1. Prostate Cancer Screening, Evaluation and Treatment
Jamison S. Jaffe, D.O.
Director of Minimally Invasive Urologic Surgery
Director of Robotic Surgery
Drexel University College of Medicine Hahnemann University Hospital

3. Objectives Prostate cancer background Screening in 2010
Prostate cancer prevention
Current treatment options
Robotic explosion

4. Prostate Cancer Definition Histology
An uncontrolled growth of cells in the prostate gland
Histology
Adenocarcinoma is most common

6. 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

10. Etiology Genetics Race Diet Hormones Strong familial predisposition
Higher risk of developing prostate cancer
Presents 6-7 years earlier
HPC1 gene and PCAP gene are on chromosome 1
Race
African American men have a higher prevalence and more aggressive prostate cancer than white men
Diet
A high-fat diet may lead to increased risks, while a diet rich in soy may be protective?
Hormones
Data implicating hormonal causes are indirect evidence ?

11. Prostate Cancer Symptoms
Pre-PSA era
Urinary retention %
Back or leg pain %
Hematuria %
PSA era
Urinary frequency - 38%
Decreased urine stream - 23%
Urinary urgency - 10%
Hematuria - 1.4%
* None of these complaints are unique to prostate cancer

12. Screening Controversial American Urological Association
American Cancer Society
National Comprehensive Cancer Network

13. 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

14. 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 age
Life expectancy
Family history
Race
Previous early detection test results.
NCCN Practice Guidelines 2009

15. Screening
Digital rectal exam (DRE)
Prostate specific antigen (PSA)

16. 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, 2008
Hankey et al: J Natl Cancer Inst, 91: 1017, 1999
Etzioni et al: Cancer Causes Control, 19: 175, 2008

18. AUA Screening Guideline
All men starting at 40 years old should be screened
Life 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 individualized
Patients should be informed of the known risks and the potential benefits

20. ACS Screening Guidelines
Men have a chance to make an informed decision with their health care provider about whether to be screened for prostate cancer
Uncertainties, risks, and potential benefits of prostate cancer screening need to be discussed
Men 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

21. 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 cancer
African Americans
Men 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)

22. 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

24. Mortality results from a randomized prostate-cancer screening trial
Randomized 76,693 men at 10 U.S. study centers
Annual screening
Control group (usual care)
7 years of follow-up
No statistically significant difference between the mortality rates of the two groups
Heavily flawed
Short follow-up
Unusually high contamination rate (40-52% in the control)
Andriole GL et al N Engl J Med. 2009;360:

25. European Randomized Screening for Prostate Cancer Study
182,000 men between the ages of 50 and 74
Study groups
PSA 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:

26. 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
Conclusions
Screening 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:

27. 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

28. Prostate Specific Antigen
PSA
Absolute
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

29. Thompson IM et al : N Engl J Med 2003 Jul 17; 349(3): 215-224

30. Diagnosis Any abnormality in the PSA or DRE will require
Transrectal ultrasound of the prostate
Biopsy of the prostate

31. Gleason Grading System
Prostate cancer graded on appearance of cancer cells
Gleason grading system
Gleason 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)

32. Prostate Cancer Prevention
5 Alpha Reductase Inhibitors
Finasteride
Dutasteride
Vitamin E
Selenium
Lycopene
Omega 3 fatty acid
Zinc

33. The Influence of Finasteride on the Development of Prostate Cancer
18,882 men randomized
55 years or older
Normal DRE and PSA
Study 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):

34. The Influence of Finasteride on the Development of Prostate Cancer
Prostate cancer detection
Finasteride group of the 4368 men (18.4 %)
Placebo group 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 tumors (22.2 %) P = 0.005
Thompson IM et al : N Engl J Med 2003 Jul 17; 349(3):

35. Effect of Dutasteride on the risk of prostate cancer
8122 men enrolled
Looked at men at high risk of developing prostate cancer
PSA from
Previous 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):

36. Effect of Dutasteride on the risk of prostate cancer
Results
Cancer detection
Dutasteride group of the 3305 men (20 %)
Placebo group 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):

37. Treatment Options Watchful waiting / Active surveillance
Radiation Therapy
Surgery

38. 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 up
More rigorous in younger men than older men
Follow up should include
PSA every 3 months
DRE every 6 months
Repeat biopsy at 1 year if all other factors stable

39. 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:

40. Active Surveillance Advantages Disadvantages
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

41. Radiation Therapy External Beam Radiation Therapy
Brachytherapy (Radioactive seeds)
High dose brachytherapy
Proton beam therapy

42. 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

43. Brachytherapy Placing radioactive seeds into the prostate
Surgical procedure
Used for low risk prostate cancers
May be combined with external beam in higher risk cancers
Not as effective as external beam therapy
Main advantage is treatment is given in 1 day
Minimal down time

44. 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

45. Surgical Therapy Open Surgery Conventional Laparoscopic Surgery
Robotic-Assisted Laparoscopic Surgery
Cryosurgery

46. 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?

47. Surgical Therapy Appropriate for tumors confined to the prostate
Must have a 10 year life expectancy
Excellent cancer survival
15-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:

48. Surgical Therapy Multiple techniques
Open
Laparoscopic
Robotic
High volume surgeons have superior results

49. 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

50. Effects of Marketing
Percent of prostatectomies performed with the da Vinci® in Philadelphia in 2008
85%
Patients are requesting robotics
Searching out centers with robots
Increasing number of hospitals acquiring robotic technology
Surgeons are pressured to adapt their techniques

52. Masters in Urology Meeting July 31, 2008
RALP very surgeon-dependent as learning curve is over 100 cases
RALP has lower blood loss
RALP in the US is the most common form of surgical treatment of CaP
Biochemical recurrence shown to be 17.9% in the first 10 RALP cases on the learning curve, becoming 10.7% after 250 cases
Centers of excellence vs. everyone in practice??

53. da Vinci Surgical System

54. Benefits of the da Vinci® Surgical System
Three-dimensional vision
12x magnification
Instruments with six degrees of freedom
Tremor filtration
Ergonomic surgeon console to limit fatigue

57. Comparing Incisions

60. 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, :175–178

61. Multiple Learning Curves?
293 consecutive RALP
Data collected
Operative time
Blood loss
Length of stay
Margin status
Two learning curves were observed
First break – 12 cases
Second break – 189 cases
Jaffe et al. UROLOGY 73: 127–133, 2009

62. Multiple Learning Curves?
Jaffe et al. UROLOGY 73: 127–133, 2009

63. Multiple Learning Curves?
Jaffe et al. UROLOGY 73: 127–133, 2009

64. “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”

65. 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

66. 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 surgeons
Centers of excellence

67. Jjaffe@UCSEPA.com 215-762-3200 (office) 267-992-0523 (mobile)