kyabram urology update 2015 - murray phn · the optimum treatment for oab is yet to be determined....

Kyabram Urology Update 2015

Mr Stephen LindsayUrological Surgeon

Bendigo

www.bendigourology.com

50 year old man – Prostate Cancer Risk Assessment

PSA - 5.4 ng/ml (normal <3.5 ng/ml)DRE - firm prostatic nodule on the right side, with no

extension into the lateral sulcus or seminal vesicle (T2b)FHx - No

PCPT Risk Calculator

Risk of high grade CaP 5%Risk of low grade CaP 18%

Likelihood that the biopsyis negative 77%

Digital Rectal Examination (DRE)

Increased firmness, hardness, nodularity, irregularity, asymmetry, cragginess

Sensitivity of DRE in detecting Prostate cancer

• GP 26.5%

• Specialist Urologist 61.8%

One in four men with a normal PSA have an abnormal DRE due to Prostate cancer

Health professionals need to be trained to do DRE properly if they are to competently assess Prostate cancer risk

Multiparametric-MRI (mp-MRI) for Risk Stratification

mp-MRI combines diffusion-weighted, dynamic contrast-enhanced sequences (or MR Spectroscopy) with conventional T2 weighted sequences.

This shows anatomy, tissue density and blood supply.

Potential Advantages• Only detects cancers

• 7mm or larger• Gleason grade 4 or 5

• Has the potential to offer improved detection and risk stratification of intermediate/high risk cancers.

• mp-MRI targeted biopsies may lead to• fewer biopsies, with fewer cores at each biopsy• reduced detection of clinically insignificant disease• better representation of disease burden "cancer core length,

Gleason score"

Multi-parametric MRI for Prostate Cancer diagnosis

Multiparametric MRI (mp-MRI) for Risk Stratification

BUT….

• Mp-MRI is highly technique and operator dependent, requiring two dedicated Uro-Radiologists for each report. The technique and exact use is evolving and still in its infancy.

• Mp-MRI should not be considered as a definitive study on its own but rather one part of a comprehensive assessment. Biopsy must still be performed to confirm the presence of tumour and to assess Gleason score

We need prospective randomised trials to assess the role of mp-MRI in Prostate cancer screening.

mp-MRI is not currently reimbursed by Medicare or private health funds for prostate imaging.

Multi-parametric MRI for Prostate Cancer diagnosis

What type of Prostate Biopsy?

Trans-Rectal vs Trans-Perineal Ultrasound-guided Biopsy

Trans-Rectal Trans-Perineal

• 14-16 cores• Inadequate sampling of

anterior prostate

• Sepsis 1-2% (ESBL)• Retention <1%• Bleeding mild

• 20 areas sampled with multiple cores

• mp-MRI fusion

• Sepsis almost 0%• Retention 2-5%• Bleeding increased, pelvic

haematoma• Erectile dysfunction• Peri-prostatic scarring• Anaesthetic Risk• Dramatically increased cost

50 year old man – Prostate Cancer Risk Assessment

TRUS Biopsy

• Hypoechoic area right side corresponding to palpable nodule• 5/14 cores involved (2-5mm right side)• Gleason score 3+3=6

Radiological Staging

• CT Abdomen/Pelvis - negative• Bone Scan - negative

Stage T2b N0 M0

Patient Factors

• Does the patient (or his family) want treatment?

• What is his life expectancy, and his expected quality of life?

• Active surveillance – can he live with cancer diagnosis and no treatment/delayed treatment?

• What quality of life is he prepared to sacrifice to be cured of his cancer (continence, sexual function, bowel dysfunction, time off work)?

The Cancer

• Is this Prostate cancer life threatening or likely to cause significant morbidity?

• Is this Prostate cancer curable with the treatment options available?

Treatment Options

• What potentially curative treatment options are available for this man?

