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

Jjaffe@UCSEPA.com

215-762-3200 (office)267-992-0523 (mobile)