Prostate Cancer and Genomic Testing

Transcript

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00:13 --> 00:15Welcome to Yale Cancer
00:15 --> 00:16Answers with your host
00:16 --> 00:18Doctor Anees Chagpar. Yale Cancer
00:18 --> 00:20Answers features the latest
00:20 --> 00:22information on cancer care by
00:22 --> 00:23welcoming oncologists and specialists
00:23 --> 00:26who are on the forefront of the
00:26 --> 00:27battle to fight cancer. This week,
00:27 --> 00:29it's a conversation about prostate
00:29 --> 00:31cancer with Doctor Michael Leapman.
00:31 --> 00:33Doctor Leapman is assistant professor of
00:33 --> 00:36urology at the Yale School of Medicine,
00:36 --> 00:38where Doctor Chagpar is a
00:38 --> 00:39professor of surgical oncology.
00:40 --> 00:43Michael, maybe we can start off by
00:43 --> 00:45laying the groundwork and giving us
00:45 --> 00:48a bit of a landscape of prostate cancer.
00:48 --> 00:51How common is it? How lethal is it?
00:51 --> 00:53Who gets it? Why should we care
00:53 --> 00:55about this disease?
00:55 --> 00:57Prostate cancer is something
00:57 --> 00:59that I think is always on our minds.
00:59 --> 01:02We hear a lot about it on the news.
01:02 --> 01:04It is the most commonly diagnosed non
01:04 --> 01:06skin cancer in men and over 230,000
01:06 --> 01:09American men are expected to be
01:09 --> 01:11diagnosed with prostate cancer next year.
01:11 --> 01:13And it's also the second leading
01:13 --> 01:15cause of cancer death in men,
01:15 --> 01:17and so that imbalance between how common
01:17 --> 01:20it is and the risk of death from prostate
01:20 --> 01:23cancer is really quite interesting,
01:23 --> 01:25because the majority of men who are
01:25 --> 01:27diagnosed with prostate cancer will
01:27 --> 01:29not have a very aggressive cancer.
01:29 --> 01:30But then again,
01:30 --> 01:32there is a lot of aggressive prostate
01:32 --> 01:34cancer that requires treatment,
01:34 --> 01:36and so figuring out that balance,
01:36 --> 01:38figuring out where one lives
01:38 --> 01:39on that spectrum is really
01:39 --> 01:42important.
01:42 --> 01:46How does that happen? Is it a matter of
01:46 --> 01:49seeing how aggressive the cancer
01:49 --> 01:53cells look by their grade on a biopsy?
01:53 --> 01:56Or are there other factors that kind
01:56 --> 01:59of play into figuring out how
01:59 --> 02:02aggressive this cancer is?
02:02 --> 02:05A lot of factors really come
02:05 --> 02:08together to help make that distinction
02:08 --> 02:11about the risk level that someone has.
02:11 --> 02:14Historically, we really had a very
02:14 --> 02:16monolithic approach where if someone had
02:16 --> 02:18cancer there was treatment right away.
02:18 --> 02:20There was very little disconnection there.
02:20 --> 02:24It was just kind of a one way path from a
02:24 --> 02:27diagnosis of prostate cancer to treatment.
02:27 --> 02:29And that really continued for decades
02:29 --> 02:31and decades until the understanding came
02:31 --> 02:33that many of the prostate cancers did
02:33 --> 02:35extremely well and probably did extremely,
02:35 --> 02:37extremely well without treatment.
02:37 --> 02:39And there was growing data and really
02:39 --> 02:42strong information that these are very,
02:42 --> 02:45very common in men in their 80s.
02:45 --> 02:47They may be as prevalent as 60%
02:47 --> 02:50of people might have a low grade,
02:50 --> 02:51non aggressive prostate cancer.
02:51 --> 02:54So this story began to be written over
02:54 --> 02:5730 years ago where there was increasing
02:57 --> 02:58awareness of
02:58 --> 03:00the spectrum of aggressiveness in
03:00 --> 03:03prostate cancer and so the main criteria
03:03 --> 03:06that we use to estimate a given man's
03:06 --> 03:09risk of prostate cancer and the risk of
03:09 --> 03:11cancer will behave aggressively relate
03:11 --> 03:14to what it does look like on under a biopsy,
03:14 --> 03:17and there is a scale used called
03:17 --> 03:18the Gleason scale,
03:18 --> 03:19which is a pathologist,
03:19 --> 03:23will take a look at the biopsy under
03:23 --> 03:23microscope
03:23 --> 03:26and look at how normal or abnormal
03:26 --> 03:27the cancer cells look.
03:27 --> 03:29Look at the architectural pattern
03:29 --> 03:31of the glands and assign a level.
03:31 --> 03:33And that level is highly related
03:33 --> 03:35to the outcome of the cancer.
03:35 --> 03:37So that's a very good
03:37 --> 03:39way of beginning to estimate
03:39 --> 03:41the trajectory of prostate cancer.
03:41 --> 03:44Some of the other tools we use,
03:44 --> 03:46are PSA levels. PSA is a common blood
03:46 --> 03:49test that is ordered and it's a
03:49 --> 03:52protein that is made by the prostate.
03:52 --> 03:55And it can be found in the blood.
