1. health and fitness
2. disease
3. cancer

GP Masterclass in Urology
Problems with the
Prostate
Mr Alvan Pope - Urological Surgeon, Hillingdon Hospital
Functions of the prostate
• The role of the prostate gland in
ejaculation and continence is uncertain
• The prostate gland secretes nutrients and
fluid
• The prostatic epithelium secretes prostatespecific antigen (PSA), which is
responsible for liquefying semen
BPH
Benign Prostatic Hyperplasia
• Increasingly common over 50 y
• Symptoms have major QOL impact
• Potential serious complications
• Both medical and surgical treatments
Men with BPH
The Patient
- who seeks advice?
- who to investigate?
- who to treat?
- who to refer?
Who seeks advice?
• The worried well (esp. about cancer)
• Incidental findings on health screening (poor
stream, nocturia, urgency)
• symptomatic lower urinary tract symptoms (LUTS)
• other causes - eg: prostatitis, urethral stricture,
bladder dysfunction
Who to investigate?
• LUTS with IPSS > 8
• Prostate cancer concern
• Examination - enlarged bladder, genital pathology
(eg. phimosis,meatal stenosis)
- DRE (enlarged or not?, benign or not?)
• Invests.
- urinalysis (sugar and blood), MSU
- PSA, creatinine
- imaging, residual urine and flow rate
Who to treat?
• Reassurance often sufficient (c.f. cancer)
• Watchful waiting is legitimate management
• Treat those with moderate symptoms who
are bothered (IPSS > 8-10)
Medical therapy for BPH
• Consider the dynamic (urethral pressure) and static
(prostate bulk) components
• Most of the enlarged prostate is stroma which has lots
of smooth muscle. Bigger = more glandular tissue
• Alpha blockers (Tamsulosin, Alfuzosin, Doxazosin)
• 5 alpha reductase inhibitors (Finasteride, Dutasteride)
5-AR inhibitors
Block conversion of testosterone to DHT in prostate
The ONLY randomised double blind placebo
controlled trial of Finasteride versus Dutasteride
demonstrated NO differences in any of the
outcome measures at any of the time points
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The EPICS trial
• Enlarged Prostate International Comparator Study (EPICS)
• Multicentre trial, Intention to treat analysis
• Number randomised: 1630
• IPSS >12
G
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• Prostate volume >30ml
• Qmax <15ml/s
• Data collection: 3, 6 and 12 months
Drugs for bladder dysfunction
• Overactive bladder - anticholinergics
• Oxybutynin (Ditropan, Lyrinel XL, Kentera patch)
• Tolterodine & Fesoterodine (Detrusitol XL, Toviaz)
• Solifenacin (Vesicare)
poorly tolerated esp. dry throat, constipation
contraindicated in closed-angle glaucoma
• Nocturnal polyuria (Diuretics, DDAVP)
Symptomatic BPH
Monotherapy or combination therapy ?
Alpha blocker and 5aRI
Evidence for:
• increased symptom benefit
• reduction in complications or need for intervention
• possible reduction in prostate cancer risk
MTOPS Study
• Combination therapy with doxazosin and finasteride led
to a greater decrease in the risk of clinical progression
of BPH than either drug alone, in patients with a
baseline prostate volume above 25ml
• With smaller prostates the benefit was towards the
dozasosin only arm, except for the need for surgery
CombAT Study
• 4 yr study of nearly 5000 men with
moderate to severe BPH symptoms
• Randomised to either Dutasteride or
Tamsulosin alone or to the combination
• The combination group were best for:
symptom improvement (IPSS down 6)
reduction of risk of AUR (66% over T)
Who to refer?
• Abnormal DRE examination
• PSA raised (>6ng/ml below 70 or >10 in older men)
• Failed medical treatment
• Haematuria, recurrent UTI, retention
• Severe symptoms (IPSS>19)
• (Anxious patients)
Hospital assessment
• Integrated prostate clinics (CNS run one-stop shop)
• flow rates, residuals
• urodynamic assessment (esp. if predominately
irritative symptoms)
• TRUS and biopsy
• flexible cystoscopy
Surgical Treatment
• TURP is still the ‘gold standard’ - some new angles
• Laser techniques (safer in frail, anticoagulated etc.)
