Define prostate cancer.
A malignant tumour of glandular origin, situated in the prostate.
How common is prostate cancer? Who is most affected?
- Second leading cause of cancer mortality in men in the US.
- Uncommon in men aged under 50 years.
- Median age of diagnosis is 66years,
What is the aetiology of prosate cancer?
Unknown but high fat diet and genetic factors have been suggested in the aetiology. Black men in US have highest incidence of prostate cancer of any ethnic group.
What are the risk factors for prostate cancer?
- Age >50yrs
- Black ethnicity, north American or northwest European descent
- Family history
- High levels of dietary fat - x1.6-1.9
- BRCA 2 gene
What are the presenting signs/symptoms of prostate cancer?
- Asymptomatic; raised PSA
- LUTS - obstruction (frequency/urgency/incontinence/nocturia) and voiding (hesitancy, poor stream, straining, long micturition, incomplete emptying, dribbling)
- Urinary retention / renal failure
- Abnormal DRE - normal prostate is walnut-sized
- Haematuria
- Lethargy, palpable lymph nodes, bone pain, weight loss, spinal cord compression (Mets) - could present as an old male not being able to walk
What is PSA? How does it change with age?
PSA is a serine protease that is produced by the prostate gland and secreted into the seminal fluid where it is involved in the liquefaction of the seminal coagulum. It is also found in blood either free or bound to plasma proteins.
PSA increases with age.
What is a normal PSA? What are the causes of RASIED PSA?
Normal PSA = 0-4 micrograms/L (ng/ml)
- Ageing
- BPH
- Urinary Retention
- Urine infection
- Catheterisation / instrumentation of urethra
- Prostate cancer - increase in PSA of 0.75 micrograms/L/year may be cancer
Not significant:
- Digital rectal examination
What invasive technique is used to diagnose prostate cancer?
- TRUS biopsy is used for TISSUE DIAGNOSIS (transrectal ultrasound guided biopsy)
- This should be done when PSA is >3micrograms/L
- 10-12 cores are taken
- Pathology reports on presence of intraepithelial neoplasia/carcinoma, Gleason score, % of each core that is positive, and invasion.
- MRI-TRUS detects clinically significant prostate cancer in a greater number of men compared with standard ultrasound-guided biopsy
Alternatives:
- Transperineal Biopsy
- Template Biopsy
- Saturation Biopsy
What is the grading system used for prostate cancer?
Gleason score - grades aggressivenes of the cancer cells; scores from 2 areas with the most cancer cells are added.
- Low risk 3+3
- High risk 5+5 and up
Grade - 2 is best prognosis and 10 the worst
Staging is done by TNM
What investigations would you do for prostate cancer?
- PSA (free and bound form total) - >4micrograms/L (but this needs to be correlated with age). % of free PSA may be useful e.g. if <10% of total it suggests an aggresive cancer may be present.
- Prostate biopsy (TRUS) - malignant cells detected in one or more biopsy specimens (assigned to grade group 1 to 5, max total 10)
- Testosterone - normal
- LFTs - normal
- FBC - normal except in metastatic disease
- Renal function - as above
- Bone scan - done if PSA >20micrograms/L
- X-rays - lytic or blastic lesions
- Pelvic CT scan - enlarged prostate +/- enlarged pelvic lymph nodes. Performed if the patient has clinical stage T3/T4 disease, or T1/T2 disease with a risk of lymph node involvement of >10% (e.g., assessed using the Partin nomogram)
Is there a screening programme for prostate cancer?
No - randomised 20-year study which combined regular DRE and PSA measurements showed no survival benefit between men who were screened and those who were not
What is the incidence of prostate cancer in each age group?
The general rule-of-thumb for age related incidence of prostate cancer is:
- 40 % over 40,
- 50 % over 50,
- 60 % over 60
- 80 % over 70.
By 90 almost all have neoplastic change in prostate gland.
