New Developments In The New Developments In The Management of Prostate CancerManagement of Prostate Cancer

Dr. Manish Patel Dr. Manish Patel

Urological Cancer SurgeonUrological Cancer Surgeon Westmead Public and Private HospitalWestmead Public and Private Hospital

Sydney Adventist HospitalSydney Adventist HospitalSenior Lecturer, University of SydneySenior Lecturer, University of Sydney

New Developments In The New Developments In The Management of Urological CancersManagement of Urological Cancers

AgendaAgenda• Prostate Cancer- PSA testing

– Controversy on screening.

• Prostate Cancer- New developments in treatment.– Pros and cons of each treatment.

Prostate Cancer- PSA testingProstate 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?

Prostate Cancer- PSA testingProstate Cancer- PSA testing• Digital Rectal Exam

– Important

– 15% of cancers have abnormal DRE but “normal” PSA

• PSA– Blood test

– Can detect early Cancer

Potential Benefits

Prostate Cancer Screening

Potential Harms

Need to discuss the individual benefits and risksof screening with all male patients 50-70years.

• PSA screening detects cancers earlier.

• Treating early CaP does improve survival.

• Not shown to improve survival yet.

• False positives are common.• It is possible to miss a cancer• Indolent cancers are treated

inadvertantly

Prostate Cancer- PSA testingProstate Cancer- PSA testing

PSA Test: 3.0 ng/ml, F/T 9%, Normal DRE

Is this normal?AgeAge Median PSAMedian PSA Normal RangeNormal 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

Prostate Cancer- PSA testingProstate Cancer- PSA testingRisk of Prostate Cancer in Men with Normal DRERisk 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%

Prostate Cancer- PSA testingProstate Cancer- PSA testing Free to Total (%) Does Help Specificity.

Prostate Cancer- PSA testingProstate Cancer- PSA testingPSA Velocity is important to calculatePSA Velocity is important to calculate

• Men with PSA below 4.0ng/ml– PSA velocity > 10%/yr =30% risk CaP– PSA velocity >0.5ng/ml/yr = 45% risk CaP– PSA velocity >2.0ng/ml/yr = high risk of death– More accurate with multiple measures over time.

1.5

2

2.5

3

3.5

Jan-05 Jul-05 Jan-06

Patient 1Patient 2Patient 3

Prostate Cancer- PSA testingProstate Cancer- PSA testingProstate Biopsy With Local Anaesthetic BlockProstate 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.

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

• Biopsy results:• Gleason Score 3+3=6• In 2/12 cores involving 25%-50% of the cores.

• Treatment Decisions Depend On:– Patient’s normal life expectancy

– Aggressiveness of cancer

– Cure rates of individual treatments

– Tolerability of side effects.

• What Are His Options Of Treatment?

Prostate Cancer-Options of TreatmentProstate Cancer-Options of Treatment

• Active Surveillance

• Radical Prostatectomy

• Seed Brachytherapy

• External Beam Radiotherapy

• HIFU (High Intensity Focused Ultrasound)

Indolent Cancer• A cancer that is small and low

grade and unlikely to grow in the man’s lifetime.

• Incidence of indolent cancers is increasing (>30%).

• Mr J.B. Could have active surveillance.

Prostate Cancer-Options of TreatmentProstate Cancer-Options of TreatmentActive SurveillanceActive 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

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.

A Biopsy At 6 Months Is Very Predictive

Of Cancer Growth.

Months

140120100806040200

Fre

edom

Fro

m P

rogre

ssio

n

1.0

.8

.6

.4

.2

0.0

2nd Biopsy -ve

Log Rank Test p=0.002

2nd Biopsy +ve

Patel et.al. J Urol. 2004;171(4):1520

Prostate Cancer-Options of TreatmentProstate Cancer-Options of Treatment Radical Prostatectomy

(R) Cavernous(R) Cavernous|nerve|nerve

ProstateProstate

FeetFeet

HeadHead

Recovery of Erections after RP By Extent of Preservation of Neurovascular

Bundles

Sural Nerve Grafts- For patients Undergoing NVB Resection

Undergoes radical prostatectomy with unilateral neurovascular bundle resection

Also has sural nerve graft placed

Recovery of Potency for Unilateral Resection with Nerve Graft compared to No Nerve Graft

