
- 01:40important.
- 01:42How does that happen? Is it a matter of
- 01:47seeing how aggressive the cancer
- 01:50cells look by their grade on a biopsy?
- 01:53Or are there other factors that kind
- 01:56of play into figuring out how
- 02:00aggressive this cancer is?
- 02:02A lot of factors really come
- 02:06together to help make that distinction
- 02:08about the risk level that someone has.
- 02:12Historically, we really had a very
- 02:14monolithic approach where if someone had
- 02:16cancer there was treatment right away.
- 02:18There was very little disconnection there.
- 02:20It was just kind of a one way path from a
- 02:24diagnosis of prostate cancer to treatment.
- 02:27And that really continued for decades
- 02:29and decades until the understanding came
- 02:31that many of the prostate cancers did
- 02:34extremely well and probably did extremely,
- 02:36extremely well without treatment.
- 02:37And there was growing data and really
- 02:40strong information that these are very,
- 02:42very common in men in their 80s.
- 02:45They may be as prevalent as 60%
- 02:48of people might have a low grade,
- 02:50non aggressive prostate cancer.
- 02:52So this story began to be written over
- 02:5530 years ago where there was increasing
- 02:57awareness of
- 02:58the spectrum of aggressiveness in
- 03:01prostate cancer and so the main criteria
- 03:03that we use to estimate a given man's
- 03:06risk of prostate cancer and the risk of
- 03:09cancer will behave aggressively relate
- 03:11to what it does look like on under a biopsy,
- 03:15and there is a scale used called
- 03:17the Gleason scale,
- 03:18which is a pathologist,
- 03:20will take a look at the biopsy under
- 03:23microscope
- 03:24and look at how normal or abnormal
- 03:26the cancer cells look.
- 03:28Look at the architectural pattern
- 03:29of the glands and assign a level.
- 03:32And that level is highly related
- 03:33to the outcome of the cancer.
- 03:35So that's a very good
- 03:37way of beginning to estimate
- 03:40the trajectory of prostate cancer.
- 03:42Some of the other tools we use,
- 03:44are PSA levels. PSA is a common blood
- 03:47test that is ordered and it's a
- 03:50protein that is made by the prostate.
- 03:53And it can be found in the blood.
- 03:55Now,
- 03:55having a PSA level doesn't mean
- 03:57that you have prostate cancer,
- 03:59but there is a relationship between
- 04:01how high that PSA level is and the
- 04:03risk that a man can have prostate cancer.
- 04:06So that level of PSA is also prognostic,
- 04:08meaning it can help us estimate how likely
- 04:11the cancer is to be aggressive or not.
- 04:14And the last classic thing that
- 04:16we do is is a rectal examination of
- 04:19physical examination where we feel the
- 04:21prostate and see if we can feel a lump
- 04:23or a bump which is also kind of an
- 04:26indicator of how big a tumor might be,
- 04:29or if there's something that has
- 04:31reached a significant level.
- 04:32So those are historically how we
- 04:34estimate aggressiveness and
- 04:35the appropriateness of treatment,
- 04:37or what treatment should be
- 04:38undertaken. So before we kind of
- 04:40dig into a little bit more on that
- 04:43just to take one step back when
- 04:45people often hear about PSA
- 04:47and digital rectal exams,
- 04:49they often think about screening more
- 04:51than they do about prognostication.
- 04:53And yet there have been some changes
- 04:56I understand to what people are
- 04:58recommending in terms of screening.
- 05:01So can you take us back and tell
- 05:03us a little bit about who should
- 05:06get screened when and with what?
- 05:09Should all men get screened if
- 05:12prostate cancer is really prevalent,
- 05:14should this be a foregone conclusion,
- 05:16or is there a benefit to screening?
- 05:20And if so, in what populations?
- 05:22I'm so happy you asked that because
- 05:25that really I think begins to speak
- 05:27to the heart of the controversy and
- 05:29what I see in my daily practices.
- 05:31There is so much
- 05:34ongoing communication about that and
- 05:36different perceptions about screening.
- 05:38And so the story does go back even further,
- 05:42again, probably several decades
- 05:43ago when that PSA blood test was
- 05:46discovered in the late 1980s,
- 05:48and they found that if you check PSA
- 05:53you will find some people
- 05:55who have abnormal PSA levels,
- 05:57and we typically do a biopsy next and we're
- 06:00identifying prostate cancer so historically,
- 06:02back in the late 80s and early
- 06:0490s and into the early 2000s,
- 06:07there was a lot of PSA testing.