Which zone do prostate cancers mostly arise?
Peripheral zone of the prostate
What is the histopathology of most prostate cancers?
95% are adenocarcinomas
Often multifocal - 70% lie in the peripheral zone
Where does prostate cancer spread first?
Lymphatic spread occurs first to the obturator nodes and local extra prostatic spread to the seminal vesicles is associated with distant disease.
Summarise the management of prostate cancer.
- Active surveillance (low risk low volume disease)
- Surgery – radical prostatectomy (robotic or laparoscopic) + removal of obturator nodes
- Radical Radiotherapy/Brachytherapy - radiation proctitis and rectal malignancy are late problems;
- Watchful waiting (elderly / co-morbid patients)
- Hormones e.g. LHRH agonists can be used to shrink the prostate before surgery
- Chemotherapy
Which patients can have active surveillance?
Low risk patients with a PSA <10, Gleason score 6, and disease that cannot be felt clinically on rectal examination.
When does NICE recommend surveillance in prostate cancer?
Low risk patients:
- Stage T1c
- Gleason score 3+3
- PSA density <0.15ng/ml
- Cancer in <50% of their biopsy cores and with <10mm of any core involved
Candidates for surveillance also need:
- at least 10 biopsy cores taken
- at leas one re-biopsy
If there is any sign of progression radical prostatectomy is needed.
How do you manage low risk low volume prostate cancer in a young man?
Active suirveillance - no risk of erectlie dysfunction/incontinence. Might therefore be a better option than surgery.
But if the disease is aggressive then radical prostatectomy
Describe active surveillance in post prostate cancer patients.
- Gleeson 6 (?7)
- Less than 2 cores
- PSA <10
- T1c or T2
Surveillance:
- PSA FU 3 monthly
- MRI scan annually
- Re-biopsy year 1,3 & 7
Treat it…
- PSA >10
- PSA dt <3 years
- Grade progression on rebiopsy
- Clinical progression
- Patient choice
Why is surgery for prostate cancer unpopular?(3)
- More bleeding
- higher incontinence
- Likely erectile dysfunction
- May not die anyway
What must you monitor patients on hormonal/radiotherapy treatment for postate cancer?
PSA must be followed up in post RRP
- <0.01 in 6/52
- Failure initial PSA >0.2
- Early rapid rise indicates disease beyond prostate
- Later slow rise local recurrence
- Biopsy to confirm
- Restage- bone scan /MRI
What hormonal therapies are available for prostate cancer?
- LHRH agonists e.g. Zoladex
- Anti-androgen e.g. Bicalutaminde, Casodex
(beware tumour flare)
How do hormonal therapies for prostate cancer work?
Paradoxically result in lower LH levels longer term by causing overstimulation, resulting in disruption of endogenous hormonal feedback systems. The testosterone level will therefore rise initially for around 2-3 weeks before falling to castration levels.
Initially therapy is often covered with an anti-androgen to prevent a rise in testosterone - ‘tumour flare’. The resultant stimulation of prostate cancer growth may result in bone pain, bladder obstruction and other symptoms
e.g. goserelin + docetaxel
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Acute kidney injury (AKI)24
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Benign prostatic hyperplasia (BPH)29
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Bladder cancer20
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Chronic kidney disease (CKD)16
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Epididymitis and orchitis12
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Glomerulonephritis32
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Hydrocele13
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Hydronephrosis12
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Nephrotic syndrome13
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Polycystic kidney disease11
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Prostate cancer33
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Rhabdomyolysis10
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Renal artery stenosis9
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Renal cell carcinoma18
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Testicular cancer20
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Testicular torsion16
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Urinary tract calculi33
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Urinary Tract Infection28
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Varicocele12
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Procedures (circumcision, dialysis, nephrostomy& ureteric stenting, orchidectomy, prostatectomy, transplant, TURBT, vasectomy)32
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Urology Lecture85
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