>> From the Library of
Congress in Washington, D.C.
[ Silence ]
>> Well, good morning all.
>> Morning.
>> It's a nice crowd here.
Thank you for coming and, for this
session we're having with Dr. Platz
on Prostate Cancer Update.
We've done several sessions
in our LCPAHSO brown bags
with the men's health month,
and I see several of the people
who participated in
that here today as well.
And, so, this is bring us full
circle now that we're in the month
in which we observe prostate cancer
awareness and try to find answers.
We have an expert with us from
the Johns Hopkins Bloomberg School
of Public Health, and as we were
chatting here, she was telling me
about the many departments.
And, so, she's deputy chair of
the department of epidemiology,
and she'll share with you where
all the inspiration comes from even
as she shares some of the new
updates and things that are going
on in the world of prostate cancers.
Something that is important,
not just for the men in room,
which I'm glad to see several, but,
also, the women who live with them,
care for them, and are related
to them in one way or the other.
So, it is my pleasure, as chief
of health services, to welcome all
of you here, and, particularly, to
welcome Dr. Platz and my colleague,
that's Tomoko Steen from
Science and Technology
with whom we're partnering,
will introduce Dr. Platz to you.
Thank you.
[ Applause ]
>> Thank you so much, Dr. Charles.
It is my pleasure to introduce
my dear friend, Elizabeth Platz.
She's already introduced the
professor at epidemiology
at the Johns Hopkins University.
She studies association of genetics,
in epigenetics, factors as well
as saturating markers of under
[inaudible] city, information,
and oxidation with prostate cancer.
She has study is not
only doing science,
but she wants to educate
people as well as the,
looking at the association
lifestyle.
So, her team has sociologists,
not only epidemiologists,
and this is a good example of
the transformation of medicine.
We started about two years
ago, Dr. Jim Watson came
and we had a Pernell discussion
on transformation of medicine
and this is a continuation of the
discussion on the transformation
of medicine, and we also had got
micros talk earlier this year.
Before further due, I'd
like to introduce Dr. Platz.
[ Applause ]
>> So, thanks to all of
you for being here today,
and I'm very excited
to speak with you
about my favorite cancer,
prostate cancer.
So, it might seem odd that a
woman studies this disease.
I study this disease because we know
very little about what causes it.
And, so, my whole goal in my career
has been to try to find risk factors
that men can do something
about to reduce their risk
of developing the disease
and for men
who already have prostate cancer,
things they might be able to do
in their lives to reduce
the risk of poor outcome,
including dying of the disease.
Okay. I do want to indicate to you
that I do not have any
financial conflicts of interest.
All right.
September is National Prostate
Cancer Awareness month.
You all know that blue is the
color for prostate cancer.
How many of you know where your
prostate is, if you're a man?
Okay. You probably, as you
get older, you become more
and more aware of your prostate.
Some men do experience
symptoms related
to benign prostatic hyperplasia.
It's an organ that is
involved in reproduction.
It's an important organ to have,
although, clearly, once it's removed
in the setting of prostate cancer,
a man can live a perfectly
functional life.
Okay? The lifetime risk of
developing this disease is one
in seven, and this
is the lifetime risk.
This is not the risk at any moment.
So, it is a common
cancer, and, right now,
there are about 2.8 million men
who are living with this disease.
Okay? So, they've survived,
they've had their treatment
or they've undergone
active surveillance,
and they're living with it.
Okay? So, today, I want
to cover four areas.
The first is the national and
global burden of this disease.
I want to tell you a little
bit about what we know
about what may cause this disease
and what we might be able to do
to prevent poor outcome, not
treatment, but modifiable factors,
what men may be able to change to
change their risk of poor outcome.
And I also want to show you a
little bit about ongoing research
on both the causes of this disease
and about prognostic
factors for poor outcome.
And, then, we'll talk very
briefly about the controversies
in the early detection
of prostate cancer.
Okay? So let's start with
the burden of this disease.
So, I do want to tell you where
we get our national statistics.
So, you'll hear statistics
in the news
about prostate cancer
being number one.
So, where does that
information come from?
Well, the American Cancer Society
produces summery statistics
for us every year, which is
very helpful for people like me.
It's important for people
who do program development
for programs related to education
about screening and so on.
Those data come from the
national cancer institutes,
specifically the SEER
Program, the U.S. Surveillance,
Epidemiology, and Results Program.
And, so, we do have in this
country a system of surveillance.
SEER started in 1973.
It doesn't cover the entire
country, but it does include
about 28 percent of the country.
Places are sampled, cancer
registries are sampled
to have diversity, and, then,
through statistical means,
national estimates are produced.
And, then, how do the
data get to SEER?
Well, we do have a U.S.
cancer surveillance system.
In most states, diagnosing
physicians
and mythologists are
required to report
to their hospital cancer registry
as well as private mythology labs.
These enter the state and regional
cancer registries, and, then,
they enter the SEER Program
or The National Program
of Cancer Registries,
which is a CDC program.
And, then, in addition,
information on death
from cancer comes from
vital statistics.
Okay? So, let's look at where you
can look up details on the burden
of cancers, and so, again, one
place to look is the SEER Program.
They have a lovely
website that's interactive.
You can look at the CDC's
website, The National Program
of Cancer Registries, or you can
look at the annual cancer facts
and figures produced by the
American Cancer Society, and, so,
we can make these slides.
I guess they'll be available on the
web so you can go to these links
if you'd like to review
these statistics.
Okay. So, new cases in the US.
So, as I mentioned, prostate
cancer's the number one diagnosed
cancer in U.S. men.
Okay? Aside from non-melanoma
skin cancer,
which does not get recorded
in cancer registries.
Okay. This amounts to about
more than 220 thousand men.
This is an estimate for this year,
2015, and for those of you who care
about incidence rates, it's about a
138 per 100 thousand men per year.
Okay? Let's look at the trends
in this cancer over time.
So, this graph shows 1975 to 2011.
Again, these are slides from
the American Cancer Society
from cancer facts and figures.
Here's prostate cancer incidence.
Okay? You can see in the
late 1980's, early 1990's,
we had this tremendous peak.
This is due to PSA-based
prostate cancer screening.
Okay? And, then, you
may know that in 2012,
the U.S. Preventive Services Task
Force changed the recommendation.
So, now, the recommendation is
against prostate cancer screening
using the PSA test, and at the end,
I'll talk about why
they made that decision
and why it may be controversial.
Okay. I also want to show you the
five-year cancer survival rates
[inaudible] prostate cancer
back in the mid to late 1970's.
The rate was about 68 percent
five-year survival, and, then,
by the late 1980's, it was up
to about 83 percent, and, then,
today, it's at a 100 percent.
And we'll talk about why it's
now a 100 percent, and, again,
the 68 percent and the 83
percent were before the PSA era.
Okay? And for prostate cancer death,
death in prostate cancer's
the number two cause
of cancer death in U.S. men.
Just under 30 thousand men will
die of this disease this year,
this is the estimate, and,
again, for those who like rates,
the mortality rate is about 21
per 100 thousand men per year,
and you can see it's two behind
lung and bronchial cancer.
Okay? Which far exceeds
the proportion
of deaths from prostate cancer.
Okay. Let's look at the
trends in death from cancer.
Let me point out first, lung cancer.
Lung and bronchus, you can see this
tremendous rise and then decline.
This is related, almost
fully, to smoking.
Okay? And changes in
smoking status over time.
This is one of the most impressive
cancer-related public health
benefits that we have had.
