1. 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

2. 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.

3. 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?

4. Prostate Cancer- PSA testing
Digital Rectal Exam
Important
15% of cancers have abnormal DRE but “normal” PSA
PSA
Blood test
Can detect early Cancer

5. 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.
What we have attempted to show here is a balance between the potential benefits and harms or side effects of screening and early treatment.
On the benefits side, evidence appears strong that PSA screening leads to early detection of prostate cancer. There is evidence that treating PSA-detected prostate cancer may be effective in reducing the likelihood that patients will die from the disease, but other evidence makes this uncertain. PSA use may contribute to the decline in U.S. prostate cancer mortality, but the evidence is not consistent.
For harms or side effects, false positives are common. Overdiagnosis is a problem, but we are uncertain about the magnitude. Treatment-related side effects are fairly common.
The balance of potential benefits and possible side effects is uncertain. This uncertainty leads the clinician to ask the next question.
Need to discuss the individual benefits and risks
of screening with all male patients 50-70years.

6. Prostate Cancer- PSA testing
PSA Test: 3.0 ng/ml, F/T 9%, Normal DRE
Is this normal?
Age Median PSA Normal Range
ng/ml ng/ml
ng/ml ng/ml
ng/ml ng/ml
ng/ml ng/ml

7. Risk Of Prostate Cancer
Prostate Cancer- PSA testing Risk 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%

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

9. Prostate Cancer- PSA testing PSA 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.

10. Prostate Cancer- PSA testing Prostate 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.

11. Prostate Cancer-Options of Treatment Mr 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?

12. Prostate Cancer-Options of Treatment
Active Surveillance
Radical Prostatectomy
Seed Brachytherapy
External Beam Radiotherapy
HIFU (High Intensity Focused Ultrasound)

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

14. Prostate Cancer-Options of Treatment Active 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

15. Pros and Cons of Active Surveillance
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.

16. A Biopsy At 6 Months Is Very Predictive Of Cancer Growth.
Log Rank Test p=0.002
2nd Biopsy -ve
2nd Biopsy +ve
Patel et.al. J Urol. 2004;171(4):1520

17. Prostate Cancer-Options of Treatment Radical Prostatectomy

18. Feet
Prostate
(R) Cavernous |nerve
Head

19. Recovery of Erections after RP By Extent of Preservation of Neurovascular Bundles

20. Sural Nerve Grafts- For patients Undergoing NVB Resection
Undergoes radical prostatectomy with unilateral neurovascular bundle resection
Also has sural nerve graft placed

21. Recovery of Potency for Unilateral Resection with Nerve Graft compared to No Nerve Graft
Unilateral nerve graft n=45
No nerve graft n=17
As there are no patients who had normal potency preoperative, who underwent unilateral NVB resection without NG in our cohort, we compared ou published historical series of unilateral resection without NG to our present series of patients with resection and NG, using the previously validated interview scale of potency.
Potency grade 1 or 2 correlated to IIEF 17 or greater.
You can see that althoug statisitical significance was not reached because of small numbers there does appear to be a difference, which is more marked when the definition of potency is relaxed to include grade 3 as well.
Patel et.al. AUA 2003

22. Pros and Cons of Surgery
Excellent cancer control
Evaluate the lymph nodes
Accurate prognosis
Radiotherapy possible after surgery
Cons
Recovery 2-3 weeks
Major Surgery
Possible incontinence
Possible impotence

23. Prostate Cancer-Options of Treatment Seed Brachytherapy
Prostate Outline
Rectum
Urethra

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

25. Pros and Cons of Brachytherapy
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

26. Prostate Cancer-Options of Treatment External Beam Radiotherapy
Machine
Target
DRR Image (AP)

27. External Beam Radiotherapy
Toxicity
Urinary
Frequency/Urgency
Retention/Stricture
Bleeding
Rectal
Same
Impotence
L/T same as surgery (bilateral nerve sparing)

28. Pros and Cons of Radiotherapy
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

29. 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.

30. 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.

31. 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.

32. Case 2
Mr AB
72 year old HT
Coronary stents
PSA 15.2ng/ml
Rectal exam: large hard right sided nodule.

33. Case 2
Prostate Biopsy:
Gleason 4+4
6/12 cores involved

34. Following Diagnosis- Need to Be Staged.
A CT Scan Will detect metastases to the lymph nodes.
Stage T1 (also known as Stage A)
a small tumor that is confined to the prostate, (not detected during a digital rectal exam)
this stage of prostate cancer usually produces no symptoms
treatment may involve observation, surgery to remove the prostate or radiation
Stage T2 (also known as Stage B)
the tumor is confined to the prostate gland but may be detected during digital rectal exam
possible symptoms may include a need to urinate frequently, especially at night
treatment may involve surgery or radiation, possibly combined with hormone therapy (to shrink the tumor)
Stage T3 (also known as Stage C)
the tumor has begun to spread beyond the prostate to areas surrounding the gland
treatment may involve radiation combined with hormone therapy, or for some patients surgery to remove the prostate.
Stage T4 (also known as Stage D1)
the tumor has spread beyond the prostate into surrounding structures including the pelvic lymph nodes (N+)
possible symptoms may include a need to urinate frequently, painful, obstructed urine flow (blood may appear in urine), and fatigue
treatment may involve hormone therapy, possibly with radiation to ease symptoms
Stage M+ (also known as Stage D2) When cancer has spread beyond the prostate it is said to have metastasized. Cancer may spread to distant sites such as bone, liver or lung via the lymphatics system and the blood supply. Cancer that has reached this stage may produce symptoms such as difficult or painful urination, obstructed urine flow, pain if the cancer has spread to the bone, and fatigue. Treatment for this stage of cancer is aimed at easing symptoms and slowing the progression of the disease. This usually includes hormone therapy.
A Bones Scan will detect cancer in the bones

35. Treatment Options Watchful Waiting XRT plus Hormone therapy
HDR Brachytherapy plus Hormone Therapy
Radical Prostatectomy

36. Prostate Cancer-Options of Treatment Need Adjuvant Androgen Deprivation Therapy For High Risk Disease.
Hot flushes
Lethargy
Depression/mood swings
Weight gain
Anaemia
Osteoporosis
Impotence
Muscle loss

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

38. External Beam Radiotherapy
On the left is a dose distribution diagram for 3D conformal radiotherapy (3D-CRT), with the highest doses in red. On the right the dose distribution has been modified by intensity modulation (IMRT). There is less exposure to radiation of the anterior rectal wall and of the surrounding tissue with IMRT.
From Liebel and Fuks. MSKCC, 2000

39. Prostate Cancer-Options of Treatment High Dose Rate Brachytherapy.
Increases dose to the prostate locally
For high risk disease

40. 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

41. Pros and Cons Of Prostate Cancer Treatments
Cancer Cure
Side Effects
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
External Beam Radiotherapy
Moderate cure rate
Same as above
HDR Brachytherapy
Effective for high risk disease
Severe urinary SE
HIFU
Possibly equivalent to XRT.
Minimally invasive
Multiple treatments
Irritative urinay SE

42. 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.