• Clinical factors

• Increased risk of side effects in this man (LUTS, rectal toxicity, sexual dysfunction)

• Access to services (eg. geography, family support, travel)

• Cost – treatment, transport and accommodation, time off work

Treatment options for Localised Prostate cancer

Active Surveillance

Radical Prostatectomy

• Open Retropubic, Perineal , Laparoscopic, Robotically-Assisted RP

Radiotherapy

• Intensity Modulated External Beam (IMRT)

• +/- Neo-adjuvant LHRH to downsize

• +/- Adjuvant LHRH for 2-3 years (survival advantage)

• Brachytherapy

• Low Dose Rate Seeds (I125)

• High Dose Rate + EBRT

Hormone Therapy

• LHRH (eg Goserelin, Leuprorelin)

• Antiandrogen (steroidal or non-steroidal)

Consensus statement:

Prostate cancer diagnosis must be uncoupled from prostate cancer intervention.

• Active surveillance protocols have been developed and shown to be a safe option for many men with low volume, low risk prostate cancer. This does not address the issue of over-diagnosis, but does reduce excessive intervention.

The Melbourne Consensus Statement on Prostate Cancer Testing (2013)

Active surveillance is a management strategy for a man who would benefit from treatment but where the cancer is too small to recommend active treatment.• The cancer is closely monitored for change in PSA, size or aggressiveness

(which requires repeat biopsy at defined intervals).

• If the cancer is found to progress, then definitive treatment with surgery or radiotherapy is offered.

• Currently around 40% of men newly diagnosed with Prostate cancer in Australia are commenced on Active Surveillance.

Watchful waiting is the no treatment option for elderly men who are not likely to benefit from definitive treatment.• Observation of PSA and symptoms, no repeat biopsy.

Intensity Modulated Radiotherapy (IMRT)

Radiotherapy can be accurately focused onto the Prostate, minimising radiation toxicity to the adjacent bladder and bowel

• 78Gy in 39 fractions

• x5 treatments/wk = 8 weeks

• Fiducial (gold) seeds are inserted into the prostate (using TRUS) for targeting

• Neoadjuvant LHRH therapy is often given to patients for 3-6 months prior to Radiotherapy to downsize intermediate to high risk cancers

LDR Brachytherapy Seed Implantation

I125 seeds (x 60-130) are implanted into the prostate by a Urologist and Radiation Oncologist.

The I125 seeds deliver a high dose of photons to a small, precise volume of prostate around the seed.

I125 seeds decay with a T½ of 60 days.

Patients are radioactive - radiation safety precautions must be taken.

LDR Brachytherapy Seed Implantation

1. TRUS volume study • 3D Volume & shape, position of

bladder, urethra and rectum. • A dose plan is made, calculating seed

number & position.

2. Implantation Procedure• TRUS is used to guide seed placement

following the dose plan.• 60 to 120 I125 seeds are inserted• Procedure takes approx 45 minutes,

overnight hospital stay. • CT scan next morning for post-implant

dosimetry

Radical Prostatectomy - History

1906 – first Radical Prostatectomy at Johns Hopkins University

Early 1980’s - Dr Patrick Walsh et al published anatomical studies on pelvic venous and nerve anatomy.

The Walsh Radical Prostatectomy (or open Radical Prostatectomy) revolutionised the surgical technique and dramatically reduced blood loss and surgical morbidity.

1990’s – now - Subsequent refinements in technique, including "nerve sparing" Radical Prostatectomy followed.

Open Radical Prostatectomy - Technique

• Retropubic approach

• ? Pelvic Lymph Node Dissection

• Dorsal Venous complex ligated and divided

• ? Nerve sparing prostate dissection

• Urethra transected, prostate mobilised, Bladder neck divided

• Vesico-urethral Anastamosis

Robot-assisted Radical Prostatectomy (RARP)

- da Vinci™ Technique

• Console surgeon uses 3D HD images to drive computer simulation to manipulate the robotic arms

• Table-side surgeon inserts the laparoscope and x 4-5 laparoscopic ports for the robotic arms

• “Endowrist” instruments provide precise control with increased range of motion and improved dexterity

• The prostate is removed through the large port site

• Operative time 2½-6 hours

• Hospital stay 1-3 days, patient home with urethral catheter for 2-3 weeks

Urinary Incontinence

“The involuntary loss of urine that is a social or hygienic problem”.

