Cognitive Decline and Prostate Cancer

June 22, 2020

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June 21, 2020

Yale Cancer Center

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00:10More information at astrazeneca-us.com.
00:14Welcome to Yale Cancer Answers with
00:16your host doctor Anees Chagpar.
00:18Yale Cancer Answers features the
00:20latest information on cancer care by
00:22welcoming oncologists and specialists
00:23who are on the forefront of the
00:26battle to fight cancer. This week
00:28it's a conversation about
00:29cognitive decline after prostate
00:31cancer with doctor Herta Chao.
00:33Doctor Chao is the deputy director
00:35at the VA Comprehensive Cancer
00:37Center and an associate professor
00:38of Medicine and medical oncology
00:40at the Yale School of Medicine,
00:42where doctor Chagpar is a
00:45professor of surgical on oncology.
00:48I hear you work at the VA.
00:50Tell us a little bit about the
00:53VA and about cancer services
00:55at the VA?
00:58I feel very fortunate to work at the West Haven VA
01:01Cancer Center because it's so closely
01:04affiliated with Yale Cancer Center,
01:06we basically can take advantage of a
01:09lot of the knowledge and expertise and
01:12resources that are available at your
01:14Cancer Center as well.
01:17A particularly important thing for the
01:20VA is that we're a tertiary center,
01:23and many resources are available
01:26that are not necessarily
01:29available in the private sector.
01:32For instance,
01:33if veterans need transportation,
01:35we can actually ask our social worker
01:38to help. If a veteran needs additional
01:42support and therapy,
01:43we can actually ask the physical
01:46therapist to meet them in the Cancer Center,
01:49so it's
01:51very tailored to veterans.
01:53Tell us a little bit about,
01:55you know when we think about cancer
01:58we kind of think of it ubiquitously
02:00but tell us about the prevalence of
02:03cancer in the veteran population and
02:06whether the the incidence of cancers
02:08and particular kinds of cancers are
02:11different in the veteran population as
02:13opposed to the general population?
02:16That's a very very important point.
02:21I think we continue to
02:24learn. For many decades
02:26it was actually debated whether certain
02:29cancers are really related to an herbaside,
02:33like Agent Orange.
02:34We know it was widely used
02:37during the Vietnam War and many veterans
02:41develop cancers
02:44that are unusually aggressive,
02:46unusually early in their lifetime,
02:49and it took many decades before it was
02:53recognized that Agent Orange is a carcinogen.
02:56For instance,
02:58I think soft tissue sarcoma,
03:01which is a connective tissue cancer,
03:04occurs early in our lifetime.
03:06It was recognized earlier that this is
03:09probably related to Agent Orange.
03:12Exposure has increased the risks of
03:15these veterans to develop these cancers.
03:18Prostate cancer, for instance,
03:20is so common among men and is
03:22the most frequent cancer among veterans.
03:25But for the many decades it was actually not
03:30acknowledged to be Agent Orange related.
03:33Not until 2008 there was a very
03:36important study done by Doctor Karen
03:39Shami at UCLA that actually proved
03:42that the
03:45rate of prostate cancer and
03:48aggressiveness of prostate cancer was much,
03:51much higher in the veterans that were
03:54exposed to Agent Orange compared to
03:57veterans during the same era but not
04:00exposed to Agent Orange, so we know
04:04more and more that veterans may be
04:07at risk due to service related
04:09exposures to certain type of cancer,
04:12including lung cancer,
04:14prostate cancer, leukemia
04:15and lymphomas.
04:18These days for men and women
04:21who are in combat al ot of times
04:24we don't think about
04:27people using a particular agent
04:30like Agent Orange in combat,
04:32but more it's artillery,
04:36there's more
04:38roadside bombs and so on.
04:41Are those also associated
04:44with a higher risk of cancers?
04:47I think we will find out very soon.
04:53Unfortunately my colleagues
04:56and myself have been
05:00unpleasantly surprised about how many
05:03aggressive cases of cancer we see in very
05:08young veterans like in the 40s and 50s,
05:11and a whole variety of
05:14different type of cancer,
05:16not just one specific cancer and the
05:20common thread of the story is really
05:24they were exposed to the burn pits,
05:28where apparently many things were burned,
05:31including
05:32what I was told was equipment that
05:39they wanted to be destroyed,
05:42and so there were many
05:44toxic exposures and I fear,
05:46and I believe it will be true
05:48that we will see many other risk
05:52factors for different types of
05:54malignancies.
