prostate cancer screening, evaluation and treatment jamison s. jaffe, d.o. director of minimally...
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Prostate CancerScreening, Evaluation and
Treatment
Jamison S. Jaffe, D.O.
Director of Minimally Invasive Urologic Surgery
Director of Robotic SurgeryDrexel University College of
Medicine Hahnemann University Hospital
Objectives
Prostate cancer background
Screening in 2010
Prostate cancer prevention
Current treatment options
Robotic explosion
Prostate Cancer
DefinitionAn uncontrolled growth of cells in the prostate
gland
HistologyAdenocarcinoma is most common
Prostate Cancer Statistics
Prostate cancer is the most common non-skin cancer in America
A nonsmoking male is more likely to get prostate cancer than the next 7 most common cancers combined
EtiologyGenetics
Strong familial predisposition Higher risk of developing prostate cancer Presents 6-7 years earlier
HPC1 gene and PCAP gene are on chromosome 1
RaceAfrican American men have a higher prevalence
and more aggressive prostate cancer than white men
DietA high-fat diet may lead to increased risks,
while a diet rich in soy may be protective?
HormonesData implicating hormonal causes are indirect
evidence ?
Prostate Cancer Symptoms
Pre-PSA eraUrinary retention - 20-25%Back or leg pain - 20-40%Hematuria - 10-15%
PSA era Urinary frequency - 38%Decreased urine stream - 23%Urinary urgency - 10%Hematuria - 1.4%
* None of these complaints are unique to prostate cancer
Screening
ControversialAmerican Urological AssociationAmerican Cancer SocietyNational Comprehensive Cancer Network
Screening
It is inherent that as we maximize the detection of early prostate cancer we will increase the detection of both non-aggressive and aggressive prostate cancers
The challenge is to identify the biology of the cancer that is detected and thus identify cancers that, if treated effectively, will result in a significant decrease in morbidity and mortality
NCCN Practice Guidelines 2009
Screening
The decision to participate in an early detection program for prostate cancer is complex for both the patient and physician
Important factors that must be considered when beginning an early-detection program include Patient ageLife expectancyFamily history RacePrevious early detection test results.
NCCN Practice Guidelines 2009
ScreeningDigital rectal
exam (DRE)
Prostate specific antigen (PSA)
PSA Screening
There has been a gradual but steady decline in prostate cancer mortality in the U.S. of approximately 30%.
This trend began fairly soon after the introduction of PSA testing
Ries et al: Posted to the SEER web site, 2008Hankey et al: J Natl Cancer Inst, 91: 1017, 1999Etzioni et al: Cancer Causes Control, 19: 175, 2008
AUA Screening Guideline
All men starting at 40 years old should be screenedLife expectancy of 10 year
Annual screening
Screening should be stopped at 75 years old
The decision to use PSA for the early detection of prostate cancer should be individualizedPatients should be informed of the known risks
and the potential benefits
ACS Screening Guidelines
Men have a chance to make an informed decision with their health care provider about whether to be screened for prostate cancerUncertainties, risks, and potential benefits of
prostate cancer screening need to be discussedMen should not be screened unless they have
received this information
Men without symptoms of prostate cancer who do not have a 10-year life expectancy should not be offered testing since they are not likely to benefit
ACS Screening Guidelines
Screening should take place at age 50 for men who are at average risk of prostate cancer
Screening should take place starting at age 45 for men at high risk of developing prostate cancerAfrican AmericansMen who have a first-degree relative (father,
brother, or son) diagnosed with prostate cancer at an early age (younger than age 65)
Screening should take place at age 40 for men at even higher risk (those with several first-degree relatives who had prostate cancer at an early age)
ACS Screening Guidelines
Men who choose to be tested who have a PSA of less than 2.5 ng/ml, may only need to be retested every 2 years.