Okay? It's very remarkable.
Now, let's look at prostate cancer.
We can see this bump
that's concurrent
in time with the peak incidents.
You would think that screening
should reduce mortality,
we did have that peak.
That's probably due to better
attribution of cause of death
because it's probably
what's going on there.
And, then, this decline is
probably due to two things.
One, it could be due to PSA-based
prostate cancer screening,
so detecting early, treating early,
and it's also likely due the
better treatments for men
who have advance disease at
the time of diagnosis or who,
after the diagnosis,
develop advanced disease
and then need to be treated.
Okay? So, let's talk
about the global burden
of prostate cancer
using statistics again
from the American Cancer Society.
For these data, they receive
information from Globocan,
which is part of the
International Agency
for Research on Cancer, so IARC.
And IARC uses a variety of means to
obtain estimates of incidence rates
and mortality rates for
countries around the world,
including excellent registries
in some places, and, then,
in other places where there
aren't registries, registries are
of poor quality, IARC
uses information
from neighboring regions.
Okay? And they impute.
Okay. So, per the American
Cancer Society, this cancer,
prostate cancer's the second
most common cancer globally.
There are about 1.1
million cases in 2012.
A big chunk of them, the
majority of these cases,
are diagnosed in countries
like the U.S.,
so economically-developed countries.
And the incidence of this
cancer varies tremendously
across the globe, and this is in
part due to differences in the use
of PSA-based prostate
cancer screening.
Okay? Also per the
American Cancer Society,
about 300 thousand deaths
likely occurred in 2012,
again, these are estimates.
It is the fifth leading cause
of cancer death in men globally
and the highest prostate
cancer death rates are found
in the Caribbean.
Okay? And it's unclear why this is.
All right.
So, one of the most important
differences in the global burden
of cancer is based on
economic development.
So, when we look at
economically developed countries,
prostate cancer is, again,
number one, and, then,
for death, it's about number three.
When we look at economically
developing countries,
you can see prostate cancer
is much lower on the list.
Now, number one, for
incidents and mortality
in economic developing
countries is lung cancer.
Okay? So the global burden
of lung cancer related
to smoking is a disaster, actually.
Okay? All right.
So, now let's move on to known
and suspected risk factors
for prostate cancer and poor
outcomes in men with the disease.
Okay? So, what causes
prostate cancer?
So, although we've been
studying this disease for decades
and decades, very little's known
conclusively about what causes it.
What we do know is age, so
older age, the family history
of prostate cancer, meaning a father
or brother who has the disease,
and in the U.S., being
of African ancestry.
So being an African American
man in the U.S. is associated
with a substantially higher risk
of developing the disease
and dying of it.
Okay? None of these three
factors is modifiable.
Okay? That's a problem, right?
The goal of public health
is to prevent disease.
If we don't know what the risk
factors are, we cannot come
up with strategies for primary
prevention, and, of course,
we prefer primary prevention.
We don't want people
to get disease, right?
We don't want to just pick
it up early and treat it.
We don't want men to
get this disease.
Okay? And, then, to show
you some statistics.
So, the blue line is prostate
cancer incidence over age.
So the X access is age,
and so you can see the risk
of prostate cancer increases
dramatically over decades of age.
This is not a disease of young men.
Okay? The typical age of
diagnosis is about 66.
You can also see that
the risk of death
from prostate cancer increases
notably with age, and the median age
at death from prostate cancer in men
with the disease is 80 years old.
Okay? So you might ask
me what's going on here.
Why is it as men continue to age,
it looks like there's
a decline in the risk?
Well, you have to remember these
are not the same men ageing
through time.
These are birth cohorts of men.
Okay? And, so, the men out here,
the men who are currently 75
and older are from birth
cohorts some time ago.
We've had changes in
exposure factors.
So either exposure at all or the
prevalence of exposure over time,
and so what we're probably seeing
here is not suddenly is susceptible
or a lack of susceptible
susceptibility in these men.
It's probably that the
nature of the exposures
that they experience
produced a lower risk
of developing the disease.
It's something very important to
know when we look at age effects.
Okay? So, now let's look at
the second known-risk factor
for prostate cancer, family history.
So, this is work that we did a
little bit ago looking at a group
of men who are called
health professionals.
It's a cohort.
The Health Professionals
Follow-Up Study.
So, large cohort of men who
were other than doctors,
they were already enrolled
in a clinical trial, and, so,
the men who were recruited
were dentists
and veterinarians,
optometrists, and so on.
And, so, like all the other
studies that have been conducted
in this large cohort study,
what we observed was that men
who had a family history, again, a
father or brother with the disease,
had twice the risk of dying
of this cancer, and, also,
had an increased risk of
developing the cancer.
It turns out, we see this for most
cancers, not just prostate cancer.
People who have a family history,
again, father, brother, mother,
sister, have about twice the risk.
We have no idea why that is, but
it's consistent across cancers.
Okay? So, this type of
finding led to this search
for inherited genetic
differences among men
that might explain the family
history finding, and, so,
I would call this a mad dash.
It started very slowly, individual
changes in the genome were targeted
to evaluate associations with
prostate cancer, and, then,
the field of genetics exploded.
And as the field exploded, the ways
that we studied, the relationship
between genetic variation, again,
this is inherited genetic variation,
in prostate cancer risk evolved.
So we moved from these, looking at
single variants into these studies,
looking across the entire genome.
So these are called
genome-wide association studies.
And the news exploded when,
suddenly, multiple places
across the genome were found to be
associated with prostate cancer.
It was one of our first
breakthroughs, but, as it turns out,
the associations are tiny.
They're minuscule for any
individual SNP, we call it,
single nucleotide polymorphism,
and most of these polymorphisms
weren't even in genes.
They're in regions between genes,
and so we don't actually
know why they're related,
even though they've been validated.
They've been found over
and over in many studies.
Okay? You can see this was 2008
that these types of studies,
these genome-wide association
studies, began to be published.
So, we're now up to about a 100
risk SNPs that have been found, and,
again, most are not in genes
and we do not know what
they're function is.
Okay? Most of those
100 SNPs are associated
with prostate cancer overall
but not with aggressive disease.
So, now, the hunt is for
SNPs that'll will tell us
which men may be at risk
of developing disease
that will cause premature mortality.
Okay? So one of our goals is to find
factors that influence the prognosis
of the disease and the development
of disease with a poor prognosis.
Okay? Another area that's still
genetics, instead of looking
for common variation
across the genome,
the field has moved toward
looking for rare variants.
Now, one of the most exciting
findings recently was, I --
a series of variants in a gene
called HOXB13 were identified
in a small number of families to
be associated with prostate cancer.
These are families that have
familial prostate cancer.
And, so, the search
continued into groups of men
who don't have familial disease.
They have sporadic disease, and
what was found is that these SNPs
in this gene tend to
be in men who were
from Northern European heritage.
Okay? So it seems to be particular
subpopulation who are enriched
for this, for changes in this gene,
and then increased risk
of prostate cancer.
Okay? And, so, other rare
variants are being sought.
The third known-risk factor for
prostate cancer, as I mentioned,
is being a man of African
heritage in the U.S. Okay?
So, when you look at
this, these are U.S. data,
so we've got non-Hispanic White
men, non-Hispanic Black men,
Asian Pacific Islander, American
Indian, Alaskan Native, and, then,
Hispanic and Latino, and
you can see, this is death.
You can see that U.S. Black men have
more than twice the risk of dying
of prostate cancer, and
we have no idea why.
