New Developments In The Management of Prostate Cancer

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New Developments In The Management of Prostate
Cancer

• Dr. Manish Patel
• Urological Cancer Surgeon
• Westmead Public and Private Hospital
• Sydney Adventist Hospital
• Senior Lecturer, University of Sydney

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New Developments In The Management of Urological
Cancers Agenda

• Prostate Cancer- PSA testing
• Controversy on screening.
• Prostate Cancer- New developments in treatment.
• Pros and cons of each treatment.

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Prostate Cancer- PSA testing

• Mr J.B. 51 year old.
• Mild LUTS
• Hypertension
• Asks his G.P. for a test for prostate cancer?
• What should the G.P discuss with him?

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Prostate Cancer- PSA testing

• Digital Rectal Exam
• Important
• 15 of cancers have abnormal DRE but normal PSA
• PSA
• Blood test
• Can detect early Cancer

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Prostate Cancer Screening
Potential Benefits
Potential Harms

• Not shown to improve survival yet.
• False positives are common.
• It is possible to miss a cancer
• Indolent cancers are treated inadvertantly

• PSA screening detects cancers earlier.
• Treating early CaP does improve survival.

Need to discuss the individual benefits and
risks of screening with all male patients
50-70years.
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Prostate Cancer- PSA testing

• PSA Test 3.0 ng/ml, F/T 9, Normal DRE
• Is this normal?

Age Median PSA Normal Range 40-49 0.7ng/ml 0
-2.5ng/ml 50-59 0.9ng/ml 0-3.5ng/ml 60-69 1
.2ng/ml 0-4.5ng/ml 70 1.4ng/ml 0-6.5ng/ml
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Prostate Cancer- PSA testingRisk of Prostate
Cancer in Men with Normal DRE
PSA Levels Risk Of Prostate Cancer
1-1.99 17
2-2.99 24
3-3.99 27
4-10 29
10 45
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Prostate Cancer- PSA testing Free to Total ()
Does Help Specificity.
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Prostate Cancer- PSA testingPSA Velocity is
important to calculate

• Men with PSA below 4.0ng/ml
• PSA velocity gt 10/yr 30 risk CaP
• PSA velocity gt0.5ng/ml/yr 45 risk CaP
• PSA velocity gt2.0ng/ml/yr high risk of death
• More accurate with multiple measures over time.

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Prostate Cancer- PSA testingProstate Biopsy With
Local Anaesthetic Block

• Mr J.B.s risk of cancer is approx 50.
• Chooses to have a prostate biopsy
• Very well tolerated under local anaesthetic.
• Pudendal nerve block.

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Prostate Cancer-Options of TreatmentMr J.B. Has
Prostate Cancer

• Biopsy results
• Gleason Score 336
• In 2/12 cores involving 25-50 of the cores.
• Treatment Decisions Depend On
• Patients normal life expectancy
• Aggressiveness of cancer
• Cure rates of individual treatments
• Tolerability of side effects.
• What Are His Options Of Treatment?

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Prostate Cancer-Options of Treatment

• Active Surveillance
• Radical Prostatectomy
• Seed Brachytherapy
• External Beam Radiotherapy
• HIFU (High Intensity Focused Ultrasound)

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Indolent Cancer

• A cancer that is small and low grade and unlikely
  to grow in the mans lifetime.
• Incidence of indolent cancers is increasing
  (gt30).
• Mr J.B. Could have active surveillance.

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Prostate Cancer-Options of TreatmentActive
Surveillance

• Treatment for small low grade cancers with low
  biological potential.
• Very close monitoring 3 monthly
• PSA
• DRE
• Biopsy at 6 months, 18 months and 2 yearly after.
• Treat curatively if any sign of cancer growth.
• Patel et.al J Urol 2004

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Pros and Cons of Active Surveillance

• Pros
• No major procedure
• No side effects of treatment

• Cons
• Anxiety will lead to treatment in 15
• 50 will progress over 10 years
• Although no side effects not likely to improve
  overall quality of life.

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A Biopsy At 6 Months Is Very PredictiveOf Cancer
Growth.
Log Rank Test p0.002
2nd Biopsy -ve
2nd Biopsy ve
Patel et.al. J Urol. 2004171(4)1520
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Prostate Cancer-Options of Treatment Radical
Prostatectomy
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Feet
Prostate
(R) Cavernousnerve
Head
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Recovery of Erections after RP By Extent of
Preservation of Neurovascular Bundles
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Sural Nerve Grafts- For patients Undergoing NVB
Resection
Undergoes radical prostatectomy with unilateral
neurovascular bundle resection
Also has sural nerve graft placed
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Recovery of Potency for Unilateral Resection with
Nerve Graft compared to No Nerve Graft
Unilateral nerve graft n45
No nerve graft n17
Patel et.al. AUA 2003
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Pros and Cons of Surgery

