Problem: Patients, physicians and carriers need a simple, unbiased means to compare the cancer control rates of modern prostate cancer treatment methods. To solve this problem, we have assembled experts from key treating disciplines: Surgery, External Radiation, Internal (or Brachytherapy), High Frequency Ultrasound, and Proton Therapy to do a complete review study of the current literature on prostate cancer treatment.

1. 4/15/2014
1
Peter Grimm, DO
Prostate Cancer Center of Seattle
Comparing Treatment Results Of PROSTATE CANCER
Prostate Cancer Results Study Group 2014

2. 4/15/2014
2
Problem: Patients, physicians and carriers need a simple, unbiased means to compare the cancer control rates of modern prostate cancer treatment methods.

3. 4/15/2014
 To solve this problem, we have assembled experts from key treating disciplines: Surgery, External Radiation, Internal (or Brachytherapy), High Frequency Ultrasound, and Proton Therapy
The purpose of this work is to do a complete review study of the current literature on prostate cancer treatment
3

4. 4/15/2014
4
Ignace Billiet, MD F.E.B.U., Urologist Kortrijk, Belgium
David Bostwick, MD Bostwick Laboratories
David Crawford, MD Univ Colorado, Denver
Brian Davis, MD Mayo Clinic Rochester, Minnesota
Adam Dicker, MD Thomas Jefferson U Philadelphia,PA
Steven Frank, MD MD Andersen, Houston Texas
Peter Grimm, DO Prostate Cancer Center of Seattle
Jos Immerzeel, MD De Prostaat Kliniek Netherlands
Stephen Langley, MD St Luke's Cancer Centre, Guildford England
Alvaro Martinez, MD William Beaumont , Royal Oak, Mi
Mira Keyes, MD BC Cancer Agency , Vancouver Canada
Patrick Kupelian, MD UCLA Med Center Los Angeles
Robert Lee , MD Duke University Medical Center
Stefan Machtens, MD University Bergisch, Gladbach Germany
Jyoti Mayadev, UC Davis Davis ,California
Brian Moran, MD Chicago Prostate Institute Chicago

5. 4/15/2014
5
Gregory Merrick, MD Schiffler Cancer Center Wheeling West Virginia
Jeremy Millar, MD Alfred Health and Monash University, Melbourne Australia
Mack Roach, MD UCSF San Francisco California
Richard Stock, MD Mt. Sinai New York
Katsuto Shinohara, MD UCSF San Francisco California
Mark Scholz, MD Prostate Cancer Research Institute Marina del Ray California
Edward Weber, MD Prostate Cancer Center of Seattle
Anthony Zietman, MD Harvard Joint Center Boston Ma
Michael Zelefsky, MD Memorial Sloan Kettering New York
 Jason Wong, MD UC Irvine California
 Robyn Vera, DO Radiant Oncology Lacey Washington

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 28,000+ prostate studies were published between 2000 and June 2013
 1,127 of those studies featured treatment results
 233 of those met the criteria to be included in this review study. (*1st & 2nd group)
Some treatment methods are under- represented due to failure to meet criteria
ABOUT THIS REVIEW STUDY

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“Will I be cured?” or “Will my treatment make me cancer free?” are valid patient questions. However, PSA values (our best measurement tool today) cannot answer this absolutely. The current state-of-the-art can only indicate that the treatment was “successful” if PSA numbers do not indicate cancer progression.

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8
After prostate removal, PSA numbers usually fall rapidly to very low numbers and stay low.
After radiation, PSA numbers usually come down slower, might increase then fall in the 1 to 3 year range (called a “PSA Bump”), and then usually level out at a higher number than the surgery patient.
 These different PSA expectations result in dissimilar ways to review a man’s PSA history to judge treatment success.
 This study makes no attempt to standardize those evaluation systems.

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Brachy = Seed implantation, either permanent or temporary seeds
EBRT= External Beam Radiation Therapy includes
IMRT = Intensity Modulated Radiation
RP = Standard open radical prostatectomy
Robot RP = Robotic Radical Prostatectomy
HIFU = High frequency Ultrasound
Cryo= Cryotherapy
Protons = form of External Radiation using Protons
ADT= Hormone Therapy

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1.Patients should be separated into Low, Intermediate, and High Risk
2.Success must be determined by PSA analysis
3.All Treatment types considered: Seeds (Brachy), Surgery (Standard or Robotic), IMRT (Intensity Modulated Radiation), HIFU (High Frequency Ultrasound), CRYO (Cryo Therapy), Protons, HDR (High dose Rate Brachytherapy)
4. Article must be in a Peer Reviewed Journal
Criteria for Inclusion of Article*
* Expert panel consensus

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5. Low Risk articles must have a minimum of 100 patients
6. Intermediate Risk articles must have a minimum of 100 patients
7. High Risk articles, because of fewer patients, need only 50 patients to meet criteria
8. Patients must have been followed for a median of 5 years
For additional criteria information contact: lisa@prostatecancertc.com

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12
RP
EBRT/ IMRT
Cryo
Brachy/ HDR
Robot RP
Proton
HIFU
9%
13%
5.4%
21%
5.3%
24%
8%
28/320
40/302
2/37
64/306
4/76
4/17
3/38
Total of 1,127 Treatment Articles. Some articles addressed several treatments and were counted as separate articles for each treatment. *A few articles evaluated other/minor treatments and are not listed here. These calculations only include primary accepted articles, and do not include secondary acceptance totals.