- 06:09It was routinely used in pretty much all men,
- 06:12adult men,
- 06:13and a lot of prostate cancers
- 06:16were being found as a result.
- 06:18And so you know,
- 06:20it became clear that
- 06:22since a lot of prostate
- 06:24cancer is being detected,
- 06:25that more rigorous evidence was
- 06:27needed to be undertaken so very
- 06:29large national and International
- 06:31Studies were done to look at the
- 06:34benefits of PSA testing to determine
- 06:36and really quantify how beneficial it
- 06:38is to have a PSA checked and find a
- 06:41cancer that could be in the prostate
- 06:43which was previously undetected,
- 06:45because they generally don't
- 06:47cause symptoms and so
- 06:49when we talk about screening,
- 06:50we mean taking people who have no
- 06:52symptoms who are otherwise, well., NOTE Confidence: 0.90424776
- 06:53they have no evidence of prostate cancer,
- 06:55but trying to find something
- 06:57early before it is manifest before
- 07:00it comes to the surface.
- 07:01And a few studies have been done,
- 07:04and one landmark study was performed in
- 07:07the United States which really didn't
- 07:09find a big survival benefit to screening.
- 07:12And so as a result in 2012,
- 07:15the US Preventive Service Task Force,
- 07:17which is a guideline issuing
- 07:19body in the United States,
- 07:21said that because of that absence of benefit
- 07:25and the great potential for harm by
- 07:28treating that no men should undergo
- 07:30PSA testing under any circumstance.
- 07:32It was kind of a blanket recommendation.
- 07:36And this was really kind of a
- 07:38controversial statement for people,
- 07:40especially in the prostate cancer field,
- 07:42because it was clear that in the
- 07:4420 years where prostate cancer
- 07:46screening was occurring,
- 07:47there was a substantial reduction in
- 07:50the risk of death from prostate cancer.
- 07:53And so right after that guideline came to be,
- 07:56there was another study
- 07:57that finally came to fruition,
- 08:01which had been conducted for over 10 years,
- 08:03but the results weren't available,
- 08:05which was performed in Europe,
- 08:06which did find a large benefit to
- 08:09screening with PSA in terms of reducing
- 08:12the risk of prostate cancer death.
- 08:14So here you have these two conflicting
- 08:17randomized trials which create
- 08:18a lot of uncertainty at which
- 08:20that uncertainty still exists,
- 08:22and there's still a lot of
- 08:24controversy about which one is
- 08:26right and which one is flawed.
- 08:28There are some
- 08:29substantial flaws with the
- 08:32study performed in the United
- 08:34States because
- 08:35many of the patients who were in
- 08:36the trial were actually already
- 08:38screened for prostate cancer,
- 08:39so it was a bit hard to
- 08:43distinguish those who had been
- 08:45screened already versus those
- 08:46who were not being screened.
- 08:47So it was almost as if everyone
- 08:50was really getting the same thing.
- 08:51So the controlled element of the
- 08:54trial was hard to appreciate.
- 08:57So that's kind of a long winded
- 08:59way of saying that it's still
- 09:01a very controversial question,
- 09:03but the evidence has really continued
- 09:05to accumulate as these studies have
- 09:08been followed for more and more years,
- 09:10and it really does appear to
- 09:12be as a substantial risk reduction
- 09:15in death from prostate cancer by
- 09:18having a PSA checked and finding
- 09:20early stage cancers and
- 09:22so do you recommend that for all men
- 09:24or men over a certain age or men with a
- 09:29certain demographic characteristic?
- 09:30I mean, perhaps the difference
- 09:32between the two studies and
- 09:34I'm just surmising here,
- 09:36maybe that there were different
- 09:38characteristics of the people participating,
- 09:40such that some men may
- 09:43really benefit from early detection
- 09:45and other men, not so much.
- 09:48I think you're absolutely right.
- 09:50And so we really kind of
- 09:53have to be anchored in what the
- 09:57studies have shown and the studies
- 10:00in both Europe and the United States,
- 10:03really focus on men in their 50s and 60s,
- 10:06and so the best evidence would suggest
- 10:08that men who are above the age of
- 10:1175 really don't benefit very much
- 10:13from having a routine PSA checked.
