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Queens University Q Prostate D. Robert Siemens, M.D.

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Presentation on theme: "Queens University Q Prostate D. Robert Siemens, M.D."— Presentation transcript:

1 Queens University Q Prostate D. Robert Siemens, M.D.

2 GU Oncology l Prostate Cancer – 20,700 cases, 4200 deaths (2006, CCS) l Bladder Cancer – 6400 cases, 1700 deaths l Kidney Cancer – 4600 cases, 1550 deaths l Testes – 840 cases, 30 deaths

3 Web Resources l s.html l l l

4 Objectives l To be able to state the two components that can cause bladder obstruction in benign prostatic hyperplasia l To be able to state 3 management options for early prostate cancer l To understand the importance of the grading of prostate cancer

5 Prostate Diseases l Benign Prostatic Hyperplasia (BPH) l Prostate Cancer l Prostatitis

6 BPH l Prostate size increases with age l Total prostate volume increases from approximately 25 mL for a man in his 30s to 35– 45 mL for a man in his 70s l Increased cell numbers – Balance between cell proliferation and impaired apoptosis

7 BPH l Hyperplasia of epithelial (glandular) or stromal (smooth muscle) components l Commonly cause lower urinary tract symptoms in men (over 50) – Relative obstruction of bladder




11 BPH Risk Factors l Male l Aging l Androgens (testosterone, DHT) l Androgen receptor l Intraprostatic 5 alpha reductase l Estrogens l Apoptosis regulation l Stromal-epithelial interactions l Growth Factors – bFGF, KGF, EGF, TGF-beta, IGF

12 StaticDynamic Increased muscle tone BPH Components

13 Lower Urinary Tract Symptoms (LUTS) Obstructive (voiding) Irritative (filling) Weak stream Hesitancy Sensation of incomplete emptying Intermittent stream Prolonged urination Frequency Nocturia Urgency Urge incontinence

14 Differential Diagnosis Phimosis Vesicosphincter dyssynergia Bladder cancer Stenosis of urinary meatus Urethritis Urethral carcinoma Hypertrophy or stenosis of bladder neck Cystolithiasis Neurogenic Myogenic Cystitis Bladder dysfunction (diabetes) Polyuria Extrinsic pelvic mass BPH Prostate Cancer Urethral stricture (Ouslander JG. Am J Med Sci 1997;314(4):214-8; Kasraeian A.; other references upon request)

15 -Blockers: Mode of Action -Blockers: Mode of Action l Relaxes prostate and bladder neck smooth-muscle tone

16 5 -Reductase Inhibitors Block conversion of testosterone to dihydrotestosterone (DHT) within the prostate

17 Transurethral Resection of Prostate (TURP) Resectoscope Bladder Prostate Removal of Hypertrophied Tissue

18 Prostate Cancer is Common! l 13% lifetime risk of prostate cancer l 3% lifetime risk of dying of prostate cancer

19 Prostate Cancer is Common! l Most common cancer in men (27%) l 18,200 new cases in 2002 l 4316 deaths in 2002 l 1 death every 13 minutes

20 Roberts 99 Prostate Cancer Incidence

21 Risk factors? l Male l Testosterone l Age l Others….. – family history, race, diet etc

22 Family History in Prostate Cancer l First degree relative affected ? – NoRR= 1 x – YesRR= 2-3 x – Diagnosed <65RR= 6 x – 3 relativesRR= 11 x

23 GENETICS l HPC1 l CAG repeats l SDR5A2

24 VITAMIN E l Antioxidant l Plant derived oils l Induces cell cycle arrest in PC-3, LNCaP l ATBC trial – 1/3 rd reduced incidence @ 4 yrs – 41% reduced mortality @ 6 years

25 SELENIUM l Inconsistent dietary intake l Antioxidant l Induces cell cycle arrest in LNCaP l Clarke 1312 men with NMSC – 200 micrograms selenium as Brewers yeast – 69 % reduced incidence of CaP

26 SOY l Japanese paradox l Isoflavones : Genistein / Daidzein – Phytoestrogens – Tyrosine kinase inhibition – Induce apoptosis in PC-3 / LNCaP

27 Diagnosis l Digital rectal examination l PSA – Serine protease secreted into lumen of prostate glands – Liquefies semen – Elevated in BPH, prostate cancer, prostatitis l PSA test characteristics – PSA 4-10 … cancer risk ~25% – PSA >10 … cancer risk ~50-60%

28 Prostate Cancer Stage T1 incidental T1a, T1b, T1c T2 confined T2a, T2b, T2c T3 locally invasive T3a, T3b, T3c T4 fixation T4a, T4b



31 Organ Confined Disease Treatment Options l Radical Surgery l Radiation (ext beam and brachytherapy) l Watchful Waiting



34 Advanced Prostate Cancer

35 Management of Advanced Prostate Cancer l Use hormonal therapy to control progressive or metastatic disease

36 Charles Huggins 1901-1998 l Awarded Nobel Prize in 1966 l Only Canadian-born doctor to win the Nobel Prize in Physiology or Medicine

37 Castration l Decrease prostate volume l Primary tumor shrinks (30-40%) l Metastatic deposits decrease (40-80%) and disappear (5-10%)

38 Surgical Castration l Immediate and complete castrate levels (0.2 ng/ml) l Adrenal androgens (5-10%) $1940

39 Medical Castration l LH-RH agonists – suppression after initial flare of LH and T – castrate levels of T (0.2-0.5 ng/ml) in 9 days to 4 weeks – need to treat flare with antiandrogen

40 Medical Castration l LH-RH agonists – goserelin (Zoladex ® ), leuprolide (Lupron ® ), buserelin (Suprefact ® ) – depot injections 1 to 3-4 months $4500-8000/year

41 Adverse Effects l Castration – loss of libido and potency (>75%) – hot flashes (50-60%) – sweating (10%) – painful gynecomastia (~1-2%) – osteoporosis (5% fracture) – cardiovascular effects – weight gain, loss of muscle mass

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