New Developments In The Management of Prostate Cancer

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 CancersAgenda • 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. 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 Screening PotentialBenefits PotentialHarms 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 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

7. Prostate Cancer- PSA testingRisk of Prostate Cancer in Men with Normal DRE

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

9. Prostate Cancer- PSA testingPSA 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 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.

11. Prostate Cancer-Options of TreatmentMr 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. 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.

14. 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

15. 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.

16. A Biopsy At 6 Months Is Very PredictiveOf 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 TreatmentRadical 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 Patel et.al. AUA 2003

22. 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 Pros and Cons of Surgery

23. Prostate Cancer-Options of TreatmentSeed Brachytherapy Prostate Outline Rectum Urethra

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

25. 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. • 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. DRR Image (AP) Machine Prostate Cancer-Options of TreatmentExternal Beam Radiotherapy Target

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

30. 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. HIFU

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. 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 TreatmentNeed 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 From Liebel and Fuks. MSKCC, 2000

39. Prostate Cancer-Options of TreatmentHigh 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

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.