- 10:15Now it's a different story if people are
- 10:18having urinary symptoms or have a reason
- 10:20to suspect that they have prostate cancer.
- 10:22But when we talk about screening,
- 10:24we're saying being asymptomatic,
- 10:26having no problems,
- 10:27but getting a PSA checked and going
- 10:29looking for potential prostate cancer.
- 10:31So the US Preventive Services Task Force
- 10:34which issues these these guidelines in
- 10:372018 revised their recommendation to
- 10:40suggest that prostate cancer screening
- 10:42with PSA can be considered kind of
- 10:45in a shared decision-making fashion,
- 10:47which means that a patient and their
- 10:50physician should have a conversation
- 10:52about the potential harms and benefits,
- 10:55and find a way to balance the potential
- 10:58harms of undergoing a PSA test,
- 11:01which could include
- 11:02having a prostate biopsy,
- 11:04having invasive testing or finding a
- 11:06cancer which is non aggressive and
- 11:09might not have changed their life expectancy.
- 11:12And balancing that with the potential
- 11:14benefit of reducing their risk from
- 11:16prostate cancer death so it is really
- 11:19kind of not a one size fits all approach,
- 11:21but it really should occur for men
- 11:23who are in the age of 55 to 69,
- 11:26which is kind of the recommended group.
- 11:28Some demographics appear to be higher
- 11:30risk and we do recommend earlier
- 11:32screening beginning at
- 11:3445 and potentially even earlier for
- 11:36people who are falling into a high
- 11:38risk demographic based on a strong
- 11:40family history of prostate cancer,
- 11:42and that means having a
- 11:44first degree family relative
- 11:45with prostate cancer,
- 11:46such as a brother or father.
- 11:48Or having a known genetic alteration,
- 11:50such as a mutation in the BRCA2
- 11:53gene which is known to be associated
- 11:55with prostate cancer risk and other
- 11:57certain racial demographics such as
- 11:59African American men are at higher
- 12:01risk for prostate cancer detection
- 12:03and death from prostate cancer,
- 12:04and so they also fall into a higher
- 12:07risk category where screening may
- 12:09be appropriate earlier.
- 12:10But it's definitely not a one size
- 12:12fits all approach.
- 12:14I do think that the way to do it
- 12:17is to really have a thoughtful
- 12:19conversation to understand
- 12:20the whole picture here and
- 12:22why we would even consider prostate
- 12:24cancer screening what we could find,
- 12:26what the outcomes could be,
- 12:28what could happen
- 12:30and so doing that in the context
- 12:32of a relationship with a physician
- 12:34or health care provider who
- 12:36you trust is really important.
- 12:39And going back to our
- 12:43earlier conversation,
- 12:44even if you're screened and an
- 12:46early prostate cancer is detected,
- 12:48not all men will undergo treatment
- 12:51for their prostate cancer, right?
- 12:53So how do you decide who gets treatment?
- 12:56Who doesn't get treatment,
- 12:58and what that looks like?
- 13:00Yes, and I think that has
- 13:02really been the transformational shift that
- 13:05has happened in the past ten years or so.
- 13:08And you know the harms of PSA testing really
- 13:12relate to treating cancers that we find,
- 13:15and there are real
- 13:18risks of cancer treatment,
- 13:20including changes to urinary function,
- 13:24and GI and rectal toxicity.
- 13:26So the big change is
- 13:29the acknowledgement that it
- 13:31is appropriate to not treat
- 13:33initially patients who have cancer that
- 13:35appear to be non aggressive and that is a
- 13:38process that we call active surveillance,
- 13:41which is a period of close
- 13:43monitoring of prostate cancer
- 13:45rather than immediate treatment.
- 13:47And so what's so
- 13:49transformative about that is that
- 13:52it sort of allows us to have
- 13:53the benefits of early detection,
- 13:55which are finding
- 13:56potentially lethal cancers earlier,
- 13:58treating those ones and forgoing or
- 14:01deferring treatment altogether for
- 14:02those cancers that are non aggressive.
- 14:05So we're going to have to take a
- 14:08short break for medical minute,
- 14:10but when we come back,
- 14:12we're going to dig into who gets treated,
- 14:14how they get treated,
- 14:15and how we can really personalize
- 14:17treatment for prostate cancer.
- 14:19So please stay tuned with my
- 14:21guest Doctor Michael Leapman.
