Professional Documents
Culture Documents
Carcinoma of The Prostate
Carcinoma of The Prostate
Objectives
List risk factors for prostate cancer, and
discuss relative strength
Discuss potential prevention strategies
Discuss benefits and risks of prostate cancer
screening, including expected survival rates
Counsel patients about primary treatment
options for local disease
Recommend systemic therapy for advanced
cancer.
Carcinoma of Prostate
Most common cancer in United States with
exception of skin cancer
Increases in new cases by 50% between 1980
and 1990
New cases in 2009 192,280 (Est.), 80 % early
disease
Deaths 27,360 (Est.)
Increasing number of non-lethal tumors being
diagnosed
1 in 6 will be diagnosed, 1 in 35 will die from it.
(10% of cancer related deaths in men.)
Chemoprevention - Other
The Selenium and Vitamin E cancer
Prevention Trial was a large randomized
placebo-controlled trial of Vitamin E and
selenium, alone or in combination. It failed
to demonstrate that these drugs reduce
prostate cancer in relatively healthy men.
Lippman SM, Klein EA, Goodman PJ, et al.: Effect of selenium and vitamin E on risk of prostate
cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
JAMA 301 (1): 39-51, 2009
BPH
Age
Prostatitis
Ejaculation
Decrease
Finasteride, dutasteride
Some herbal mixtures
Obesity
???
Sources: Nelson WG, DeMarzo AM, Isaacs WB. Prostate cancer. NEJM. 2003;349:366-381.
Aging and
Prostate Cancer
As men age, prostate cells
are increasingly likely to turn
cancerous
Autopsies reveal:
- Age 30-40: 29% prevalence
- Age 60-70: 64% prevalence
Bad News: American male has a 16.7% risk of being
diagnosed with prostate cancer
Good News: In most cases, the cancer cells are slow
growing and occur late in life only 3.5% of U.S males die
from prostate cancer
Sources: Nelson WG, DeMarzo AM, Isaacs WB. Prostate cancer. NEJM. 2003;349:366-381.
Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, et al. Prevalence of prostate cancer among men with a prostate-specific antigen
level 4.0 ng per milliliter. NEJM. 2004;350:2239-2245.
Clinical experts
Unresolved dilemma:
Over-treating clinically unimportant disease revealed by PSA testing
vs.
Under-treating clinically important disease that goes undetected
without extensive use of PSA testing
Sources: Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, et al. Prevalence of prostate cancer among men with a prostate-specific
antigen level 4.0 ng per milliliter. NEJM. 2004;350:2239-2245.
In those with cancer and low PSA levels, 12.5% had aggressive, rapidly multiplying
high-grade tumors likely to spread.
Sources: Cooner WH, Mosley BR, Rutherford CL Dr. et al. Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal
examination and prostate specific antigen. J Urol. 1990;143:1146-52. Cited in Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, et al.
Krumholtz JS, Carvalhal GF, Ramos CG, et al. Prostate-specific antigen cutoff of 2.6 ng/mL for prostate cancer screening is associated with
favorable pathologic tumor features. Urology. 2002;60:469-473.
Sources: Max W, et al. The economic burden of prostate cancer in California. Cancer. June 2002;94:2906-13.
Establishing a Diagnosis of
Prostate Cancer
DRE
PSA/PSA velocity/percent-free PSA
Transrectal U/S
U/S- guided biopsy
Gleason grading
DNA analysis by flow cytometry
PSA level
Predictive models for organ-confined versus
non-organ confined disease
PSA < 10
Intermediate Risk:
T2b-T2c or Gleason score 7 or PSA 10-20
High Risk:
T3a or Gleason score 8-10 or PSA > 20
http://www.intuitivesurgical.com
Prostate
Brachytherapy: Distribution
Cross-Section of Prostate
Urethra
Uneven
Distribution
Ultrasound-guided
bead placement for
even distribution
RT: Complications
EBRT
Most symptoms occur during treatments and
subside after completion.
Diarrhea, rectal irritation, fatigue, frequent and
painful urination, blood in the urine.
Erectile dysfunction: less common than radical
prostatectomy following treatment but slower
recovery.
RT: Complications
Brachytherapy
High initial dose of radiation that slowly fades over
1 year.
Prostate inflammation and swelling, sometimes
with severe urinary symptoms.
Other, more rare symptoms include persistent
urinary and bowel frequency and urgency.
Erectile dysfunction: similar to EBRT.
Watchful Waiting
A.K.A. observation, expectant therapy or
deferred therapy.
Diagnosis of an early-stage (T1-T2), lowgrade tumor.
