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Prostate Cancer Screening:
The Other Side of the Story
Tracie Gadler RN, MSN, RNFA, NP-C
(Edited by Carol Salem MD)
Urologic Oncology Surgery
Robotic Surgical Services Nurse Practitioner, Scripps
Mercy Hospital
Outcomes
• Understand function and location of the
prostate glad
• Be informed on prostate cancer
screening
• Identify diagnostic tools and treatment
options currently available
Prostate Anatomy
Prostate Anatomy
• Normal prostate size: 20 grams, by
about fifty over half men have enlarged
prostates.
– Data base 738 patients avg size 50.8 (avg
age 62.8)
• Prostate Function: Male accessory
gland which secrets fluid into ejaculate
Prostate Cancer (PCA)
• Prostate cancer occurs when the DNA in
prostate cell is changed.
• Prostate cancer is either inherited or
acquired
• Prostate cancer tends to be slow growing,
survival rate at 5 years is 100% and 15
years 91%
American Cancer Society Prostate Cancer 2012
Acquired PCA
• Oncogenes are genes that help cells divide
and grow
• Tumor suppressor genes slow cell division
• DNA mutations can turn ocogenes on or turn
off suppressor genes thus causing cancer
• Trigger environmental factors, chemicals,
radiation
American Cancer Society Prostate Cancer 2012
Inherited PCA
• HPC1 (Hereditary Prostate Cancer Gene)
• Other inherited genes found across male family
members with prostate cancer can include BRCA1
(Breast Cancer Susceptibility Gene or BRCA2 more
commonly found in women with females with breast or
ovarian cancer
• Men with first degree relative with PCA have double
the risk of developing PCA
American Cancer Society Prostate Cancer 2012
Prostate Cancer Facts
• Prostate Cancer is the most common cancer
diagnosed in men (estimated 238,590 in
2013 National Cancer Institute)
• Yet, Only a small percentage of men die
from prostate cancer ( est.10%2013)
= second leading cause of cancer death in
men (29,720 est. 2013 lives/year).
Prostate Cancer Detection
• No symptoms of early stage prostate cancer.
• Usual risk increases after age 50, though can be
found at much earlier ages.
• Increased risk: African-American/
Family History (brother/father/uncle)
American Cancer Society 2012
Prostate Cancer Screening
No symptoms, so Detection of prostate
cancer requires SCREENING
Prostate Cancer Screening
The goal of early detection is to reduce
the overall morbidity and mortality
(side effects and death from the
disease )
Consideration Prior to Screening
•
•
•
•
•
•
Age
Race
Risk factors
Other illnesses
Patient preference
Consider health care delivered on an
individual basis
Prostate Cancer Detection
Screening:
• Rectal examination
• PSA (Prostate Specific Antigen)
blood test
NOT PSA blood test by itself
PSA
• Prostate Specific Antigen is a glycoprotein
enzyme that is secreted by epithelial cells.
PSA makes ejaculate liquid and will help
to dissolve cervical mucus.
– Increases in quantity when the glad is
damaged or harmed.
• Most labs consider 0-4ng/mL “normal
range”
Guidelines for PCA Screening
Age
DRE
PSA
Age to be
screened
American
Cancer
Society
Annual
< 2.5 ng/ml
every 2 years
> 2.5 ng/ml
yearly
American
Urologic
Society
Annual
Annual
> 50 years
> 45 years if at
RISK
> 40 years if
higher RISK
> 50 years
> 40 if at RISK
If >10 years life expectance. RISK: African-American, first degree relative PCA.
HIGHER RISK: more then one first degree relative with PCA history.
Different PSA Screening
Tests
•
•
•
•
•
Percent-free PSA
PSA Velocity
PSA Density
Age Specific PSA tests
Other
Percent-free PSA (fPSA)
•
•
•
•
•
•
•
Helpful in bx determination
PSA is protein bound or unbound
fPSA is a ratio unbound PSA: total PSA
fPSA lower in PCA
<10% = bx
10-25%= strong bx consideration
(complexed PSA (cPSA) determines PSA
attached to other proteins)
American Cancer Society :Prostate Cancer 2012
PSA Velocity (PSAV)
• Measure of how fast the PSA raises over time
– Biopsy: PSA >4ng/mL if PSA velocity >0.75 within
one year
– Biopsy: PSA >0.4ng/mL if PSA velocity >0.75 over
three PSA blood draws within 18 months of
eachother
AUA Prostate-Specific Antigen Best Practice Statement 2009
PSA Density (PSAD)
• PSA levels can be higher in patients with large
prostate glands.