05:56I mean I don't know whether we still
05:59see veterans who were exposed to Hiroshima
06:02and Nagasaki, but radiation
06:04also can expose you to a variety
06:07of malignancies too, right?
06:09Absolutely, in fact
06:10I can talk about this because
06:14one of my veterans really wanted
06:17to raise more awareness and he and
06:21his wife really wanted want to
06:25publicly speak more about it.
06:28He was actually exposed,
06:34in regular service to radiation in
06:37the nuclear powered submarines,
06:39and unfortunately,
06:40he was in very close proximity
06:42to it and unfortunately now deals
06:45with a very aggressive cancer.
06:47They were fortunately able
06:49to control it with chemotherapy,
06:50but it does look like he will
06:54be on chemotherapy
06:55probably for rest of his life.
06:58What about other agents?
06:59Do we have any idea
07:00about the carcinogenic
07:03potential of things like tear gas,
07:06which is commonly used both
07:08I guess in combat and in
07:11civilian crowd control?
07:13I'm not
07:16an expert in this regard,
07:18so I have to apologize that I can't
07:21answer this question correctly.
07:23But I do think that we have
07:27to be aware about all the herbicides
07:30we are using still commercially and
07:33also in the private sector that I
07:36believe is under recognized
07:40so certainly there are
07:43a whole host of exposures that
07:46are unique to veterans and our
07:48military families and we have to
07:50remember that. And
07:53cancer is not uncommon
07:55even in the general public.
07:57And so when you are seeing patients
08:00at the VA, you're seeing people
08:02who may be at increased risk
08:05because of their military service.
08:07But you're also seeing people who
08:09are just diagnosed with cancers
08:11that they would get as part of
08:14the general population as well.
08:17We serve all veterans,
08:20whether they've been in combat or not
08:24and if they fulfill the criteria
08:27to receive care at the VA,
08:30we will absolutely see all veterans
08:33that are eligible for VA health care.
08:37We will also see the cancers
08:40that are not related to service
08:43connection and we will treat
08:47these veterans, as much as we can do,
08:50and one of the benefits for me to
08:55be an oncologist at the VA,
08:58is that we have many other people
09:00helping me with their care.
09:03One of the things that I do not miss is
09:07the billing issues and medication issues.
09:10I mean, as you know,
09:13there so many
09:16very very expensive
09:17cancer medications, in fact,
09:19we see a stream of
09:22new patients into the VA because
09:24of the very very expensive drug
09:27prices and any veteran that finds
09:29out that they can probably get
09:32these medications for $9 copay
09:35at the VA a month will come to
09:37the VA.
09:40For those who may or may not know, if you are
09:43a veteran, you can get coverage
09:46through the VA for your family,
09:49your spouse, and your children?
09:51That's a very interesting question.
09:55I ask the social worker all the
09:59time and it turns out that spouses
10:03of 100% service connected veterans
10:06are eligible to get care at the VA
10:10until the immediate Medicare age.
10:13I believe that the children
10:15are not necessarily,
10:16but I think there might
10:19be mechanisms to take care of
10:22the children of veterans,
10:24but the spouses of 100% service connected
10:27veteran are eligible for care here at the VA.
10:31What does 100% service connection mean?
10:33It means that these veterans have
10:36a condition that disables them and
10:39it originated during the time of
10:42the military service.
10:43And you see
10:45patients with all kinds of cancers,
10:48and you treat them at the VA.
10:51Are there particular things that
10:53you're thinking about in terms of
10:56their treatment in terms of side
10:59effects and so on that may be of
11:02particular concern to veterans?
11:05I think there's several
11:08things that we do have to consider,
11:12and that is, for instance, service
11:15connected post traumatic stress disorder.
11:17We unfortunately take care of a fair
11:20number of veterans that suffer from
11:24post traumatic stress disorder,
11:26and one of the things that
11:29we have to be aware of is
11:33sometimes when the cancer treatment itself
11:37causes stress,
11:38some of the PTSD
11:41symptoms can
11:43flare up and that is the reason why
11:47we really right from the beginning
11:50even before we start treatment,
11:52we actually frequently have palliative
11:55care and the health psychology team,
11:57in addition to psychiatry, if necessary,
12:00be involved in the
12:02management of the patient.
