Prostatic Adenocarcinoma

It is the first common cancer of American men while it is the sixth

common cancer of Iraqi . There are many more prostatic cancer that
occur without being clinically apparent,even among those evident cases
there is wide variability in biologic behavior and metastatic potential.
Etiology and predisposing factors:
1.It is a disease of aging, rarely occur under age of 40 and its incidence
increase progressively with age. Its peak in the Seventh decade of life.
2.Genetic predisposing factor . patient relative have higher incidence of
prostatic adenocarcinoma also the incidence vary between racially
different countries. It is very common in north America and European
countries while it of low incidence in far eastern countries, black have
higher incidence than white
3.Hormonal influence. It is believed that testosteron is a promotor of
prostatic cancer, and prostatic cancer not occur in eunuchs, the majority
of prostatic cancer are hormone sensitive, grow rapidly in presence of
male hormone and castration produce dramatic regression.
4.Dietary and envirometal factors. Different incidence of cancer in
racially similar group as in second and third generation Japanese
Americans have similar incidence as other north Americans while the
clinical incidence of prostatic cancer in Japan is only 10% of that in
U.S.A.
5.Bacterial and viral agent also may be suggested. There is increase
incidence related to venereal disease, some show relation to prostatitis.
6.Heavy consumption of alcohol changes the hormonal state and affect
the diet.
Pathology: 70% of prostatic cancer origenated in the prepherial zone of
the prostate, 20% in the central zone and 10% in the transition zone, most
prostatic cancer are multicentric.
Prostatic cancer has 3 grade, well, moderately and poorly differentiated
adenocarcinoma, prostatic cancer grade is one of the most clinically
useful indicators of prostatic growth and progression.
Prostatic cancer staging
T1 Clinically unapparent tumor, not palpable or visible by imaging.
T2 Tumor confined with the prostate.
T3 Tumor extends through prostatic capsule.
T4 Tumor is fixed or involves adjacent structures other than seminal
vesicles.
Prostatic lymph drainage to obturator and internal iliac group,
hematogenous spread commonly to the axial skeleton which is found in
85% of patients who die by prostatic cancer. It frequently to upper
femors, pelvic bone, lumber and thoracic spines, ribs, sternum and skull,
extension to axiale skeleton is by Batson’s venous plexus which connect
pre sacral and pre prostatic venous plexus. 85% of those secondary are
asteoblastic in nature.
Clinical finding
Patients may present with hard prostatic nodule discovered by routine
physical exam or malignancy discovered incidentally during
histopathological exam of enlarged prostate after adeno prostatectomy.
Urological symptoms as poor urinary stream, frequency or terminal
dribbling, some present with acute urinary retention, other with
incontinence, other with over flow incontenance (obstructive feature) or
incontenance due to sphencter involvement by malignant growth.
Features of metastasis as bachach, pathological frecture, paraplegia,
some have anemia due to bone marrow replacement by malignant tissue.
Sub trigonal growth of tumor may cause lower ends ureteric obstruction
and uremia.
From clinical signs may there hard prostatic nodule or hard irregular
gland, some time there signs of obstructive uropathy as palpable bladder ,
kidneys or signs of spinal cord compression.
Diagnosis:Biopsy by true-cut needle biopsy by transperenial or
transrectal approach, or by TUR- prostatectomy for obstructive prostate.
Malignant tissue can be localized by multiparameteric MRI and through
TRUS needle can be guided to the lesion.
Staging
1.DRE digital rectal exam- which has its drawback that it is subjective
exam depend on examiner experience and it miss stagsT 1 and it has false
positive result that only 50% of hard nodule of the prostate are malignant.
Hard nodule may by granuloma, calcification, prostate stone, benign
prostatic hyperplasia.
2.TRUS- transrectal ultrasound- it is effective to evaluate locally
advanced tumor. It gives idea about tumor size, site, capscular invasion,
seminal vesicals invasion. Only 2/3 of prostatic tumor are evidant by
TRUS as hypoechoic lesion, 2% of prostatic cancer are hyperechoic and
1/3 are isoechoic so not evident by U/S
3.Multiparumeteric MRI for evaluation of prostatic tissue and local
staging with in pelvies including seminal vesicle, lymph nodes.
4.Skeletal survey, that 50% of the bone must be replaced by tumor before
it can be detected radiologically, 20% of secondaries not evident by X-
ray. By hormonal therapy osteoblastic lesion may disappear and
osteolytic lesion may recalcified.