Months

60483624120

Pro

po

rtio

n P

atie

nts

Re

cove

rin

g E

rect

ile F

un

ctio

n 1.0

.8

.6

.4

.2

0.0

Unilateral nerve graft n=45

No nerve graft n=17

Patel et.al. AUA 2003

Pros and Cons of SurgeryPros 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

Prostate Outline

UrethraRectum

Prostate Cancer-Options of TreatmentProstate Cancer-Options of TreatmentSeed BrachytherapySeed Brachytherapy

Brachytherapy (seed)• Toxicity

– Urinary• Frequency/Urgency• Retention• Bleeding

– Rectal• Same

– Impotence• L/T same as surgery (bilateral nerve sparing)

Pros and Cons of BrachytherapyPros• 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.• Won’t know prognosis for 1-2

years• L/T impotence same as surgery• Significant rectal and urinary

side effects.• Unable to have surgery after

Prostate Cancer-Options of TreatmentProstate Cancer-Options of Treatment External Beam Radiotherapy

DRR Image (AP)

MachineTarget

External Beam Radiotherapy• Toxicity

– Urinary• Frequency/Urgency• Retention/Stricture• Bleeding

– Rectal• Same

– Impotence• L/T same as surgery (bilateral nerve sparing)

Pros and Cons of RadiotherapyPros• Not major surgery• Initially potency

preserved

Cons• 7 weeks treatment• Won’t know prognosis

for 1-2 years• L/T impotence same as

surgery• Significant rectal and

urinary side effects.• Unable to have surgery

after

Prostate Cancer-Options of TreatmentProstate 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.

HIFUAdvantages• 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.

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.

Case 2

• Mr AB

• 72 year old

• HT

• Coronary stents

• PSA 15.2ng/ml

• Rectal exam: large hard right sided nodule.

Case 2

• Prostate Biopsy:

• Gleason 4+4

• 6/12 cores involved

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

Treatment OptionsTreatment Options

• Watchful Waiting

• XRT plus Hormone therapy

• HDR Brachytherapy plus Hormone Therapy

• Radical Prostatectomy

Prostate Cancer-Options of TreatmentProstate Cancer-Options of TreatmentNeed Adjuvant Androgen Deprivation Therapy Need Adjuvant Androgen Deprivation Therapy

For High Risk Disease.For High Risk Disease.

• Hot flushes

• Lethargy

• Depression/mood swings

• Weight gain

• Anaemia

• Osteoporosis

• Impotence

• Muscle loss

Dose of Radiotherapy is very important in Intermediate and high risk cancer.

External Beam RadiotherapyExternal Beam Radiotherapy

From Liebel and Fuks. MSKCC, 2000From Liebel and Fuks. MSKCC, 2000

Prostate Cancer-Options of TreatmentProstate Cancer-Options of TreatmentHigh Dose Rate Brachytherapy.High Dose Rate Brachytherapy.

Increases dose to the prostate locallyFor high risk disease

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

Pros and Cons Of Prostate Cancer Treatments

Cancer CureSide Effects

Pros Cons

Radical Prostatectomy

Highest Cure RateCancer removedLymph nodes treatedSalvage XRT

Recovery timeIncontinenceED

Robotic Prostatectomy

Lower than open operation.

Earlier discharge Worse incontinence

BrachytherapyOnly effective in low risk disease

Early recoverySevere urinary and rectal SEED

External Beam Radiotherapy

Moderate cure rate Same as above

HDR Brachytherapy

Effective for high risk disease

Severe urinary SEED

HIFUHIFUPossibly equivalent to XRT.

Minimally invasiveMultiple treatments

Irritative urinay SE

SummarySummary

• Age specific PSA is Important but PSA velocity Age specific PSA is Important but PSA velocity and F/T ratio are important when PSAs are low.and F/T ratio are important when PSAs are low.– Have a low threshold to referHave a low threshold to refer..

• Treatment decisions for prostate cancer depend onTreatment decisions for prostate cancer depend on– likely threat of the cancer to lifelikely threat of the cancer to life– cure rate achieved by the treatmentcure rate achieved by the treatment– side-effect profile.side-effect profile.