Okay? This is a major difference
in risk and we have no idea why.
Okay? In the studies
that we've done, again,
this is the health
professional's follow-up state,
this is actually a Harvard cohort.
The men are all over the
country, the cohort itself,
the PI is up at Harvard, and
my colleague is Giovannucci,
who's the first author this paper.
And, so, what we did is we
looked at the men in this cohort,
we looked by race, and we asked
the question: If we adjust it
for all the factors that may differ
between Black men and White men
with respect to diet and lifestyle,
could we explain away the
racial disparity in this cancer?
And the answer is we couldn't.
In fact, the association
is the same.
It's about twice the risk.
Okay. So Black men, twice
the risk of White men.
And this cohort is high
socio economic status cohort.
They're all health professionals,
so there's not noise, let's say,
due to differences in
socio economic status.
Okay? So that's held constant here.
All right.
So, in general, we already know
what causes about 50 percent
of cancers in the U.S. Okay?
And I always like audience
participation.
Do you know what those risk factors
are for most cancers in the U.S.?
>> Smoking.
>> So, modifiable.
Left's do modifiable.
Smoking.
>> Sun.
>> So, sun for skin cancer,
and, so, we tend not to talk
about skin cancer basal,
squamous cell skin cancer
because cancer registries
don't collect it.
So, yes, you're absolutely right.
For skin cancer, sun exposure
is the key risk factor.
So, can you think of one
other important risk factor
for cancer, modifiable?
So diet, and what's related to diet?
>> Exercise.
>> Exercise, and what else?
>> Obesity.
>> Obesity.
Thank you.
He said obesity.
Yes, thank you.
Thank you.
So, obesity.
So, these factors, smoking,
number one, and two,
the complex of obesity, inactivity,
and poor diet account for more
than 50 percent of all
cancers in the U.S. Okay?
And for some reason, as a public,
we cannot think, for some reason,
we can't think about if we
removed this constellation,
how much better off we'd all be.
Okay? So, I just want
us all to know this.
This was information
that we knew about.
Okay? This is work from 1981.
We knew this in 1981.
Okay? We continue to know this.
Okay? So, this is my
colleague, Graham Colditz.
He's at Wash U in Saint Louis, and
he had a piece not too long ago
in science translational
medicine saying, we know this.
We need to do something about it.
Okay? Of course, smoking
we've done a lot about,
but I'm going to tell you in
a minute, about 20 percent
of Americans still smoke.
Okay? It's not equal
across the country.
There are pockets.
Okay? And it's not equal
across socio economic status.
Okay? So things we
need to think about.
All right.
So, these risk factors, smoking,
and the constellation of obesity,
inactivity, and poor diet
are also risk factors,
not just for other cancers, right,
but for most chronic diseases.
Heart disease, stroke, diabetes.
Okay? So these are excellent targets
for intervention and
also for prevention.
So, preventing the risk factors.
Okay? But are these risk
factors for prostate cancer
because it'd be great
if they would be.
Well, oddly, no.
At least not at face value.
Okay? So, what we've realized,
when we look at these factors
and prostate cancer as an
outcome, we don't see association,
but once we start looking at
the fine details of the disease,
for example, by whether the
disease resulted in death, then,
we start seeing associations.
Okay? So we have to
look very carefully.
We can't just say in general.
So, let me just take a moment
and tell you why we now focus
on lethal disease and by "lethal",
we mean death from the disease,
and we also mean the
development of metastasis.
Okay. So, advanced stage disease.
That disease is more likely
to reduce the life span.
Okay? So those are the statuses
we care about in our studies.
Okay? So, I need to
tell you that we now
over detect prostate cancer
because of the PSA test.
Okay? It's very clear
we over detect it.
Meaning, we pick up disease that
would have never caused harm.
Okay? We also pick up
disease that would cause harm,
the problem is we can't
differentiate.
Okay? So we pick up
a lot of disease.
You saw that peak in prostate
cancer incidence rates
because of this test.
Okay? So, which means, in our
studies since the early 1990's,
the majority of cases that
we're studying are PSA detected.
Well, it turns out, when we start
dividing by disease that's detected
by PSA and disease that's not,
the risk factors aren't the same.
So we don't want to
contaminate our studies
by studying total prostate cancer
because we may not be finding
the right risk factors.
So, again, lethal prostate cancer,
we mean metastatic at diagnosis,
we mean metastatic
during follow-up time,
and we mean death from the disease.
And, so, in our studies
now, we have shifted
to using lethal as the outcome.
Okay? I know that sounds
horrible to say it that way.
We use lethal as the outcome,
but you follow what I mean.
That we specifically
look at the subset in men
who have experienced
lethal prostate cancer.
Okay? And, then, just to show
you, this is sort of a model
of the natural history
of prostate cancer,
so normal prostate epithelial,
meaning that the cells
that are the secretory
cells of the prostate.
It's unclear exactly what the
intermediate disease states are
that then result in
prostate adenocarcinoma.
We think there may be
something called focal atrophy.
We know there's something called
prostatic intraepithelial neoplasia
that seems to be on
route to the disease,
but we're not a 100 percent sure.
Okay? And, then, most men with
this disease die of something else
when they eventually die.
Okay? But there's a subset of
men who develop metastasis,
and the typical treatment for men
when they have metastatic disease is
something called androgen ablation.
So, basically, knocking
down androgens,
either chemically or surgically.
And these men, unfortunately,
a subset of them will develop
something called hormone refractory
disease, and many of those men will
go on to die of prostate cancer,
and so it's these men that
we want to be able to study.
We want to find risk
factors for this disease
and be able to intervene on them.
Okay? And, then, what about men
who already have prostate cancer?
What are the right
outcomes in those men?
Well, I should tell you, about
a third of men who were treated
for a local disease, meaning at the
time that they're being treated,
the disease is confined
to the prostate.
It hasn't spread yet.
About a third of those
men will actual recur.
Disease will come back
after surgical treatment.
Okay? And, so, how do we know
that the disease has recurred?
Well, after a man has had a
prostatectomy, a few months later,
his PSA should drop
to not detectable.
The prostate is the source of
PSA, so once the prostate is out
and enough of time has gone by
that the half-life of PSA would,
you have to have that clearance,
the concentration should
be not detectable.
Okay? So, men who recur, if they
have biochemical recurrence,
it means their PSA
level has gone back up.
Not all of those men, though, will
go on to develop metastasis and die.
Okay? So, we tend not to use
now recurrence based on PSA
as the sole outcome
that we want to study.
We actually do want to study,
again, the worse prognosis,
which is progression to
men's metastasis and death.
Okay? So in our association
studies, our epidemiology studies,
that's the outcome
that we want to study.
So, now, for these, the next
slides, I'm going to only show you,
or mostly focus on, lethal
disease, and, then, also,
progression to death from prostate
cancer in men with the disease.
All right.
Let's start with cigarette smoking.
So, we know it's a major
risk factor for lung cancer,
head and neck cancer, kidney,
pancreas, among many other cancers.
Is it a risk factor
for prostate cancer?
And let me show you, I told you,
but let me show you,
Americans still smoke.
So, we've got tremendous
declines in smoking.
This is 1965 immediately after
the U.S. Surgeon General's report
on smoking and health.
People did quit.
We'd see the tremendous declines.
Okay? But we're still
about at 20 percent.
I can tell you in my
state, in Maryland --
how many of you are Marylanders?
Okay. Just a few of you.
In my state, in our state,
among those who do not have
a high school education,
so people who have less than a high
school education, about 30 percent
of them smoke, even though
in the state of Maryland
as a whole, only 15 percent smoke.