12:04For instance, when
12:06our veterans
12:07have to undergo complicated cancer surgery
12:10there is actually a service for
12:13elderly veterans called
12:15Champions where the geriatrician
12:18and the psychologists are involved
12:20before even the surgery and really
12:23prepare the patients for the surgery
12:26and follows them all along through
12:29the hospitalization and after discharge.
12:32Yeah, because I can imagine
12:34that for any patient cancer is
12:37a big diagnosis, it's a scary diagnosis,
12:40but for veterans it may be even
12:43more so that it kind of adds to the
12:47stress that they've already gone
12:49through.
12:50And that is one of the things where
12:54we are incredibly grateful for at
12:56the VA in Connecticut, we actually
12:58over the years we have developed
13:01a cancer care coordination
13:03system where the cancer
13:06care coordinator actually
13:08tracks patients that may
13:10develop cancer,
13:11but it's still in the work up
13:14and the primary care physician or
13:17any provider can council the cancer
13:20care coordination team to try to
13:22expedite the work up and navigate
13:25for the patients
13:27going through the treatment.
13:29Yeah, that's so important.
13:31We're going to talk a lot more
13:34about cancer treatment and the
13:36side effects in our veterans
13:38right after we take a short
13:40break for a medical minute.
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13:55This is a medical minute
13:57about smoking cessation.
13:59There are many obstacles to
14:01face when quitting smoking.
14:02As smoking involves the potent drug nicotine.
14:05But it's a very important lifestyle change,
14:08especially for patients
14:10undergoing cancer treatment.
14:11Quitting smoking has been shown to
14:13positively impact response to treatments,
14:15decrease the likelihood that patients
14:18will develop second malignancies
14:19and increase rates of survival.
14:21Tobacco treatment programs are
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14:27and operate on the principles
14:29of the US Public Health Service
14:31clinical practice guidelines.
14:33All treatment components are evidence
14:35based and therefore all patients are
14:37treated with FDA approved first line
14:40medications for smoking cessation as
14:42well as smoking cessation counseling
14:44that stresses appropriate coping skills.
14:47More information is available at
14:49yalecancercenter.org. You're listening
14:50to Connecticut public radio.
14:53Welcome back to Yale Cancer Answers.
14:55This is doctor Anees Chagpar
14:57and I'm joined tonight by
15:00my guest doctor Herta Chao.
15:02We're talking about cancer,
15:04particularly in veterans and
15:06right before the break you
15:08were telling me about
15:10the really fabulous
15:12services that the VA offers
15:14veterans who are diagnosed with cancer.
15:16It is really a comprehensive approach
15:18a multidisciplinary approach with
15:20social work, with geriatricians, with
15:23psychologists and psychiatrists to
15:25really provide the best treatment
15:27to veterans facing cancer.
15:29Because many of these veterans may
15:31face an increased risk of cancer
15:34due to military based exposure.
15:37The other thing that I think a lot
15:40of people may not know about the VA
15:44is that the VA actually supports
15:47a lot of research in the area of cancer.
15:51Can you talk a little bit about the DoD,
15:56the Department of Defense,
15:58and the support that it provides for
16:01research into cancer?
16:03Yes, they had several mechanisms at the
16:06VA to apply for funding for research
16:10in veterans,
16:11including veterans with cancer.
16:13One is the DoD Department of Defense
16:15has several grant mechanisms
16:18in many different cancers,
16:20including prostate cancer,
16:22lung cancer, breast cancer,
16:24there's another mechanism
16:25that's called VA Merit
16:28which is internally
16:31within the VA you can apply
16:34for funding to conduct research,
16:37an obviously there are others
16:39like the National Institutes of Health
16:43sponsored grants that
16:45physicians and researchers at the
16:47VA can apply to so I certainly
16:51benefited from these grant mechanisms.
16:54One of my research interests,
16:57in addition to conducting clinical
16:59trials at the VA and making clinical
17:03trials accessible for veterans,
17:05is to look at the potential cognitive
17:09side effects and toxicity of prostate
17:12cancer treatment with hormonal therapy.
17:15And this actually was not
17:18something that I thought about,
17:20this was prompted by one of my patients
17:24who is a decorated Vietnam War veteran,
17:29and he developed aggressive prostate
17:31cancer at a fairly young age.
17:35He was just in his early 60s when
17:38he was diagnosed with metastatic
17:42gleason 8 prostate cancer and
17:45he was diagnosed in the private
17:47sector and then found out that it
17:50was eligible for the VA benefits.
