PROGRESS IN UROLOGY

Raymond Paul-Blanc, MDAMHE 2010

Château Montebello, Québec, Canada

“The greater the ignorance the greater the dogmatism.” -Sir William Osler

WHAT IS PROGRESS?-Dynamic state that includes

Advancement

Improvement

Adoption of New Methods and Insights

Purpose: Benefit of Mankind

Progress Limitations

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”)

SOCIOECONOMICSNIH (2007) Reports Urology Care costs $11 Billion UTIs 3.5 BKidney stones 2.1 BProstate Cancer 1.3 BBladder Cancer 1.1 BKidney Cancer 401 MBPH 84 MED 328 MInterstitial Cystitis 66M

Progress in Urology will include the following Topics:

1) PROSTATE CANCER

2) ERECTILE DYSFUNCTION

3) TESTOSTERONE REPLACEMENT

4) EJACULATORY DISORDERS

What's New in Prostate Cancer?

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, exerciseImpact of chemoprevention

finasteride PCPT study (2006) dutasteride REDUCE study (2009)

Early Detection Not Screening

DRE+PSA+PCA-3

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

Mortality Results from a Randomized Prostate Cancer Screening Trial by Andriole, MD et al(NEJM 2009;360:1310-9 (USA)

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.

Morality Results from a Randomized Prostate Cancer Screening Cont’d : Europe by Schroder et. al (NEJM 2009; 360:1320-8)

182,000 men started in 1999-2009PSA screening only vs. case control

Conclusion: Mortality decreased by 20 % with risk of overdiagnosis

TOOLS FOR DIAGNOSISPSA: ( Free/Total)

PSA VelocityPSA Density

PCA-3 (urine) Crawford- Colorado

EPCA-2 ( serum)(Partin-Hopkins)

DOGS Detection of VOC (Volatile organic compound) (Cornu, Paris 2009) 66 ptsSens 100%, spec 96%

Complimentary Alternative Medicine for Prostate CancerLow-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

FATSRaised BMI index is associated with increase in cancers, heart diseases, DM, and deaths

Prostate Cancer higher BMIs have: Diagnosed with lower PSAsHigher positive marginsHave independent higher reoccurrence

Vitamin D and Prostate Cancer 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. 2006 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

Prostate Cancer and Vitamin D deficiency 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. 1990 Sept- Oct ; 10 (5A) : 1307-11

Pomegranate and Prostate Cancer

Pre-clinical Data Survey : in vitro studies show69-75% growth inhabitation of PC3 Delayed progression into S phaseLow levels of apoptosis

In vivo studies in SCID mice show : 52% growth inhibition of LAPC-9 tumors 70% reduction in PSAProlonged survival

-A. Katz, Columbia University 2010

Soy Isoflavones

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

Sources of IsoflavonesChick peas, soy, navy beans, lentilsLegumes

Intake should include 20-50 mg /day in Asian, African, and Mediterranean diets1-3 mg/day in Western Diets

ACTIVE SURVEILLANCE – PROSTATE CANCER

Criteria: Low grade disease -PSA <10PSA density <0.15Gleason Score 6<2/3 coresNo more than 50 % involvement in each coreShould repeat prostate biopsy in 1 year

http://www.haiti-vacations.com/wp-content/uploads/2010/02/Saut-Mathurine.jpg

•AUA Guidelines T1C Low Risk Cancer

RoboticOpenXRTBrachytherapyCryoablationHIFU? Outcome at 5 years similar

APPROACHES

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

General Predictors of Success and Failures for Treatment

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

PREMATURE EJACULATION occurs prior or within approximately one minute of vaginal penetration

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

Premature Ejaculation- New ApproachA) PDE-5 inhibitors- Viagra, Cialis, LevitraB) SSRI – Prozac, ZoloftC) Combination of aboveD) Topical Aerosol (Lidocaine, Prilocaine)

http://upload.wikimedia.org/wikipedia/commons/1/15/Haiti_deforestation.jpg

Erectile DysfunctionWhat’s New in Erectile Dysfunction?

Endothelial DiseaseCoronary Artery 3mmPenile Artery 1mm

Mayo Clinic Proceedings:“40-49 year old men with E.D. twice as likely to develop E.D.”

Satisfactory Sexual Activity

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

Nocturnal Erection(N.E.)

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

Oxygen Dynamic in N.E.

•Flaccid Penis: O2 tension 25-40 mm Hg•Erect Penis: O2 tension 90-100 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

Restoring Penile O2

•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)

What’s New in Testosterone Replacement

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

The Testosterone Dependent Model of Prostate Cancer Growth

Huggins and Hodges-1941- 2 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 1941.Huggins C, Hodges CV.

Counter-Point To Higgins:•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

Counter-Point To Higgins: (cont’d)

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)

Counter-Point To Higgins: (cont’d)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)

Conclusion

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.