CARCINOMA OF THE PROSTATE

Male Urinary Bladder

Peripheral zone-70%.

70% adenoCa arise here Transition zone-5-10% 20% adenoCa Central zone-25% 1-5% adenoCa

 Carcinoma

of the prostate is now becoming the leading malignancy in men beyond middle age Life time risk of developing microscopic Ca prostate is 30% Risk of developing clinical Ca prostate is 10% The risk of dying from the disease is 3%

Carcinoma of the prostate (Cont.2)

From

postmortem specimens 14% of men over 50 years and 80% of men over 70 years have the disease. The highest incidence is in Africans followed by Caucasians. The least incidence is in Asians

RISK FACTORS
(a)

(b)
(c) (d)

(e)

Age strongest Family and genetic factors Race Dietary fat. High intake of animal fat increases the risk. Intake of vegetables rather decreases the risk. Functioning testes and testosterone

PATHOLOGY
Greater

than 95% of prostate cancers are acinar adenocarcinomas. Prostate specific antigens is high in adenocarcinomas. Less than 5% of Ca prostate are ductal carcinomas e.g.carcinosarcomas and lymphomas. Ductal carcinomas: e.g. are transitional cell carcinoma, squamous cell carcinoma.

 These

non-adenocarcinomas commonly present as haematuria, positive urinary cytologies, normal PSA. The rest of this discussion is on adenocarcinomas.
Adenocarcinoma of the Prostate Primarily found in the peripheral zone (70%) Spread is by direct local extension and by lymphatic and vascular channels.

Adenocarcinoma of the Prostate (Cont.)

Aggressive

tumour first invades the capsule, seminal vessicles and then the bladder base. Ureteric obstruction occurs in about 1035% of patients with advanced disease Direct extension to the rectum is rare Lymphatic spread is primarily to obturator and hypogastric nodes.

Adenocarcinoma of the Prostate(cont.2)

Osteoblastic

bony metastases commonly goes to lumbar spine proximal femur, pelvis thoracic spine, ribs, sternum and skull. Visceral metastasis commonly goes to the lung, liver and adrenal.

GLEASONS GRADING SYSTEM

Gleasons System uses five (5) different histologic patterns (1-5) to characterise the degree of glandular differentiation under low power magnification. It grades the two most representative areas of the tumour namely primary and secondary grades. These two grades are added together to obtain the Gleason score or sum or combined Gleasonss grades.

Gleasons Grading System (Cont.)

The score is between 2 and 10 A high Gleasons score indicates (i) Poor differentiation (ii) increased risk of nodal metastases and (iii) a more malignant potential There is good correlation between Gleasons sum and prognosis The presence of Gleasons pattern 4 or Gleasons sum 7 or more, implies tumour is predictive of a poor prognosis.

PRESENTATION
(1)

(2)

(3)

Asymptomatic Cases Discovered on routine screening e.g. Abnormal DRE findings or Raised PSA Localised Disease Mainly Lower Urinary Tract Symptoms e.g. irritative and obstructive symptoms Locally Invasive or Advanced Disease In addition to obstructive and irritative symptoms other symptoms that indicate

Presentation (Cont)
the

involvement of surrounding structures are seen. Tenesmus, rectal bleeding (constipation) rectal involvement Sphincter involvement leads to incontinence. Haemospermia seminal vesicle involvement

4.
(a) (b) (c)

(d)

Presentation as Metastatic Disease Low back pain and sciatica metastases to the lumbar spine Pathological fractures from metastases in the femoral neck Paraplegia collapse of vertebrae or compression of the spinal cord by metastases Metastases to lymph nodes i.e. obturator, internal iliacs leads to palpable lymph nodes and pedal lymphoedema

5. Widespread Metastases Cerebral metastases lead to headache, nausea or vomiting, drowsiness, epilepsy or paresis,coma. 6. Incidental Prostate Cancer Found after histological examination of TURP or open prostatectomy specimen.

