CARCINOMA OF THE PROSTATE

PRESENTED BY-
DR. MOHAMMAD ALAMGIR
MS(UROLOGY) 3rd PART STUDENT.
CHITTAGONG MEDICAL COLLEGE.
WHAT IS
THE PROSTATE GLAND?
 The prostate is part of the male reproductive system

 Its major function is to secrete a fluid to nourish

semen during intercourse

 The prostate is about the size of a walnut but it can

grow with age

 It is located below the urinary bladder, in front of the

rectum surrounding the urethra (the canal for the
discharge of urine that extends from the urinary
bladder to the outside)
 Anatomy of the prostate gland
A) Capsules -
True capsule
False capsule
B) Glandular and non glandular elements-
1.Glandular prostate
a) outer components-
Central zone(CZ)
peripheral zone(PZ)
contd…..
 b) Inner components–
Periurethral glands
Transitional zone(TZ)
2.Non glandular portions
Prostatic urethra
Ant. fibromuscular band
Prostate Cancer

Facts That Every Man Over 40

Should Know
 What Is Prostate Cancer?

What do you Not

know about Much!
prostate cancer?
• Cancer is a cellular disease
• It is a disordered and abnormal cell growth
• In prostate cancer, as in other types of cancer, cells grow
out of control and form tumors
• If the tumor is within the gland, the cancer is said to be
localized and curable
 If the cancer escapes the gland it is considered advanced
and incurable
• Early detection before the cancer escapes the gland
becomes very important.
Distribution of prostate cancer
 Tumor location—
.70% in peripheral zone(PZ)
.20% in transitional zone (TZ)
.10% in cental zone( CZ)
 Central gland most difficult to localize
carcinoma, because of overlaping signal
intensity with normal gland / hypertrophy.
 How much threat of PROSTATE
CANCER?
 Most common malignancy of men in US after skin
cancer.
 At autopsy ,CaP is found in
30% of men in age 50.
90% of men in age 90.
 Despite the long latent period, 2nd most common
cause of cancer death in American men over age
55.
 About 1 in 6 men will be diagnosed with
carcinoma prostate during life time.
 Aging and
Prostate Cancer

• As men age, prostate cells

are increasingly likely to turn
cancerous
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
 Prostate cancer risk factors:

 Age: The risk increases with age, but 25% of

diagnoses are made under age 65.
 Race: African-Americans have a rate of
incidence double that of Caucasian men
 Family history of prostate cancer: Men with
a family history have two- to three-fold
increase in the risk of prostate cancer
 Risk Factors
DIET
 Eating red meat increases the risk of developing prostate
cancer 2.64 times
 Total fat intake and animal fat intake are associated with
prostate cancer.
 Vitamin D and calcium also increase risk.
 Vegetable oil is rich in alpha linolenic acid (a fatty acid)
 By-products of these fats promote the growth and
seriousness of prostate cancer
 So what CAN WE eat?
 A balanced diet rich in fruits
and vegetables!
 Lower your intake of red
meat, processed and fried
foods. Eat more plant-based
food like soy protein.
 Eat foods with lycopene
(tomatoes, watermelon
and red grapefruit) which
may be associated with a
decreased risk of prostate
cancer.
 Vitamin E, selenium, and
omega -3 fatty acids(fish)
have been shown to be
protective.
 Classification of carcinoma
prostate
 Primary-
 Adenocarcinoma---95%
Others—5%
.TCC----90%
.Neuroendocrine carcinoma
.Sarcoma
 Secondary-
From adjacent organs.
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
 Possible Levels of Prostate Cancer At Diagnosis
Systemic Spread
Local-Regional Disease Spread
Lymph
Node
Other Organs
Tumor

GLAND
PROSTATE
Tumor Bone

CAPSULE
 How does early detection
help?
 Survival rate at 5 years is
99% 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 31%
Early detection and screening
 Digital rectal exam – Feel for nodules
 PSA – How high?
 Transrectal ultrasound – not for
screening

First two tests are convenient and

inexpensive, but consequences may not
be
Why do I have to have a DRE?

 In the DRE the doctor

examines you by feeling
the prostate gland through
the rectum with his finger
(digit)
 DRE improves the value
of PSA testing in early
disease detection
 DRE and PSA together are
often able to detect
prostate cancer better and
sooner than either test
alone
When do I need to start getting tested?