Stress Urinary Incontinence

“involuntary leakage occurring due to increased intra-abdominalpressure” on sneezing, coughing or physical activity including effort,exertion or positional change.

Urge Urinary Incontinence (Overactive Bladder or OAB)

“involuntary leakage associated with a sensation of urgency”.

Nocturnal Enuresis

Overflow Incontinence

Post-micturition dribble

Continuous urinary leakage due to urinary fistulae.

Urinary Incontinence - Definitions

History

• Frequency, Urgency or fear of leakage, Nocturia

• Urge incontinence on way to toilet

• Stress incontinence, triggers

Examination – abdomen & pelvis

MSU and urinalysis

Post-void residual urine by ultrasound

Bladder diary

Use a questionnaire?

Urinary Incontinence –Overactive Bladder (OAB)

Behavioural treatment (Bladder retraining)

First line treatment for overactive bladder.

• Start with initial voiding interval (as determined by diary)

• increase by 15-30 min until 2-3 hour voiding interval is reached. This may take several weeks or several months

• suppression of urge with distraction/relaxation techniques

• increase bladder capacity and continence

Combine retraining with pelvic floor muscle retraining, particularly if there isstress incontinence

Results (Cochrane):

• Better than placebo

• Similar to pelvic floor muscle training alone

• Similar to or better than drug therapy (Roe 2000)


What is the Role of a Continence Physiotherapist?

•Assess & rehabilitate pelvic floor muscle function • Neuro-muscular re-education• Adjunctive therapies• Functional retraining

•Bladder training

•Biomechanics of defaecation

•Treatment of perineal and pelvic pain

•Conservative management of prolapse

•Prevention and education


Fluid management

• perception that some is good, a lot is better.

• FDA recommend “the equivalent of six to eight 8 ounce glasses of fluid a day,much of which may be in the form of solid food”.

The optimum treatment for OAB is yet to be determined.

The right options for the right patient, optimal drug treatment regimen andbalancing of cost-benefit ratios for patients.


Medications

• Anti-Muscarinics

• Long-term low dose antibiotic prophylaxis (if persistent infections)

• Botulinum Toxin Type a (BOTOX)

Neuromodulation

Surgery

• Bladder Augmentation

• Detrusor Myomectomy (Autoaugmentation)

• Urinary Diversion


AGENT Intro Selectivity AU Formulation

Oxybutynin

(Ditropan)

1970’s Non-selective

Tertiary amine

Oral, Topical Patch on PBS

Tolterodine

(Detrol LA)

1990’s Bladder >salivary

gland

N/A

Darifenacin

(Enablex)

2000’s M3 Oral not on PBS

Solifenacin

(Vesicare)

2000’s M3 Oral not on PBS

Fesoterodine 2000’s Similar to

tolterodine

N/A


Anti-Cholinergic/ anti-Muscarinic Medication

The Classical View

Normal bladder contraction is caused by:

•release of ACh from Cholinergic nerves

•stimulation of muscarinic receptors on the detrusor smooth muscle

The efficacy classically thought to be mediated through the blockade of muscarinic receptors in the detrusor muscle.

The Contemporary View

Muscarinic receptors are present in urothelium, spinal cord and brain and in efferent nerves, as well as in the detrusor muscle.

There are probably multiple sites of activity, including effects on sensory nerve activity.


Are anti-Muscarinics effective?

•Improved symptoms from 46-92%

•placebo rates are high, up to 50%.

Most comparisons/reviews have concluded that efficacy rates are similar between drugs, and that the real differences are in side-effects.

