Newly-Diagnosed
Prostate Cancer
Mark Scholz MD
Prostate Oncology Specialists
The PSA Net
Types of Things We
Find in the PSA Net
• BPH
• Recent sexual activity
• Lab errors
• Prostate infections
• High-Grade prostate cancer
• Low-Grade prostate cancer
260
240
220
PSA Testing
Started 1987
200
180
Prostate
160
140
120
100
80
60
Lung and Bronchus
Colon and Rectum
40
Urinary Bladder
Non-Hodgkin Lymphoma
Melanoma of the Skin
Year of Diagnosis
Adapted from Jemal A, et al. CA Cancer J Clin. 2006;56:106-130.
2001
1999
1995
1997
1993
1989
1991
1987
1983
1985
1981
1979
0
1975
1977
20
2002
Rate per 100,000 Population
Annual Age-Adjusted Cancer Incidence Rates
Among Males for Selected Cancers, 1975-2002
Epidemic Prostate “Cancer”
• Prior to PSA (1987) 1 of 41 men died of PC (2.4%)
• In 2009, with screening and early treatment, the
•
risk of dying from PC is 1 of 53 (1.9%)
However:
– 200,000 diagnosed annually instead of 90,000
– 1.5 million men are biopsied annually
– The lifetime risk of biopsy is 1 out of 2
“Six-Core” Biopsy of 3000 Men
Age 55-75 with Normal PSA
PSA Level
Cancer Diagnosis Rate
1 – 2
17%
2 – 3
24%
3 – 4
27%
radical prostatectomy
specimen
transition zone
prostate cancer
urethra
peripheral zone
Prostate Biopsy
Points of
needle entry
Posterior View Prostate
Tests to Detect
Prostate Cancer
–PSA blood test
–PCA-3 urine test
–Digital rectal examination
–Ultrasound and MRI scans
“Risk of Biopsy-Detectable
Prostate Cancer”
•
•
•
•
•
•
Age
BMI (are you fat?)
Race
PSA
Rectal exam
PCA-3
55
22.5
Not African American
2.0
Risk of any prostate
normal
Cancer = 23%
not done
Risk of High-Grade
prostate cancer =
2.5%
Prostate Cancer Types
• Growth rate
• Ability to spread
“Gleason” Grading of Prostate Cancer
• Low grade (3)
• Higher Grade (4)
• Highest Grade (5)
• Score = “Adding Up”
two grades
Staging
Risk
Gleason
PSA
Digital
Low (all)
<7
< 10
Normal
7
10-20
Nodule
>7
> 20
Mass
Intermediate (any)
High (any)
Risk Status
• Low = Monitor
• Intermediate = Seeds,
Surgery or IMRT
• High-Risk = IMRT with
Hormone Blockade
Treatment Selection Flow Chart
Low-Risk
Determine
Disease
Risk
Intermediate
High-Risk
Active Surveillance
Seeds or IMRT or Cryotherapy or
Surgery or Hormones or
Active Surveillance or
IMRT plus Short-Term Hormones
Long-Term Hormones plus
IMRT plus Seeds
10-Year Survival by Risk Category
Low
More than 100%
Brenner: Journal of Clinical Oncology 2005
Intermediate
With treatment 98%
Mayo Clinic Journal of Urology 2008
High
Surgery 95%
Mayo Clinic Journal of Urology 2008
Very High
Early Hormone blockade: 87%
Late Hormone blockade: 59%
Messing: New England Journal Medicine 1999
Prostate Snatchers
The Prostate is “Built In”
Collateral Damage
Loss of Sexual and Urinary Function
Impotence Five Years after Surgery: 1288 Men
David Penson Journal of Urology 2005
• Incapable of an erection adequate for
intercourse with Viagra
Age < 54
55-59
60-64
> 65
39%
51%
56%
82%
Urinary Continence
Surgeon
12 mo
Pat Walsh
(Open)
93%
Ahlering
(Robotic)
94%
Shalhav
(Robotic)
84%
Lee
(Robotic)
90%
“Optimal Surgical Competency Requires a
minimum of 250 Practice Cases”
• In the New York during the whole of the
years in 2005:
– 25% of the urologists did a single radical
prostectomy
– 80% of the urologists did <10 cases
Savage & Vickers, Memorial Sloan Kettering
Journal of Urology December 2009
Radiation
Implant Procedure
Implant Procedure
X-Ray of Seed Implant
Robotic Prostatectomy
 Computer enhanced
 Surgeon operates at the
console within a 3D view
 Bedside surgical
assistant is next to the
patient
 Instruments move like a
human wrist (↑ dexterity
and precision)
The Surgeon Directs The Instruments
 The surgeon’s
hands are placed
in special devices
that direct the
instrument
movement
Robotic Prostatectomy: Difference
Big, Ugly Scar
Standard Surgery
little, tiny scars
Robotic Surgery
Robotic vs. Standard Prostatectomy
in 2700 Patients
• Good:
– Shorter hospital stays (1.4 vs. 4.4 days)
– Slightly less complications (30 vs. 36%)
• Not so Good:
– Higher likelihood of needing salvage radiation
therapy (28 vs 9%)
– More urethral strictures (40% more likely)
Hu, Jim et al. Journal of Clinical Oncology, May 2008
Cure Rates: Surgery vs. Seeds
• 15,000 studies reviewed
• Expert panel determined inclusion criteria
• 603 studies met criteria
Criteria for the Study Inclusion
1. Patients divided into low, intermediate &
high-risk groups
2. Standardized PSA endpoints such as
ASTRO, Phoenix, and PSA < 0.2
(surgery)
Intermediate Risk:
Percentage Progression Free
% Progression Free
1
1540
0.9
Brachy
24
8
23
2
22
17
0.8
12
0.7
4 40
3612
32
34
0.6
16
31
43
37
Surgery
8
0.5
0.4
1
2
3
4
5
6
7
Years
8
9 10 11 12 13 14 15
Brachy
Surg
Side Effects
Comparison of:
Surgery, Brachytherapy and
Beam Radiation
Talcott, Journal of Clinical Oncology, 2003
Quality of Life
• Prospective study at MGH and Harvard
• Questionnaire prior, 3, 12, 24, 36 mo. post Rx.