Okay? So, we do have socio
economic disparities in smoking.
Okay? So it's something to know
and something we need to act on.
Okay. So, the U.S. Surgeon General's
report, there's been an update.
The 50th anniversary update was
published January last year,
and here's what it says
about prostate cancer.
The evidence is suggestive of no
causal relationship between smoking
and risk of incident
prostate cancer.
Okay? There's no association.
And, so, for a very long time,
that's what was in
the public domain.
Smoking is not related to prostate
cancer, so let's not worry about it.
But here's what's now been found.
Okay? So, once the evidence
has been put together,
we now see that the evidence is
suggestive of a higher risk of death
from prostate cancer in
smokers than in nonsmokers.
So the worse outcome, smoking
is a risk factor for it.
Okay? And, then, in men
who have prostate cancer,
smoking is associated with disease
that has a worse phenotype
for prognosis.
So at the tissue level, the grade
is poorer, and it's a risk factor
for progression of the disease
in men with the disease.
Okay? So we now believe,
based on evidence,
That smoking is a risk factor for
the most aggressive prostate cancer.
Okay? So, this is a
point for prevention.
So, let me show you
some research, again,
that we did in Health
Professionals Follow-Up Study.
There's no relationship.
Okay? So, this is the relative risk.
Says the risk comparing risk of
the development of prostate cancer
in men who smoke compared to
the risk in men who don't smoke.
There's no relationship.
Okay? So. Here's the never
smokers, here are the men
who quit a long time ago, and here
are the current or recent quitters.
No relationships.
But for fatal prostate
cancer, here's what we see.
The blue bar, again, is men who are
current smokers or recent quitters,
meaning, they quit
within the last ten years.
These men have a 40 percent higher
risk of developing prostate cancer
that will lead to their death.
Okay? And here's another study.
This is an American
Cancer Society cohort.
Cancer prevention study, too.
It's the same findings.
Same rough strength of association.
Okay? All right.
And, then, taking a look at
men who have prostate cancer,
looking at risk of poor outcome.
Okay? So, here, the never smokers,
these are men who have
a prostatectomy.
Former smokers, meaning, they quit
a long time ago, no increased risk.
But men who were current smokers,
meaning, they continue to smoke
after their diagnosis and treatment
for prostate cancer, they have more
than twice the risk of recurrence.
Okay? And if we look at this as
accumulative incidence, okay,
over across about seven years, 34
percent of the smokers recurred,
and 12, 14 percent of the never
smokers and the former smokers,
those who quit a long
time ago, recurred.
Big difference in the
likelihood of recurrence.
Okay? So, public health action.
So, I'm here to tell you about
research, but I'm also here
to tell you what we need
to do to make a difference.
Okay? So, what's the
public health action?
So, we need to continue to promote
smoking cessation and prevention
of starting smoking, right,
in the general population.
So, we know we need to do that,
but we need to continue to do it
and we have to make sure
men know this too, right?
And this is including to prevent
fatal prostate cancer among a very
long list of other
poor health outcomes.
And, then, from men who have
this disease and actually
for all cancer patients, we have
to make sure we promote
smoking cessation.
Okay? Traditionally,
we didn't do this.
Okay? Once someone was
diagnosed with cancer, we just --
that was no longer
on the to-do list.
Okay? But there are now guidelines
that were just released earlier this
year that say we need to promote,
in a very active way at the time
of diagnosis, smoking cessation
in cancer patients, and, again,
this should include men
with prostate cancer.
Okay? Let's move on to
the epidemic of obesity.
So, we know that this is a major
concern in the U.S. and globally.
We all know -- everybody
know your body mass index?
Okay. More or less where you fall?
Okay. So, overweight is 25 plus
kilograms per meter square,
obesity is 30 plus kilograms per
meter square, and BMI is calculated
as your weight in kilograms divided
by the square of height in meters.
Okay? So, obesity is a risk factor
for many common cancers
including colon cancer.
Okay? And we do know that we've
had this massive rise in obesity
in the U.S. starting
in the mid 1970's.
I mean, this is a horrible
rise, right?
We're up to about 66
percent of American, adults,
being overweight or obese.
Same thing's happening globally.
Not to the same extent,
but it's on the rise.
Okay? So, are these types
of factors, so, obesity,
physical inactivity, risk
factors, for prostate cancer?
Well, for years, we thought
there was no relationship.
Okay? This is a consensus
document, 2007.
This is specific to prostate cancer,
and you can see here a limited
no conclusion body fatness.
Okay? So we thought there
was nothing going on.
Well, now, in 2014, that same
organization updated the evidence
base, meaning, they
looked at the literature,
they found all the new studies, they
put it together in a systematic way,
and, now, what they find is
that there's strong evidence
that being overweight or
obese increased the risk
of advanced prostate cancer.
So, the way we used
to our studies, again,
was to look at total
prostate cancer,
but that PSA problem
messed up our studies.
Okay? So, once we started
sorting out the men
with most the aggressive disease,
finding them within our cohorts,
and, then, studying
these common risk factors
for many chronic diseases,
now we see associations.
The evidence base is there.
Okay? And, then, just to
show you example studies.
This was a landmark study.
It was back in 2003.
This is the cancer
prevention study II
out in the American Cancer
Society, and you can see
as body mass index
increases, the risk of death
from prostate cancer increases.
Okay. Here's another cohort.
This is by my colleagues at
the National Cancer Institute.
This is the NIH-ARP
diet and health study.
The darker blue bars are
for fatal prostate cancer,
the lighter blue bars are for the
incidence of the disease, and,
again, as you may see,
as BMI goes up,
the risk of fatal prostate
cancer goes up.
And, then, something to
note as obesity goes up,
the risk of incidence
disease goes down.
And, so, when all this was
combined together in the past,
it made it look like
there was no association.
So, it wasn't until we
partitioned into advanced or fatal
and incident disease, which
was primarily PSA based,
that PSA detected base
disease, then,
we were able to see
these associations.
Okay? And what about men
who have prostate cancer?
This is, again, work by my group.
Cory Joshu was the first author.
So, these are men who
underwent treatment
for prostate cancer,
they had early disease.
If they maintained their weight from
the years before their diagnosis
to after their diagnosis,
that was the reference group,
and when we said maintain,
it was a five-pound range.
Men who gained weight,
some more than five pounds,
the typical weight gain
was about 11 pounds
from five years before
to one year after.
We see that these men have
twice the risk of recurring.
Okay? Men who lost weight,
there weren't that many.
[ Laughs ]
But there's a hint of
an inverse association.
All right.
How about physical inactivity?
Well, it doesn't appear to be
associated with prostate cancer,
but it does appear to be
associated with outcomes
in men who have the disease.
So, this is from my
colleagues, again,
it's The Health Professionals
Follow-Up Study.
Stacy Kenfield is the first author.
And, so, this is level
of physical activities,
so you can see number of med hours.
This is just a measure
of both frequency
and intensity of the activity.
So, increasing med hours is
increasing activity and intensity,
and what we can see is, as the
number of med hours increases,
in general, the risk of
poor outcome decreases.
All right.
So, how we're going to intervene?
Again, public health action.
It's perhaps even harder to
combat obesity and inactivity,
and I didn't really
talk about poor diet.
That's a very complex literature.
It's hard to intervene.
And you know when we take public
health action and we try to do it
through policy and laws,
it's a tough sell, right?
It's been a tough sell,
but we've done it.
