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Prostate Cancer:
Evaluation & New
Treatments
Christopher L. Coogan, M.D.
Charles F. McKiel, M.D.
Kalyan C. Latchamsetty, M.D.
В©2007 RUSH University Medical Center
What is the prostate?
• Male sexual gland
• Adds nutrients and
fluids for sperm
• This fluid is added to
sperm during
ejaculation
• Urethra (urine channel)
runs through the middle
of the prostate
• Weight ~ 20 – 30gms
В©2007 RUSH University Medical Center
Anatomy
• 1 = Peripheral Zone
– 75% of CA
• 2 = Central Zone
– 5% of CA
• 3 = Transitional Zone
– 20% of CA
• 4 = Anterior Fibromuscular Zone
– CA rare
В©2007 RUSH University Medical Center
What is prostate cancer?
• Abnormal cells growing without
regulation
• Spreads and invades local tissues
• Prostate Cancer…
– Begins with a small tumor in the gland
– First spreads to the local lymph nodes
– Then spreads to the bony skeleton and other
areas of the body
В©2007 RUSH University Medical Center
Introduction
• CAP пѓ most commonly diagnosed (non-skin)
cancer in American в™‚
• 2nd most common cause of ♂ cancer death
• ~ 217,730 new cases of CAP in 2010
• American Cancer Society
• ~ 32,050 deaths in 2010 in the U.S.
В©2007 RUSH University Medical Center
Incidence of prostate cancer
В©2007 RUSH University Medical Center
What are the symptoms of prostate cancer?
• You might not have any at all!
– Often there are none, or they are not recognized
• Major symptoms:
–
–
–
–
–
–
Urinary frequency
Slow urinary flow
Painful urination
Blood in urine or semen
Impotence
Lower back or thigh pain
В©2007 RUSH University Medical Center
How Significant Is Prostate Cancer?
• In the USA, 217,730 men will be diagnosed with
prostate cancer in 2010. That is one man
diagnosed every 3 minutes
• Prostate cancer deaths are estimated at 32,050 in
2010. That is one death every 18 minutes
• In Illinois, 8,730 men were diagnosed in 2010
• 1,420 men died of prostate cancer during 2010 in
Illinois
Source: Cancer Facts and Figures –2006- American Cancer Society
В©2007 RUSH University Medical Center
Prostate cancer risk factors:
пЃ¬ Age: The risk increases with age, but 25% of
diagnoses are made under age 65.
пЃ¬ Race: African-Americans have a rate of incidence
double that of Caucasian men
пЃ¬ Family history of prostate cancer: Men with a
family history have two- to three-fold increase in the
risk of prostate cancer
пЃ¬ Diet: A diet high in saturated animal fat can double
the risk of developing prostate cancer.
В©2007 RUSH University Medical Center
Risk Factors - Age
AGE
0 - 39:
40 – 59 :
60 – 69 :
70 – 79 :
0 - Death :
RISK
1 per 10149
1 per 38
1 per 14
1 per 7
1 per 6
Source: ACS 2000 to 2002
В©2007 RUSH University Medical Center
Risk Factors - Race
Race
Afr.-Am.
Cauc.
Hisp.
Asian
Incidence
272.0
169.0
141.9
101.4
Death
68.1
27.7
23.0
12.1
Source:
Rates per 100,000 and age-adjusted. SEER incidence and U.S. cancer death rates, 1975-2002,
in (SEER = NCI Surveillance, Epidemiology, and End-Results Program
В©2007 RUSH University Medical Center
RACE
• Prostate cancer is almost twice
as common in AfricanAmerican men than in
Caucasian men
• African Americans are more
than twice as likely to die
when diagnosed than
Caucasian men
• Why? Uncertain.
–
–
–
–
Socioeconomic
Diet
Genetic
???