03:55 --> 03:55Now,
03:55 --> 03:56having a PSA level doesn't mean
03:56 --> 03:58that you have prostate cancer,
03:58 --> 04:00but there is a relationship between
04:00 --> 04:03how high that PSA level is and the
04:03 --> 04:05risk that a man can have prostate cancer.
04:05 --> 04:08So that level of PSA is also prognostic,
04:08 --> 04:11meaning it can help us estimate how likely
04:11 --> 04:13the cancer is to be aggressive or not.
04:13 --> 04:15And the last classic thing that
04:15 --> 04:18we do is is a rectal examination of
04:18 --> 04:21physical examination where we feel the
04:21 --> 04:23prostate and see if we can feel a lump
04:23 --> 04:26or a bump which is also kind of an
04:26 --> 04:28indicator of how big a tumor might be,
04:28 --> 04:30or if there's something that has
04:30 --> 04:32reached a significant level.
04:32 --> 04:33So those are historically how we
04:33 --> 04:35estimate aggressiveness and
04:35 --> 04:36the appropriateness of treatment,
04:36 --> 04:38or what treatment should be
04:38 --> 04:40undertaken. So before we kind of
04:40 --> 04:42dig into a little bit more on that
04:42 --> 04:45just to take one step back when
04:45 --> 04:47people often hear about PSA
04:47 --> 04:48and digital rectal exams,
04:48 --> 04:50they often think about screening more
04:50 --> 04:53than they do about prognostication.
04:53 --> 04:55And yet there have been some changes
04:55 --> 04:58I understand to what people are
04:58 --> 05:00recommending in terms of screening.
05:00 --> 05:03So can you take us back and tell
05:03 --> 05:06us a little bit about who should
05:06 --> 05:09get screened when and with what?
05:09 --> 05:11Should all men get screened if
05:11 --> 05:13prostate cancer is really prevalent,
05:13 --> 05:16should this be a foregone conclusion,
05:16 --> 05:19or is there a benefit to screening?
05:19 --> 05:21And if so, in what populations?
05:21 --> 05:24I'm so happy you asked that because
05:24 --> 05:26that really I think begins to speak
05:26 --> 05:28to the heart of the controversy and
05:28 --> 05:31what I see in my daily practices.
05:31 --> 05:33There is so much
05:33 --> 05:35ongoing communication about that and
05:35 --> 05:37different perceptions about screening.
05:37 --> 05:41And so the story does go back even further,
05:41 --> 05:43again, probably several decades
05:43 --> 05:46ago when that PSA blood test was
05:46 --> 05:48discovered in the late 1980s,
05:48 --> 05:52and they found that if you check PSA
05:52 --> 05:55you will find some people
05:55 --> 05:56who have abnormal PSA levels,
05:56 --> 05:59and we typically do a biopsy next and we're
05:59 --> 06:01identifying prostate cancer so historically,
06:01 --> 06:04back in the late 80s and early
06:04 --> 06:0690s and into the early 2000s,
06:06 --> 06:09there was a lot of PSA testing.
06:09 --> 06:12It was routinely used in pretty much all men,
06:12 --> 06:13adult men,
06:13 --> 06:15and a lot of prostate cancers
06:15 --> 06:18were being found as a result.
06:18 --> 06:19And so you know,
06:19 --> 06:22it became clear that
06:22 --> 06:24since a lot of prostate
06:24 --> 06:25cancer is being detected,
06:25 --> 06:27that more rigorous evidence was
06:27 --> 06:29needed to be undertaken so very
06:29 --> 06:30large national and International
06:30 --> 06:33Studies were done to look at the
06:33 --> 06:35benefits of PSA testing to determine
06:35 --> 06:37and really quantify how beneficial it
06:37 --> 06:40is to have a PSA checked and find a
06:40 --> 06:42cancer that could be in the prostate
06:42 --> 06:44which was previously undetected,
06:44 --> 06:46because they generally don't
06:46 --> 06:48cause symptoms and so
06:48 --> 06:49when we talk about screening,
06:49 --> 06:51we mean taking people who have no
06:51 --> 06:53symptoms who are otherwise, well., NOTE Confidence: 0.90424776
06:53 --> 06:55they have no evidence of prostate cancer,
06:55 --> 06:57but trying to find something
06:57 --> 06:59early before it is manifest before
06:59 --> 07:01it comes to the surface.
07:01 --> 07:04And a few studies have been done,
07:04 --> 07:06and one landmark study was performed in
07:06 --> 07:09the United States which really didn't
07:09 --> 07:12find a big survival benefit to screening.
07:12 --> 07:14And so as a result in 2012,
07:14 --> 07:17the US Preventive Service Task Force,
07:17 --> 07:19which is a guideline issuing
07:19 --> 07:21body in the United States,
07:21 --> 07:25said that because of that absence of benefit
07:25 --> 07:27and the great potential for harm by
07:27 --> 07:29treating that no men should undergo
07:29 --> 07:32PSA testing under any circumstance.
07:32 --> 07:35It was kind of a blanket recommendation.
07:35 --> 07:38And this was really kind of a
07:38 --> 07:39controversial statement for people,
07:39 --> 07:41especially in the prostate cancer field,
07:41 --> 07:43because it was clear that in the
07:43 --> 07:4520 years where prostate cancer
07:45 --> 07:46screening was occurring,
07:46 --> 07:49there was a substantial reduction in
07:49 --> 07:52the risk of death from prostate cancer.