Many people treated for overactive bladder receive drugs and instruction in bladder retraining simultaneously

Caution should be used in the elderly due to increased side-effects (particularly confusion).


Anti-Muscarinic Medications

Reduce:

• frequency and incontinence episodes• nocturnal voiding• incidence and severity of urgency

Increase:

• voided volume• urgency free interval• warning time

All have similar efficacy.

What about tolerability?


Tissue Distribution Potential Adverse Events

EyeM3

Decreased lacrimation Decreased accommodation

Salivary glandsM3

Xerostomia (dry mouth)

HeartM2-M3

Cardiovascular

IntestineM2-M3

Constipation

Urinary retentionBladder

M2-M3

• M2 reverses sympathetically-mediated smooth muscle relaxation• M3 causes detrusor contraction

BrainM1-M5

Decreased cognitive functionShort-term memory lossAltered sleep cycle


Antimuscarinic Therapy : Balancing Efficacy and Tolerability

Urgency

UUI episodes

Frequency

Dry mouth,

constipation, blurred vision,

headache, etc.

TolerabilityEfficacy


“Involuntarily loss of urine caused by elevation in intra-abdominal pressure

during physical activities.”

This type of incontinence is usually seen in women as they reach middle age,and is usually (but not invariably) associated with previous childbirth, obesityor both.

Activities commonly precipitating stress incontinence include: Coughing, sneezing Exercising Laughing Lifting/Straining Rising from a chair or bed, getting out of a car

Urinary Incontinence –Stress Incontinence

Stress Incontinence with Hypermobility (Type I, II)

• Pelvic floor muscle exercises, Bladder retraining

• Retropubic suspension procedures eg Colposuspension (open, lap)

• Needle suspension (Stamey, Ras)

• Sling operations - Fascial Pubovaginal, Prosthetic (TVT, Sparc, Intac)

Intrinsic Sphincter Deficiency (Type III)

• Bulking agents (Collagen, Macroplastique)

• Sling operations – Fascial, Pubovaginal, Prosthetic (TVT, Sparc, Intac)

• Artificial Urinary Sphincter


Mid-Urethral Slings

• Tension-free Trans-vaginal Tape (TVT) mid-urethral sling first described in 1996

• For female stress urinary incontinence due to urethral and bladder neck hypermobility and/or intrinsic sphincter deficiency

• Daycase or overnight stay, with return to normal activity in 3-4 weeks

• The “Gold-standard” for uncomplicated stress incontinence withcure in 89% (+/- 9%) and improved continence in additional 5% of patients.


Injectable soft-tissue urethral bulking agents are used for treating adult female stress urinary incontinence primarily due to intrinsic sphincter deficiency. They can also be used in men.

•Collagen

•Carbon coated

•Silicone coated

•Macroplastique ®• a rubber-like, silicone elastomer implant material (cross-linked polydimethylsiloxane) that is permanent and not absorbed by the body.

•Injected into position (combined with a water-soluble gel that is absorbed), leaving the microscopic silicone beads that cause the bulking effect around the urethra.

•Bulkamid


Penile Clamp

Advantages

• Non-medical, non-surgical

• Easy to use

• Works well

Disadvantages

• Bulky

• Pressure necrosis

• Generally not a turn on


This Sling creates gentle compression on the

urethra for urinary control

• Effective treatment for mild to

moderate incontinence

• Minimally invasive, 45± minute outpatient procedure

• Continence is immediately restored

• Nothing to operate

• Device is completely hidden inside the body

• 88% satisfaction rate

Stress Incontinence – InvanceTM Male Sling

The Advance sling restores urethra to its proper

anatomical position for optimal sphincter function,

compressing the urethra and restoring urinary control.