• 522 pts treated with, IMRT, Surgery or
• Average age: Surgery patients younger than
Brachytherapy patients, who were younger
than IMRT patients
Urinary
Obstruction/Irritation
(Higher score = worse function)
30
25
20
RP
15
Brachy
10
5
0
0 mo
3 mo
12 mo
24 mo
Incontinence
(Higher
score = worse function)
30
25
20
Brachy
15
RP Nerve Spare
10
5
0
0 mo
3 mo
12 mo
24 mo
Bowel Problems
(Higher score = worse function)
9
8
7
6
5
RP
4
Brachy
3
2
1
0
0 mo
3 mo
12 mo
24 mo
Sexual Dysfunction
(Higher score = worse function)
90
80
70
60
50
RP
40
Brachy
30
20
10
0
0 mo
3 mo
12 mo
24 mo
Health Related Quality Of Life
Validated Instrument Studies
• ~ 4230 patients in 7 studies comparing
surgery, IMRT and brachytherapy:
• Davis JW, et al. J Urol. 2001;166:947-952
• Wei JT, et al. J Clin Oncol. 2002;20:557-566
• Lee WR, et al. IJROBP. 2001;51:614-623
• Talcott JA et al. JCO 2003; 21(21): 3979
• Miller DC et al. JCO 2005; 23 (12):2772
• Frank SJ et al. J Urol 2007; 177: 2151
• Sanda MG et al. NEJM 2008; 358(12):1250
Summary Treatment Side Effects
of the Seven Studies
• Seed implants result in:
– less incontinence than surgery
– more urinary symptoms like urgency or frequency
– Better potency than surgery
Risks for Men with Low-Risk
Prostate Cancer
• Unskillful or
unnecessary
therapy
• Inaccurate
staging
“Either this is the wrong chart or
—lets just hope this is the wrong chart”
77777777
777777777
777
“Because of your age, I’m going to recommend doing nothing.”
Active Surveillance = Watchful Waiting
Active Surveillance
Watchful Waiting
Aim
Individualize therapy
Avoid treatment
Age
Any
Older or sicker
Monitoring
Aggressive
Lax
Treatment timing
Early
Late
Indications for
treatment
PSA increase, changes
on ultrasound or biopsy
Cancer symptoms
such as bone pain
Treatment intent
Cure
Symptom control
Surgery Vs. “Watching”
Bill-Axelson, New England Journal Medicine
• Randomized prospective trial 695 men
• Mean PSA 12.8
• 75% stage B (palpable nodule)
• 25% Gleason 7 (6% with Gleason >8)
• Cancer detected by DRE, not PSA
Bill-Axelson: 10-Year Results
Surgery “Watching”
Cancer
Survival
90%
85%
Risk
Reduction
5%
Benefit of Surgery
Compared to Doing Nothing at All
• Intermediate risk or
High Risk disease
• “Watching” not Active
Surveillance
• No early treatment for
a rising PSA
=
20 men operated
to save 1 life 10
years later
Projected Outcome in Low-Risk
Disease on Active Surveillance
Journal of Clinical Oncology 2005
• Grade 6
• Rectal exam normal
• PSA < 10
• Cancer in <1/3 of cores
• Early treatment
=
100 men
Operated to
Save 1 Life 10
Years in the
Future
Active Surveillance
Delaying curative
therapy until evidence
of cancer growth at
which time curative
treatment is
administered
Active Surveillance in 450 Men with
Low to Intermediate Risk Disease
Klotz—Journal of Clinical Oncology 2010
• Surveillance
– PSA and DRE every 3 months
– Biopsy every 2-4 years
• Progression
– Increase in Gleason score
– PSA doubling in less than 3 years
– New or enlarging nodule on rectal examination
Results Ten Years
• Patients:
– Average age 70
– 71% “Low Risk”
• 83% Gleason 3+3, 17% Gleason 3+4
• 85% PSA < 10, 12% PSA 10-15
• 10-year overall survival was 68%
– 97 died of causes besides prostate cancer
– 5 died of prostate cancer
Enhancement of Active Surveillance
•
•
•
•
Biopsy showing < 1/3 cores positive
Color doppler ultrasound every 6 months
Multi-Phasic MRI annually
Proscar or Avodart
Color Doppler Ultrasound
• Identifies lesions for monitoring
• Measures tumor progression
Color Doppler Image
Six Months Earlier
3-Tesla Prostate MRI
Anatomy
Chemical
concentrations
Cellular density
Blood flow
Proscar and Avodart
Advantages
• Inhibit cancer
• Improve PSA
•
•
•
accuracy
Increase biopsy
accuracy
Improve urination
Grow hair
Side Effects
• Lower libido
• Breast growth
Conclusions: Active Surveillance
• Aggressive, hurried prostate cancer treatment
benefits very, very few men
• The window of opportunity to defeat early-stage
disease is measured in years, not months
• Active surveillance rather than immediate radical
treatment allows men with low-risk disease to avoid
the side effects of treatment for many years if not
indefinitely.