07:52 --> 07:55And so right after that guideline came to be,
07:55 --> 07:57there was another study
07:57 --> 07:59that finally came to fruition,
08:00 --> 08:03which had been conducted for over 10 years,
08:03 --> 08:04but the results weren't available,
08:04 --> 08:06which was performed in Europe,
08:06 --> 08:09which did find a large benefit to
08:09 --> 08:11screening with PSA in terms of reducing
08:11 --> 08:14the risk of prostate cancer death.
08:14 --> 08:16So here you have these two conflicting
08:16 --> 08:18randomized trials which create
08:18 --> 08:20a lot of uncertainty at which
08:20 --> 08:21that uncertainty still exists,
08:21 --> 08:23and there's still a lot of
08:23 --> 08:25controversy about which one is
08:25 --> 08:27right and which one is flawed.
08:27 --> 08:28There are some
08:29 --> 08:31substantial flaws with the
08:31 --> 08:33study performed in the United
08:33 --> 08:34States because
08:34 --> 08:36many of the patients who were in
08:36 --> 08:37the trial were actually already
08:37 --> 08:39screened for prostate cancer,
08:39 --> 08:42so it was a bit hard to
08:42 --> 08:44distinguish those who had been
08:44 --> 08:45screened already versus those
08:45 --> 08:47who were not being screened.
08:47 --> 08:49So it was almost as if everyone
08:49 --> 08:51was really getting the same thing.
08:51 --> 08:54So the controlled element of the
08:54 --> 08:56trial was hard to appreciate.
08:56 --> 08:58So that's kind of a long winded
08:58 --> 09:01way of saying that it's still
09:01 --> 09:03a very controversial question,
09:03 --> 09:05but the evidence has really continued
09:05 --> 09:07to accumulate as these studies have
09:07 --> 09:10been followed for more and more years,
09:10 --> 09:12and it really does appear to
09:12 --> 09:14be as a substantial risk reduction
09:14 --> 09:17in death from prostate cancer by
09:17 --> 09:20having a PSA checked and finding
09:20 --> 09:21early stage cancers and
09:21 --> 09:24so do you recommend that for all men
09:24 --> 09:28or men over a certain age or men with a
09:28 --> 09:30certain demographic characteristic?
09:30 --> 09:32I mean, perhaps the difference
09:32 --> 09:34between the two studies and
09:34 --> 09:36I'm just surmising here,
09:36 --> 09:38maybe that there were different
09:38 --> 09:40characteristics of the people participating,
09:40 --> 09:43such that some men may
09:43 --> 09:45really benefit from early detection
09:45 --> 09:47and other men, not so much.
09:47 --> 09:50I think you're absolutely right.
09:50 --> 09:53And so we really kind of
09:53 --> 09:56have to be anchored in what the
09:56 --> 10:00studies have shown and the studies
10:00 --> 10:03in both Europe and the United States,
10:03 --> 10:06really focus on men in their 50s and 60s,
10:06 --> 10:08and so the best evidence would suggest
10:08 --> 10:10that men who are above the age of
10:10 --> 10:1275 really don't benefit very much
10:12 --> 10:15from having a routine PSA checked.
10:15 --> 10:17Now it's a different story if people are
10:17 --> 10:19having urinary symptoms or have a reason
10:19 --> 10:22to suspect that they have prostate cancer.
10:22 --> 10:24But when we talk about screening,
10:24 --> 10:25we're saying being asymptomatic,
10:25 --> 10:26having no problems,
10:26 --> 10:29but getting a PSA checked and going
10:29 --> 10:31looking for potential prostate cancer.
10:31 --> 10:34So the US Preventive Services Task Force
10:34 --> 10:37which issues these these guidelines in
10:37 --> 10:392018 revised their recommendation to
10:39 --> 10:41suggest that prostate cancer screening
10:41 --> 10:44with PSA can be considered kind of
10:44 --> 10:46in a shared decision-making fashion,
10:46 --> 10:49which means that a patient and their
10:49 --> 10:52physician should have a conversation
10:52 --> 10:54about the potential harms and benefits,
10:54 --> 10:58and find a way to balance the potential
10:58 --> 11:01harms of undergoing a PSA test,
11:01 --> 11:02which could include
11:02 --> 11:04having a prostate biopsy,
11:04 --> 11:06having invasive testing or finding a
11:06 --> 11:09cancer which is non aggressive and
11:09 --> 11:12might not have changed their life expectancy.
11:12 --> 11:14And balancing that with the potential
11:14 --> 11:16benefit of reducing their risk from
11:16 --> 11:18prostate cancer death so it is really
11:18 --> 11:21kind of not a one size fits all approach,
11:21 --> 11:23but it really should occur for men
11:23 --> 11:26who are in the age of 55 to 69,
11:26 --> 11:28which is kind of the recommended group.
11:28 --> 11:30Some demographics appear to be higher
11:30 --> 11:32risk and we do recommend earlier
11:32 --> 11:33screening beginning at
11:33 --> 11:3645 and potentially even earlier for
11:36 --> 11:38people who are falling into a high
11:38 --> 11:40risk demographic based on a strong
11:40 --> 11:41family history of prostate cancer,
11:41 --> 11:43and that means having a
11:43 --> 11:44first degree family relative
11:44 --> 11:45with prostate cancer,
11:45 --> 11:48such as a brother or father.