• Pros
• Excellent cancer control
• Evaluate the lymph nodes
• Accurate prognosis
• Radiotherapy possible after surgery

• Cons
• Recovery 2-3 weeks
• Major Surgery
• Possible incontinence
• Possible impotence

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Prostate Cancer-Options of TreatmentSeed
Brachytherapy
Prostate Outline
Rectum
Urethra
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Brachytherapy (seed)

• Toxicity
• Urinary
• Frequency/Urgency
• Retention
• Bleeding
• Rectal
• Same
• Impotence
• L/T same as surgery (bilateral nerve sparing)

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Pros and Cons of Brachytherapy

• Pros
• Not a major procedure
• Quick recovery
• Initially potency preserved

• Cons
• Only controls low risk disease
• L/T outcomes not known thus hesitate in young
  patients.
• Wont know prognosis for 1-2 years
• L/T impotence same as surgery
• Significant rectal and urinary side effects.
• Unable to have surgery after

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Machine
Prostate Cancer-Options of Treatment External
Beam Radiotherapy
Target
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External Beam Radiotherapy

• Toxicity
• Urinary
• Frequency/Urgency
• Retention/Stricture
• Bleeding
• Rectal
• Same
• Impotence
• L/T same as surgery (bilateral nerve sparing)

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Pros and Cons of Radiotherapy

• Pros
• Not major surgery
• Initially potency preserved

• Cons
• 7 weeks treatment
• Wont know prognosis for 1-2 years
• L/T impotence same as surgery
• Significant rectal and urinary side effects.
• Unable to have surgery after

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Prostate Cancer-Options of Treatment New
Treatments- HIFU

• Minimally invasive
• US focused in the prostate causes coagulative
  necrosis
• Temporary catheter for 2 weeks.
• Experimental, but recent results are encouraging.

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HIFU

• Advantages
• Minimally invasive
• Relieves obstructive symptoms
• Early cancer cure appears similar to XRT
• Treatment is repeatable
• Possible to have surgery afterwards.
• 90 potency

• Disadvantages
• New technology- L/T results unknown.
• Expensive
• Limited to small prostates and Gleason 7 or less.

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Mr J.B

• Chose radical prostatectomy
• Continent after 2 weeks.
• Started penile rehabilitiation at 6 weeks
• Potent at 4 months.
• PSA recurrence free so far.

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Case 2

• Mr AB
• 72 year old
• HT
• Coronary stents
• PSA 15.2ng/ml
• Rectal exam large hard right sided nodule.

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Case 2

• Prostate Biopsy
• Gleason 44
• 6/12 cores involved

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Following Diagnosis- Need to Be Staged.

• A CT Scan Will detect metastases to the lymph
  nodes.

A Bones Scan will detect cancer in the bones
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Treatment Options

• Watchful Waiting
• XRT plus Hormone therapy
• HDR Brachytherapy plus Hormone Therapy
• Radical Prostatectomy

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Prostate Cancer-Options of TreatmentNeed
Adjuvant Androgen Deprivation Therapy For High
Risk Disease.

• Hot flushes
• Lethargy
• Depression/mood swings
• Weight gain
• Anaemia
• Osteoporosis
• Impotence
• Muscle loss

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Dose of Radiotherapy is very important in
Intermediate and high risk cancer.
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External Beam Radiotherapy
From Liebel and Fuks. MSKCC, 2000
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Prostate Cancer-Options of TreatmentHigh Dose
Rate Brachytherapy.
Increases dose to the prostate locally For high
risk disease
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HDR Brachytherapy Boost

• Used for high risk prostate cancers
• Used in conjunction with hormones and external
  beam radiotherapy
• Advantages
• Higher radiation dose
• Theoretically better cancer result
• Disadvantages
• Much higher urinary side effects
• No Long term studies

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Pros and Cons Of Prostate Cancer Treatments
Cancer Cure Side Effects Side Effects
Cancer Cure Pros Cons
Radical Prostatectomy Highest Cure Rate Cancer removed Lymph nodes treated Salvage XRT Recovery time Incontinence ED
Robotic Prostatectomy Lower than open operation. Earlier discharge Worse incontinence
Brachytherapy Only effective in low risk disease Early recovery Severe urinary and rectal SE ED
External Beam Radiotherapy Moderate cure rate Same as above
HDR Brachytherapy Effective for high risk disease Severe urinary SE ED
HIFU Possibly equivalent to XRT. Minimally invasive Multiple treatments Irritative urinay SE
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Summary

• Age specific PSA is Important but PSA velocity
  and F/T ratio are important when PSAs are low.
• Have a low threshold to refer.
• Treatment decisions for prostate cancer depend on
• likely threat of the cancer to life
• cure rate achieved by the treatment
• side-effect profile.