- 14:23Support for Yale Cancer Answers
- 14:25comes from AstraZeneca, working to
- 14:28eliminate cancer as a cause of death.
- 14:31Learn more at astrazeneca-us.com.
- 14:35This is a medical minute about breast cancer,
- 14:39the most common cancer in
- 14:41women. In Connecticut alone,
- 14:42approximately 3000 women will be
- 14:44diagnosed with breast cancer this year,
- 14:47but thanks to earlier detection,
- 14:49noninvasive treatments, and novel therapies,
- 14:51there are more options for patients to
- 14:54fight breast cancer than ever before.
- 14:56Women should schedule a baseline mammogram
- 14:59beginning at age 40 or earlier if they have
- 15:02risk factors associated with breast cancer.
- 15:05Digital breast tomosynthesis or
- 15:073D mammography is transforming
- 15:08breast screening by significantly
- 15:10reducing unnecessary procedures
- 15:12while picking up more cancers and
- 15:15eliminating some of the fear and anxiety
- 15:18many women experience.
- 15:19More information is available
- 15:21at yalecancercenter.org.
- 15:22You're listening to Connecticut Public Radio.
- 15:27Welcome
- 15:27back to Yale Cancer Answers.
- 15:29This is doctor Anees Chagpar and
- 15:31I'm joined tonight by my guest doctor
- 15:34Michael Leapman and we're talking about prostate
- 15:36cancer and right before the break,
- 15:39Michael you were talking about the
- 15:41fact that some men can have
- 15:44what's called active surveillance,
- 15:45just monitoring their prostate cancer,
- 15:47particularly if it's found early.
- 15:50Because there is toxicity to
- 15:53prostate cancer treatment.
- 15:55But other men really do require treatment,
- 15:57so let's dig into that group.
- 15:59How do you figure out who
- 16:02requires treatment and who doesn't?
- 16:04Yes, so that is one of the
- 16:06really important things
- 16:07that we do at the time of diagnosis.
- 16:10So if a man has had a prostate biopsy,
- 16:13we detect prostate cancer,
- 16:15the first thing that we really want
- 16:17to do is is trying to gather all the
- 16:20information possible to come up with that
- 16:23estimate of what we're dealing with.
- 16:26And so, in addition to the
- 16:29things that we discussed previously,
- 16:31the Gleason score of the PSA level,
- 16:33the physical exam,
- 16:34there are other tools that can help
- 16:36us predict what we're dealing with,
- 16:38what the outcome would be
- 16:39if we did treatment,
- 16:41or if we didn't do treatment,
- 16:43and two of those tools that we
- 16:45want to talk about,
- 16:47one is called a prostate MRI,
- 16:49which essentially is a high
- 16:51resolution MRI of the prostate.
- 16:53That often actually precedes the
- 16:55biopsy and helps us to a more
- 16:57accurate biopsy by finding areas
- 16:59within the prostate that could
- 17:01harbor prostate cancer and allowing
- 17:03us to more accurately target them
- 17:05so that we can identify cancer.
- 17:07If we don't find something,
- 17:11the absence of an aggressive
- 17:12cancer is also reassuring to us,
- 17:15so that is an important component
- 17:16that helps us identify potentially
- 17:18more aggressive prostate cancer
- 17:20that could be present.
- 17:21And again increasingly happens
- 17:23before the time of diagnosis.
- 17:25But we incorporate that information
- 17:27to help come up with a sort
- 17:29of an assessment of risk.
- 17:31The other are a host of validated
- 17:33genomic tests which measure expression
- 17:34levels of panels of genes that are
- 17:36associated with prostate cancer outcome,
- 17:38and so these are not the tests that tell you
- 17:42do you have a good gene or a bad gene.
- 17:44These are genes that we all have
- 17:47present in all cells and what what we
- 17:49do is we sort of look at the tumor
- 17:52tissue and we send it off to various
- 17:55companies that can perform these
- 17:56tests and essentially get a score back,
- 17:58which is an estimate of risk.
- 18:01An estimate of the likelihood of a
- 18:04prostate cancer spreading beyond the
- 18:06prostate or returning after treatment.
- 18:09Now these tests are not recommended
- 18:11for all men with prostate cancer.
- 18:13They are not an absolute requirement
- 18:15because if the cancer appears to be
- 18:17sufficiently aggressive based on
- 18:19their Gleason score or PSA level,
- 18:21there appears to be little utility
- 18:23in doing the testing.