 DRE: 40 years and older every year

(American Cancer Society guidelines)

 PSA: 50 years and older every year

(American Cancer Society guidelines)
 If family history of prostate cancer and/or
African-American: 45 years and older every year
(American Cancer Society guidelines)
 What You Should Know About the PSA Test

PSA is a glycoprotein .
 It exists in two form- complexed & bound form.
 Its normal value is <4ng/ml & raises wth
increasing age & size of the prostate gland.
 The real value of the PSA test is in testing year
to year and observing the rate of change
 Medical opinion is divided about the usefulness
of a single PSA
 One test out of range could be caused by other
problems
 PSA is not prostate cancer specific
Under investigation: PSA Density,
PSA Velocity, % free PSA
 PSA Density - Normalized to prostate
volume
 PSA Velocity - Change in PSA over time
(e.g., more than 15% per year)
 Free PSA/Total PSA - lower ratio
suggests cancer, since more free PSA
from normal prostate is degradated (<
10% - biopsy)
 Confounding Factors for PSA
 Increase
 BPH
 Age
 Prostatitis
 Ejaculation
 Decrease
 Finasteride, dutasteride
 Some herbal mixtures
 Obesity
Establishing a Diagnosis of
Prostate Cancer
 DRE
 PSA/PSA velocity/percent-free PSA
 Transrectal U/S
 U/S- guided biopsy
Staging and grading
 Two staging systems-
Whitmore –Jewett staging.
TNM staging.
 Two grading systems-
Gleasons grading
Mostofis grading
 TNM Staging
T= Tumor
T1a and T1b (Incidental, early)
T1c --Confirmed by needle biopsy
T2a—Tumor involved one lobe
T2b –Tumor involved both lobes
. T3a—Extracapsular extension.
T3b—Tumor invades seminal vesicles
T4 –Tumor invaded adjacent structures.
N= Regional Lymph nodes involvement
M= Distant metastasis.
 Gleason score
 Characterize the degree of glandular
differentiation under microscope.
 It grades two most representative areas of
tumor (primary grade & secondary grade).
 Adds two values together—Gleason score
(2—10).
 Gleason score-
2—4 well differentiated
5—6 moderately differentiated
8—10 poorly differentiated
 Chemoprevention for Prostate
Cancer
 Finasteride = 5-alpha reductase inhibitor, blocks
intracellular conversion of testosterone to
dihydrotestosterone

 Based on solid evidence, chemoprevention with

finasteride reduces the incidence of prostate cancer
(6% absolute; 25% relative risk reduction), but the
evidence is inadequate

 Harms: erectile dysfunction, loss of libido,

gynecomastia, higher grade cancers.
Prognostic Factors
Age
Health
Race
Clinical staging
Gleason grading
PSA level
Predictive models for organ-confined versus
non-organ confined disease.
In Case of a Diagnosis With a
Positive Biopsy…

 Do not panic,

 Get a second opinion on the biopsy sample by a

pathologist specializing in prostate cancer.
Your treatment decision depends on a good
assessment of the biopsy material.

 Get a second opinion about your diagnosis and

treatment options from an unbiased specialist in
prostate cancer treatment.
Prostate Cancer Survival
 Related to
 Stage
 Grade
 Extent of tumor at diagnosis

 Local disease - Median Survival > 5 years

 Metastatic disease Median Survival 1-3 years, but

individuals may survive 10 or more years
TREATMENT
 Treatment of localized disease
 Treatment of locally advanced disease
 Treatment of recurrent disease
 Treatment of HRPC.
 Treatment of metastatic disease
Treatment of Localized
Disease(T1+T2)
 Watchful Waiting & active surveillance .
 Radical Prostatectomy.
 Definite radiation therapy -
External beam radiotherapy (XRT)
Brachytherapy
 Cryo surgery & HIFU.
Watchful Waiting
 Life expectancy less than 10 years.
 Diagnosis of an early-stage (T1-T2),
low-grade 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.
Radical Retropubic Prostatectomy
(RRP)
 “Nerve Sparing” procedure developed by Walsh
consisted of modified surgical technique to
control blood and enhance visibility within
surgical site.

 Allowed for the identification and potential

preservation of the nerves that control erectile
function (potency).