No medical treatment is provided.
Patient receives regular follow-up to
monitor tumor.
Why Wait?
PSA and DRE can detect prostate cancer at a very early
stage.
Average doubling time of a prostate tumor is quite slow (2-4
years).
Immediate radical therapy may constitute over-treatment and
an introduce unnecessary urinary and potency risks.
May be appropriate if the patient is elderly and/or in poor
health, and will live out their life spans without the cancer
causing problems.
May also be appropriate for a younger patient who is willing to
be vigilant and accept the risk of the cancer spreading.
Treatment of Symptomatic
Metastatic Disease
1. Hormonal Therapy - initial therapy for
locally advanced or metastatic disease
Orchiectomy
Estrogens (No longer used)
LHRH analogs (+/- anti-androgens)
Antiandrogens + finasteride
Second line therapies consist of one of
therapies not used before, e.g., anti-androgens
if used only LHRH analogs
Hormone Therapy
Prostate cells and prostate cancer cells are dependant upon
androgens (male sex hormones) for survival and growth.
Removal of androgens kills a majority of prostate cancer cells.
Testosterone
95%
Testes
Prostate
Growth and
Function
Adrenal
Androgen
5
%
Removing Androgens
1.
2.
3.
4.
5.
LHRH Analogs
Goserelin (Zolodex)
Leuprolide (Lupron)
Available as every 1, 3, or 4 month
injections
Castrate levels of testosterone attainable in
a few weeks
Antiandrogens
Flutamide
Bicalutamide
Nilutamide
Combined androgen blockade not superior to
LHRH therapy alone
Higher cost and more side effects than LHRH
therapy alone
Primary value when starting LHRH to limit the
flare reaction
Treatment of Symptomatic
Metastatic Disease
3. Radiation therapy
External beam radiotherapy
Radioisotopes, such as Strontium 89
Evaluation of Response
PSA and Acid Phosphatase are useful in
selected circumstances
Bone scans are difficult, because increase
can be seen in healing as well as
worsening
Conclusions
Risk factors are age, family history, race, and possibly diet
and exercise
Overall survival excellent (many years)
Early detection can find localized cancer, but survival
benefits still uncertain
Treatment depends on grade, extent and location of
disease
Surgery and radiation are equivalent therapeutic tools for
localized prostate cancer
Hormonal therapy is effective for metastatic prostate
cancer
Hormone refractory prostate cancer responds to
chemotherapy, with occasional long term improvement.
Rectum
Neurovascular
Bundles of
Walsh
Approach
Pelvic
Bone
(Pubis)
Bladder
Rectum
Urethra
Prostate
RRP: Complications
Severe or life-threatening complications are
rare.
Incontinence (Urinary Control): complete
incontinence is uncommon, although a
significant number of patients experience some
stress-incontinence. Usually improves with
time.
Impotence (Erectile Dysfunction): if both
neurovascular bundles were spared, potency
rates range from 30-86%, depending on
institution. Usually improves over time, and
other ED treatments can work.
RRP: Advantages
Whole prostate - and thus the entire tumor can be examined histologically.
Surgeon has access to regional lymph nodes to
test if prostate cancer cells have left the
tumor.
Surgical margin can be examined.
T
Negative
Surgical
Margin
OR
Positive
Surgical
Margin
Not all
of tumor
removed
Prostate
Bladder
(Pubis)
Rectum
Incision:
Between Anus and base
of Scrotum.
Urethra
Surgical
Approach
Perineal Prostatectomy
Comparison with RRP: Comparable cure
rates as well as similar urinary and
potency complications.
Disadvantages:
Laparoscopic Prostatectomy
Advantages:
Disadvantages:
Longer procedure
Variable surgical margins rates.
Slower return of urinary continence.
Variable potency rates.
General Procedure:
EBRT and Brachytherapy
EBRT:
1.
2.
Brachytherapy
1.
2.
History of Brachytherapy
1909 Minet first placed a radium tube in a
catheter to irradiate prostate cancer.
1970s Real interest occurred when Whitmore
described an implant technique using I-125.
Inconsistent dose distribution was a problem.
1985 Holm and Ragde used TransRectal
UltraSound (TRUS) to position Pd-103 implants
and established a national brachytherapy
implant course.
Cryotherapy
Destroys prostate cells by freezing tissue.
Old idea that is making a comeback due to greater
precision and better methods of imaging and
temperature monitoring.
Method: insertion of sub-zero cryoprobes into
prostate perineally (between scrotum and anus).
As yet unresolved how effective cryotherapy is
compared to surgery or radiation.