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Each treatment is given a symbol. For example Seed implant alone (Brachy) is given a blue dot with a number in it.
The number in the symbol refers to the article. The article can be found in the notes section below the slide ( go into “view” in up left corner of PowerPoint and click on note section, then click on this portion and scroll down to see all the references)
Treatment Success % = Percent of men, whose PSA numbers indicate no cancer progression. (progression free) at a specific point in time
The bottom line indicates the number years the study is out An example, the blue dot with 27 inside indicates that, as per article 27, 97% of the patients treated with seeds alone in low risk patients at 12 years were free of disease progression according to PSA numbers
27
How to Interpret the Results

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First Establish your clinical risk group* by looking at the definitions or ask your physician. Refer only to those slides for your risk group
Make your own judgment and then ask a doctor in each discipline ( Seeds, External Radiation Surgery, etc) to tell you where his/her own peer reviewed published Treatment Success % would fit on this plot.
How to Interpret the Results
*Next Slide

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Low Risk
Stage: T1 or T2a,b Gleason Sum < 6 PSA < 10 ng/ml

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BJU Int, 2012, Vol. 109(Supp. 1)
7
5
22
← Years from Treatment →
CRYO
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
1
12
24
14
8
2
HIFU
% PSA Progression Free
11
15
Protons
4
18
9
10
EBRT & Seeds
25
Robot RP
26
Prostate Cancer Center of Seattle
27
HDR
28
29
31
32
33
34
19
36
37
LOW RISK RESULTS
Treatment Success
39
35
40
100
101
13
16
103
102
6
16
104
105
106
107
108
Update of z
20
109
109
110
111
112
113
114
115
7
3
17

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7
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Seeds
Surgery
EBRT
5
22
← Years from Treatment →
CRYO
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
1
12
24
14
8
2
HIFU
% PSA Progression Free
11
15
Protons
4
18
9
10
EBRT &
Seeds
25
Robot RP
26
Prostate Cancer Center of Seattle
27
HDR
31 29 28
33 32
34
19
36
37
LOW RISK RESULTS
Weighted
39
35
40
100
101
13 EBRT
Brachy
Surgery
Treatment Success
103
102
6
16
104
105
106
107
108
Update of
109 20
110
112 111
113
114
115
7
3
17
109

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“The PCRSG criteria is pretty strict and not a lot of studies fit. What happens if you include articles with only 40 months of follow up or have a long follow up but less than 100 patients?”

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7
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Seeds
Surgery
EBRT
5
22
← Years from Treatment →
CRYO
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
1
12
24
14
8
2
HIFU
% PSA Progression Free
11
15
Protons
4
18
9
10
EBRT &
Seeds
25
Robot RP
26
Prostate Cancer Center of Seattle
27
HDR
31 29 28
33 32
34
19
36
37
LOW RISK RESULTS
>40 months follow-up or less than 100 patients
Treatment Success
39
35
40
41
100
101
13
65
49
76
80
56
59
63
41
75
51
71
72
90
73
74
70
42
57
85
84
66
43
64
44
EBRT &
ADT
53
82
81
62
54
79
Hypo EBRT
86
87
88
45
58
69
78
77
46
48
91
+ Seeds &
ADT
93
89
50
67
68
94 95
55
83 52
47
61
96
103
102
97
98
60
6
16
104
105
106
99
107
108
Update of
20
109
110
201
202
112 111
113
114
7
3
17
203 n

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20
7
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Seeds
Surgery
EBRT
5
22
← Years from Treatment →
CRYO
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
1
12
24
14
8
2
HIFU
% PSA Progression Free
11
15
Protons
4
18
9
10
EBRT &
Seeds
25
Robot RP
26
Prostate Cancer Center of Seattle
27
HDR
31 29 28
33 32
34
19
36
37
38
LOW RISK RESULTS Weighted
>40 months follow-up or less than 100 patients
Treatment Success
39
35
40
41
100
101
13
65
49
76
80
56
59
63
41
75
51
71
72
90
73
74
70
42
57
85
84
66
43
64
44
EBRT &
ADT
53
82
81
62
54
79
86
87
88
45
58
69
78
77
46
48
91
+ Seeds &
ADT
93
92
89
50
67
68
94 95
55
83 52
47
61
EBRT Brachy
Surgery
Hypo EBRT
96
103
102
97
98
60
6
16
104
105
106
99
107
108
Update of
20
109
110
201
202
112 111
113
114
115
7
3
17
203