Procedure:

• Spinal or general anesthesiacan be used

• Three small incisions: 1 under the scrotum, 2 over groin creases

• Specially designed surgical toolsare used to position the sling

• Sling is gently tensioned

Stress Incontinence –AdvanceTM Male Sling

AMS 800 Artificial Urinary Sphincter

•Surgically implanted, fluid-filled, solid silicone prosthesis used to treat incontinence caused by intrinsic sphincter deficiency.

•The prosthesis simulates normal sphincter function by opening and closing under patient control.

•It is usually used in men following prostate cancer surgery, but can be used in women.

Stress Incontinence –Artificial Urinary Sphincter

Male Incontinence Severity Level Guidelines

Increasing elderly population• Frail, poor mobility

• More controlled cardiac disease (diuretics)

• More cancer survivors with continence problems as a result of treatment

Health budget is effectively capped, and continence problems do not have a high priority for funding.

Major advances eg Bladder transplants, artificial bladders

Urinary Incontinence – the Future

“Man survives earthquakes, epidemics, the horrors of disease, and all of the agonies of the soul.

But for all time he most tormenting tragedy is,

and will be,

the tragedy of the bedroom.”

Leo Tolstoy

Erectile Dysfunction can include:

• total inability to achieve an erection

• inconsistent ability to attain (situational or partner

specific, transitional)

• inability to maintain an erection to orgasm (not

premature ejaculation)

Sexual Dysfunction following Radical Prostatectomy

• Erectile Dysfunction• Anejaculation• Anorgasmia• Dysorgasmia (Painful Ejaculation)• Orgasm associated urinary leakage• Penile shortening• Penile fibrosis or curvature

Recovery of Erectile Function after Radical Prostatectomy

• Nerve-sparing techniques (unilateral or bilateral) are used routinely (when possible)

• Older patients are much less likely to recover sexual function• < 60 years - potency rates of 59-82%• > 60 years – potency rates of 36-57%

• Type of Radical Prostatectomy (open, laparoscopic or robotic) may influence initial recovery but at 6 months postop recovery rates are equivalent

• Early penile rehabilitation improves rates of recovery of spontaneous erections by 20%

Treatment Options

Sexual therapy/counselling

Oral medicationsPDE5 Inhibitors (Viagra®, Cialis®, Levitra®)(Apomorphine)

Vacuum erection devices

(Urethral suppositories) (Alprostadil or MUSE®)

Injection therapySingle agent (Prostaglandin E1 – Caverject Impulse®, Papaverine)Multi-agent (“Trimix”, “Promix”)

Penile Prosthesis Surgery

PDE-5 Inhibitors

The cyclic GMP/NO pathway is the final neurotransmitter responsible for penile erection in the vascular smooth muscle of the corpus cavernosum in the penis.

PDE5 inhibitors selectively block cGMP degradation, increasing the effect of Nitric Oxide.

PDE-5 Inhibitors

Successful treatment requires:

• patient education

• the right medication• short or long acting• intermittent or continuous dose

• correct dosing instructions to match the patients pattern of sexual activity and psychological needs

PDE-5 Inhibitors

• PDE5i medications need to be individually tailored to meet each patient’s needs.

• optimize effectiveness

• improve compliance

• reduce treatment failure

Cause of ED Placebo (%) Sildenafil (%)

Psychogenic 24 84

Mixed 27 77

Organic 19 68

Efficacy of PDE5 Inhibitors

PDE5 Inhibitors

Contraindications

Nitrate Medications

• Short acting sublingual/spray

• Long acting oral/topical

Cardiac disease

• Assess physical and cardiac fitness eg. stairs, stress testing

PDE5 Inhibitors

Side effects

• Headache 16%

• Flushing 10%

• Dyspepsia 7%

• Nasal congestion 4%

• Visual disturbances 3%

• Priapism 0%

• Death ?

Penile Injection Treatment

Injected directly into the corpora cavernosum of the penis causing arteriolar smooth muscle and increasing blood flow.