• Volume (transrectal u/s)/ PSA level =PSAD
– Higher number = greater chance of cancer
Age Related PSA (ng/mL)
Age Range AsianAfricanAmericans American
40-49 yr
0-2.0
0-2.0
Whites
0-2.5
50-59 yr
0-3.0
0-4.0
0-3.5
60-69 yr
0-4.0
0-4.5
0-4.5
70-79 yr
0-5.0
0-5.5
0-6.5
AUA Prostate-Specific Antigen Best Practice Statement 2009
Potential Factors Affecting PSA
■ BPH
■ Age
■ Urinary infection
■ Ejaculation
■ Riding Bike
■ Urinary or rectal instrumentation
■ Prostatitis
■ Obesity
■ Medications: Proscar, Avodart, Saw
palmetto/testosterone
Rectal examination
• Perform DRE
• Important to perform DRE not only for prostate
cancer detection but rectal cancers and bleeding.
Prostate Biopsy
IF:
– Abnormal rectal exam and/OR
– Abnormal PSA blood test and
– Patient desires further work-up
THEN:
- Prostate Biopsy
Prostate Biopsy
•
•
•
•
Transrectal ultrasound
lidocaine gel
lidocaine injection
antibiotics
Potential side effects (3-4%)
• infection (prostatitis)/urinary retention
• Bleeding
J Urol 168:558,2002;171:247, 2004;174:510,2005.
Transurethral Ultrasound
Guided Biopsy
Transrectal Ultrasound Guided Biopsy
Evidence
• Growing body of research.
• Reduction in the death rate of prostate
cancer (since 1990).
• Obvious shift in finding earlier stage
prostate cancers (PSA).
Recommendation: PSA
Screening
Should “INFORM” Patients Risks and Benefits of
Screening
– American Medical Association
– National Cancer Institute
– American Urologic Association
– American Cancer Society
Do not Discuss (PSA-based prostate cancer screening)
- U.S. Preventative Services Task Force
USPSTF
• “Prostate cancer is a serious health problem
that affects thousands of men and their families.
But before getting a PSA test, all men deserve
to know what the science tells us about PSA
screening: there is a very small potential benefit
and significant potential harms. We encourage
clinicians to consider this evidence and not
screen their patients with a PSA test unless the
individual being screened understands what is
known about PSA screening and makes the
personal decision that even a small possibility
of benefit outweighs the known risk of harms.”
• —USPSTF Co-Chair Michael LeFevre, M.D., M.S.P.H.
May 22, 2012
USPSTF
“Based on this work, the Task Force concludes
that many men are harmed as a result of
prostate cancer screening and few, if any,
benefit”.
“A better test and better treatment options are
needed. Until these are available, the USPSTF
has recommended against screening for prostate
cancer.”
http://www.uspreventiveservicestaskforce.org/prostatecancerscreening.htm
USPSTF
• “RateD: The USPSTF recommends against the
service. There is moderate or high certainty that
the service has no net benefit or that the harms
outweigh the benefits.”
• “Suggestions for practice: Discourage the
use of this service”.
• http://www.uspreventiveservicestaskforce.org/uspstf/gradespost
.htm#drec
USPSTF
• U.S Department of Health and Human Services
• 1984
• “independent group of national ‘experts’ in
prevention and evidence-based medicine that
works to improve the health of all Americans by
making evidence –based recommendations about
clinical preventative services, such as
screenings…”
• 16 VOLUNTEER members
medicine/prevention/nursing/pediatrics
• Government supported activities/research
USPSTF
• Government supported.
• Volunteers
• Not required to have an EXPERT in the field of
which they are making a recommendation.
• Medicare/health care insurance agencies
typically weigh these recommendations heavily
when considering health care coverage.
Their Evidence
USPSTF: Literature Review 80 Articles
screenings based primarily on 2 Studies:
1. NIH Prostate, Lung, Colorectal, Ovarian
Cancer Screening Trial (PLCO)
2. The European Randomized Study of
Screening for Prostate Cancer (ERSPC)
PLCO Study
Time: 1993-2006
Population:76,685 men (38,340 intervention/38,345 control)
Age: 55-74 yr
Intervention Group:
annual PSA for 6 years and DRE 4 years
Control Group:
“usual care” which sometimes included opportunistic
screening
By 2009, 57% of the men had been followed for at least 13
years.92% of men followed for 10 years.