11:48 --> 11:50Or having a known genetic alteration,
11:50 --> 11:52such as a mutation in the BRCA2
11:52 --> 11:54gene which is known to be associated
11:54 --> 11:56with prostate cancer risk and other
11:56 --> 11:58certain racial demographics such as
11:58 --> 12:01African American men are at higher
12:01 --> 12:02risk for prostate cancer detection
12:02 --> 12:04and death from prostate cancer,
12:04 --> 12:06and so they also fall into a higher
12:06 --> 12:08risk category where screening may
12:08 --> 12:09be appropriate earlier.
12:09 --> 12:12But it's definitely not a one size
12:12 --> 12:14fits all approach.
12:14 --> 12:16I do think that the way to do it
12:16 --> 12:19is to really have a thoughtful
12:19 --> 12:20conversation to understand
12:20 --> 12:21the whole picture here and
12:21 --> 12:24why we would even consider prostate
12:24 --> 12:26cancer screening what we could find,
12:26 --> 12:28what the outcomes could be,
12:28 --> 12:30what could happen
12:30 --> 12:32and so doing that in the context
12:32 --> 12:34of a relationship with a physician
12:34 --> 12:35or health care provider who
12:35 --> 12:37you trust is really important.
12:38 --> 12:42And going back to our
12:42 --> 12:43earlier conversation,
12:43 --> 12:46even if you're screened and an
12:46 --> 12:48early prostate cancer is detected,
12:48 --> 12:50not all men will undergo treatment
12:50 --> 12:52for their prostate cancer, right?
12:52 --> 12:56So how do you decide who gets treatment?
12:56 --> 12:57Who doesn't get treatment,
12:57 --> 12:59and what that looks like?
12:59 --> 13:02Yes, and I think that has
13:02 --> 13:04really been the transformational shift that
13:04 --> 13:08has happened in the past ten years or so.
13:08 --> 13:11And you know the harms of PSA testing really
13:11 --> 13:15relate to treating cancers that we find,
13:15 --> 13:17and there are real
13:17 --> 13:19risks of cancer treatment,
13:19 --> 13:22including changes to urinary function,
13:24 --> 13:26and GI and rectal toxicity.
13:26 --> 13:29So the big change is
13:29 --> 13:30the acknowledgement that it
13:30 --> 13:32is appropriate to not treat
13:32 --> 13:34initially patients who have cancer that
13:34 --> 13:38appear to be non aggressive and that is a
13:38 --> 13:41process that we call active surveillance,
13:41 --> 13:43which is a period of close
13:43 --> 13:44monitoring of prostate cancer
13:44 --> 13:46rather than immediate treatment.
13:46 --> 13:49And so what's so
13:49 --> 13:51transformative about that is that
13:51 --> 13:53it sort of allows us to have
13:53 --> 13:54the benefits of early detection,
13:54 --> 13:55which are finding
13:55 --> 13:58potentially lethal cancers earlier,
13:58 --> 14:00treating those ones and forgoing or
14:00 --> 14:02deferring treatment altogether for
14:02 --> 14:04those cancers that are non aggressive.
14:05 --> 14:07So we're going to have to take a
14:07 --> 14:09short break for medical minute,
14:09 --> 14:11but when we come back,
14:11 --> 14:14we're going to dig into who gets treated,
14:14 --> 14:15how they get treated,
14:15 --> 14:17and how we can really personalize
14:17 --> 14:18treatment for prostate cancer.
14:18 --> 14:20So please stay tuned with my
14:20 --> 14:22guest Doctor Michael Leapman.
14:22 --> 14:25Support for Yale Cancer Answers
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14:31 --> 14:33Learn more at astrazeneca-us.com.
14:35 --> 14:38This is a medical minute about breast cancer,
14:38 --> 14:40the most common cancer in
14:40 --> 14:42women. In Connecticut alone,
14:42 --> 14:44approximately 3000 women will be
14:44 --> 14:46diagnosed with breast cancer this year,
14:46 --> 14:48but thanks to earlier detection,
14:48 --> 14:50noninvasive treatments, and novel therapies,
14:50 --> 14:53there are more options for patients to
14:53 --> 14:56fight breast cancer than ever before.
14:56 --> 14:58Women should schedule a baseline mammogram
14:58 --> 15:02beginning at age 40 or earlier if they have
15:02 --> 15:04risk factors associated with breast cancer.
15:04 --> 15:06Digital breast tomosynthesis or
15:06 --> 15:083D mammography is transforming
15:08 --> 15:10breast screening by significantly
15:10 --> 15:11reducing unnecessary procedures
15:11 --> 15:15while picking up more cancers and
15:15 --> 15:18eliminating some of the fear and anxiety
15:18 --> 15:19many women experience.
15:19 --> 15:21More information is available
15:21 --> 15:22at yalecancercenter.org.
15:22 --> 15:26You're listening to Connecticut Public Radio.
15:26 --> 15:26Welcome
15:26 --> 15:28back to Yale Cancer Answers.
15:28 --> 15:31This is doctor Anees Chagpar and
15:31 --> 15:33I'm joined tonight by my guest doctor
15:33 --> 15:36Michael Leapman and we're talking about prostate
15:36 --> 15:38cancer and right before the break,
15:38 --> 15:40Michael you were talking about the
15:40 --> 15:43fact that some men can have
15:43 --> 15:45what's called active surveillance,
15:45 --> 15:47just monitoring their prostate cancer,
15:47 --> 15:49particularly if it's found early.