Screening should be done yearly for men whose PSA level is 2.5 ng/ml or higher
Mortality results from a randomized prostate-cancer screening trial
Randomized 76,693 men at 10 U.S. study centersAnnual screening Control group (usual care)
7 years of follow-up
No statistically significant difference between the mortality rates of the two groups
Heavily flawedShort follow-upUnusually high contamination rate (40-52% in
the control)Andriole GL et al N Engl J Med. 2009;360:1310-1319
European Randomized Screening for Prostate Cancer Study
182,000 men between the ages of 50 and 74
Study groupsPSA screening
Average of once every 4 years
Control group 20% “contamination”
Death from prostate cancer was the primary outcome
Schroder et al: N Engl J Med. 2009;360:1320-1328
European Randomized Screening for Prostate Cancer Study
Incidence of prostate cancer was 8.2% in the screening group versus 4.8% in the control group
214 prostate cancer deaths in the screening group compared to 326 in the control
ConclusionsScreening program reduced mortality from
prostate cancer by 20%High risk of over-diagnosis 1,410 men would need to be screened and 48
additional men would need to be treated to prevent one death from this malignancy
Schroder et al: N Engl J Med. 2009;360:1320-1328
Prostate Specific Antigen
PSA is a glycoprotein produced by the prostate gland
Serum PSA levels are normally very low
Disruption of the normal prostatic architecture allows greater amounts of PSA to enter the general circulation
Elevated serum PSA level has become an important marker of many prostate diseases – including benign prostatic hyperplasia, prostatitis, and prostate cancer
Prostate Specific Antigen
PSAAbsolute
Normal < 4.0 ng/mL Most urologists now use < 2.5 ng/mL
Free PSA < 20% higher probability of cancer Only used after someone has been biopsied
Velocity > 0.75 change in 1 year in worrisome
Density PSA/Size of the gland > 0.15 worrisome
Thompson IM et al : N Engl J Med 2003 Jul 17; 349(3): 215-224
Diagnosis
Any abnormality in the PSA or DRE will requireTransrectal ultrasound of the prostateBiopsy of the prostate
Gleason Grading SystemProstate cancer graded
on appearance of cancer cells
Gleason grading systemGleason grade ranges
from 1 (least aggressive) to 5 (most aggressive)
Gleason score (2-10)Most common cell grade
(first) added to second most common cell grade i.e. Gleason 7 (3+4)
Prostate Cancer Prevention
5 Alpha Reductase InhibitorsFinasterideDutasteride
Vitamin E
Selenium
Lycopene
Omega 3 fatty acid
Zinc
The Influence of Finasteride on the Development of Prostate Cancer
18,882 men randomized55 years or olderNormal DRE and PSAStudy groups
Finasteride (5 mg per day) or placebo for seven years
Prostate biopsy was recommended if the annual PSA level, adjusted for the effect of finasteride, exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal
Thompson IM et al : N Engl J Med 2003 Jul 17; 349(3): 215-224
The Influence of Finasteride on the Development of Prostate Cancer
Prostate cancer detectionFinasteride group - 803 of the 4368 men (18.4
%)Placebo group - 1147 of the 4692 men (24.4 %)24.8 % reduction in prevalence over the seven-
year period P < 0.001
Tumors of Gleason grade 7, 8, 9, or 10 were more common in the finasteride group (280 of 757 tumors (37.0 %) than in the placebo group (237 of 1068 tumors (22.2 %) P = 0.005Thompson IM et al : N Engl J Med 2003 Jul 17; 349(3): 215-224
Effect of Dutasteride on the risk of prostate cancer
8122 men enrolled
Looked at men at high risk of developing prostate cancerPSA from 2.5-10Previous biopsy
Men were biopsied at the start of the study and at year 2 and 4
Andriole GL - N Engl J Med - 1-APR-2010; 362(13): 1192-202
Effect of Dutasteride on the risk of prostate cancerResults
Cancer detection Dutasteride group - 659 of the 3305 men (20 %) Placebo group - 858 of the 3424 men (25%)
Risk reduction of with dutasteride of 22.8% (P<0.001)
No increase in high risk tumors seen in the dutasteride group overall Higher rate of high grade tumors in the
dutasteride group at years 3 and 4
Andriole GL - N Engl J Med - 1-APR-2010; 362(13): 1192-202
Treatment Options
Watchful waiting / Active surveillance
Radiation Therapy
Surgery
Active Surveillance
Appropriate for men with very low risk prostate cancer when life expectancy < 20 years or men with low risk prostate cancer when life expectancy < 10 years
Expectation to intervene if the cancer progresses
Need regular follow upMore rigorous in younger men than
older menFollow up should include
PSA every 3 months DRE every 6 months Repeat biopsy at 1 year if all other factors stable
Active Surveillance
23% - 42% of all U.S. screen-detected cancers are over treated
PSA detection was responsible for up to 6.9 years of lead-time bias
Draisma G et al: J Natl Cancer Inst. 2009;101:374-383
Active Surveillance
Advantages Avoid possible side
effects of definitive therapy that may be unnecessary
Quality of life/normal activities retained
Risk of unnecessary treatment of small, indolent cancers reduced
Disadvantages Chance of missed
opportunity for cure Risk of progression and/or
metastases Subsequent treatment
may be more complex with increased side effects
Increased anxiety Requires frequent medical
exams and periodic biopsies
Uncertain long-term natural history of prostate cancer
Radiation Therapy
External Beam Radiation Therapy
Brachytherapy (Radioactive seeds)
High dose brachytherapy
Proton beam therapy
External Beam Radiation
Advantages Excellent cancer
control with higher doses
Avoids complications of surgery
Low risk of incontinence
Disadvantage 8-9 weeks of
treatments Acute bowel and
bladder problems Chronic
Salvage therapy very complex
Risk of erectile dysfunction
Brachytherapy
Placing radioactive seeds into the prostateSurgical procedure
Used for low risk prostate cancersMay be combined with external beam in higher
risk cancers
Not as effective as external beam therapy
Main advantage is treatment is given in 1 dayMinimal down time
Proton Beam Radiation
Theoretically, protons may reach deeply-located tumors with less damage to surrounding tissues
Not recommended for routine use at this time
Clinical trials have not yet yielded data that demonstrates superiority or equivalence of proton beam compared to conventional external beam therapy
NCCN Guidelines v3.2010, 7/16/10
Surgical Therapy
Open Surgery
Conventional Laparoscopic Surgery
Robotic-Assisted Laparoscopic Surgery
Cryosurgery
Cryosurgery
Not recommended by either the AUA or the NCCN practice guidelines in the primary management of prostate cancer
It is not offered as primary therapy in our practice
May be useful as a salvage technique?