- 18:24However,
- 18:24for people who might be on the fence,
- 18:27who maybe are considering active
- 18:29surveillance or treatment and want
- 18:31a bit more information about their
- 18:33estimated prognosis or how they might
- 18:35do in either of those categories,
- 18:36these tests appear to have some value.
- 18:39And so putting all those together with
- 18:42of course very important things like
- 18:44a patient's personal preferences,
- 18:46what they want,
- 18:48what their functional status is,
- 18:50what their age and their overall
- 18:52medical health is helps to create
- 18:54a more holistic picture of a man's
- 18:57prostate cancer profile.
- 18:58And what treatment options
- 19:00or what management options
- 19:02would be appropriate.
- 19:03And tell us with that score,
- 19:07does it give men a concept of
- 19:10their survival rate
- 19:11or you were saying that it might give
- 19:14you a clue as to the likelihood that
- 19:16it'll spread beyond the prostate,
- 19:18what are the tangible measures
- 19:20that men get with that information
- 19:22rather than simply a score,
- 19:24which can be kind of nebulous.
- 19:27The information that they provide there are
- 19:29a few different tests, and they kind
- 19:31of frame the information differently.
- 19:33But the two main measures that they
- 19:35provide are the risk of death from
- 19:38prostate cancer within 10 years.
- 19:40And the other one would be
- 19:41a risk of recurrence of prostate
- 19:43cancer or metastasis from prostate
- 19:46cancer within five years,
- 19:47and so those are the estimates and
- 19:49keep in mind that these are not
- 19:52firm predictions because treatments
- 19:54have changed very much and they
- 19:56continue to change.
- 19:58But these are still estimates
- 19:59and they really do appear
- 20:00to be valid at distinguishing more
- 20:02aggressive and less aggressive
- 20:04prostate cancer,
- 20:05and so knowing where those risk
- 20:07estimates live are important because
- 20:09I think they can help people make
- 20:12more informed decisions about #1
- 20:14the necessity of treatment and
- 20:16the intensity of treatment.
- 20:17So should I be treated altogether?
- 20:20Should my treatment include one
- 20:22form of treatment such as surgery
- 20:24alone or should I have surgery
- 20:26and radiation therapy or
- 20:28additional sequences of treatment?
- 20:30Based on the risk level and so
- 20:32that premise of can I use genomic
- 20:34testing to make that decision is
- 20:36still being fleshed out a little bit.
- 20:39And so the number that men get, is there
- 20:43kind of a toggle where it
- 20:46will say your risk of survival
- 20:48or distant recurrence or even
- 20:51local recurrence at 10 years is X,
- 20:53but if you choose surgery alone
- 20:55it will reduce it by this much.
- 20:58If you choose surgery and radiation
- 21:00it will reduce it by that much.
- 21:03If you choose systemic therapy,
- 21:04it'll reduce it by this much.
- 21:07Is there that kind of granularity in the
- 21:10data with a toggle switch that will help
- 21:13men's decision-making that's such
- 21:14a wonderful question that I think
- 21:16we're not there yet because
- 21:18of the novelty of these tools,
- 21:20and because of that, frankly,
- 21:21the novelty of doing active surveillance,
- 21:23we don't have that longitudinal data yet.
- 21:25I think that is really the Holy Grail
- 21:28where if we could say, if you
- 21:31do active surveillance,
- 21:32your risk is X, but if you do treatment
- 21:35it would turn down to Y.
- 21:40But say if you had surgery
- 21:42as opposed to radiation,
- 21:43your risk will be A, so that that is clearly,
- 21:46I think, where the field is moving.
- 21:48It is a bit challenging because
- 21:51treatment for prostate cancer is
- 21:52very much up to the patients.
- 21:54There are many other factors that
- 21:56lead to these things and so really
- 21:58to do that in a rigorous way,
- 22:00we would need to do a randomized
- 22:02trial where we say we're going to
- 22:04flip a coin and
- 22:06half the group is going
- 22:08to have surgery and half is going
- 22:10to have radiation and we're going
- 22:11to look at
- 22:13how the genomic test or the
- 22:15MRI predicted the outcome,
- 22:16so I don't think that's ever going to happen,
- 22:19where we're going to be able to modify
- 22:21treatment decisions based on that.
- 22:22But we're getting closer with
- 22:25other studies that
- 22:27are looking at genomics to help
- 22:29guide treatment,
- 22:30and stratify risk and predict
- 22:31response to various treatments.