15:49 --> 15:52Because there is toxicity to
15:52 --> 15:54prostate cancer treatment.
15:54 --> 15:57But other men really do require treatment,
15:57 --> 15:59so let's dig into that group.
15:59 --> 16:01How do you figure out who
16:01 --> 16:03requires treatment and who doesn't?
16:03 --> 16:06Yes, so that is one of the
16:06 --> 16:07really important things
16:07 --> 16:10that we do at the time of diagnosis.
16:10 --> 16:13So if a man has had a prostate biopsy,
16:13 --> 16:14we detect prostate cancer,
16:14 --> 16:17the first thing that we really want
16:17 --> 16:19to do is is trying to gather all the
16:20 --> 16:22information possible to come up with that
16:22 --> 16:26estimate of what we're dealing with.
16:26 --> 16:28And so, in addition to the
16:28 --> 16:30things that we discussed previously,
16:30 --> 16:32the Gleason score of the PSA level,
16:32 --> 16:33the physical exam,
16:33 --> 16:35there are other tools that can help
16:35 --> 16:37us predict what we're dealing with,
16:37 --> 16:39what the outcome would be
16:39 --> 16:40if we did treatment,
16:40 --> 16:42or if we didn't do treatment,
16:42 --> 16:44and two of those tools that we
16:44 --> 16:47want to talk about,
16:47 --> 16:49one is called a prostate MRI,
16:49 --> 16:51which essentially is a high
16:51 --> 16:53resolution MRI of the prostate.
16:53 --> 16:54That often actually precedes the
16:54 --> 16:57biopsy and helps us to a more
16:57 --> 16:59accurate biopsy by finding areas
16:59 --> 17:01within the prostate that could
17:01 --> 17:02harbor prostate cancer and allowing
17:02 --> 17:05us to more accurately target them
17:05 --> 17:07so that we can identify cancer.
17:07 --> 17:10If we don't find something,
17:10 --> 17:12the absence of an aggressive
17:12 --> 17:14cancer is also reassuring to us,
17:14 --> 17:16so that is an important component
17:16 --> 17:18that helps us identify potentially
17:18 --> 17:19more aggressive prostate cancer
17:19 --> 17:21that could be present.
17:21 --> 17:22And again increasingly happens
17:22 --> 17:24before the time of diagnosis.
17:24 --> 17:26But we incorporate that information
17:26 --> 17:28to help come up with a sort
17:28 --> 17:30of an assessment of risk.
17:30 --> 17:32The other are a host of validated
17:32 --> 17:34genomic tests which measure expression
17:34 --> 17:36levels of panels of genes that are
17:36 --> 17:38associated with prostate cancer outcome,
17:38 --> 17:41and so these are not the tests that tell you
17:41 --> 17:43do you have a good gene or a bad gene.
17:43 --> 17:46These are genes that we all have
17:46 --> 17:49present in all cells and what what we
17:49 --> 17:52do is we sort of look at the tumor
17:52 --> 17:54tissue and we send it off to various
17:54 --> 17:56companies that can perform these
17:56 --> 17:58tests and essentially get a score back,
17:58 --> 18:00which is an estimate of risk.
18:00 --> 18:03An estimate of the likelihood of a
18:03 --> 18:06prostate cancer spreading beyond the
18:06 --> 18:08prostate or returning after treatment.
18:08 --> 18:10Now these tests are not recommended
18:10 --> 18:12for all men with prostate cancer.
18:12 --> 18:14They are not an absolute requirement
18:14 --> 18:17because if the cancer appears to be
18:17 --> 18:18sufficiently aggressive based on
18:18 --> 18:20their Gleason score or PSA level,
18:20 --> 18:22there appears to be little utility
18:22 --> 18:23in doing the testing.
18:23 --> 18:24However,
18:24 --> 18:26for people who might be on the fence,
18:26 --> 18:28who maybe are considering active
18:28 --> 18:30surveillance or treatment and want
18:30 --> 18:32a bit more information about their
18:32 --> 18:34estimated prognosis or how they might
18:34 --> 18:36do in either of those categories,
18:36 --> 18:39these tests appear to have some value.
18:39 --> 18:41And so putting all those together with
18:41 --> 18:44of course very important things like
18:44 --> 18:46a patient's personal preferences,
18:46 --> 18:47what they want,
18:47 --> 18:49what their functional status is,
18:49 --> 18:51what their age and their overall
18:51 --> 18:54medical health is helps to create
18:54 --> 18:56a more holistic picture of a man's
18:56 --> 18:58prostate cancer profile.
18:58 --> 19:00And what treatment options
19:00 --> 19:01or what management options
19:01 --> 19:02would be appropriate.
19:02 --> 19:06And tell us with that score,
19:06 --> 19:09does it give men a concept of
19:09 --> 19:11their survival rate
19:11 --> 19:13or you were saying that it might give
19:13 --> 19:16you a clue as to the likelihood that
19:16 --> 19:18it'll spread beyond the prostate,
19:18 --> 19:20what are the tangible measures
19:20 --> 19:22that men get with that information
19:22 --> 19:23rather than simply a score,
19:23 --> 19:26which can be kind of nebulous.
