Transcript progress in urology

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 1999-2009
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
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(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. 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
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
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
20-50 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)
B)
C)
D)
PDE-5 inhibitors- Viagra, Cialis, Levitra
SSRI – Prozac, Zoloft
Combination of above
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 25-40 mm Hg
•Erect Penis:
O2 tension 90-100 mm Hg
•
Free O2:
Nitric Oxide Synthesis (NO)
•NO + Guanylate Cyclase
•Lack of O2:
GTP to GMP (active vasodilatation)
Collagen Formation
•Restoring N.E. = Restoring O2
Fibrosis
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-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.
•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.