В©2007 RUSH University Medical Center
Risk Factors – Family History
FAMILY HISTORY
2.4 times increased risk for men with a firstdegree relative
All blood relatives need to be screened
starting at the age of 40
(Spitz, et al, “Familial patterns of prostate cancer: A case-control analysis”, J Urol,
1991, 146:1305-1307)
В©2007 RUSH University Medical Center
Risk Factors - Diet
Eating red meat increases the risk of developing prostate
cancer 2.64 times
пЃ®
Red meat and dairy products are high in saturated fat
rich in arachidonic acid (a fatty acid)
пЃ®
Vegetable oil is rich in alpha linolenic acid (a fatty
acid)
пЃ®
By-products of these fats promote the growth and
seriousness of prostate cancer
пЃ®
пЃ®
Eating a diet high in fats also lowers the body’s defenses
В©2007 RUSH University Medical Center
Trends in Obesity* Prevalence (%), By Gender, Adults
Aged 20 to 74, US, 1960-2002
45
40
33
Prevalence
35
30
28
30
26
23
25
21
20
15
17
16 17
15
13 15
11
12 13
10
5
0
Both sexes
NHES I (1960-62)
NHANES III (1988-94)
Men
Women
NHANES I (1971-74)
NHANES 1999-2002
NHANES II (1976-80)
*Obesity is defined as a body mass index of 30 kg/m2 or greater.
Source: National Health Examination Survey 1960-1962, National Health and Nutrition Examination Survey, 19711974, 1976-1980, 1988-1994, 1999-2002, National Center for Health Statistics, Centers for Disease Control and
Prevention, 2002, 2004.
В©2007 RUSH University Medical Center
Trends in Overweight* Prevalence (%), Adults 18
and Older, US, 1992-2003
1992
Less than 50%
50 to 55%
More than 55%
State did not participate in survey
*Body mass index of 25.0 kg/m2or greater
Source: Behavioral Risk Factor Surveillance System, CD-ROM (1984-1995, 1998) and Public Use Data Tape (2003),
National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention,
1997, 2000, 2004.
В©2007 RUSH University Medical Center
Trends in Overweight* Prevalence (%), Adults 18
and Older, US, 1992-2003
1995
Less than 50%
50 to 55%
More than 55%
State did not participate in survey
*Body mass index of 25.0 kg/m2or greater
Source: Behavioral Risk Factor Surveillance System, CD-ROM (1984-1995, 1998) and Public Use Data Tape (2003),
National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention,
1997, 2000, 2004.
В©2007 RUSH University Medical Center
Trends in Overweight* Prevalence (%), Adults
18 and Older, US, 1992-2003
1998
Less than 50%
50 to 55%
More than 55%
State did not participate in survey
В©2007 RUSH University Medical Center
Trends in Overweight* Prevalence (%), Adults
18 and Older, US, 1992-2003
2003
Less than 50%
50 to 55%
More than 55%
State did not participate in survey
В©2007 RUSH University Medical Center
So what CAN I eat?
• A balanced diet rich in fruits
and vegetables!
(5 servings/day)
• Lower your intake of red
meat, processed and fried
foods. Eat more plant-based
food like soy protein.
• Watch portion sizes
(3 oz meat/serving)
• Eat foods with lycopene
(tomatoes, watermelon
and red grapefruit) which
may be associated with a
decreased risk of prostate
cancer
В©2007 RUSH University Medical Center
Can we prevent prostate cancer?
• Prostate Cancer Prevention Trial (PCPT):
18,882 men randomized:
– 25% Reduction in Cancer, BUT
– 14-25% increase in high grade cancer
• REDUCE Trial: 22% decreased
– 8200 men, randomized, ? increase high grade
– Dutasteride (Avodart)
– FDA WARNING
• SELECT Trial: 35,533 men
– Vitamin E vs Selenium: no change
В©2007 RUSH University Medical Center
Screening
• American Urological Association
screening recommendations:
• Digital Rectal Examination & PSA
1.All males over the age of 40 – annually
– ?45 or 50
2.All African American males over age of 40 –
annually
3.All pts with family hx (1st degree relative)
starting at age 40 – annually
• ACS: 50
– 45 if 1st degree or AA
В©2007 RUSH University Medical Center
Anatomy - DRE
В©2007 RUSH University Medical Center
DRE not always accurate!