Surgical Therapy
Appropriate for tumors confined to the prostate
Must have a 10 year life expectancy
Excellent cancer survival15-year prostate cancer-specific mortality of
12% in patients who underwent radical prostatectomy 5% for low risk patients
Stephenson AJ et al: J Clin Oncol. 2009;27:4300-4305
Surgical Therapy
Multiple techniquesOpenLaparoscopicRobotic
High volume surgeons have superior results
Why robotic surgery?
Decreased postoperative pain
Improved cosmetics
Quicker recovery
Decreased length of hospital stay
Quicker return to baseline activity
Less bleeding
Campbell’s Urology, 8th edition, 2002
Effects of Marketing
Percent of prostatectomies performed with the da Vinci® in Philadelphia in 200885%
Patients are requesting robotics
Searching out centers with robots
Increasing number of hospitals acquiring robotic technology
Surgeons are pressured to adapt their techniques
Masters in Urology MeetingMasters in Urology MeetingJuly 31, 2008July 31, 2008
RALP very surgeon-dependent as learning RALP very surgeon-dependent as learning curve is over 100 casescurve is over 100 cases
RALP has lower blood lossRALP has lower blood loss
RALP in the US is the most common form of RALP in the US is the most common form of surgical treatment of CaP surgical treatment of CaP
Biochemical recurrence shown to be 17.9% in Biochemical recurrence shown to be 17.9% in the first 10 RALP cases on the learning curve, the first 10 RALP cases on the learning curve, becoming 10.7% after 250 cases becoming 10.7% after 250 cases
Centers of excellence vs. everyone in Centers of excellence vs. everyone in practice??practice??
da Vinci Surgical System
Benefits of the da Vinci® Benefits of the da Vinci® Surgical SystemSurgical System
Three-dimensional visionThree-dimensional vision
12x magnification12x magnification
Instruments with six degrees of freedom Instruments with six degrees of freedom
Tremor filtrationTremor filtration
Ergonomic surgeon console to limit fatigueErgonomic surgeon console to limit fatigue
Comparing Incisions
A multi-institutional comparison of radical retropubic prostatectomy, radical perineal prostatectomy, and robot-assisted laparoscopic prostatectomy for treatment of localized prostate cancer
pT2 Disease pT3 Disease
Robotic Prostatectomy
4 % 36 %
Radical Prostatectomy
14 % 53 %
Perineal Prostatectomy
19 % 90 %
p-values 0.03 0.015
Coronato et al. J Robotic Surg, 2009 3:175–178
Multiple Learning Curves?Multiple Learning Curves?
293 consecutive RALP 293 consecutive RALP
Data collectedData collected Operative timeOperative time Blood lossBlood loss Length of stayLength of stay Margin statusMargin status
Two learning curves were observedTwo learning curves were observed First break – 12 casesFirst break – 12 cases Second break – 189 casesSecond break – 189 cases
Jaffe et al. UROLOGY 73: 127–133, 2009
Multiple Learning Curves?Multiple Learning Curves?
Jaffe et al. UROLOGY 73: 127–133, 2009
Multiple Learning Curves?Multiple Learning Curves?
Jaffe et al. UROLOGY 73: 127–133, 2009
“Surgical Robot Examined in Injuries” May 4, 2010
“Some surgeons with extensive robotic experience say it takes at least 200 surgeries to become proficient at the da Vinci and reduce the risks of surgical complications”
“That's difficult for surgeons at smaller hospitals to achieve“
Article suggests the establishment of specialized “CENTERS OF EXCELLENCE”
Our Expected Outcomes of RALP
Hospital stay – 1 day
Minimal blood loss
Minimal narcotic use
Foley duration – 5 to 7 days
Continence returned within 1 year *
Potency returned within 18 months *
CANCER FREE
Conclusions
Prostate cancer is very prevalent
Screening is not as straight forward as once believed
We may be able to prevent prostate cancer
Lots of treatment options
Patients do better we high volume surgeonsCenters of excellence