- 22:33So I think that is very much
- 22:35where we should be going,
- 22:36but we're not there yet.
- 22:39So Michael, you have mentioned
- 22:41surgery and radiation a few times
- 22:43and not so much systemic therapy.
- 22:46But when we talk on this show
- 22:48as we do a lot about genomics,
- 22:51very often we're talking
- 22:53about as you said,
- 22:55genes that are turned on or turned
- 22:57off within a particular tumor.
- 23:00Oftentimes these are targets
- 23:01for various systemic therapies.
- 23:03Has that been looked at in prostate cancer?
- 23:08The cancer is interesting because
- 23:09I think in comparison to some of
- 23:12the other cancers, such as lung,
- 23:14that really do have these actionable
- 23:16driver mutations that there are drugs
- 23:18specifically targeting a certain mutation
- 23:20that has not really been the case
- 23:22in prostate cancer for many reasons.
- 23:24Number one, the main systemic
- 23:26therapies for people who have advanced
- 23:27or metastatic prostate cancer
- 23:29work by suppressing testosterone.
- 23:31Those are very effective treatments
- 23:33regardless of genomic profile,
- 23:35that is kind of the mainstay of treatment,
- 23:38and they almost universally have
- 23:40a good response.
- 23:42But there is increasing recognition that
- 23:45there are molecular and biomarker
- 23:49hallmarks such as homologous
- 23:50recombination gene mutations,
- 23:52microsatellite instability or
- 23:53DNA mismatch repair deficiencies that
- 23:55can lead to targeted treatments for
- 23:58men who do have metastatic prostate
- 24:00cancer or advanced prostate cancer,
- 24:02and so that,
- 24:02I think is one of the big changes
- 24:05that has occurred in recent years,
- 24:08is the recommendation that we do
- 24:10germline testing for patients with
- 24:12regional or metastatic prostate cancer
- 24:14to see if they have an actionable
- 24:17mutation that could be targeted.
- 24:19And so kind of getting back to
- 24:22one of the confusing parts of
- 24:25terminology that I think a lot of our
- 24:28listeners might get mixed up about,
- 24:31it goes back to something
- 24:34that you just pointed out.
- 24:36The difference between germline
- 24:38mutations and somatic mutations,
- 24:39so earlier for example you
- 24:42mentioned that men who had a
- 24:45BRCA genetic mutation may be at
- 24:47a higher risk of developing
- 24:50prostate cancer,
- 24:50but that is fundamentally different
- 24:52than this genomic testing
- 24:54that you're talking about.
- 24:55Can you flesh that out for our listeners?
- 24:58Absolutely,
- 24:58when we speak about these
- 25:01germline mutations we're talking about
- 25:03the DNA that were born with that
- 25:06that essentially has been inherited to us,
- 25:09which is in our germ line is present in all
- 25:12of ourselves and they may predispose to the
- 25:14risk of developing cancer and the BRCA2
- 25:17mutation is a very well acknowledged
- 25:20mutation that confers cancer risk.
- 25:24When we speak about the
- 25:25panel genomic testing,
- 25:26we're looking at relative expression levels,
- 25:29how turned up or turned down
- 25:31genes are within tumors,
- 25:32and these are not necessarily
- 25:34genes which have been inherited,
- 25:36or mutations within genes,
- 25:37but it's a measurement
- 25:39of how active they are,
- 25:41so this is not a good gene or a bad gene,
- 25:47we're wondering,
- 25:48how this was conferred,
- 25:50because genetics and prostate cancer
- 25:52risk is such a common question
- 25:53that we get because prostate
- 25:55cancer is very common and there's
- 25:57a thought that many
- 25:59patients have that they inherited a
- 26:01certain cancer predisposition from a
- 26:03family member and that may be the case.
- 26:05And there are certain
- 26:08well recognized genetic mutations
- 26:10that can be inherited in the germline,
- 26:13but we're looking at levels of
- 26:16cancer levels of gene expression
- 26:18associated with the cancer outcome.
- 26:21Yeah, and so you had mentioned that
- 26:24in addition to this genomic profile,
- 26:27that men will often make decisions based on
- 26:30other factors based on personal preference,
- 26:32but for a lot of men I can
- 26:35imagine that you know they come
- 26:39in and you say you've got prostate cancer.