В©2007 RUSH University Medical Center
Screening
• Only 15% of prostate cancers are
detected through this examination
• Many men with abnormal DREs do NOT
have prostate cancer
• Many men with normal DREs DO have
prostate cancer
В©2007 RUSH University Medical Center
PSA
• Prostate specific antigen
• Protein produced by the cells of the prostate
• responsible for liquefying semen
immediately following ejaculation
– Increases motility of sperm cells
– Aids in fertilization
• Initially discovered in the late �70s, but wasn’t
used for screening for CAP
• Was used mainly by forensics in rape cases
• In 1985, the FDA approved PSA test for use
in humans
В©2007 RUSH University Medical Center
PSA
• Can be elevated with benign conditions i.e.
prostatitis, BPH, UTIs, urinary retention
• Normal range: 0 - 4 ng/ml (0 - 2.5)
• PSA rises as we age
– PSA level of 3.0 in a 30 y/o male is abnormal
– PSA level of 3.0 in a 70 y/o male is nl
• PSA Velocity (>0.75/year)
В©2007 RUSH University Medical Center
PSA Screening
• Most significant and controversial development in prostate cancer
control over the last 20 years
• Initial studies:
– PSA markedly elevated in men with prostate cancer (but, also
elevated with benign conditions: UTI, BPH, prostatitis, urinary
retention)
– PSA screening resulted in dramatic shift in stage of disease
• Conclusive evidence of efficacy is still lacking! But, it’s the best
test we have.
• In late 1980s, PSA screening in US exploded
В©2007 RUSH University Medical Center
В©2007 RUSH University Medical Center
SCIENCE TIMES, April 9 2002
В©2007 RUSH University Medical Center
Prostate Cancer Screening
• Tyrol Study: 54% reduction in mortality
– 1993-2005
• PLCO Trial: No benefit to screening
– If PSA <2.0, every 2 years
• European Randomized Study for
Screening for Prostate Cancer (ERSPC)
– 20% reduction mortality, 40% mets, but
– Overdetection?
• FUTURE: Age-adjusted PSA, PSA
velocity, PCA-3
В©2007 RUSH University Medical Center
PSA – may rise in presence of CAP
• Drawbacks:
– up to 30 percent of men with prostate cancer have
a normal PSA
– 75 percent of men with an high PSA blood test do
not have prostate cancer
– the PSA blood test cannot determine if the cancer
is a slow-growing or aggressive cancer
– Still is the best test we have
В©2007 RUSH University Medical Center
Why do we screen?
To Avoid An Advanced Stage At Diagnosis:
Early detection is the goal for any cancers
Men Assuming Responsibility
for Their Health
PSA
DRE
В©2007 RUSH University Medical Center
How does early detection help?
• Survival rate at 5 years is
100.0% for those whose
cancer is still just in the
prostate gland (localized).
