Dr Guvera Vasireddy
Osmania medical college
The prostate gland is a male reproductive organ whose main
function is to secrete prostate fluid, one of the components of
The muscles of the prostate gland also help propel this
seminal fluid into the urethra during ejaculation .
One component of prostate fluid an enzyme called Prostate
Specific Antigen (PSA) also aids in the success of sperm by
liquefying semen that has thickened after ejaculation.
This thinning action allows sperm to swim more freely,
according to the medical reference book "Prostate Specific
Antigen" (Informal Health Care, 2001).
Prostate and Bladder obstruction
Unfortunately, while the prostate is in a great location for delivering this
important fluid and squeezing things along when the time is right, its
position around the urethra can be a liability if the gland swells or
A swollen prostate compresses the urethra and irritates the walls of the
bladder, interfering with normal urination.
More than half of men in their 60s suffer from a growth of the prostate called
Benign Prostatic Hyperplasia (BPH), according to the OSU Medical Center.
By age 70 or 80, a man's chance of suffering BPH jumps to 90 percent.
Symptoms include frequent urination, dribbling or leaking urine and a
stuttered or weak stream.
A growing prostate can also signal cancer. It is estimated that more than
200,000 men will be diagnosed with prostate cancer in 2010, according to
the National Cancer Institute.
Prostate: anatomy and histology
Prostate weighs 20 grams in normal adult
Retroperitoneal organ ,encircling the neck
of bladder and urethra
Devoid of a distinct capsule
Four distinct zones
Glands lined two layers of cells, basal
cells and columnar secretory cells
The normal prostate contains
several distinct regions,
including a central zone (CZ),
a peripheral zone (PZ), a
transitional zone (TZ), and a
Most carcinomas arise from
the peripheral glands of the
organ and may be palpable
during digital examination of
Nodular hyperplasia, in
contrast, arises from more
centrally situated glands and
is more likely to produce
urinary obstruction early than
Histologically the prostate is
composed of glands lined by
two layers of cells.
A basal layer of low cuboidal
epithelium covered by a layer
of columnar secretory cells.
In many areas there are small
papillary infoldings of the
These glands are separated
by abundant fibromuscular
Testicular androgens control
the growth and survival of
Castration leads to atrophy of
the prostate caused by
H&E of normal gland HMW keratin stains basal layer
Benign Prostatic Hyperplasia BPH
Extremely common lesion in men over age 50
Hyperplasia of glands and stroma
Fairly large ,well delined nodules
20% in men over age 40,up to 70% by age 60,
and 90% by age 70
Related to the action of androgen
BPH and the role of DHT
DHT ,Dihydrotestesterone is the ultimate mediator for prostatic growth.
The main component of the “hyperplastic” process is impaired cell death
resulting in the accumulation of senescent cells in the prostate.
Androgens not only increase cellular proliferation, but also inhibit cell death.
The main androgen in the prostate, constituting 90% of total prostatic
androgens, is dihydrotestosterone (DHT).
It is formed in the prostate from the conversion of testosterone by the
enzyme type 2 5α-reductase, located almost entirely in stromal cells;
Epithelial cells of the prostate do not contain type 2 5α reductase, with the
exception of a few basal cells. Thus stromal cells are responsible for
androgen-dependent prostatic growth.
Other sources of DHT
Type 1 5α-reductase is not detected in the
prostate, or is present at very low levels.
However this enzyme may produce DHT
from testosterone in liver and skin, and
circulating DHT may act in the prostate by an
Nodular hyperplasia is not considered to be a
Mechanism of DTH induced growth
DHT binds to the nuclear androgen receptor (AR) present in
both stromal and epithelial prostate cells.
DHT is more potent than testosterone because it has a higher
affinity for AR and forms a more stable complex with the
Binding of DHT to AR activates the transcription of androgen-
DHT is not a direct mitogen for prostate cells, instead DHT-
mediated transcription of genes results in the increased
production of several growth factors and their receptors.
Most important among these are members of the fibroblast
growth factor (FGF) family, and particularly FGF-7
(keratinocyte growth factor;).
FGF-7, produced by stromal cells, is probably the most
important factor mediating the paracrine regulation of
androgen-stimulated prostatic growth.
Other growth factors produced in BPH are FGFs 1 and 2, and
TGFβ, which promote fibroblast proliferation.
Although the ultimate cause of BPH is unknown, it is believed
that DHT-induced growth factors act by increasing the
proliferation of stromal cells and decreasing the death of
Simplified scheme of
the pathogenesis of
The central role of
the stromal cells in
(DHT) should be noted.
DHT may also be
produced in skin and
liver by both type 1 and
BPH , Morphology
The prostate weighs between 60 and 100 grams
Enlargement occurs almost exclusively in the inner aspect of
the prostate gland
Nodules ,vary in color and consistency
Histologic hallmark of BPH is nodularity due to glandular
proliferation or dilation and to fibrous or muscular proliferation
Aggregation of small to large and cystically dilated glands
Needle biopsy don’t sample the transitional zone BPH occur
The increased size of the gland, and the smooth muscle-mediated
contraction of the prostate cause urethral obstruction.