- 26:42You know you can have active surveillance.
- 26:45You can have surgery.
- 26:46You can have surgery,
- 26:48plus radiation and the
- 26:52genomic testing how to interpret
- 26:54that number, your 10 year disease
- 26:57free survival risk is going to be 10%.
- 27:00What does that mean?
- 27:01Can you help us to understand how
- 27:04you discuss that with the patient and
- 27:07how they might factor in that information
- 27:10and what other characteristics or
- 27:12factors they may consider when trying to
- 27:14figure out how they should be treated?
- 27:17I can just imagine that they
- 27:19say look doc, I don't want cancer.
- 27:22I want to live as long and as
- 27:25well as I possibly can.
- 27:30These conversations are universally difficult.
- 27:31I think having a cancer diagnosis
- 27:33no matter what the grade,
- 27:35no matter what the stage,
- 27:37no matter what your doctor tells you,
- 27:39is inherently an anxiety provoking
- 27:41and stressful experience.
- 27:42There has been a lot of change,
- 27:45I think in the awareness of men of the
- 27:48fact that prostate cancer is very common,
- 27:51that the outcomes without
- 27:52treatment may be excellent,
- 27:54and so that has changed.
- 27:55A lot of men are
- 27:57expecting that diagnosis and have
- 27:59had friends or family members who
- 28:01have gone through the same thing.
- 28:03But still there is the kind of reflexive
- 28:05belief that any cancer risk should be
- 28:08reduced that you hear that word you
- 28:10want it out of your body.
- 28:12You want it treated,
- 28:13no matter what
- 28:15the consequences is,
- 28:16and I think that's very often the initial
- 28:19reaction is I don't care what it does.
- 28:21I want this gone.
- 28:22I want to treat it,
- 28:24and so that's where I
- 28:26think building a personal relationship is so
- 28:28important to give people time, space,
- 28:31support for dealing with that and
- 28:33understanding what the diagnosis is
- 28:35and really in the cool light of day
- 28:38integrating all of the information and really
- 28:40trying to zone in on what the risks are,
- 28:43what the benefits are.
- 28:44And it's really not a one
- 28:46size fits all approach.
- 28:48Active surveillance is
- 28:49not right for everybody,
- 28:50but nor is treatment right for everyone.
- 28:52And so I think that really doing that in the
- 28:56context of a truly shared decision between
- 28:59stakeholders on the patient side and on
- 29:01the physician side are so important.
- 29:03These tools are just tools and
- 29:06the hope is that
- 29:08they do provide more clarity,
- 29:10but I don't believe they're
- 29:12sort of magically the answer.
- 29:13And actually we are leading a study
- 29:15right now to help understand the
- 29:17personal experience and it's an interview
- 29:19based study where we were interviewing
- 29:22people going through the experience
- 29:25and we essentially want to open
- 29:27the door and hear from them and learn
- 29:29what is the experience of having a
- 29:31prostate cancer diagnosis and what is
- 29:33the experience of having genomic testing?
- 29:35Does it help? Does it hurt?
- 29:36Does it create uncertainty?
- 29:37Does it alleviate uncertainty?
- 29:39And I'm very excited to be involved
- 29:41in that study.
- 29:42Right now I actually just came off
- 29:43of a call where we're going through
- 29:45these interviews and we've been so
- 29:48fortunate to have men share this
- 29:49very personal part of their lives
- 29:51with us and give us really new
- 29:53and what I believe will be transformative
- 29:55information about what it's like
- 29:57to go through this.
- 29:58Because when these tests are
- 30:00studied in laboratories and by companies,
- 30:02there's such an excitement to bring
- 30:05new technologies which do provide
- 30:07very helpful scientific information,
- 30:09but we're trying to anchor it back
- 30:11to the patient level and see how
- 30:13is this going to help
- 30:15a given person. How is it
- 30:17going to help their family?
- 30:18And so that's really what
- 30:20we're interested in in the in the next step.
- 30:23Doctor Michael Leapman is
- 30:24assistant professor of urology
- 30:25at the Yale School of Medicine.
- 30:27If you have questions,
- 30:29the address is canceranswers@yale.edu
- 30:30and past editions of the program
- 30:32are available in audio and written
- 30:33form at yalecancercenter.org.
- 30:35We hope you'll join us next week
- 30:37to learn more about the fight against cancer.
- 30:40Here on Connecticut public radio.