Natl Cancer Inst 2012; 104:125
PLCO Study
• Incidence of prostate cancer slightly higher
in intervention group
(4250 vs 3815)
• Prostate cancer mortality (death) did not
differ significantly between the groups
(3.7 vs 3.4 deaths per 10,000 person years)
Natl Cancer Inst 2012; 104:125
PLCO Study
Problem:
• Greater than 50% contamination rate in the control group
(PSA/rectal examinations)
– Usual care consisted of any patient or physician performing
screening if requested (52% screened by 6th year)
• Prescreening of many of them -44%- before enrolling in
the trial therefore eliminating some cancers
• 10 years not enough time re: life expectancy
N Engl J Med. 2009 1310-1319; Natl Cancer Inst 2012; 104:125
European Randomized Study
Time: Early 1990’s-December 31 2006
Population:182,000 (Core 162,243 55-69 yr)
Age: 55-74 yr
Intervention group: PSA Screening once every 4 yrs
Control group: Unscreened group
median follow-up of 11 years
New England J Medicine 2009; 360:1320
European Randomized Study
Prostate Cancer (ERSPC)
• Elevated PSA was determined by clinic 2.54ng/mL
• Incidence of prostate cancer 8.2%
intervention group vs 4.8% control group
• Reduced prostate cancer DEATH by 20%
• 1410 men need to be screened and 48 men
treated to prevent 1 death in 10 years.
New England J Medicine 2009; 360:1320
ERSPC
• Problem:
– High rate of over diagnosis aprox. 50%
ERSPC
– Overdiagnosis “ defined as the diagnosis in
men who would not have clinical symptoms
in their lifetime.”
New England J Medicine 2009; 360:1320
Goteborg Study
Goteborg Randomized Population-Based
Prostate Cancer Screening Trial
Time:1994-Dec 31st,2008
Population: 20,000 randomized
Age: 50-64 yr
Intervention:(9,952)PSA screening every 2 years
Control: (9952)Not invited for screening
Median follow-up 14 years
Lancet Oncol 2010, 11:725
Goteborg Study
• Men with raised PSA were offered DRE or
biopsies
• Results:
– 7578 continued on in the intervention group
– 1046 (12.7%) diagnosed with PCA vs 718 (8.2%)
control group
– 27 deaths intervention group vs 78 deaths
control group
• Decreased mortality rate by 44% in intervention
group
Lancet Oncol 2010, 11:725
USPSTF
• Their Conclusion:
– Any Decrease in prostate-specific
mortality amounted to too few lives saved
and did not outweigh the harms of
screening and diagnosis/and the harms of
treatment…
PSA causes more harm than good!!
Additional Flaws
• Acknowledge strong evidence that treatment of
localized prostate cancer reduced mortality
compared to observation.
• Overlooked the fact that the unscreened
population had higher stage prostate cancersresulted in more significant complications
Additional Flaws
• Unscreened group had a 40% higher incidence of locally
advanced and metastatic prostate cancer.
• Focused on “mortality”, and did not weigh in on the
substantial illness associated with living advanced
prostate cancer.
– (No comparisons made!)
• Lack focus on high risk groups.
• Lack focus on the epidemiology data re: 30% reduction
in PCA deaths since early 1990’s and 75% reduction in
presentation with advanced cancer.
To justify screening, one must
demonstrate that treatment of the
disease is beneficial
“A randomized trial comparing
radical prostatectomy with watchful
waiting in early prostate cancer”
Holmberg et al., NEJM 352/2005
Scandinavian study
After PCA Dx
10.8 years
12.8 years
Radical
47 deaths from
Prostatectomy
PCA/347 men
Watchful Waiting 68 deaths from
PCA/348 men
55 deaths from
PCA/347men
81 deaths from
PCA/348men
% Deaths
Radical
Prostatectomy
vs Watchful
Waiting
14.6% vs 20.7%
12.5% vs 17.9%
JNCI 2008;100;1144-1154:;N Engl j Med 2011;364 1708-17.
A Different Conclusion!
PSA-based screening for prostate cancer
is USEFUL in helping to save lives!
