Prostate Cancer: Adenocarcinoma

PROSTATE CANCER
Prostate cancer is a common malignancy

among the aged male population
Second cause of cancer death in developed
countries
One of the few cancers having a lot of debate
on treatment modalities.
Epidemiology and Aetiology

Hormonal influence :
Normal prostatic epithelium ,
BPH &
P Ca
are under the promotional Influence of
testosterone and its potent metabolite DHT.
To die with P ca !
To die of P ca !
Histopathology:
Adenocarcinoma
More than 95%.
Arises from the epithelium
of prostatic acini or small peripheral
prostatic ducts
Moderately elevated PSA can be present in

non-cancer cases:
BPH
Prostatitis
Transitional cell carcinoma

Less than 4%
Arises from Prostatic urethra, central
prostatic ducts
or direct extension from TCC of the urinary
bladder
In patients where DRE is suggestive of P Ca
Origin
75% : peripheral zone
20% : transition zone
5% : central zone
Aging
Ethnic factors
Family History (Genetic)
? Diet, sexual activity, viral infections
Diagnosis of prostate cancer is on the increase

(Why?)
Increasing awareness of the disease

Increasing use of serum PSA testing for
both symptomatic and nonsymptomatic aging men
Use of more extensive prostatic biopsy
protocols
Prostate cancer is rare before 40ys

The incidence increases with age
Histological prostate cancer!
Clinical prostate cancer!
P Ca is biologically heterogeneous
(low risk ,intermediate & high risk Pca)
For early detection of P Ca in males over 50

Particularly in high risk groups
Level of PSA in patients with histologically

diagnosed P Ca is important for staging of the
disease
-Example:
PSA up to 20 ng/ml : localized disease
20 -40
: Locally advanced
: Early metastatic
> 40 most probably metastatic
Prostate Specific Antigen (PSA)
PSA (with other parameters) is used for the

choice
of the suitable treatment
modality
A tumor marker used for the diagnosis, staging

and follow up of prostate cancer
Periodic estimation of PSA level is essential for

determining treatment response.
Risk Factors
Importance of serum PSA testing:
An enzyme secreted by prostatic acinar cells

Normally present in the seminal plasma
and ,in trace amounts, in the serum
It is prostate specific but not cancer specific.
Normal serum level is up to 4 ng /ml
In younger patients (2.5 ng/ ml)
Staging of Prostate Cancer

Organ confined (localized) P ca (T1 & T2)
T1: Clinically unsuspected, DRE is normal
Diagnosed by: histopathological
examination of
prostatectomy specimen (TUR) or (open)
T1a, T1 b, T1c
In patients with P Ca, PSA level correlates

positively with tumor burden (primary and
metastatic).
based on prostatic biopsy for patients with

normal DRE but elevated serum PSA
T2:
localized P ca palpable by DRE
T2a, T2b
Normal PSA level does not exclude P Ca:
Early disease (small tumor volume)
Poorly differentiated tumor
Locally advanced prostate cancer( T3 & T4)

T3: Capsular penetration seminal vesicle
invasion
T3a, T3b
T4: Direct extension to an adjacent organ

Metastatic Prostate cancer
N+
(and or) M+
Grading of Prostate Cancer

Gleason grading system
Depends on glandular differentiation
Primary grade (dominant) 1 - 5
Secondary grade
1 - 5
Gleason score = Primary + Secondary grade
=
2
10
Gleason score up to 5 : low risk
P Ca
6 : intermediate risk
> 6 : high risk
Spread
Direct spread:
Extra-capsular extension:
seminal vesicles
bladder base
Lower ureters
Vertebrae (lumbar) , ribs , skull

Visceral spread :
Late
lung
An abnormal DRE is defined by:

* Asymmetric enlargement of the gland
* A prostatic nodule
* Firm to hard consistency
Diagnosis Of Prostate Cancer

Early detection in nonsymptomatic males
over 50ys
Screening programs
- pros & cons
NOTE!
Clinical Picture
Localized P Ca (T1 & T2)
Non specific symptoms
Other causes of abnormal DRE:
Chronic prostatitis
Prostatic calculi
*
*
*
*
Asymptomatic
LUTS probably due to ( co-existing BPH)
Haemospermia
Haematuria (? co- existing BPH)
Locally advanced prostate cancer (T3 T4)

Same as previous + ? Symptoms of renal
insufficiency:
due bilateral ureteric obstruction
Metastatic prostate cancer
Lymphatic spread:
Pelvic Lymph nodes
Haematogenous spread
Bones: common
Pelvic bones:
pubic rami,
ischium
iliac bones
long bones:
femoral shafts
liver
brain
LUTS
Lower limb oedema (N+ pelvic LN)
Symptoms related to bone metastasis:
- bony pains
- pathological fracture
- spinal compression
(neurological complications)
General Symptoms of advanced
cancer:
- asthenia,
- anorexia,
- loss of weight
Digital Rectal Examination (DRE)