 Two neurovascular bundles that lie behind & on

either side of the prostate that control erectile
function.
 RRP: The Surgical
Approach Surgical
Approach
1.5-4 hours, usually
epidural anesthesia. Pelvic
Bladder
Bone
Incision: (Pubis) Rectum
Begins just below
navel and extends to
pubic bone.

Remaining Urethra Prostate

Urethra
is sewn to bladder
neck over a catheter.
The Nerve Bundles
Cross-Section
of Prostate

Urethra

Prostate Neurovascular
Bundles of
Walsh

Rectum
 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.

Not all
T T of tumor
OR removed

Negative Positive
Surgical Surgical
Margin Margin
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.
Radiation Therapy (RT)
 High-Powered X-Rays that damage
DNA and kill prostate cancer cells.

1. External Beam Radiation Therapy

(EBRT): X-rays aimed at prostate.

2. Brachytherapy: Radioactive seed

implants into prostate.
General Procedure:
EBRT and Brachytherapy
 EBRT:
1. Map precise area that will receive radiation.
2. Multiple treatments ~5 days/week for ~8 weeks.
Each treatment takes about 10 minutes and no
anesthesia is required.
 Brachytherapy
1. 40-100 rice-sized radioactive seeds are implanted
into the prostate via ultrasound-guided needles.
Anesthesia is required.
2. All radiation inside the pellets is generally
exhausted within a year.
 External Beam Radiation
Goal: Maximize damage to the prostate
and minimize damage to surrounding
tissues (i.e. bladder and rectum)
Seminal
Vesicles

Prostate
Brachytherapy:
Distribution
Cross-Section of Prostate
Urethra

Uneven Ultrasound-guided
Distribution bead placement
for even
distribution
Image of Prostate With
Radioactive Bead Implants
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.
 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.
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.
Treatment of locally advanced
disease:
 Most Pt with T3 (T3a+ T3b ) CaP are
at the present time treated with
neoadjuvent hormone therapy followed
by external beam radiotherapy .
Treatment of Recurrent
Disease :
 Following radical prostatectomy –
Salvage radiation .
 Following radiation therapy –

Androgen ablation therapy

If disease is local recurrence only—
Bracy therapy, Cryo surgery ,Salvage
prostatectomy.
 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 Adrenal
Androgen

5
95% %
Prostate
Testes Growth and
Function
 LHRH Analogs
 Goserelin
 Leuprolide

 Triptorelin

 Histrelin

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
Hormone-Refractory Prostate
Cancer (HRPC)
 Despite initial response rates of 80-90%, nearly
all men with advanced prostate cancer develop
hormone-resistant prostate cancer after 18-36
months.
 These “hormone-refractory” (HR) prostate cancer
cells can grow in the absence of androgens.
 The behavior of HR prostate cancers differ widely
between patients.
Treatment of Symptomatic, Hormone
Refractory Metastatic Disease

1.Stop Anti-androgen or Add Anti-androgen.

2. Second line regimen –

Aminoglutethimide
Ketoconazole
Corticosteroid
 Contd……
3. Cytotoxic chemotherapy
 Docetaxel (every three weeks) and prednisone
improves pain and reduces need for analgesic agents
 Docetaxel with estramustine
 Mitoxantrone
 Other agents have had limited effectiveness
 Continue hormone therapy to prevent flare with rising
testosterone levels
4. Bisphosphonates - decreases skeletal complications.
4. 5. Gene threapy.
Management of Prostate Cancer
Bone Metastases
 Goal: prevent pain, improve mobility,
prevent complications such as fractures
or compression, maintain acceptable
quality of life.

 Methods: bis-phosphonates, radiation of

detected metastatic lesions, surgery.
?
 Emerging Therapy: Laparoscopic
Radical Prostatectomy
 Eliminates the need for a
large incision by using a
telescopic instruments
called a laparoscopes.

 Small camera attached to

the laparoscope allows the
surgeon to view inside the
abdomen.
Laparoscopic Prostatectomy
 Advantages:
 Less blood loss.
 No large incision.
 Shorter hospital stay and earlier return to
activities.
 Disadvantages:
 Longer procedure
 Variable surgical margins rates.
 Slower return of urinary continence.
 Variable potency rates.
Conclusions
 Risk factors are age, family history, race, and possibly diet
.
 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.
 Hey, Smart Guy!
Can you guess who can get
prostate cancer?

Not you?
Well, guess again… any
male can get prostate
cancer