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Prostate Cancer and Genomic Testing

April 05, 2021
  • 00:00Support for Yale Cancer Answers
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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.