Per SEER Cancer Statistic Review
prostate cancer mortality has decreased
30%
AUA Prostate Specific Antigen Best Practice Guidelines 2009 Update
Prostate Cancer Screening
• Need to continue to modify our
screening criteria to aim for the best
“good” and the least harm
• PSA is TOO GOOD at finding early
stage prostate cancer!!
• Start screening efforts at younger ages look at
number trend over time
Prostate Cancer Screening
• Need to continue to improve our treatments
for prostate cancer– radiation and surgery
– LESS side-effects when treating EARLY stage
prostate cancer!!
• Continue efforts in molecular biology to
identify patients who really need treatment
vs those that can be safely watched.
The Dilemma
• Once diagnosed, cannot know with certainty
whether the prostate cancer is going to affect life
expectancy.
• Therefore, treatment is a dilemma, (and the
treatment options can affect quality of life).
USPSTF Transparency and
Accountability Act 2012
• Publish a draft research plan to guide the systematic
evidence review process
• Make the evidence review available for public
comment
• Consider findings and research by federal agencies
and departments
• Coordinate activity with Federal agencies
• Consult with “external subject matter experts,” i
• Ensure greater transparency in appointing members
through a notice and comment process
• Disclose potential conflicts of interest. AUAnet:2012
Critics of Prostate Screening
• Screening is too $$$
• Side effects from the prostate biopsy
• Abnormal PSA only (normal rectal exam)
results in high rate of cancer detection.
• Nonsignificant cancers are found,
therefore many men are over treated.
• “No significant evidence that PCA
screening results in a decrease in
mortality.”
Insignificant tumors
• No definitive test on significance of tumor
• Reliable criteria
–
–
–
–
PSA velocity
grade (Gleason score)
number cores involved
rectal exam
Insignificant tumors
• Responsibility of urologist to discuss and
educate patient on treatment or nontreatment options
• Future key:
– genetic markers (blood, urine, skin)
Is there a mortality benefit?
Implied benefit
• Since 1990, significant stage migration of
prostate cancer (earlier stages!, less
metastatic disease at time of diagnosis).
• Prostate cancer mortality has been
decreasing
The Facts
Pre-PSA era 35% of men who underwent
prostatectomy were found to have positive lymph
nodes at surgery and 75% were found to have
advanced prostate cancer
Vs.
Since PSA testing 48% of patients diagnosed with
prostate cancer have organ and capsule contained
disease and 85% are clinically localized.
AUA PSA Best Practice Statement 2009: SEER Cancer Statistics Review
• Studies are less than 10 years
• Contaminated groups
• PSA absolute values
The answer still remains UNCLEAR…
• Traditional screening-starts at age 50,
studies out to less than 10 years….
• Death from prostate cancer
– High risk ….need earlier screening efforts
– Moderate risk….need studies out to 15
years
The Challenge...
…is
not to reduce the rate of prostate cancer
detection, but to identify men whose disease
may be life-threatening.
While Prostate cancer screening is
SAFE, and EASY...
Future
-better diagnostic tools (imaging
MRI).
-better screening tools (other tumor
markers in blood, urine or skin).
-genetic markers to identify patients with
clinically relevant prostate cancer.
Prostate Cancer Prevention
•
•
•
•
•
•
•
•
Selenium
(Vit E)
Soy
Lycopenes
Green Tea
Folic Acid
Hops (xanthohumol)
Proscar (finasteride)
Selenium
• An essential component of our diet
– forms parts of many proteins throughout the
body
– antioxidant
– promotes immune function
– provokes cancer cells to programmed cell death
• 200 micrograms/day (seafood, lean meats,
grains, eggs, garlic)
pizza???
• Lycopenes
– A powerful antioxidant, found abundant in
tomato products
Obesity and risk of prostate cancer
progression and recurrence
• Body mass index (weight to height index)
• Obesity has been shown to be a statistically
significant predictor of both biochemical
failure and disease recurrence.
– Especially in younger men
• As the severity of the obesity worsened, the
risk of these negative outcomes increased.
Obesity and Prostate Cancer
• ?less likely to be detected
– difficult rectal exams
– fat makes estrogen-like compounds, which can
lower circulating PSA
– Less likely to eat right
The bottom L-I-N-E
Moderate exercise and a healthy diet consisting mostly of
food from plant sources, (fruits, vegetables, bread cereals,
rice and beans)
Treatment for PCA
• Watchful Waiting
• Radiation
– External Beam
• 3-D conformal
• intensity modulated
radiotherapy (IMRT)
• Proton beam
– Brachytherapy
• Cryotherapy
• Surgery
– open retropubic (pelvic
lymph nodes)
– open perineal
– laparoscopic/robotic
• HIFU
• Hormone Therapy
da VINCI: 2002
(Talamini, M., et al: JLAST 12: 225, 2002)
Radiation Treatment
• Intensity-Modulated Radiation Therapy (IMRT). Uses
computers to deliver radiation precisely to the cancer. It also
reduces damage to the healthy tissue nearby, such as the
rectum and bladder.