The increased resistance to urinary outflow leads to bladder hypertrophy
and distension, accompanied by urine retention.
The inability to empty the bladder completely creates a reservoir of residual
urine that is a common source of infection.
Increased urinary frequency, nocturia, difficulty in starting and stopping the
stream of urine, overflow dribbling, dysuria (painful micturition).
Increased risk of developing bacterial infections of the bladder and kidney.
In many cases, sudden, acute urinary retention appears for unknown
reasons that requires emergency catheterization.
Decreasing fluid intake, especially before bedtime;
moderating the intake of alcohol and caffeine containing
products; and following timed voiding schedules.
α-blockers, which decrease prostate smooth muscle tone via
inhibition of α1-adrenergic receptors.
Inhibitors of 5-α-reductase.
Transurethral resection of the prostate (TURP).
High-intensity focused ultrasound, laser therapy,
hyperthermia, transurethral electro vaporization, and
transurethral needle ablation using radiofrequency.
Cancer of the prostate is a disease of men over age 50 and
adenocarcinoma is the most common form.
One in six lifetime probability of being diagnosed with prostate
Prostatic cancer is uncommon in Asians and occurs most
frequently among blacks.
Increased consumption of fats has been implicated.
Dietary products suspected of preventing or delaying prostate
cancer development include lycopenes (found in tomatoes),
selenium, soy products, and vitamin D.
Prostate Cancer Risk Factors
• Advancing age
• Presence of androgens
• Family history (1st
• African ancestry
• High dietary fat
• Inherited mutations (BRCA1 or BRCA2 genes)
• Vitamin D or E deficiency
• Selenium deficiency?
• Discuss with the patient and if he decides to be screened
• Annual PSA and DRE
• Age 50-70 yrs (with at least 10 yr life expectancy)
• Begin screening at age 40 if risk factors
• African ancestry
• First degree relative(s) with prostate cancer
• A shared decision-making approach to PSA screening
seems most appropriate
Prostate Cancer: Screening with PSA
No clear cut-point between normal and abnormal PSA levels.
Even PSA cut-off of 1.1 ng/ml misses up to 15% of prostate
cancer (The Cancer Prevention Trial – 2003)
Positive predictive value for PSA > 4ng/ml = 30% (i.e. About 1 in
3 men with elevated PSA have prostate cancer detected at time
PPV increases to 45-60% for PSA > 10ng/ml
Nearly 75% of cancers detected in the grey zone (PSA 4-10) are
organ confined; potentially curable.
<50% of prostate cancers organ confined if PSA >10
What is PSA (Prostate Specific
A Serine protease
(enzyme) found in the
Secreted by prostate
Found in ejaculate
As diagnostic tool for:
Other causes of an elevated PSA
2. Prostate size (BPH)
4. Recent instrumentation (biopsy, catheterization,
5. Physiological variation
6. Recent ejaculation
Free/Total PSA Ratio:
A Way to Improve Specificity
Prostate cancer maybe
associated with more
(less free PSA) than in
F/T ratio is lower in
patients with prostate
Can improve test
Useful when total PSA
in 4-10 ng/ml range
Prostate Cancer: Presentation
Early stages usually asymptomatic
Most cases detected by serum PSA screening
Palpable nodule or firmness on DRE
Urinary retention/renal failure
Weight loss, fatigue
Spinal cord compression
Prostate Cancer: Diagnosis
Indications for trans rectal ultrasound (TRUS) guided biopsy
Palpable nodule on DRE
Elevated serum PSA
Biopsy involves 10-18 needle cores taken mostly from the
peripheral zone of the prostate
Transrectal ultrasound alone/CT scan/MRI not sensitive
enough to make the Diagnosis
The 2016 and 2004 WHO
classifications of prostatic carcinoma
Adenocarcinoma of Prostate
The most common form is
1. Acinar adenocarcinoma
2. Intraductal carcinoma
3. Ductal adenocarcinoma
Variants of acinar adenocarcinoma (AC) of
the prostate in the 2016 WHO classification
Adenocarcinoma: Gross Morphology
70% arises in the peripheral zone of the
Palpable in rectal exam
Gritty and firm
Spread by direct local invasion and
through blood stream and lymph
Local extension most commonly involves
the seminal vesicles and the base of the
Well defined gland pattern
Histologic diagnosis in some cases is one
of the most chalenges for pathologists
Peri-neural invasion is common and
Well-defined, readily demonstrable gland patterns, that are
typically smaller than benign glands.
Lined by a single uniform layer of cuboidal or low columnar
Cancer glands are more crowded, and characteristically lack
branching and papillary infolding.
The outer basal cell layer typical of benign glands is absent.
The cytoplasm of the tumor cells ranges from pale-clear as
seen in benign glands to a distinctive amphophilic
Nuclei are large and often contain one or more large nucleoli.
There is some variation in nuclear size and shape, but in
general pleomorphism is not marked.
Mitotic figures are uncommon.