17:52He came to the VA and participated
17:55in several studies.
17:57Finally,
17:57after three years taking care
17:59of him and his prostate
18:02cancer it was beautiful controlled.
18:04He finally told me,
18:08I don't want to be ungrateful,
18:10but I think these hormone shots
18:13are frying my brain.
18:15And I asked him, what do you mean?
18:18And he said well,
18:20you know I've been busy all
18:22my life I can multitask,
18:24I can do so many things.
18:26But since I started the hormone shot,
18:28I have to write down the
18:3110 things I want to do within the next hour.
18:35And that's not me.
18:36I usually can think of multiple
18:38things and I can get everything done,
18:41but now I feel like I have to
18:44write down and remind myself
18:46what I want to do.
18:48So then I thought,
18:50oh, that's easy.
18:52I'll refer you for
18:55neurocognitive testing and it turns
18:58out that he scored beautifully.
19:00There was no deficit that we could
19:03find on regular neurocognitive testing.
19:07And then I started looking into
19:10it and it's
19:13still not well understood
19:16what hormone therapy for prostate
19:19cancer can do the to the brain.
19:23I think that the breast cancer
19:26experts are way ahead.
19:28I mean the recognition that
19:32chemotherapy or hormonal therapy
19:34for breast cancer has been for
19:38many years already
19:39suspected and many
19:41studies actually support
19:44the suspicion that chemotherapy and
19:47hormonal therapy for breast cancer
19:51can cause chemo fog, or chemo brain.
19:55It's not as well understood in prostate
19:59cancer so around 2009
20:03I started looking into that.
20:07And the interesting part is
20:09that it's not very easy
20:11to characterize these impact of hormone shots
20:15for prostate cancer, effects on the brain.
20:18If you do regular testing,
20:20neurocognitive testing,
20:21whether it's a paper and pencil or
20:24whether it's on a computer,
20:26we have to be aware that there's a
20:29certain amount of practice effect.
20:32So if you do it every three months,
20:35if you do it every six months,
20:39you know what to expect to do in the test,
20:42so your test score may actually hold hold up
20:45despite the fact there might be a deficit.
20:48And that is probably true for many,
20:53many patients.
20:55That is what prompted me to think
20:59about what do other people do to study
21:04effects of anything in the brain,
21:08whether it's depression,
21:10whether it's dementia,
21:12whether it's psychiatric illnesses.
21:14So that's the reason why I approached
21:18my colleagues at the Yale Medical School
21:20in psychiatry that are involved in
21:23functional brain imaging to see whether
21:25or not hormone therapy can affect
21:28functional brain imaging.
21:30Just to clarify,
21:31what are
21:32these hormone shots that you're
21:34giving for prostate cancer?
21:36What exactly is that?
21:38Because when we talk about
21:39hormonal therapy or endocrine
21:41therapy in breast cancer,
21:43that's often a pill.
21:45Is it the same kind of thing?
21:48It's not exactly the same because we know
21:53that if we just use a pill form like
21:58something called by Bicalutamide which is a
22:03testosterone receptor blocker,
22:05it usually is not sufficient to suppress
22:09the effects on the prostate cancer cells.
22:14So usually men with both prostate cancer
22:18need to get something called Leuprolide,
22:22which is, I'm going to use
22:26the technical term LHRH
22:30agonist, that can shut down the testosterone
22:36production in a patients body
22:40and we use these shots to cause the
22:44testicles and also the remainder
22:47of the body to turn off testosterone
22:50production.
22:53So the key point being that the pills
22:57that many breast cancer patients take for
23:00five or ten years is different than these
23:04shots that men get for prostate cancer,
23:07especially advanced prostate cancer.
23:09They work through different mechanisms.
23:12They have different targets as it were.
23:15And so the side effects are pretty different,
23:18so many women, while it's true that
23:21with chemotherapy they certainly
23:23can get chemo brain or chemo fog,
23:26it's a little less common for
23:28women taking endocrine therapy,
23:30something like tamoxifen or some
23:32of the aromatase inhibitors.
23:34So how common is it that people can
23:37get this chemo brain or chemo fog
23:41or this cognitive decline when taking
23:44an LHRH agonist for prostate cancer?
23:47I think that's a very hot topic right
23:50now in prostate cancer research.
23:53I think for the longest time,
23:56and I would say like
24:0010 years ago I was equally guilty.