• Proton beam therapy Uses protons rather than x-rays. The
use of protons may allow a very high dose of radiation to
reach the prostate while reducing the amount of normal
tissue that is affected.
• 3-D conformal is a type of external beam radiation that is
often used to treat prostate cancer. It allows doctors to
carefully plan the shape of the radiation beam
http://www.cancer.gov/cancertopics/treatment/prostate/understanding-prostatecancer-treatment/page3
References
Andriole, G.L., Grubb, R.L., Buys, S.S., et al. Mortality results from a randomized
prostate cancer screening trial. N Engl J Med, 360: 1310-19,
2009
Andriole, G.L., Crawford, D., Grubb, R.L., Buys, S.S., Chia, D., Church, T.,
et
al.,Prostate cancer screening in the radomized prostate, lung, colorectal and ovarian
cancer screening trial: Mortality results after 13 years of followup. J Natl
Cancer Inst;104:125-132,2012
Hugosson, J.,Carlsson, S., Aus, G., Bergdahl, S., Khatami, A., Lodding, P., et al.
Prostate specific antigen based biennial screening issufficient to detect almost all
prostate cancers while still curable. J Urol, 169: 1720, 2003
Prostate-Specific Antigen Best Practice Statement:2009 Update. Retrieved from
http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/mainreports/psa09.pdf
Schroder, F.H., Hugosson, J., Roobol, M.J., et al. Screening and prostate-cancer
mortality in a randomized European study. N Engl J Med, 360: 11320-8, 2009
American Cancer Society Prostate Cancer (reviewed 2012). Retrieved from
http://www.cancer.org/acs/groups/cid/documents/webcontent/003134-pdf.pdf
Chou, R., Croswell, J.M., Dana, T., Bougatsos,C.,Blazina, I., Fu, R.,Gleitsmann, K.,
Koenig, H.C.,Lam, C., Maltz, A.,Rugge, J.,B., Lin, K., (2011)Screening for Prostate
Cancer A Review of the Evidence for the U.S. Preventive Services Task Force
Retrieved
fromhttp://www.uspreventiveservicestaskforce.org/prostatecancerscreening/prostate
art.htm
Obek, C., Onal, B., Ozkan, B., et al: Is periprostatic local anesthesia for transrectal
ultrasound guided prostate biopsy associated with increased infectious or
hemorrhagic complications? A prospective randomized trial. J Urol, 168: 558, 2002
Virginia A. Moyer, MD, PhD, on behalf of the U.S. Preventive Services Task Force*
(2012) Screening for Prostate Cancer: U.S. Preventive Services Task Force
Recommendation Statement. Retrieved from
http://www.uspreventiveservicestaskforce.org/prostatecancerscreening/prostatefinalr
s.pdf
References
Bill-Axelson, A., Holmberg, L., Ruutu, M., et al: Radical prostatectomy versus
watchful waiting in localized prostate cancer:the scandinavian prostate cancer
group-4 randomized trial. J Natl Cancer Inst 2008;100:1144-1154.
Bill-Axelson, A., Holmberg, L., Ruutu, M., et al: Radical prostatectomy versus
watchful waiting in early prostate cancer. N Engl J Med, 364:1708-1717
National Cancer Insitute: Treamtnet chlices for men with early stage prostate
cancer(2011) retrieved from
http://www.cancer.gov/cancertopics/treatment/prostate/understanding-prostatecancer-treatment/page3
Ragavan, N., Philip, J., Balasubramanian, S.P., et al: A randomized,
controlled trial
omparing lidocaine periprostatic nerve block, diclofenac suppository and both for
transrectal ultrasound guided biopsy of prostate. J Urol, 174: 510, 2005
The essential resource for your practice USPSTF Transparency and Accountability Act
of 2012:July 3 2012 (vol XXI. 7)retreived from
http://www.auanet.org/eforms/hpbrief/view.cfm?i=1129&a=2695