• Green-light laser
• Holmium laser
• Prostate stents (good temporary measure in unfit
men - unless large residual)
Does a 5-ARI drug reduce the
risk of prostate cancer?
Probably YES
• Several studies (PCPT, REDUCE, combAT) have
shown reduction in incidence of prostate cancer in
men on 5-aRI
• PCPT trial - 25% reduction in risk with finasteride
Gleason grade 8-10 in 6.4% of treated group, 5.1% of control group
• 40% reduction in CaP diagnosis over 4 yr with
Dutasteride vs. Tamsulosin
• Study where routine biopsies - 23% reduction.
Caes History - 76 yr man
• Longstanding lower urinary tract symptoms
• Drugs - alpha blocker (Doxasosin) and 5-ARI (Finasteride)
• O/E - large BPH on DRE
• Tests - MSU >105 coliform
• Flow rate prolonged and <10ml/s
• 350ml post-void residual
• PSA 12.8 ng/ml
• Management
• Antibiotics (quinolones) for 10 days
• Prostate surgery (TURP)
Types of retention
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Acute
Chronic (high or low pressure)
Acute Retention
Surgical emergency
Assessment
History
Examination (abdomen & prostate)
Catheterise and admit
Consider trial of voiding (a blocker)
Some catheters are tricky
Precipitating causes
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Post-operative
Constipation
Infection
Haematuria
Pelvic pathology
Neuropathy
Management of retention
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Urethral catheter (consider size & type)
Suprapubic catheter
RECORD RESIDUAL VOLUME
Watch for post-obstructive diuresis
esp. in chronic retention with obstructive nephropathy
Chronic retention
Chronic retention
Obstructive Nephropathy
Post Obstructive Diuresis
• Diuresis with high sodium excretion
represents tubular damage rather than
solute load
• Most at risk - heart failure, confusion
• Replace majority of loss with saline
• Prognosis for chronically obstructed kidney
difficult to predict (u/s, renography)
Prostatitis
•
Acute bacterial prostatitis - serious systemic infection
• High dose systemic antibiotics eg. Gentamicin
• Complications of retention and prostatic abscess
•
Chronic bacterial prostatitis (CBP)
• Significant inflammation
• Isolation of organism from urine or semen
•
Chronic pelvic pain syndrome (CPPS)
• Inflammatory - leucocytes in semen/urine/prostate fluid
• Non-inflammatory - no leucocytes
•
Symptoms
• Perigenital or perineal pain
• Voiding symptoms (frequency, straining, dysuria, UTI’s)
Prostate Cancer
Prostate Cancer Facts
• 10,000 deaths a year in UK , 30,000 new cases
• Commonest male cancer death in non-smokers
• Can only reliably cure localised disease
• No agreed screening programme
• A lot of low-risk disease
• Risk of over-treatment is substantial
Tools to aid managment
Epidemiology
z Prostate cancer is the most common form of
cancer in men in the UK. In 2002 there were
31,923 new cases diagnosed in the UK.
z It is the second commonest cause of cancer
death in men. In 2004 there were 10,209 deaths
in the UK
z The lifetime risk of being diagnosed is 1 in 13
Epidemiology
Diagnosis and screening
• DRE - digital rectal examination
• PSA - prostate-specific antigen
• TRUS-guided needle biopsy
• Bone scan and/or CT
• Diffusion weighted MRI
PSA and Prostate Cancer
• Prostate cancer more common as PSA rises
• Age specific range
• Under 3 ng/ml age 50 - 59
• Under 4 ng/ml age 60 - 69
• Under 5 ng/ml age > 70
• PSA increases with prostate size & inflammation
Signs and symptoms of
Prostate Cancer
• Often asymptomatic
• LUTS - perhaps rapid onset
• Raised PSA level - on suspicion or screening
• Look for change in PSA (eg 2ng/ml/yr, 50% in 2yr)
• Urinary tract infection
• Haematuria, haematospermia
• Urinary retention (may cause anuria, uraemia)
• Bone pain - most common symptom of
metastases
Histological grading
The Gleason grading system
Gleason score
Histological
characteristics
10-year likelihood of
local progression
<4
Well differentiated
25%
5-7
Moderately differentiated
50%
>7
Poorly differentiated
75%
Staging of prostate cancer
Clinical presentation
Three stages of prostate cancer
• Localised disease