We've taxed smoking, and
we've had tremendous declines
in smoking prevalence.
You saw what happened in New York
City with the attempt at taxation
of sugar-sweetened beverages, and
it failed because of the pushback.
Okay? So, maybe we need to go back
into the primary care
setting, right?
So, instead of doing it as
big population messages,
maybe we need to do it in
the primary care setting
and have health systems try
to deal with this problem.
Okay? And, maybe, take advantage
of the Affordable Care Act
provisions for prevention.
Okay? And, so, the Affordable Care
Act mandates that any service,
preventive service, that the U.S.
preventive service is task force
says has a recommendation
of B or A needs
to be covered without copayment.
Okay? So no cost to the person.
And, so, there is a
recommendation for adults
that all adults should
be screened for obesity,
and if individuals are obese,
they should be counseled.
Okay? All right.
And, so, what do we need?
We need research desperately
on weight loss
and inactivity for cancer patients.
Okay? So, we need to know whether
changing weight after the diagnosis,
increasing activity
after the diagnosis,
would produce better
outcomes in those patients.
Okay? And we need to know when
to start these interventions.
Is it at the time of diagnosis,
or is it sometime later?
Okay. After some survivorship time.
Okay? So, now let me
summarize the risk factors
for lethal prostate cancer.
So, we looked at non-modifiable
factors, older age,
being African American or
having African ancestry,
and family history.
For genetics, we now know there are
about a 100 risk alleles associated
with prostate cancer,
although I should point out,
this is not for lethal disease,
it's for total prostate cancer,
and there's a search for
SNPs for lethal disease.
And, then, modifiable factors,
most that have been found,
these few that I showed you,
are primarily for lethal
or fatal disease, and, again,
smoking, obesity, and inactivity.
And I highlight obesity because it's
going to be so hard to intervene on.
We have to figure out what to do.
All right.
So, now let me give you examples
of the research that's being done
on risk factors and
also prognostic tools,
and I'm going to show you
work from my own group.
So, what do I study?
So, I'm going to give you two
examples for prostate cancer.
One is a cause and one
is a prognostic marker,
inflammation and telomere length.
And, then, I'm going to show you
telomere length as a risk factor
for prostate cancer,
looking at obesity
as it influences telomere length.
Okay? And, then, I also
want to point out something
that Tomoko eluded to, which is
translational research is critical,
and that's what we're trying to do.
Translational research is best done
by bringing multiple
disciplines together.
And, so, here's part of our team.
So, we're basic, clinical,
and population scientists working
together; so, Angelo De Marzo,
a pathologist; Alan Meeker, a cancer
biologist, and, more specifically,
a telomere biologist; me, an
epidemiologist; my colleague,
Vasan Yegnasubramanian
who's a cancer biologist;
and Will Nelson who's
a medical oncologist
and also a cancer biologist,
and we all come together
to do our research.
Okay. So, let me start
with inflammation.
So, what we hypothesize is that
chronic or recurrent inflammation
in the prostate itself,
so not systemic,
but actually in the
prostate, increases the risk
of the development
of prostate cancer.
And we made this hypothesis
based on other cancers.
We know that inflammation can
serve as both an initiator
and a promoter of cancer.
Okay? So, think about H.
Pylori and stomach cancer.
Okay. So, it's a bacterium
that increases inflammation
of the stomach mucosum, it's
known to be a risk factor
and a cause of stomach cancer.
Okay? If this hypothesis is true
for prostate cancer, we would expect
that inflammation would be
incredibly common in the prostate
because prostate cancer's so common.
All right?
So, do we know whether
or not inflammation is
common in the prostate?
Well, we do know that
based on studies
where tissue was removed
for indication.
So, tissue removed when men have
benign prostatic hyperplasia,
tissue removed at the time of
biopsy if a man has an elevated PSA,
and tissue removed at the time
of surgery for prostate cancer.
But what we don't know is
in men without indication,
whether inflammation is
common in the prostate
because all these states tend
to be related to PSA level,
and it turns out that
inflammation increases PSA.
Okay? So, it's sort of circular.
So, what we needed was a
place where we could look
where men don't have an indication
for biopsy, and we'd be able
to get an unbiased estimate of
inflammation in the prostate.
Well, turns out, there was a big
trial conducted called the Prostate
Cancer Prevention Trial.
It tested the drug finasteride,
which inhibits the enzyme
that catalyzes the conversion
of the male hormone testosterone
to another male hormone,
dihydrotestosterone.
And, in that trial, they
biopsied the men at the end.
Irrespective of whether
they had an elevated PSA.
Irrespective if they had an
abnormal digital rectal exam.
And, so, we were able to collaborate
with the investigators on this trial
to use that biopsy tissue.
The majority of the men,
at tend of the trial,
did not have indication for biopsy.
They were just biopsy
as part of the trial.
Okay? So here are the results
of that study that we did.
Okay? First thing to note is that
78 percent of the controls, meaning,
men who were not diagnosed with
prostate cancer in the trial,
had at least one biopsy
core with inflammation.
About six to ten we are taken,
we sampled three per man,
so men who had at least one of
those three with inflammation
in it, that was our measure.
Okay? And 78 percent of the
controls had inflammation
and at least one core.
Okay? So, it turns out
inflammation is incredibly common
in the prostate.
It probably needs to be there.
You probably need inflammatory
cells to clear any type of agent
like E. coli that might
enter the prostate.
Prostates actually opened
to the outside environment
and will give you process.
It's open to the outside
environment,
so you need immune
cells present to be able
to clear those types of agents.
So it makes sense.
Okay? And, then, something
else to note is the prevalence
of inflammation in the cases.
So total prostate cancer, about
86 percent had one or more core
with inflammation and high
grade disease, which, again,
is a prognostic marker
by 88 percent.
Okay? And, then, if we looked at
the association between having
at least one biopsy core with
inflammation and the risk
of prostate cancer, we found
about an 80 percent increased risk
from men who at least one core
positive and even higher risk,
so it's about twice the risk for
men who had at least one core,
and the outcome here
was high grade disease.
Okay? So, again, these
were end of study biopsies.
We actually measured inflammation
in those biopsies that were used
to rule in or out the
diagnosis of prostate cancer.
Okay? So, what that means is our
study was not temporally correct,
so we didn't have biopsies
from men who, biopsies from men
and then follow them forward for
the development of prostate cancer
because not a lot of men would
volunteer for a study like that
where you, like, 100
thousand men say we're going
to biopsy your prostate and
then follow forward in time.
So, the study we did
was not prospective.
It's not temporally correct.
But turns out through collaboration,
we were able to link the
prostate cancer prevention trial
with another trial conducted
by the same cooperative group.
The next trial was called SELECT.
Some of the men in the PCPT
participated in SELECT,
which means their end of study
biopsy became the baseline biopsy
for that next trial, therefore,
we were able to conduct a
prospective cohort study
of inflammation in the
etiology of prostate cancer.
Okay? So, here's the design.
So, again, the end of study biopsy
from PCPT became the
baseline biopsy in SELECT.
We assessed inflammation in that
biopsy and then determined who ended
up with prostate cancer later.
Okay? And this work is supported
by the Department of Defense.
All right?
And here's what we saw.
We saw men who at least,
had at least one biopsy core
of inflammation in the controls
with 72 percent, so very similar
to what we had seen before.
And you can see that in, with
various outcomes, low grade disease,
men with low PSA but with prostate
cancer, men with low grade disease,
and suppose to say, and low PSA,
all these men had a higher risk
if they had at least one
core with inflammation.
