Narrator: Hi everyone, and welcome
to this lecture on the epidemiology of prostate cancer.
In this lecture, we have several goals.
We'll begin by describing the global burden
of prostate cancer and then look
at populations at high and low risk.
We'll also discuss mechanisms of pathogenesis
and studies of dietary fat, NSAIDs
and nutritional supplements in prostate cancer.
We'll also look at genetic risks.
And finally, we'll look at screening
via the prostate specific antigen test and the role
of dietary zinc in the development of prostate cancer.
So to begin with, during 2012,
1,111,689 new cases were diagnosed
and 307,471 men died of prostate cancer.
These data reflect a marked increase
in the global burden of prostate cancer.
During 2000 to 2012,
the volume of new cases more than doubled
and the number of deaths has increased more than 50%.
Carcinoma of the prostate is the second most common form
of cancer in men behind only lung cancer
and is the fifth leading cause of cancer deaths worldwide.
In high income countries, prostate cancer is diagnosed
more often than any other form of male cancer
and is the third leading cause of death from cancer in men.
Disease survival in developing countries is high
and the ratio of incidence to mortality is 0.19
which is primarily due to screening of asymptomatic men
by prostate specific antigen
and the early detection of small latent carcinomas
of the prostate, invasive prostate cancer is diagnosed
less often in low and middle income countries
but tumors are usually detected after metastasis,
resulting in a twofold higher incidence to mortality ratio
and more than 165,000 deaths annually.
In 2020 the age standardized incidence
of prostate cancer was 30.7
per 100,000 globally, and the mortality was 7.7
per 100,000 globally.
In the US, certain ethnic groups
within the country have exceedingly high mortality rates.
So African Americans living in the US
have the highest age adjusted death rate
from prostate cancer in the world
and their annual rate is more than 70 deaths per 100,000.
And this rate is more than double that
of Caucasian or Hispanic Americans
which have rates less than 35 deaths per 100,000 people.
The incidence of invasive cancer
of the prostate increases dramatically
in men over the age of 50.
The disease is rare until age 50,
after which the risk increases exponentially.
The lifetime risk of developing invasive disease
is approximately one in six among white US men.
Prostate cancer is often discovered
as an incidental finding, either at postmortem exam
or in a surgical specimen removed for other reasons
like the treatment of benign prosthetic hypertrophy or BPH.
Almost all such lesions are small
and comprised only of microscopic foci malignant cells.
This form of prostate cancer is called occult
or latent prostate cancer.
In postmortem studies of unselected men,
occult prostate cancer can be identified
in about 10% of subjects between 50 to 59 years of age
and this number rises to a prevalence
of 40 to 50% in those over the age of 70.
It's noteworthy that in the vast majority of subjects,
or 95%, these occult lesions were absolutely unexpected
or unsuspected and clinically asymptomatic.
To briefly discuss the anatomy of the prostate gland,
we see that it's roughly divisible into a central region,
the transitional zone, that's responsive
to estrogen in a more peripheral region
or the peripheral zone that is stimulated by androgens.
Benign prosthetic hyperplasia or BPH,
is an extremely common disorder that affects men
over the age of 50.
And in this, the hyperplastic nodules of BPH typically arise
from the inner regions of the prostate gland
perhaps due to the balance between androgens and estrogens.
There's longstanding controversy
regarding the development of cancer from BPH.
In 1993, a large placebo
controlled randomized clinical trial,
the Prostate Cancer Prevention Trial
or PCPT was initiated to determine
if the five alpha reductase inhibitor, finasteride,
could prevent prostate cancer.
This study looked at nearly 20,000 men age 55 and older
and randomized them to receive either finasteride,
five milligrams daily or placebo.
After seven years of follow up, 18% of men
receiving the drug developed prostate cancer
compared to 24% in the placebo group,
which is a risk reduction of 25%.
However, men who did develop prostate cancer
while receiving the drug were more likely
to have high grade tumors with metastatic potential.
Final results were based upon an analysis
of nearly 10,000 participants, which was only
about half the men who initially enrolled in the study.
Ecological correlation studies show a strong
positive correlation between diets high in fat
and calories with prostate cancer incidence
and mortality, within countries, chronological trends
and prostate cancer rates tend to follow in close parallel
with per capita trends in dietary fat intake.
Prostate cancer rates in Japan
or Japanese men have increased nearly fivefold
over a 50 year period since 1955,
concurrent with rising level of fat in the Japanese diet.
