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New Developments In The Management of Prostate Cancer

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Presentation on theme: "New Developments In The Management of Prostate Cancer"— Presentation transcript:

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 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 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 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.

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