Most prostate cancers arise in the peripheral
posterior
part of the gland, therefore, they eventually
become
palpable on DRE.
Only 50% of patients with abnormal

DRE prove to have prostate cancer
Normal DRE does not exclude cancer

Prostatic biopsy :
Is essential for the diagnosis
Transrectal ultrasound guided prostatic
(TRUS) biopsy
When to do?
Elevated PSA
abnormal DRE
Both
Imaging in the diagnosis of prostate cancer :

1. Ultrasonography (Abdominal or transrectal)
No specific sonographic pattern:
Homogenous, heterogeneous
iso..hypo..or hyper echoec
size of the gland
Post void residual
Effect on upper urinary tract
Assessment of other abdominal organs
2.
MRI
Imaging of Skeletal metastasis

Bone scan:
High sensitivity but low specificity
high false positive result
Conventional Skeletal radiography
Low sensitivity but high specificity

Bone CT
It is, therefore, recommended to start by
a bone scan then conventional x-ray
or bone CT if needed
Treatment of Prostate Cancer
A- Watchful Waiting (Wa Wa)
Active surveillance with delayed selective
intervention
Localized prostate cancer (T1 T2 )

Watchful waiting:
Life expectancy < 10 ys
Low risk tumor (low grade Tr & PSA<10)
Radical
Radical
Prostatectomy:
radiotherapy:
Life expectancy >10 ys
Good performance status
LHRH Agonists:
Medical orchiectomy
(LHRH , ant. Pituitary , Leydig cells)
Initial flare
Reversible androgen deprivation
B- Radical Prostatectomy
C- Radiotherapy:
External beam radiotherapy
Interstitial radiotherapy (Brachytherapy)
( androgen deprivation)
D- Androgen Deprivation Therapy ( hormonal)
Factors affecting the choice of treatment

modality:
Factors related to tumor: Risk stratification
Tumor stage
Gleason grade
PSA level
Factors related to the patient:
Life expectancy
Performance status (general condition

&
co-morbidity)
Patient counselling on side effects of

treatment and quality of life
parameters:
- sexual function & urinary continence
Locally advanced Prostate cancer (T3 4)

Watchful waiting:
no symptoms with life expectancy <10ys
Radiotherapy:
Symptomatic or non symptomatic cases
Life expectancy >10 ys
Hormonal therapy:
Symptomatic cases with short life expectancy
Patient refusing radiotherapy
Metastatic Prostate cancer
Androgen deprivation therapy:
Bilateral orchiectomy
LHRH agonists
Anti-androgens
Oestrogen
Bilateral Orchiectomy
Immediate , sustained , Irreversible
androgen deprivation
Side effects of androgen deprivation
Sexual dysfunction
Diminished muscle mass
Osteoporosis
Diminished cognitive abilities
Depression
Anti androgens
*Monotherapy
*Along with hormonal deprivation (CAB)
Estrogens
Feed back inhibition
Side effects:
sexual dysfunction
gynecomastia
thrombo-embolic com.

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PROSTATE CANCER

Prostate cancer is a common malignancy

Epidemiology and Aetiology

Moderately elevated PSA can be present in

Transitional cell carcinoma

In patients where DRE is suggestive of P Ca

75% : peripheral zone

20% : transition zone

Diagnosis of prostate cancer is on the increase

Increasing awareness of the disease

Prostate cancer is rare before 40ys

For early detection of P Ca in males over 50

Level of PSA in patients with histologically

Prostate Specific Antigen (PSA)

PSA (with other parameters) is used for the

A tumor marker used for the diagnosis, staging

Periodic estimation of PSA level is essential for

Importance of serum PSA testing:

An enzyme secreted by prostatic acinar cells

Staging of Prostate Cancer

In patients with P Ca, PSA level correlates

based on prostatic biopsy for patients with

Normal PSA level does not exclude P Ca:

Early disease (small tumor volume)

Poorly differentiated tumor

Locally advanced prostate cancer( T3 & T4)

T4: Direct extension to an adjacent organ

Grading of Prostate Cancer

Vertebrae (lumbar) , ribs , skull

An abnormal DRE is defined by:

Diagnosis Of Prostate Cancer

Other causes of abnormal DRE:

Locally advanced prostate cancer (T3 T4)

Digital Rectal Examination (DRE)

Only 50% of patients with abnormal

Normal DRE does not exclude cancer

Imaging in the diagnosis of prostate cancer :

Imaging of Skeletal metastasis

High sensitivity but low specificity

high false positive result

Conventional Skeletal radiography

Low sensitivity but high specificity

Localized prostate cancer (T1 T2 )

Factors affecting the choice of treatment

Performance status (general condition

Patient counselling on side effects of

Locally advanced Prostate cancer (T3 4)

Side effects of androgen deprivation

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