24:04We recognized the potential effect
24:07on the brain and we really just
24:10focus on like how to control cancer.
24:14Because as Oncologists,
24:15we want to control cancer.
24:18Now I think we have to recognize
24:21there so many different treatments,
24:24and that's the exciting part about
24:25being a cancer doctor nowadays.
24:27There's so many different treatments
24:29and you can treat cancer so many
24:33different ways that I think
24:35it's actually very important to
24:37know what each treatment could
24:39cause in terms of side effects,
24:42whether it's inside the body
24:44or whether it's inside the
24:46brain.
24:50And what did you find with the
24:53functional imaging study that you
24:55did?
24:57It's still a very active,
24:59ongoing study.
25:01We're trying to right now look at the
25:04effect of lowering the testosterone
25:06level what we call androgen deprivation,
25:10what it does over two years.
25:13My original pilot study only
25:16investigated effects in 30 veterans.
25:1915 leuprolide injection and
25:2215 as a control that underwent
25:26surgery or just radiation alone.
25:30It actually showed that the newer
25:33cognitive testing was the same.
25:35People scored the same,
25:37but when you look at the functional
25:40brain imaging just six months
25:43of hormone therapy for prostate
25:46cancer completely changed the way
25:49the brain shows activation.
25:51What does this mean?
25:53That's something I think I need to find out,
25:58but it was very striking
26:01and to be honest I was a bit surprised
26:05because I initially thought if the
26:09newer cognitive test scores are the same,
26:12why should the brain MRI be different?
26:15And so I was educated that it can be
26:18different and apparently in other disease
26:22processes it can be different too.
26:24Thanks to the support
26:27of pilot studies through the Yale Cancer
26:31Center through Dr. Herbst,
26:34who supported this project,
26:36we were able to do an additional study
26:40of these 30 patients.
26:43It actually turns out that certain
26:46circuits that are connecting
26:49different brain areas to process
26:51things seem to be affected by
26:54hormone therapy for prostate cancer,
26:57so I suspect that the longer we give
27:00somebody hormone therapy for prostate cancer,
27:04the more effects we can see.
27:08Now that being said,
27:10I don't want to create any fear among
27:13patients to get hormone therapy.
27:16I think it's a very,
27:18very important treatment for prostate cancer,
27:21especially for stage four prostate cancer,
27:24and I think this is actually
27:26part of the cognitive
27:29side effects of hormone therapy.
27:32That's something we need to study,
27:34and I believe not everybody
27:37is vulnerable to it.
27:39There are certain individual vulnerability
27:41that we have to identify and study.
27:44That was going
27:46to be one of my questions.
27:48Was that in that functional MRI
27:50study where you had some
27:53patients who had the LHRH agonist
27:55therapy and some patients who didn't,
27:58and you found that there was a
28:00difference in the functional brain
28:02imaging between the two groups
28:04were all of the patients who had the
28:08LHRH agoinst therapy still thinking that
28:10the hormones were frying their brain
28:11or were some of them quite functional?
28:14I would say some of them
28:17were quite functional and
28:19that is the reason why I was
28:22surprised to find on the brain imaging
28:25study that they're still changes.
28:27And some were
28:30complaining of maybe hot flashes.
28:32So I think frequently we say,
28:35maybe you feel more fatigued
28:38because of hot flashes that you
28:40can get with those LHRH agonist,
28:43or whether there could be
28:46some component of depression
28:48affecting your cognitive out,
28:50but I think that's the reason why it's
28:54actually important to have something
28:56that's not just subjective,
29:00it's actually fairly objective for the
29:03patients to see actually on brain imaging,
29:07there are changes and
29:09while this is all still
29:12very much a topic of research,
29:15for my patient,
29:18who was the original one to actually
29:20complain to me about it, was very,
29:23very comforted actually,
29:24to know that it's not just in his mind.
29:28It is actually something that
29:29we can see.
29:31Dr. Herta Chao is the deputy
29:33director at the VA comprehensive Cancer
29:35Center and an associate professor
29:38of Medicine and medical oncology
29:40at the Yale School of Medicine.
29:42If you have questions,
29:44the address is canceranswers@yale.edu.
29:46And past editions of the program
29:47are available in audio and written
29:49form at Yalecancercenter.org.
29:51We hope you'll join us next week to
29:53learn more about the fight against
29:56cancer here on Connecticut public radio.