19:26 --> 19:28The information that they provide there are
19:28 --> 19:31a few different tests, and they kind
19:31 --> 19:32of frame the information differently.
19:32 --> 19:35But the two main measures that they
19:35 --> 19:37provide are the risk of death from
19:37 --> 19:39prostate cancer within 10 years.
19:39 --> 19:41And the other one would be
19:41 --> 19:43a risk of recurrence of prostate
19:43 --> 19:45cancer or metastasis from prostate
19:45 --> 19:47cancer within five years,
19:47 --> 19:49and so those are the estimates and
19:49 --> 19:52keep in mind that these are not
19:52 --> 19:54firm predictions because treatments
19:54 --> 19:56have changed very much and they
19:56 --> 19:57continue to change.
19:57 --> 19:58But these are still estimates
19:58 --> 20:00and they really do appear
20:00 --> 20:02to be valid at distinguishing more
20:02 --> 20:03aggressive and less aggressive
20:03 --> 20:04prostate cancer,
20:04 --> 20:07and so knowing where those risk
20:07 --> 20:09estimates live are important because
20:09 --> 20:11I think they can help people make
20:11 --> 20:13more informed decisions about #1
20:13 --> 20:15the necessity of treatment and
20:15 --> 20:17the intensity of treatment.
20:17 --> 20:19So should I be treated altogether?
20:19 --> 20:21Should my treatment include one
20:21 --> 20:23form of treatment such as surgery
20:23 --> 20:26alone or should I have surgery
20:26 --> 20:28and radiation therapy or
20:28 --> 20:30additional sequences of treatment?
20:30 --> 20:32Based on the risk level and so
20:32 --> 20:34that premise of can I use genomic
20:34 --> 20:35testing to make that decision is
20:35 --> 20:38still being fleshed out a little bit.
20:39 --> 20:43And so the number that men get, is there
20:43 --> 20:45kind of a toggle where it
20:45 --> 20:48will say your risk of survival
20:48 --> 20:50or distant recurrence or even
20:50 --> 20:53local recurrence at 10 years is X,
20:53 --> 20:55but if you choose surgery alone
20:55 --> 20:57it will reduce it by this much.
20:57 --> 21:00If you choose surgery and radiation
21:00 --> 21:02it will reduce it by that much.
21:02 --> 21:04If you choose systemic therapy,
21:04 --> 21:06it'll reduce it by this much.
21:06 --> 21:09Is there that kind of granularity in the
21:09 --> 21:12data with a toggle switch that will help
21:12 --> 21:14men's decision-making that's such
21:14 --> 21:15a wonderful question that I think
21:15 --> 21:17we're not there yet because
21:17 --> 21:19of the novelty of these tools,
21:19 --> 21:21and because of that, frankly,
21:21 --> 21:23the novelty of doing active surveillance,
21:23 --> 21:25we don't have that longitudinal data yet.
21:25 --> 21:28I think that is really the Holy Grail
21:28 --> 21:31where if we could say, if you
21:31 --> 21:32do active surveillance,
21:32 --> 21:34your risk is X, but if you do treatment
21:34 --> 21:36it would turn down to Y.
21:39 --> 21:41But say if you had surgery
21:41 --> 21:42as opposed to radiation,
21:42 --> 21:45your risk will be A, so that that is clearly,
21:45 --> 21:48I think, where the field is moving.
21:48 --> 21:51It is a bit challenging because
21:51 --> 21:52treatment for prostate cancer is
21:52 --> 21:54very much up to the patients.
21:54 --> 21:56There are many other factors that
21:56 --> 21:57lead to these things and so really
21:57 --> 21:59to do that in a rigorous way,
21:59 --> 22:01we would need to do a randomized
22:01 --> 22:03trial where we say we're going to
22:03 --> 22:05flip a coin and
22:05 --> 22:07half the group is going
22:07 --> 22:09to have surgery and half is going
22:09 --> 22:11to have radiation and we're going
22:11 --> 22:13to look at
22:13 --> 22:15how the genomic test or the
22:15 --> 22:16MRI predicted the outcome,
22:16 --> 22:18so I don't think that's ever going to happen,
22:18 --> 22:21where we're going to be able to modify
22:21 --> 22:22treatment decisions based on that.
22:22 --> 22:24But we're getting closer with
22:24 --> 22:26other studies that
22:26 --> 22:29are looking at genomics to help
22:29 --> 22:29guide treatment,
22:29 --> 22:31and stratify risk and predict
22:31 --> 22:32response to various treatments.
22:32 --> 22:34So I think that is very much
22:34 --> 22:36where we should be going,
22:36 --> 22:38but we're not there yet.
22:38 --> 22:40So Michael, you have mentioned
22:40 --> 22:43surgery and radiation a few times
22:43 --> 22:45and not so much systemic therapy.
22:45 --> 22:48But when we talk on this show
22:48 --> 22:51as we do a lot about genomics,
22:51 --> 22:52very often we're talking
22:52 --> 22:54about as you said,
22:54 --> 22:57genes that are turned on or turned
22:57 --> 22:59off within a particular tumor.
22:59 --> 23:01Oftentimes these are targets
23:01 --> 23:02for various systemic therapies.
23:02 --> 23:06Has that been looked at in prostate cancer?