Now, what's missing from
here is high grade disease,
and it's because very few men in
the study had high grade disease.
They had to make it through the
PCPT and then enter SELECT, and, so,
once they got into this trial,
we had served depleted the men
of more aggressive disease.
Okay? Never the less, we do
see evidence of an association.
And, so, this is the number of cores
with inflammation, so some cores
and then all cores, we
see a dose response.
When we see dose response, we
tend to believe more strongly
that there's an association verses
when we don't see dose response.
Okay. So what's the
clinical import of this work?
Well, if there's truly a causal
association between inflammation
and prostate cancer,
which we're hoping it is,
we need to do more
research, we may be able
to identify what it
is about inflammation.
Which cells, which immune
cells are increasing the risk?
Okay? So, additional
work we could do.
What's not going to happen is
inflammation will never be able
to be used as a tool to
screen for this disease,
and the reason is it would
have a poor predictive value.
So many men have inflammation
of prostate,
so I have no predictive
capacity whatsoever.
Okay? But from understanding
the etiology of the disease,
we think that these findings
have potential import.
Okay? So, move on to the
next topic, telomere length.
So, telomeres are the
ends of the chromosomes.
Okay? They help maintain the patency
of the structure of the chromosome.
They're known telomere shorten
with each round of replication,
and it's well recognized that
cancers have shorter telomeres
than normal tissue
from the same organ.
So, we wanted to address
the question
of whether there's
prognostic information
in knowing telomere
length in prostate cancer.
Okay? Again, this is a
multidisciplinary study done
with our colleagues in
cancer biology, and, so,
what we did is we had tissue
from men with prostate cancer,
we had the cancer, and we had the
cells near by called stromal cell.
The stromal cells, the supportive
cells, so fiberglass, for example,
smooth muscle cells,
all from the prostate.
We determined telomere length
using a technique called FISH.
We were able to imagine
the telomeres,
we were able to determine
the length of the telomeres,
and what we found was it
wasn't how short the telomeres
in the cancers were because they
were short across the board,
it was how variable telomere length
was from cancer cell to cancer cell.
The greater the variability,
the higher the risk of death
from prostate cancer in those men.
Okay? When we looked at the
cells near by, the stromal cells,
it turned out how short the
telomeres were was associated
with risk of death
from prostate cancer.
And when we put those two parameters
together, those two measurements,
what we found is that men
who had the combinations,
purple bar is the combination
of more variable telomere length
from cell to cell in the cancer
combined with shorter telomeres
in the stromal cells was associated
with 14 times the risk of dying
of prostate cancer in men with
prostate cancer, even after taking
into account the other
known prognostic markers.
Okay? This is a very
strong association.
We tend not to see associations
like this in epidemiology.
Okay? The men in the middle
bars had other combinations.
So, they either had variable
in the cancer and not short,
or they had not variable and short.
Okay? And, so, you can see that they
also have increased risk but not
on the order of the men
with the poor combination.
Okay? All right?
And, so, let's talk a
little bit about these men.
So, the men who had this better
profile, so the men who are here,
they had less variability in their
telomere length from cancer cell
to cancer cell, and they had longer
telomeres in their stromal cells.
Only one man died of
his prostate cancer.
Okay? We had expected about six
men to have died in this cohort.
The time for this one man,
from diagnosis to death,
was a very long time, 16.5
years, which is longer
than the usual life expectancy for
a man who had Gleason 9 disease.
Okay? This is the very,
usually considered
to be a very aggressive disease, but
he managed to live a very long time.
And, again, there was only one man
who died of his disease in those
who had what we considered to
be the good combination, so.
Less variable and longer.
Among the men who had more variable
telomere length in the cancer
and shorter telomeres
in the stromal,
20 men died, about 10 were expected.
Okay? So that's a big,
big difference.
And the median time from diagnosis
to prostate cancer death
was about eight years.
So, you can see this one
man live twice as long
as would have been expected.
Okay? So, we don't
think this was an error.
Okay? So we -- if our biomarker
works very well, you'd expect no men
in that group to have
died of prostate cancer.
Well, this one man who did died
of it, his time to death was twice
that in the group that we
think has the worse prognosis.
All right?
So, now let's tie together
the findings that we just,
I just showed you for
telomere length with some
of the modifiable factors.
And, so, this is work done in
collaboration with Cory Joshu.
She's an assistant
professor in our department,
and this work was supported,
her specific work,
was supported by the
Prostate Cancer Foundation.
Okay? So, I've told you that
her work showed that men
who gained weight had a
higher risk of recurring
after treatment for prostate cancer.
So, what she wanted to
do was to look at obesity
in relation to telomere length.
Okay? We didn't want to look into
cancer because the cancer we know
because of its higher proliferation
rate and just greater damage
that goes on in cancer cells.
It didn't make sense
to look at obesity
and telomere length in the cancers.
Instead, what she did, she
looked in stromal cells.
So, recall that we saw
that short telomeres
in the stromal were
related to an increased risk
of prostate cancer death.
So, when she looked in the
stromal, men who were overweight,
were obese, had shorter telomeres.
Okay? So, men who were overweight
had shorter telomeres, overweight
or obese, than men who
were of normal weight.
Okay? This is in the stromal cells.
Okay. When she looked
at physical activity,
men who had low physical activity
levels had shorter telomeres.
Okay. This had not been seen before.
No one has been able to look in the
tissue, in the target organ itself.
Okay? So, now we're seeing
evidence of potential impact
of these modifiable risk factors
for prostate cancer, lethal disease,
and poor outcome, and their effects
potentially on telomere length.
Okay? When she combined obesity and
inactivity, she found that the men
who were obese and had low
physical activity levels had
about 21 percent shorter telomeres
in their stromal cells than men
who were normal weight
and were active.
Okay? And she also
looked at smoking.
So, remember her finding.
Men who continue to smoke have
a higher risk of recurrence.
She looked at smoking
and telomere length.
There was no relationship with
how short the telomeres were,
but in the stromal and
actually in the cancer as well,
she noted relationships between
smoking and how variable,
and just to remind you,
more variability is worse.
Okay? So, variables worse.
So, these are the men who are never
smokers, and, so, they have --
here's never smokers again.
These are people who quit recently
and these are the current smokers.
So variabilities worse.
This is more variable.
Okay? All right.
So, that's some few examples
of contemporary research
on prostate cancers.
The last thing I want to do
is discuss the controversies
in the early detection
of prostate cancer,
and by early detection,
we mean screening.
And, so, I want to remind
you what screening is.
So, screening is the use of a test
in individuals who
are A symptomatic.
Okay? And that test is used to
determine whether a person is likely
or not likely to have
the disease or state.
It doesn't mean they have it.
Okay? So, it's that they're likely
to have, more likely to have it.
Okay? And, then, usually, there's
diagnostic workup that needs
to happen to actually determine
whether or not disease is present.
Okay? So that's what screening is.
And, so, we know that PSA-based
prostate cancer screening has had a
profound effect on prostate cancer
in the U.S. and in other places
where this type of screening
has been used more widely.
Okay? And, so, recall this figure
from the American Cancer Society.
We saw this huge bump in the
incidence, the number of new cases,
because of PSA-based
prostate cancer screening.
And I also showed you the change
in survival, five-year survival,
and this change is because of
PSA-based prostate cancer screening.
But I should also tell
you that a lot
of this 100 percent
survivorship consists of men,
if their cancer hadn't
been detected,
it would have never
killed him, killed them.
Okay? Because we've over
detected the disease.
