Raymond Paul-Blanc, MD AMHE 2010 Château Montebello, Québec, Canada

-Dynamic state that includes  Advancement  Improvement  Adoption of New Methods and Insights  Purpose: Benefit of Mankind

A) Socioeconomics B) Education burden from patient (cultural, emotional) C)Education burden from provider( persistence of old habits and limited or absence of “esprit critique”)

NIH (2007) Reports Urology Care costs $11 Billion  UTIs 3.5 B  Kidney stones 2.1 B  Prostate Cancer 1.3 B  Bladder Cancer 1.1 B  Kidney Cancer 401 M  BPH 84 M  ED 328 M  Interstitial Cystitis 66M

1) PROSTATE CANCER 2) ERECTILE DYSFUNCTION 3) TESTOSTERONE REPLACEMENT 4) EJACULATORY DISORDERS

192,000 new cases (NIH,2009) 23,000 deaths, decreasing from 30,000 in the 1980s (NIH, 2009)  Impact of nutrition: fat, soy, pomegranate, herbs, exercise  Impact of chemoprevention finasteride PCPT study (2006) dutasteride REDUCE study (2009)

DRE+PSA+PCA-3 NIH Mathematical Formula -Age -Race -Family Hx- -PSA -DRE -Prior prostate biopsy

DRE +PSA as screening vs control group F/U 7-10 yrs mortality from prostate cancer not different from case control. 50 deaths vs. 40 deaths.

182,000 men started in PSA screening only vs. case control Conclusion: Mortality decreased by 20 % with risk of overdiagnosis

PSA: ( Free/Total) PSA Velocity PSA Density PCA-3 (urine)Crawford- Colorado EPCA-2( serum)(Partin-Hopkins)  DOGS Detection of VOC (Volatile organic compound) (Cornu, Paris 2009) 66 pts Sens 100%, spec 96%

Complimentary Alternative Medicine for Prostate Cancer Low-Risk Prostate Cancer Patients Weight reduction (aerobic) Low fat diet Fresh vegetables Fish oils 2-4 cups of green tea Vitamin E Selenium Lycopene Soy supplementation Vitamin D

Raised BMI index is associated with increase in cancers, heart diseases, DM, and deaths Prostate Cancer higher BMIs have:  Diagnosed with lower PSAs  Higher positive margins  Have independent higher reoccurrence

50,ooo men at Harvard School of Public Health suggested that vitamin D may reduce the risk of all cancers by at least 30 % - Giovannucci. J Natl Cancer Inst Apr 5:98 (7): 428 Increased cancer mortality associated with decreased sunlight.- including the following cancers: breast, colon, cancer, prostate, bladder, esophagus, kidney, lung, pancreas, rectum, stomach, non- Hodgkin’s Lymphoma - Grant. Cancer. 2002; 94 (6):1867

Vitamin D deficiency may underlie the major Risk factors for prostate cancer (rage, black race, and northern climate) Prostate cancer in the US are inversely related with ultraviolet radiation. Schwartz, GG, Hulka BS. Anticancer Res Sept- Oct ; 10 (5A) :

Pomegranate and Prostate Cancer

69-75% growth inhabitation of PC3 Delayed progression into S phase Low levels of apoptosis In vivo studies in SCID mice show : 52% growth inhibition of LAPC-9 tumors 70% reduction in PSA Prolonged survival -A. Katz, Columbia University 2010

Genistein and Daidzein are active metabolites - Genistein has shown to reduced DNA synthesis in LNCaP cells and inhibit the effect of testosterone in development of CaP in rats (Geller et al. Prostate, 34:75, 1998) A reduction of prostate cancer is associated with consumption of soy milk in the Adventist Health Study 1997

Chick peas, soy, navy beans, lentils Legumes Intake should include mg /day in Asian, African, and Mediterranean diets 1-3 mg/day in Western Diets

Criteria: Low grade disease -PSA <10 PSA density <0.15 Gleason Score 6 <2/3 cores No more than 50 % involvement in each core Should repeat prostate biopsy in 1 year

 Robotic  Open  XRT Brachytherapy  Cryoablation  HIFU? Outcome at 5 years similar

Robotics: costs 2.3 million per machine, needs 150 cases per year for surgical expertise Will need 250 robotic cases to pay for machine No large difference in outcome when compared to open prostatectomy

- Partin Table PSA-Gleason -Low Testosterone -Obesity -Diabetes (Co-factor) -Smoking -Economical Status

Nat’l Health and Social Life Survey (2008) total 1410 men (18-59 yrs old) PE- 31 % ED-10% Results show increase in anxiety, distress, interpersonal difficulty, and loss of sexual satisfaction

A) PDE-5 inhibitors- Viagra, Cialis, Levitra B) SSRI – Prozac, Zoloft C) Combination of above D) Topical Aerosol (Lidocaine, Prilocaine)

What’s New in Erectile Dysfunction? Endothelial Disease Coronary Artery 3mm Penile Artery 1mm Mayo Clinic Proceedings: “40-49 year old men with E.D. twice as likely to develop E.D.”

Desire Libido (testosterone) Erection Quality (sustainability/rigidity) Ejaculation (timely/powerful) testosterone Partner Satisfaction

Loss of N.E. related to: Testosterone Sleeping Disorders Surgery Atherosclerosis

Flaccid Penis: O2 tension mm Hg Erect Penis: O2 tension mm Hg Free O2: Nitric Oxide Synthesis (NO) NO + Guanylate Cyclase GTP to GMP (active vasodilatation) Lack of O2: Collagen Formation Fibrosis Restoring N.E. = Restoring O2 Restoring Erection

V.E.D. : daily 5-10 minutes. Increases girth/length? Low-Dose PDE5 H/S (Viagra, Cialis, Levitra, etc.) Self-Injection Program(3 P’s Solution) Topical Application (MUSE- Prostagladin)

Provider more aware of T.D. 25% Depression 25% Diabetes Natural Decline (Andropause)

Huggins and Hodges Articles Conclusion: Testosterone administration caused and “enhanced” growth of Prostate Cancer. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res Huggins CHuggins C, Hodges CV.Hodges CV

31 patients who received TRT after Brachytherapy all maintained a PSA less than 1.0 ng/mL with a median follow-up of 5 years. Meta-Analysis from eighteen prospective studies involving 3,886 men with prostate cancer and 6,438 controls showed no association between circulating levels of testosterone and estrogen and incidence of prostate cancer. JNCI 2/2008

Study involved 272 patients with prostate cancer who underwent radical prostatectomy, 49 patients who were found to have a testosterone less than 300 ng/dl did worse than patients with normal testosterone. ( Euro Urology 9/07) Testosterone and PSA-PSA did not rise above baseline during the testosterone “flare” in men with metastatic prostate cancer treated with LH-RH agonists. (NJM 1989; JU 2001). In hypogondal men. TRT results in only modest results in prostate size, approximately 15% for PSA and prostate volume increasing to match eugonadal men. But rising no higher. (NJM 2004)

Low Testosterone and Prostate Cancer Possible Increased Risk Possible Higher Grade Disease Possible Higher-Stage at Presentation Possible Worse Prognosis (Jama 2006; J. Urol 200; AJ Clin 1997)

The current data with TRT following prostate cancer treatment is changing; further data will provide clarity and will hopefully lead to new guidelines. Raymond Paul-Blanc, M.D.