α-methylacyl-coenzyme A-racemase (AMACR) is up-
regulated in prostate cancer and can be detected by
perineural invasion by
malignant glands with enlarged nuclei,
prominent nucleoli, and dark cytoplasm
foamy gland (xanthomatous) variant
mucinous (colloid) adenocarcinoma signet ring cell variant
Other morphological variants
Hematogenous extension occurs chiefly
to the bones
The bony metastasis are typically
Adenocarcinoma ,Clinical Course
Microscopic cancers are asymptomatic,
Patients with clinically localized disease
do not have urinary symptoms
Most arise peripherally ,away from
urethra, therefore ,urinary symptoms
Prognosis depends mainly on the extent
of the disease at the time of the diagnosis.
Depends upon grade, stage and
Early stage/well-differentiated Ca treated
by radical prostatectomy:
85% + 10 year survival
<10% 5 year survival
Adenocarcinoma: Gleason’s Grading
Gleason grading system is the best known
Five grades on the basis of glandular pattern
and degree of differentiation as seen under
Grading is of particular important in prostate
cancer, because it is the best marker ,along
with the stage ,for predicting prognosis
Adenocarcinoma: Gleason’s Grading
Gleason grade is from 1-5 based on glandular
Gleason score is the total primary grade (1-5) +
secondary grade (1-5) = 2-10
Grading and grouping
Grade Group 1 (Gleason score ≤6) – Only individual discrete well-
Grade Group 2 (Gleason score 3+4=7) – Predominantly well-formed
glands with a lesser component of poorly-formed/fused/cribriform
Grade Group 3 (Gleason score 4+3=7) – Predominantly poorly-
formed/fused/cribriform glands with a lesser component of well-
Grade Group 4 (Gleason score 8) - Only poorly-
formed/fused/cribriform glands or - Predominantly well-formed
glands with a lesser component lacking glands†† or - Predominantly
lacking glands with a lesser component of well-formed glands.
Grade Group 5 (Gleason scores 9-10) – Lacks gland formation (or
with necrosis) with or w/o poorly-formed/fused/cribriform glands.
Can spread to adjacent organs (seminal
vesicles, bladder), lymph nodes, bone
Most bone mets are osteoblastic
Prior to initiating treatment consider
Bone scan (PSA>10, Gleason Score >7)
CT scan pelvis/abdomen (PSA >10, Gleason
These tests are typically not required in
asymptomatic men with low risk prostate cancer
Grading and Staging
Staging in prostate cancer depends on
the TNM system .
Clinical staging includes combined clinical
and radiological findings and PSA levels.
Pathological staging includes tumor extent
on biopsy and Gleason's grade.
AJCC staging combines the both.
N and M
Status of Regional Lymph Nodes (N)
N0 NO REGIONAL NODAL METASTASES
N1 METASTASIS IN REGIONAL LYMPH NODES
Distant Metastases (M)
M0 NO DISTANT METASTASES
M1 DISTANT METASTASES PRESENT
M1a Metastases to distant lymph nodes
M1b Bone metastases
M1c Other distant sites
Prostate Cancer – Treatment - Survival
Tumor grade (Gleason
Often a patient choice
Surgery ,radiotherapy ,and hormonal therapy
90% of treated patients expected to live for 15
Currently the most acceptable treatment for
clinically localized cancer is radical surgery
Too locally advanced cancers can be treated by
Hormonal therapy (Antiandrogen therapy) could
induce remission .
Early Stage Prostate Cancer
Early stage Cancer
1. Radical Prostatectomy
2. External Beam Radiotherapy
3. Radioactive Seeds (Brachytherapy)
4. Active Surveillance
5. Observation – Watchful Waiting
Prostate Cancer Treatment:
1. Radical Prostatectomy
Advanced Prostate Cancer:
for bone health
Last line of treatment
Spinal Cord Compression
Metastatic prostate cancer is a
common cause of spinal cord
Clinical recognition is critical
Signs and symptoms
Neurological symptoms in
Lack of rectal tone, fecal and
Paraplegia below the level of
MRI is diagnostic
Spinal Cord Compression
Emergency decompression laminectomy
by spinal surgeons
Emergency radiation to affected level
Emergency bilateral orchidectomies if
patient not already on androgen
Prostate Cancer Prevention
Two major studies using 5 α reductase inhibitors
Similar reduction in prostate cancer diagnosis
in the treatment arms (23-24%)
Not currently approved by Health Canada for
prostate cancer prevention
PCPT (Thompson et al NEJM 2003)
Reduce (Andriole et al NEJM 2010)
Notas do Editor
2x risk if one 1st degree family relative 2x risk if 1st degree relative with prostate cancer; 9x risk if 2 or more relatives with prostate cancer
PSA is involved in liquefaction of the seminal fluid- essential for sperm function. Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland. PSA is produced for the ejaculate, where it liquefies semen in the seminal coagulum and allows sperm to swim freely. It is also believed to be instrumental in dissolving cervical mucus, allowing the entry of sperm into the uterus. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders. PSA is not a unique indicator of prostate cancer, but may also detect prostatitis or benign prostatic hyperplasia.
Prostate biopsy not a good gold standard Morbidity from a biopsy (pain, UTI, sepsis) Prostate biopsy not a good gold standard. Possible morbidity from a biopsy (pain, UTI, sepsis)
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