Okay. And the pre-PSA era, these
were men who were symptomatic
at diagnosis or had clinically
palpable disease of their prostate.
Okay? So, we have to consider
the benefits verses the harms.
We, as a public health discipline
and also the medical community,
convinced everybody that screening
for cancer is necessarily
good, right?
We wanted people to be screened.
It was the right thing to do.
We made people feel guilty about it,
but that was a population-level
recommendation.
We now realize that we've
overdone it to some extent,
and so what we're doing now is we're
pulling back and we're thinking
about who should be
targeted for screening.
Who is at highest risk and that risk
may change throughout the lifetime.
Okay? We need to think about
this because there's a tradeoff
between the benefits of screening
and the harms of screening.
A lot of people say, well, there
aren't harms for screening.
Well, but they are.
Okay? So, we pick up disease that
may not be cancer at all, but, yet,
are medically worked up,
surgically worked up.
We pick up cancers
that are indolent,
would have never caused
premature mortality,
so you're better off not
knowing if you have it.
And, then, there's
adverse effects related
to the tests themselves including
the diagnostic workup, and,
certainly, the adverse effects
of associative treatments.
Okay? There's also
psychological harms, right?
There's the worry.
If someone turns out
to be a false positive,
they're told that their
screening test is positive,
but on diagnostic workup they're
negative, imagine the worry.
Okay? A person will always think, I
probably do have the disease, right?
It's a problem.
Okay? Plus, we have the burden
on our healthcare system, right?
There's cost.
There's actual cost.
Okay? So we have to
be cognizant of that.
All right?
And, then, we have this problem
where our guidelines keep evolving,
but that's important, right?
We're updating our evidence base,
but the public isn't
able to respond to that.
Okay? And, so, there's confusion.
Doctors are confused.
They don't know what they're
supposed to do, who are you supposed
to screen, when you screen.
It's very complicated.
And, again, these uncertainties are
coming up because of good reasons.
We have new knowledge, new
evidence, and we have new tools.
But as these come online, the
recommendations are not changing
across all of our societies,
right, our professional societies.
They're not changing at
the same time concurrently
in the U.S. Preventive
Services Task Force
for the American Cancer Society,
so everyone's getting confused.
Okay? Before the message
was you should be screened,
now the message is changing.
Okay? So for prostate
cancer, the first thing
that happened just a few years
ago, was there was a recommendation
to stop screening after age 70.
Okay? And the idea was that the risk
of other reasons why people
might die, why men might die,
actually become greater in that
age range than for prostate cancer,
especially for men who've made
it to 70, they've been screened,
the prior probability of
later having prostate cancer,
if you've been negative on those
screens multiple times, is low.
And, so, the idea was
just stop screening.
But, then, the most recent change,
again, 2012, was to not screen
at all using PSA-based approach.
Okay? So, here's the U.S. Preventive
Services Task Force website.
Here's the recommendation.
Okay? They gave it a grade
of D. And, basically,
what they did is they
looked at the evidence base.
There were two large
trials that were published.
One was done in Europe.
One was done in the U.S. The study
in Europe was done in a background
of populations that did not have
a history of routine screening.
The use of the test did result in
reduced prostate cancer mortality,
but at the expense
of over detection.
They're very clear on their paper.
They say that over 14 hundred
men would need to be screened
and 48 additional cases of
prostate cancer would need
to be treated to prevent one death.
Okay? So, a lot of men
would need to be medicalized
to be able to prevent one death.
Okay? In the U.S. study,
it was done on a background
of PSA-based prostate cancer
screening, and the prevalence
of that uptake increased
during the trial.
So, by the end of the trial,
they did not find a relationship
between PSA and reduction
in mortality.
Okay? So, we already
have a background.
So, these studies are not
inconsistent with each other,
even though when it got into the
news, they were called inconsistent.
It's the nature of what population
was included in the two studies.
Okay. So, based on
this evidence base,
the U.S. Preventive Services
Task Force found good evidence
that PSA screening can detect
early stage prostate cancer,
so the test does pick up the
disease, but there's mixed
and inconclusive evidence that early
detection improves health outcomes.
Okay? And they go on to talk about
the harms associated with screening,
so at the end, they concluded
that the evidence is insufficient
to determine whether the
benefits outweigh the harms
for a screened population.
Of course, men got very upset.
Okay? So, we had told everybody
go be screened, and then,
suddenly, we're going, nope!
Don't be screened.
Okay? And, so, we saw
letters, we heard --
I had a man stop me in
a hotel hallway once.
I was there to give a talk and was
in a hotel, and the man stopped me,
he said, "I'm a survivor.
You can't let this happen."
Right? And, so, the
message that a lot of men
who were survivors was that,
but it saved me, right?
I was screened.
I had prostate cancer.
I was treated.
I'm alive.
It saved me.
Okay. Well, I'm sympathetic to this,
but we lack the counterfactual
state.
We don't know what
would have happened
to this man had he
not been screened.
Okay? Undoubtedly,
some men are saved.
That decline in prostate cancer
mortality that we showed you,
no doubt is in part due to
prostate cancer screening.
The problem is we pick up disease
we shouldn't be picking up.
We do not have a tool
that, at this time,
will specifically identify
the cases that are likely
to result in premature mortality.
Okay? We do have differences
in guidelines.
The American Cancer Society
guidelines say in men
in average risk, screening
should start at age 50 plus,
DRE couple with PSA, and it should
be based on informed decision making
between the individual and
the healthcare provider.
Man's own values need
to come into play.
His other health characteristics
need to come into play.
Okay? And that decision,
is that a joint decision,
between that patient
and his provider.
Okay?
The AUA, based on the European
trial, has a series of guidelines.
They recommend that screening could
occur for men 55 to 69 years old,
and, again, this would be in a
shared decision making setting.
Okay? So, I do want to remind you
that under the Affordable Care Act,
there are certain preventive
services
that are covered without
cost sharing.
You'll notice that PSA-based
prostate cancer screening is not
here, but others are.
So, colorectal cancer screening,
mammography, and there's age ranges
and timing that are here.
Okay? All right.
So, what do we need urgently,
given the burden of this disease,
given that men do die
of this disease?
We need to figure out strategies
to improve the benefits verses the
harms in the screening that we do.
And, so, we need new
algorithms for use
of our current technology,
so who should we screen?
Which men?
When? How often?
And so on.
So, that's an active
area of research.
And we need new screening
tests all together,
whether they're blood based or maybe
even better based on imagining.
Okay? So, all of this
is under active study.
Okay? So, I hope that
I've met the objectives
of talking with you today.
We described the burden
of this disease.
We talked about known and
suspected risk factors
for the disease and
including outcomes.
I gave you examples
of ongoing research,
and we discussed the controversies
in the early detection
of prostate cancer.
And I just want to point out,
major knowledge gaps where we need
to put lots of attention.
Why do African American men have
a higher risk of prostate cancer,
especially disease that kills?
Are there additional modifiable
factors for lethal disease
in poor outcome in men with a
disease that we can intervene on?
And what is the optimal prostate
cancer screening approach?
Okay? Going forward, make sure
we emphasize as risk factors,
not just for prostate cancer, but
for cancer in general, smoking,
obesity, inactivity, poor
diet, doing so is going
to desilo our diseases, right?
So, we tend to say, oh,
cardiovascular disease is
over there, diabetes
is here, cancer's here.
Well, these are all
the same risk factors.
We have to desilo and get the most
bang for our public health dollars.