This dietary fat hypothesis was examined by a study
in 1993, which found that men reporting fat intake
in the highest quintile experienced a 79% increase
in the risk of invasive prostate cancer
compared to men in the lowest quintile.
In another study in 2007, it was found that a high intake
of essential N6 polyunsaturated fatty acids
produced a 2.6 fold increase
in the risk of invasive prostate cancer.
Animal studies also support the ideological link
between prostate cancer development and intake
of specific types of dietary fat.
And this westernized lifestyle or increase
in consumption of fats has been linked
to an increased risk for prostate cancer.
Traditional non-steroidal anti-inflammatory drugs
or NSAIDs with cyclooxygenase two
or COX2 blocking activity
have consistently shown potential
in the chemo prevention of several forms
of malignant neoplasms, including prostate cancer.
Inter meta-analysis of 17 epidemiologic studies,
regular intake of aspirin, ibuprofen
or other over-the-counter NSAIDs were found
to reduce the risk of prostate cancer by 27%.
This primarily occurs through the reduction
of COX-2 and the inflammatory cascade.
Prostate cancer shows a significant familial component.
In studies in 1982, brothers of prostate cancer cases
had four times higher
cumulative rates of prostate cancer
than brothers in law or males of the general population,
thereby reflecting existence
of genetic factors that increased the risk
of neoplastic development in the prostate gland.
Recently, a mutant gene
that altered the androgen receptor
was developed in African American men
with a family history of prostate cancer.
The findings of a number of observational studies
plus two randomized control studies
indicate that supplemental intake of selenium
in vitamin E might be effective
in preventing the development of prostate cancer.
In 2001, a large randomized placebo
controlled clinical trial
was initiated to determine whether selenium,
vitamin E or both could prevent prostate cancer.
This study was inconclusive and found no effect
on the risk of developing invasive prostate cancer.
Some studies have also examined the impact
of sexual activity on prostate cancer risk.
Though these studies are inconclusive.
Screening for prostate cancer
using serum prostate specific antigen
or PSA test gained favor
in the US and other developed countries during the 1990s.
It is estimated
that 20 million PSA tests are performed annually
in North America and possibly 20 million more
outside of North America, a high level of serum PSA
or more than four nanograms per milliliter
when coupled with digital rectal examination,
ultrasonography and directed biopsy
of suspicious prostatic tissues can be effective
in identifying men with invasive disease
confined to the prostate gland that can be completely
surgically excised without recurrence.
PSA screening is controversial
since prostate cancer often develops so slowly
that it will never lead to symptoms during a man's lifetime.
Furthermore, prostatectomy for removal
of a cancerous prostate gland
often produces major debilitating side effects
like urinary incontinence,
erectile dysfunction and impotence.
The major consideration
for any screening protocol is to weigh the benefits
of early detection and lifesaving treatment
against the risk of harm from unnecessary intervention.
Results of two large randomized clinical trials,
a PSA screening have now been published.
The first study did show 20% fewer deaths
in the group that received PSA testing.
However, the study also found that a large number
of men who were treated unnecessarily
resulted in a high rate of major side effects.
Another randomized study in the US compared PSA
to quote, unquote usual care
in the detection and treatment of prostate cancer.
And in this study, there were actually 13% fewer deaths
in in the group that received quote, unquote usual care
rather than regular prostate specific antigen tests.
After careful for review of the scientific evidence,
the US Preventative Service Task Force
concluded that the data were insufficient
to recommend screening for men under 75,
and that men 75 and older should not be screened.
Clinicians are now advised to use a process
of shared decision making
with each patient that includes candid discussion
about the potential risks and benefits of screening.
Finally, we turn to studies looking at the relationship
between zinc and prostate cancer survival.
So zinc is an essential mineral
with known antioxidant anti-inflammatory effects
and it's an important co-factor
in DNA repair, apoptosis and cellular immunity.
The concentration of zinc is higher in prostate tissue
than in any other tissue in the human body.
And Swedish men have one
of the highest annual mortality rates
from prostate cancer in the world.
So a study was launched to examine the level
of dietary zinc as the potential predictor
of survival among 525 Swedish men
diagnosed with invasive prostate cancer
during 1989 to 1995.
In this study, zinc intake was estimated
based on the average content in grains, meat,
dairy products, fruits, nuts
and vegetables consumed by the individual patients.
And the study found
that high dietary zinc intake was associated
with a reduced risk of death due to prostate cancer.
This protective effect of high dietary zinc was stronger
among men diagnosed with localized tumors.
And these results suggest that high intake
of dietary zinc has therapeutic benefit
in men diagnosed with prostate cancer.