• PGE1 Alprostadil (Caverject Impulse®)• Papaverine• Phentolamine• “Trimix” – all 3

Results 70-90%Dropout rates 25-60%Side effects pain at injection site (36%)

fibrosispriapism (PGE1 - 0.25%, Trimix – 0.9%)

Vacuum Constriction Device

The penis is placed in plastic tube and air pumped out to create vacuum. Blood is trapped in the penis with a constriction ring

• Erection limited to 30 minutes

• Cheap (one-off cost of purchase)

• Must remove ring before ejaculation

• Results

• 50% success, but high drop out rate


• Surgical implantation of a device to produce a functional erection.

• It is usually seen as a “last resort” for patients who have tried and failed tablets, injections or a vacuum pumps, but may be considered as an option earlier, particularly in young men.

• Diabetics

• Pelvic (prostate and bowel) cancer surgery

• Severe vasculogenic disease

• Peyronie’s disease (improve erection and correct curve)


A Penile Prosthesis is a surgically implanted saline-filled silicone device used to treat Erectile Dysfunction in men.

It is used for patients who have tried and failed tablets, injections or pumps – it is the “last resort”.

Considered as an earlier option in • younger men • following pelvic cancer surgery • Diabetes Mellitus • severe vasculogenic disease• Peyronie’s disease

Penile Implant - One-Piece Non-Inflatable

Advantages

• Easy for patient or partner to activate

• Easier to use for men with limited dexterity

• Least expensive prosthesis

• Simplest surgical procedure

Disadvantages

• Stays firm when not in erect position

• May “show” through clothing

Penile Implant - Three–Piece Inflatable

Advantages

• Acts and feels more like a natural erection

• Feels softer and more flaccid when deflated

• Easier to “conceal”

• expands in girth (and length) on inflation

• Simple to use with one-step deflation

Disadvantages

• Surgical implantation

• Requires some manual dexterity

• Risk of infection, leakage, erosion

• Possibility of unintentional erections

Issues when considering a Penile Prosthesis

• Age, Lifestyle

• Coexisting medical conditions that may increase operative risk

• Hand function (to manipulate the scrotal pump)

• Cost, Insurance coverage

• Complications - there is a small risk of need for reoperation to fix problems (infection, erosion).


Advantages

• Full, immediate and dependable control over inflation and deflation

• High patient (92%) and partner (96%) satisfaction

• Sexual activity from 6 weeks postoperatively

• Low risk of serious side effects

• infection, erosion, mechanical failure <5% at 5 years

Disadvantages

• Implantation surgery required (2-3 nights in hospital)

• Complications (infection, erosion) require further surgery to remove prosthesis

• Non-reversible

• Cost – but fully rebatable through private health insurance

Results

Overall Patient Satisfaction with ED Treatments

0% 20% 40% 60% 80% 100%

Penile

Implant

Oral

Medication

Penile

Injection

Percent Satisfied

93%

51%

40%

0

10000

20000

30000

40000

50000

60000

0 years 5 years 10 years 15 years

Viagra x1/wk

Viagra x3/wk

Caverject x1/wk

Caverject x3/wk

Penile Prosthesis

Years of Treatment

Cost ($)

• Erectile Dysfunction is a common problem.

• It is not a medical disease but should be considered a normal consequence of physiological aging in most men. Some men develop ED due to medical problems (or as a consequence of our treatment).

• Men should be aware that ED treatment is available and that it may be able to restore erectile function.

• The assessment and treatment of ED requires time and sensitivity – not the “sniff and stiff” approach.

• Treatment is often not needed – just reassurance that there is no underlying problem.

• The simplest, safest and cheapest treatment options should be tried first (unless there are contra-indications).

• Penile Prosthesis surgery is available and offers a long-term solution for ED. In most men it is the treatment of “last resort” but should be considered earlier in some men (particularly young, diabetic or cancer survivors).

kyabram urology update 2015 - murray phn · the optimum treatment for oab is yet to be determined....

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