• Survival rate at 5 years for
those whose cancer has
spread beyond the gland
(late diagnosis) is only
33.5%
В©2007 RUSH University Medical Center
Screening
• American Urological Association
screening recommendations:
• Digital Rectal Examination & PSA
1.All males over the age of 40 – annually
– ?45 or 50
2.All African American males over age of 40 –
annually
3.All pts with family hx (1st degree relative)
starting at age 40 – annually
• ACS: 50
– 45 if 1st degree or AA
В©2007 RUSH University Medical Center
Screening
• If PSA or Digital Rectal Examination is
abnormal, then patient needs a prostate
biopsy
В©2007 RUSH University Medical Center
В©2007 RUSH University Medical Center
В©2007 RUSH University Medical Center
Staging of Prostate Cancer
•
•
•
•
•
•
•
PSA
Digital Rectal Exam
Trans Rectal Ultrasound
Gleason Score
Bone Scan
+/- CT scan or MRI
Biopsy and TNM staging system
– Tumor, Nodes, Metastases
В©2007 RUSH University Medical Center
Stage I or Stage A Prostate Cancer
• Stage I cancer is
found only in the
prostate and usually
grows slowly
В©2007 RUSH University Medical Center
Stage II or Stage B Prostate Cancer
• Stage II cancer has
not spread beyond
the prostate gland,
but involves more
than one part of the
prostate, and may
tend to grow more
quickly
В©2007 RUSH University Medical Center
Stage III or Stage C Prostate Cancer
• Stage III cancer has
spread beyond the
outer layer of the
prostate into nearby
tissues or to the
seminal vesicles, the
glands that help
produce semen
В©2007 RUSH University Medical Center
Stage IV or Stage D Prostate Cancer
• Stage IV cancer has spread to
other areas of the body such as the
bladder, rectum, bone, liver, lungs,
or lymph nodes
В©2007 RUSH University Medical Center
Biopsy Results – Gleason Score
• Gleason Score = sum of the
two most common histologic
patterns (primary and
secondary)
• Range: Gleason 1(well
differentiated) – 5 (poorly
differentiated)
• The higher the Gleason Score,
the more poorly differentiated
the cancer (more aggressive)
• i.e. Gleason 3 + 3 = 6
•
Gleason 4 + 3 = 7
•
Gleason 5 + 4 = 9
• Gleason 3 + 4 ≠4 + 3
В©2007 RUSH University Medical Center
Gleason Score
• Gleason Score = sum of the two most common
histologic patterns (primary and secondary)
• Range: Gleason 1(well differentiated) – 5 (poorly
differentiated)
• The higher the Gleason Score, the more poorly
differentiated the cancer (more aggressive)
• i.e. Gleason 3 + 3 = 6
•
Gleason 4 + 3 = 7
•
Gleason 5 + 4 = 9
• Gleason 3 + 4 ≠4 + 3
В©2007 RUSH University Medical Center
Risk Groups
Low
Intermediate
High
Stage
≤ T2a
T2b
T2c or >
Gleason
Score
≤6
7
8-10
PSA
< 10
>10 & < 20
≥ 20
В©2007 RUSH University Medical Center
Treatment Options
Dependent upon……
• Stage of disease
• Patient’s age and health
• Patient’s personal preference
В©2007 RUSH University Medical Center
Treatment Options (early diagnosis)
 Watchful waiting пѓ Active Surveillance
 Radiation Therapy
 External Beam Radiation Therapy
 Brachytherapy (Radioactive seeds)
 HDR
 Cryosurgery (Freezing prostate)
 Surgery (Radical Prostatectomy)
 Open Surgery
 Conventional Laparoscopic Surgery
 da Vinci™ Prostatectomy (Robotic-Assisted
Laparoscopic Surgery)
В©2007 RUSH University Medical Center
Active Surveillance
• Appropriate in patients:
– with a less than 10 year life expectancy
– GS ≤ 6
– Non palpable disease
• DRE, serum PSA q 6 months
• Patients become symptomatic and
require treatment 30-50% of time
В©2007 RUSH University Medical Center
Treatment Options (early diagnosis)
 Watchful waiting пѓ Active Surveillance
 Radiation Therapy
 External Beam Radiation Therapy
 Brachytherapy (Radioactive seeds)
 HDR
 Cryosurgery (Freezing prostate)
 Surgery (Radical Prostatectomy)
 Open Surgery
 Conventional Laparoscopic Surgery
 da Vinci™ Prostatectomy (Robotic-Assisted
Laparoscopic Surgery)
В©2007 RUSH University Medical Center
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