DIAGNOSIS
History and complete physical examination. DRE It is the simplest way of detecting posteriorlyplaced cancer. It is inferior to PSA in its sensitivity in early cancer since most early cancers are not palpable DRE is performed with the patient in left lateral position, or standing and leaning forward or knee-elbow positions or Lithotomy position or kneeling positions
(1)

Findings indicative of prostate cancer are: (i) A nodule (ii) Hard or woody consistency of part or all of the prostate (iii) Fixed rectal mucosa (iv) Irregular edges of the gland

INVESTIGATIONS
(i)

Serum PSA The most efficient single test for detecting prostate cancer. It is produced by the epithelium of the prostate gland. High levels of PSA may indicate the presence of Ca prostate PSA is raised in Ca prostate, prostatitis, BPH, prostatic trauma, prostatic infarct.

Serum PSA (Cont)

PSA

levels may be reduced by 50% in patients on finesteride (proscar.) (ii) Prostate Biopsy Indications for biopsy A palpably suspicious nodule on DRE regardless of PSA level PSA >4.0ng/ml regardless of DRE PSA greater than the patients age specific range

(iii)

Transrectal Ultrasound TRUS aids in the localisation of prostate cancers and is indispensable for accurate needle biopsy of the prostate. Indications To aid prostatic needle biopsy To measure prostate size for PSA density.

(iv)

(v)

(vi)

Other imaging investigations CXR (P-A) Skeletal survey Nuclear bone scan. These are done to rule out or confirm distant bone spread. CT scan for staging Blood for Haematology (FBC) and BUN, Creatinine, Electrolytes, FBS MSU Urinalysis + C/S

STAGING OF PROSTATE CANCER

MANAGEMENT OF CARCINOMA OF THE PROSTATE Localised prostate cancer T1/T2
(a) (b) (c) (d)

(1)

Watchful waiting Radical prostatectomy Radiotherapy Treatment methods under investigations

Management Of Carcinoma Of The Prostate(Cont.) (2) Locally Advance Prostate Cancer Non Metastatic Disease (T3NoMo)
(a) (b)

(c)

(d)

Watchful waiting Neo-adjuvant hormonal therapy followed by surgery Neo-adjuvant hormonal therapy and radiotherapy Hormonal treatment alone

Indications for Repeat Biopsy Persistently abnormal or rising PSA PSA between 4.0 and 10.0ng/ml with a low percent free PSA (<15%) Evidence of high grade prostatic intraepithelial neoplasia on a prior biopsy. Prostate biopsy confirms diagnosis of Ca prostate.

(3)
(a)

Management of Metastatic Disease

Hormonal treatment (b) Localised radiotherapy HORMONAL TREATMENT (a) LHRH agonists (analogues) goserelin (Zoladex) buserelin acetate after initial antiandrogen.This is medical castration (b) Anti-androgens (steroidal and non steroidal) steroidal cyproterone acetate (CPA) non-steroidal Casodex (bicalutamide) 50mg daily, Flutamide 250mg daily

Hormonal Treatment (Cont.)

(c) Bilateral Total Orchidectomy (BTO) Effective within 3-12hrs of surgery. This is surgical castration. Reduces androgen levels by 90-95% to 5-10% of normal (d) Oestrogen Diethylstilboesterol (DES) 3-5mg daily (e) Progestogens

Maximal Androgen Blockage

This refers to simultaneous blockage of testicular, adrenal and other extra testicular androgens as first time treatment e.g. BTO or LHRH agonist plus antiandrogen therapy.

Management of Hormone Resistant (Hormone Escape or Refractory) Prostate Cancer

Over 75% of cells in advanced prostatic cancers are hormone dependent or hormone sensitive whereas the rest are hormone independent cells. Hormone dependent cells are ablated by apoptosis when anti-androgens are given. After the death of hormone dependent cells, the hormone independent cells begin to proliferate and PSA levels begin to rise again and patients condition worsens again.

Treatment
Anti-androgen

withdrawal Steroid administration Cytotoxic chemotherapy Inhibition of growth factors Palliative care e.g. bone pain control using bisphosphonate, external beam radiation

PROSTATIC INTRA-EPHTHELIAL NEOPLASIA (PIN)

This architecturally has benign acinilined by intraductal dysplasia Low grade PIN (PIN 1) is indistinguishable from BPH High grade PIN (PIN 2 and PIN 3) is associated in subsequent biopsies with finding of carcinomas in 30-50% of cases. Repeat TRUS guided prostatic biopsy should be performed when high grade PIN is found on needle biopsy.

Prostatic intra-ephthelial neoplasia (pin)(Cont.)

High

grade pin is a precursor to peripheral prostatic adenocarcinoma