It avoids duplication of efforts and
expenses, creates a seamless model
for public health promotion.
Okay? And we want to
deemphasize controversial factors
and quick fixes, like magic pills.
Okay? We have to be active.
We have to maintain
our weight, right?
We've got to quit smoking
or not start.
Those are things we should work
on, and I'd like to acknowledge all
of my collaborators from both
Johns Hopkins, from Harvard.
I've had a ton of trainees
over the years
who have contributed to this work.
Also want to thank
the PCT investigators
who have provided a great
setting for us to do or our work.
And, then, here's our school.
We're celebrating our 100
anniversary this year.
Here are my close colleagues,
Dr. Marzo, Dr. Meeker, Dr. Joshu,
and here's some of the team
members in my office one day,
and we just got a shot of us all.
And, of course, the funders
for the work, NCI, DOD,
the Marilyn Cigarette Restitution
Fund at Johns Hopkins as well
as the Prostate Cancer
Foundation for Dr. Joshu.
So, I thank you all for coming
today, and I'm open to questions.
Thank you.
So, the question was whether hormone
replacement therapy effects the
aggressiveness, either the presence
of prostate cancer or
its aggressiveness.
And, so, you know, there is
some research that's being done.
There are panels that are being
convened to try to understand,
do we have enough information
yet to say one way or another?
So, the answer's I don't
have an answer for you yet.
Yup. So, the question is whether
there's a coordination of effort
for men who have BPH, and, yeah.
It depends on what order you want to
say the words, and, so, basically,
in large prostate that
produces symptoms
in prostate cancer,
and, so, you're right.
These men tend to overlap.
The region where BPH
occurs in the prostate
and where the cancer occurs
are actually different regions.
And, so, some people try to
study whether ones a risk factor
for the another.
At this time, it doesn't appear that
one is a risk factor for the other,
instead, they seem to
have common risk factors.
So, factors that influence
prostate cancer risk also tend
to influence the development of BHP.
Yeah. Okay.
So the question is: One,
Asian men have a lower risk
of prostate cancer.
Given that there are differences in
what men eat and what they do based
on where they live
globally, has anyone tried
to evaluate whether an Asian diet
would prevent prostate cancer
in Western men?
Okay. And, so, one, I should
tell you when Asian men,
these are historical studies, when
Asian men move from Asia to the US,
which is actually Hawaii in
these studies, their own risk
of prostate cancer goes up.
Their sons have a risk of
prostate cancer that begins
to approach the risk of
White men living in Hawaii.
Okay? So, that says it's probably
not genetics that are counting
for this profound racial
variation in prostate cancer risk.
It says it's probably
diet, lifestyle,
things people have control over.
We haven't been able to
work out what is different
about the Asian diet, in Asia,
and risk of prostate cancer.
So, we have not done major
trials of Asian style, diet,
and other factors, but we've tried
to isolate individual
factors in cohort studies.
So, prospective studies, not
trials, but observational studies.
We've tried to look at,
for example, soy intake.
The problem is that people in the
U.S., in places like the U.S.,
don't eat a lot of soy
intentionally, right?
We have soy that's mixed into our
foods that we don't even know about,
but what men can report that
they're eating is low levels of soy.
So we cannot pick up association.
So, it's a great question.
We do not know what explains
the racial differences,
the profound racial differences,
including the much lower
rate in Asian man in Asia.
So the question is: Beyond
looking at individual factors,
have we looked at contextual
factors.
So, where people live,
their social structures,
not just whether healthcare's
available,
but whether people are able
to actually access healthcare,
and how this may affect differences
in risk of prostate cancer and,
in particular, prostate
cancer death.
And, so, there are studies that
try to look at contextual factors.
So, these are factors that are
above individual decision making
about whether you're going
to smoke and, you know,
physical inactivity, for example.
And, so, if you don't even have
sidewalks in your neighborhood,
how are you going to walk?
So, it's work like that.
And, so, my group has not
done that style of research,
but there are researchers who
are working in those areas.
Thus far, we have not been
able to find those types
of contextual factors, aside
from looking at disparities
in prostate cancer outcomes
in equal access care systems
like within the VA.
So, within the VA, it doesn't
matter who you are, there's a system
in place to make sure people
have equal access to care,
and so in those settings,
some studies have found
that the disparities are reduced,
others still see disparities
that the disease still
looks more aggressive,
for example, in African
American men.
The question is: Who
is it that we are able
to study based on who participates?
Okay. So, historically, studies
were primarily White men,
these are prostate cancer studies,
maybe a little more well to do,
maybe less opposed to, sort of,
the worries about hospital
systems and so on.
We have made, in the field,
not just for prostate cancer,
but just in health research in
general, a concerted effort to reach
out to communities that were not
represented in earlier studies,
and there are now a
number of cohort study.
I'm an observational researcher.
A number of cohort studies
that focus on communities
that were traditionally
harder to reach,
so my colleague Bill Blot has a
cohort study called the Southern
Community Cohort Study.
He went into clinics that
are federally subsidized,
recruited middle Asian
older individuals
to participate in those studies.
Those studies are primarily
African Americans,
and he has done a really
tremendous job
of people, keeping people engaged.
But we're still missing out
on the poorest of poor, right?
We're missing out on
people who are not connected
to health systems, right?
And, so, your question about
whether it could make a difference
in findings, it could, right?
It could because it's not just a
single risk factor that we study,
it's a risk factor on a
background of other factors.
Okay? So, we do need
to keep this in mind.
We need to make sure
we reach everybody.
We have to make sure we, not
just recruit people into studies,
but maintain equal follow up.
It can be quite difficult.
There are people whose research,
career, is around identifying,
recruiting, and retaining
people in studies.
I think it's a very important point.
The NIH, when we receive money
for our research studies,
we report on the diversity
of those we've recruited.
We've tried to make sure we
have sufficient representation
that we can look within
subgroups of individuals defined
by race ethnicity, defined by socio
economic status where possible.
Okay. So, it's actually
two parts to your question.
And, so, he wanted to know what's
the research on sedentary behavior
in risk of prostate cancer,
and, then, more specifically,
sedentary behavior that
puts pressure, actually,
it may not even be sedentary,
it could be active behavior,
that puts direct pressure
on the prostate.
So, with respect to sedentary
behavior, that's a newer area.
So, it's more newly recognized that
there's a separate contribution
to risk of cancers in other diseases
from being sedentary
verses just not being active
because there are some
people who are not,
they're not exercising, right?
There's no leisure
time physical activity,
but they're also not
seated all day long.
And, then, there are people like me.
I'm seated all day long, and,
then, I go to the gym, right?
So, I get my exercise in, but
I'm seated most of the day.
And, so, again, activity level
seems to have a different
and independent contribution from
the sedentary part of one's day.
So, for prostate cancer,
that's a new area.
So we don't have a
body of evidence yet.
The question you asked
about behavior activity
and sedentary behaviors that put
district pressure on the prostate,
it's an interesting question.
We certainly know that if a man has
just ridden a bicycle and then goes
and has a PSA test, PSA will have
been, I'm going to use the word
"expressed", it leaks into
circulation, so there's advice not
to do that right before PSA test.
But there's not, they're not, again,
not a body of studies
addressing that question.
It's an interesting one.
Yes?
>> You can have some
private conversation.
>> Great. So, thanks to all of you.
>> Please join me in
the thanks [inaudible].
[ Applause ]
>> Thank you.
[ Applause ]
>> This has been a presentation
of the Library of Congress.
Visit us at loc.gov.
[ Silence ]