23:07 --> 23:09The cancer is interesting because
23:09 --> 23:11I think in comparison to some of
23:11 --> 23:13the other cancers, such as lung,
23:13 --> 23:15that really do have these actionable
23:15 --> 23:17driver mutations that there are drugs
23:17 --> 23:19specifically targeting a certain mutation
23:20 --> 23:22that has not really been the case
23:22 --> 23:23in prostate cancer for many reasons.
23:23 --> 23:25Number one, the main systemic
23:25 --> 23:27therapies for people who have advanced
23:27 --> 23:29or metastatic prostate cancer
23:29 --> 23:31work by suppressing testosterone.
23:31 --> 23:32Those are very effective treatments
23:32 --> 23:34regardless of genomic profile,
23:34 --> 23:37that is kind of the mainstay of treatment,
23:37 --> 23:40and they almost universally have
23:40 --> 23:41a good response.
23:41 --> 23:45But there is increasing recognition that
23:45 --> 23:48there are molecular and biomarker
23:48 --> 23:50hallmarks such as homologous
23:50 --> 23:51recombination gene mutations,
23:51 --> 23:53microsatellite instability or
23:53 --> 23:55DNA mismatch repair deficiencies that
23:55 --> 23:57can lead to targeted treatments for
23:57 --> 23:59men who do have metastatic prostate
23:59 --> 24:01cancer or advanced prostate cancer,
24:01 --> 24:02and so that,
24:02 --> 24:04I think is one of the big changes
24:04 --> 24:07that has occurred in recent years,
24:07 --> 24:10is the recommendation that we do
24:10 --> 24:12germline testing for patients with
24:12 --> 24:14regional or metastatic prostate cancer
24:14 --> 24:16to see if they have an actionable
24:16 --> 24:18mutation that could be targeted.
24:19 --> 24:22And so kind of getting back to
24:22 --> 24:24one of the confusing parts of
24:24 --> 24:28terminology that I think a lot of our
24:28 --> 24:31listeners might get mixed up about,
24:31 --> 24:33it goes back to something
24:33 --> 24:35that you just pointed out.
24:35 --> 24:37The difference between germline
24:37 --> 24:39mutations and somatic mutations,
24:39 --> 24:41so earlier for example you
24:41 --> 24:44mentioned that men who had a
24:44 --> 24:47BRCA genetic mutation may be at
24:47 --> 24:49a higher risk of developing
24:49 --> 24:50prostate cancer,
24:50 --> 24:52but that is fundamentally different
24:52 --> 24:53than this genomic testing
24:53 --> 24:54that you're talking about.
24:54 --> 24:57Can you flesh that out for our listeners?
24:57 --> 24:58Absolutely,
24:58 --> 25:01when we speak about these
25:01 --> 25:02germline mutations we're talking about
25:02 --> 25:05the DNA that were born with that
25:05 --> 25:08that essentially has been inherited to us,
25:08 --> 25:11which is in our germ line is present in all
25:11 --> 25:14of ourselves and they may predispose to the
25:14 --> 25:17risk of developing cancer and the BRCA2
25:17 --> 25:20mutation is a very well acknowledged
25:20 --> 25:23mutation that confers cancer risk.
25:23 --> 25:25When we speak about the
25:25 --> 25:26panel genomic testing,
25:26 --> 25:28we're looking at relative expression levels,
25:28 --> 25:30how turned up or turned down
25:30 --> 25:32genes are within tumors,
25:32 --> 25:33and these are not necessarily
25:33 --> 25:35genes which have been inherited,
25:35 --> 25:37or mutations within genes,
25:37 --> 25:38but it's a measurement
25:38 --> 25:40of how active they are,
25:40 --> 25:44so this is not a good gene or a bad gene,
25:47 --> 25:48we're wondering,
25:48 --> 25:49how this was conferred,
25:50 --> 25:51because genetics and prostate cancer
25:51 --> 25:53risk is such a common question
25:53 --> 25:54that we get because prostate
25:54 --> 25:56cancer is very common and there's
25:56 --> 25:59a thought that many
25:59 --> 26:01patients have that they inherited a
26:01 --> 26:02certain cancer predisposition from a
26:02 --> 26:05family member and that may be the case.
26:05 --> 26:07And there are certain
26:08 --> 26:10well recognized genetic mutations
26:10 --> 26:13that can be inherited in the germline,
26:13 --> 26:15but we're looking at levels of
26:15 --> 26:17cancer levels of gene expression
26:17 --> 26:20associated with the cancer outcome.
26:21 --> 26:24Yeah, and so you had mentioned that
26:24 --> 26:26in addition to this genomic profile,
26:26 --> 26:29that men will often make decisions based on
26:29 --> 26:32other factors based on personal preference,
26:32 --> 26:35but for a lot of men I can
26:35 --> 26:38imagine that you know they come
26:38 --> 26:42in and you say you've got prostate cancer.
26:42 --> 26:44You know you can have active surveillance.
26:44 --> 26:46You can have surgery.
26:46 --> 26:47You can have surgery,
26:47 --> 26:49plus radiation and the
26:51 --> 26:54genomic testing how to interpret
26:54 --> 26:56that number, your 10 year disease
26:56 --> 26:59free survival risk is going to be 10%.
26:59 --> 27:00What does that mean?
27:00 --> 27:04Can you help us to understand how
27:04 --> 27:06you discuss that with the patient and
27:06 --> 27:09how they might factor in that information
27:09 --> 27:11and what other characteristics or
27:11 --> 27:14factors they may consider when trying to
27:14 --> 27:16figure out how they should be treated?