• Locally advanced disease
• Advanced (metastatic disease)
Treatment options:
localised prostate cancer
• Watchful waiting/active surveillance
• Surgery - Radical Prostatectomy
• Radiotherapy
• External Beam (with or without LHRH analogue)
• Brachytherapy (low/high dose)
• Combination (EBRT with HDR boost)
• Cyber Knife (possible future role)
• Cryotherapy and HIFU (experimental as first line)
• TURP if symptomatic
Treatment options:
localised prostate cancer
• Young men (<60) - AM or surgery
• Middle age (60 - 70)
• Low risk - AM or brachytherapy (LDR)
• High risk - surgery or radiotherapy (HDR)
• Older men (70 - 80) - WW or Ext beam RT
• Very old men (>80) - watchful waiting
Radical Prostatectomy
Da Vinci Robotic Prostatectomy
Problems after surgery - 1
Incontinence - sphincter weakness
• Pelvic floor exercises
• Yentreve early on
• Male urethral sling (cf: TVT)
• Rarely need for artificial urinary sphincter
Problems after surgery - 2
Erectile Dysfunction
• Still 40% even with nerve sparing
• Worse with increased age and wide excision
• New technologies not proven better
• Oral drugs often ineffective - Caverject
• Rationale for penile rehabilitation - Vacuum
device and regular low-dose Tadalafil
Treatment options:
locally advanced disease
• Watchful waiting
• Radiotherapy with hormonal therapy
• Hormonal therapy – LHRH analogue or antiandrogen monotherapy, surgical castration
• TURP for symptom relief
• Radical prostatectomy in selected cases
Treatment options:
advanced prostate cancer
• Androgen ablation therapy - medical castration
(LHRH analogue) or surgical castration
(orchidectomy)
• Maximal androgen blockade (MAB) LHRH analogue/surgical castration
with anti-androgen therapy
• Chemotherapy (Taxotere based, Abiaterone)
Usually only when established hormonal resistance
• TURP for relief of symptoms
• Radiotherapy
Treatment options:
Advanced disease
(distant metastases - esp. bone)
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Palliation of bone pain and urinary symptoms
Hormonal therapy - androgen ablation
Radiotherapy can relieve pain
Radiopharmaceuticals can provide targeted
pain relief
• Chemotherapy should be considered if tumour
is resistant to hormonal therapies
Prostate cancer:
Hormonal treatment options
Aim to block production or action of testosterone
• LHRH agonists
Goserelin (Zoladex), Leuprorelin (Prostap)
Triptorelin (Decapeptyl)
Histrelin - 1 year implant
• LHRH antagonists
Degarelix (Firmagon) - no flare, rapid effect
• Oestogens - either oral (Stilboestrol) or
transcutaneous (Fem7 patches)
Side effects of Androgen
Deprivation Therapy
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Lethargy, sweats, hot flushes (CPA)
Lack of libido, loss of erections
Loss of muscle mass/gain fat
Loss of physical capacity, fatigue
Changes in mental capacity
Gynaecomastia and breast pain (Tamoxifen)
Osteoporosis/fractures
Salvage Prostate Cryotherapy
For failed primary radiotherapy - NICE approved
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
2 freeze/thaw cycles down to 40oC with rectal warming
Prostate Cancer Follow-up
Largely PSA surveillance
• Hospital Based?
clinic visits or telephone
• Patient triggered
• GP for stable patients (SCP, SLA)
CASE HISTORY Prostate Disease
• A fit 64 year old man volunteered a history of
mild voiding symptoms at routine medical
• IPSS 7
• DRE mild enlargement of prostate, sulcus
intact but a firm nodule in the right lobe,
prostate not tender
• Urinalysis clear
• PSA 9 ng/ml
CASE HISTORY Prostate Disease
Questions
• What is a possible cause of a prostatic nodule?
• What is the significance of the PSA result?
• How should this patient be further investigated?
• If the PSA had been normal how would your
management have differed?
Screening for PC
Only way to pick up early disease whilst curable
Still cannot separate tigers from pussycats
• Happening by default
increased public awareness
more media exposure
• March 2010 - PC awareness month
• Charities, fundraising, support groups
That’s all Folks!
Questions to the panel
after all the talks please