5.Bone scan using Tc 99 labeled methylene diphosphonate. It is the most
sensitive mean to detect ossous rnetstasis. Patient with secondaries in the
bone may have positive bone scan with undetected lesion by radiography.
This exam has 2% false positive result due to previous trauma or
osteoarthrosis or paget disease all give false positive result.
6.CT chest and obdamen for any seconderoes in the chest and abdomen in
cluding local staging and bove involvment
7.S. acid phosphatase, which excreted normally by prostatic gland, its
value in the serum increase in presence of extra prostatic spread. Normal
value is 1-3 KAS/dl in the serum. It increases in 1/3-2/3 of cases of extra
capscular disease. It is used as tumor marker to have idea about tumor
stage and to fellow patient’s management and progression.
8.PSA. Prostatic specific antigen, is another tumor marker it is
glycoprotein that it secreted from cytoplasm of prostatic cells, normally
aid in semen liquefecation Normal value in young adult is 0-4
nanogram /ml (nano= 10-9 gram), increase value PSA usually correlate
with the stage of the disease but its accuracy in staging is just 50%, the
greatest value of PSA is to follow up patient management.
Treatment Patient with T1 what need is only active survillance as
treatment strategy, those may be well by observation as those with
aggressive early therapy with 10 years fellow up. Patient with stage T 1
who have clinical evidence of tumor progression should be treated
according to his stage of progression.
Stage T2 - the options of treatment is radical prostatectomy, radical
radiotherapy or hormonal treatment depends on patient general condition
whether fit for operation, patient life expectancy, preference of treatment
option, patient with life expectancy more than 10 years and fit for surgery
managed by radical prostatectomy, if he refuse surgical treatment with its
possible complications the option is radical radiotherapy other wise
managed by hormonal treatment.
Radiotherapy either in the form of external beam irradiation or brachy
therapy which is interstitial radiation. External beam irradiation has result
comparable to radical surgery by giving dose up to 7000 rad. Brachy
therapy is by implantation of small balls by transrectal ultrasound guide,
by this method up to 17000 rad can be given.
Locally advance Pca T3- radical surgery or irradiation are both with
unsatisfactory results. The approach for those patients is by hormonal
cytoreduction followed 3 months later by irradiation or radical
prostacatony.
Metastatic disease- is treated by hormonal therapy. The medium
response period to hormonal therapy is 18 months and the mediam
survival is 2 years. Prostate cancer are heterogeneous tumor compose of
hormone sensitive and hormone resistance cells. By androgen deprivation
about 40% of patients have regression of the disease and 40% of patients
have stabilization of the disease and 20% will have continued growth.
Hormonal therapy has many forms:
1.Bilateral orchidectomy which is the most efficient way for androgen
ablation of testicular origin. The main drawback is psychological trauma.
2.Estrogen as Diethyl stillbesterol 3mg/day act by suppressing LH
production so no testosteron production and it may have direct effect on
cancer cells itself. Some patients have to discontinue this drug because of
its side effects which are cardiac and pulmonary complications also
prepheral odema, thrombo embolism, fluid retention and painful
gynecomastia.
3.LHRH agonist. Those agents stimulate the pitutary in the first 3 weeks
because of its continuous high level. After 3 weeks it cause decrease of
LH. Its efficiency as that of estrogen or orchidetomy. In the first 3 weeks
anti androgen must be given with those drugs. Otherwise, it causes
increased testosterone production.
4.LHRH antagonis are injectable antagonist
5.Anti androgen which are of 3 groups.
A-Anti androgen synthesis as aminoglutethamide, ketoconazole act by
enzymatic block of both adrenal and testicular androgen synthesis. Those
drugs are useful for initial rapid acting agent in patients with sever
symptoms of bone pain or impending spinal cord compression. Those
drugs have serious side effect by blocking other adrenal steroid and cause
GIT intolerance,hepatotoxicity and gynecomastia.
B-Non streoidal anti androgern. as flutamide. This drug preserve normal
testosteron level that it not causes medical castration. Its action by
competitive inhibition of testosterone at recepters lavel. Potency is
preserved by this drug.
C- Streoidal anti androgen as cyproteron acetate or megesterol acetate.
Them action by competitive receptors blocking also by negative feed
back on pituitary. They inhibit release of ACTH and LH so decreases
androgen production.
 Patient with bone pain usually responds to hormonal therapy
otherwise local radiotherapy 3000 rads over 3 weeks.
 Patient with urinary retention is managed by TUR prostatectomy
with hormonal therapy.
 For metastatic tumor, chemothreapy can be given with hormonal
therapy for fit patient . that Doxetaxl (chemo therapy of choice).