27:16 --> 27:19I can just imagine that they
27:19 --> 27:22say look doc, I don't want cancer.
27:22 --> 27:25I want to live as long and as
27:25 --> 27:26well as I possibly can.
27:29 --> 27:31These conversations are universally difficult.
27:31 --> 27:33I think having a cancer diagnosis
27:33 --> 27:35no matter what the grade,
27:35 --> 27:36no matter what the stage,
27:36 --> 27:39no matter what your doctor tells you,
27:39 --> 27:41is inherently an anxiety provoking
27:41 --> 27:42and stressful experience.
27:42 --> 27:44There has been a lot of change,
27:44 --> 27:47I think in the awareness of men of the
27:47 --> 27:50fact that prostate cancer is very common,
27:50 --> 27:52that the outcomes without
27:52 --> 27:53treatment may be excellent,
27:53 --> 27:55and so that has changed.
27:55 --> 27:56A lot of men are
27:56 --> 27:58expecting that diagnosis and have
27:58 --> 28:00had friends or family members who
28:00 --> 28:03have gone through the same thing.
28:03 --> 28:05But still there is the kind of reflexive
28:05 --> 28:07belief that any cancer risk should be
28:07 --> 28:10reduced that you hear that word you
28:10 --> 28:12want it out of your body.
28:12 --> 28:13You want it treated,
28:13 --> 28:15no matter what
28:15 --> 28:16the consequences is,
28:16 --> 28:18and I think that's very often the initial
28:18 --> 28:21reaction is I don't care what it does.
28:21 --> 28:22I want this gone.
28:22 --> 28:23I want to treat it,
28:23 --> 28:26and so that's where I
28:26 --> 28:28think building a personal relationship is so
28:28 --> 28:30important to give people time, space,
28:30 --> 28:33support for dealing with that and
28:33 --> 28:35understanding what the diagnosis is
28:35 --> 28:37and really in the cool light of day
28:37 --> 28:40integrating all of the information and really
28:40 --> 28:42trying to zone in on what the risks are,
28:42 --> 28:44what the benefits are.
28:44 --> 28:46And it's really not a one
28:46 --> 28:47size fits all approach.
28:47 --> 28:48Active surveillance is
28:48 --> 28:50not right for everybody,
28:50 --> 28:52but nor is treatment right for everyone.
28:52 --> 28:55And so I think that really doing that in the
28:55 --> 28:58context of a truly shared decision between
28:58 --> 29:01stakeholders on the patient side and on
29:01 --> 29:03the physician side are so important.
29:03 --> 29:05These tools are just tools and
29:05 --> 29:08the hope is that
29:08 --> 29:09they do provide more clarity,
29:09 --> 29:11but I don't believe they're
29:11 --> 29:13sort of magically the answer.
29:13 --> 29:15And actually we are leading a study
29:15 --> 29:17right now to help understand the
29:17 --> 29:19personal experience and it's an interview
29:19 --> 29:21based study where we were interviewing
29:21 --> 29:24people going through the experience
29:24 --> 29:26and we essentially want to open
29:26 --> 29:28the door and hear from them and learn
29:28 --> 29:30what is the experience of having a
29:30 --> 29:32prostate cancer diagnosis and what is
29:32 --> 29:34the experience of having genomic testing?
29:34 --> 29:36Does it help? Does it hurt?
29:36 --> 29:37Does it create uncertainty?
29:37 --> 29:38Does it alleviate uncertainty?
29:38 --> 29:40And I'm very excited to be involved
29:40 --> 29:41in that study.
29:41 --> 29:43Right now I actually just came off
29:43 --> 29:45of a call where we're going through
29:45 --> 29:47these interviews and we've been so
29:47 --> 29:49fortunate to have men share this
29:49 --> 29:51very personal part of their lives
29:51 --> 29:53with us and give us really new
29:53 --> 29:55and what I believe will be transformative
29:55 --> 29:56information about what it's like
29:56 --> 29:57to go through this.
29:57 --> 29:59Because when these tests are
30:00 --> 30:02studied in laboratories and by companies,
30:02 --> 30:04there's such an excitement to bring
30:04 --> 30:07new technologies which do provide
30:07 --> 30:08very helpful scientific information,
30:08 --> 30:11but we're trying to anchor it back
30:11 --> 30:13to the patient level and see how
30:13 --> 30:14is this going to help
30:14 --> 30:16a given person. How is it
30:16 --> 30:18going to help their family?
30:18 --> 30:19And so that's really what
30:19 --> 30:22we're interested in in the in the next step.
30:22 --> 30:24Doctor Michael Leapman is
30:24 --> 30:25assistant professor of urology
30:25 --> 30:27at the Yale School of Medicine.
30:27 --> 30:28If you have questions,
30:28 --> 30:29the address is canceranswers@yale.edu
30:29 --> 30:31and past editions of the program
30:31 --> 30:33are available in audio and written
30:33 --> 30:34form at yalecancercenter.org.
30:34 --> 30:36We hope you'll join us next week
30:36 --> 30:39to learn more about the fight against cancer.
30:39 --> 30:41Here on Connecticut public radio.

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April 4, 2021

Yale Cancer Center

visit: http://www.yalecancercenter.org

email: canceranswers@yale.edu

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