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Zelefsky definition
Only 1 factor
▪Clinical Stage T2c
▪Gleason score > 7
▪PSA > 10 ng/ml
D’Amico definition
PSA 10-20 Gleason Score 7 or Stage T2b

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40
50
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Brachy
Surgery
EBRT
CRYO
HIFU
29
22
21
5
% PSA Progression Free
18
12
28
17
10
9
8 2
1
13
Protons
EBRT & Seeds
HDR
← Years from Treatment
→
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
15
4
36
Prostate Cancer Center of Seattle
37
EBRT, Seeds +
ADT
38
+
Seeds Alone
Seeds + ADT
40
Robot RP
41
42
44
43
45
46
Hypo EBRT
INTERMEDIATE RISK RESULTS
Treatment Success
7
11
14
20
35
34
39
24 23
16
6
26
30
27
47
48
49
150
151
31
Update of
152
152
153
154
155
155
156
157
157
EBRT + ADT
158
159
19
25
32
160 32
160
33
161
156

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23
40
50
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Brachy
Surgery
EBRT
CRYO
HIFU
29
22
21
5
% PSA Progression Free
18
12
28
3
17
10
9
8 2
1
13
Protons
HDR
← Years from Treatment
→
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
15
4
36
37
38
+
Seeds Alone
Seeds + ADT
40
Robot RP
41
42
44
43
45
46
INTERMEDIATE RISK RESULTS
Weighted
7
11
14
20
35
34
39
24 23
16
6
26
EBRT & Seeds
EBRT Surgery
Brachy
EBRT & Seeds
Hypo EBRT
EBRT, Seeds +
ADT
Treatment Success
Prostate Cancer Center of Seattle
30
27
47
48
49
150
151
31
Update of
152
152
153
154
155
155
156
157
158
159
19
25
32
32
160
160
33
161
156

24. Favorable
▪Single feature
▪Gleason 3+4=7
▪< 50% of biopsy cores +
Unfavorable
All other Intermediate
4/15/2014
24
*Zumsteg et al (MSKCC) New Risk Classification system for therapeutic decision making PCA pts undergoing dose escalated EBRT European Urology 64 p 895-902 2013 Favorable vs Unfavorable

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29
22
21
5
% PSA Progression Free
18
12
28
3
17
10
9
8
2
1
13
Protons
HDR
← Years from Treatment →
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
15
4
36
37
38
+
Seeds Alone
Seeds + ADT
40
Robot RP
41
42
44
43
45
46
INTERMEDIATE RISK
Favorable Vs Unfavorable* Weighted
7
11
14
20
35
34
39
23
24
16
6
26
EBRT & Seeds
EBRT
Surgery
Brachy
EBRT & Seeds
Hypo EBRT
EBRT, Seeds + ADT
Treatment Success
Prostate Cancer Center of Seattle
30
27
47
48
49
150
151
31
Update of
152
152
153
154
155
155
156
157
158
159
19
25
32
32
F33
U33
160
160
156

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40
50
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Brachy
Surgery
EBRT
CRYO
HIFU
29
22
21
5
% PSA Progression Free
18
12
28
3
17
10
9
8 2
1
13
Protons
EBRT & Seeds
HDR
← Years from Treatment
→
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
15
4
36
Prostate Cancer Center of Seattle
37
EBRT, Seeds +
ADT
38
+
Seeds Alone
Seeds + ADT
40
Robot RP
41
42
44
43
45
46
INTERMEDIATE RISK RESULTS
>40 months follow-up or less than 100 patients
Treatment Success
7
11
14
20
35
34
39
24 23
16
6
26
82
66
88
67
70
97
63
65
103 102
101
86
85 87
68 58
81 71 50
EBRT + ADT
94
93
92
77
51 91
69
Hypo EBRT
99
75
90
89
56
55
54
80
57
83
60
73
72
98
53
52
79
95
64
100
84
78
59
62
74
96
76
104
59
59
105
30
27
47
48
49
150
151
106
107
31
109
108
Update of
152
152
153
154
155
155
156
110
157
158
159
19
25
32
160 32
160
33
161
156

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40
50
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Brachy
Surgery
EBRT
CRYO
HIFU
29
22
21
5
% PSA Progression Free
18
12
28
3
17
10
9
8 2
1
13
Protons
HDR
← Years from Treatment
→
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
15
4
36
Prostate Cancer Center of Seattle
37
38
+
Seeds Alone
Seeds + ADT
40
Robot RP
41
42
44
43
45
46
INTERMEDIATE RISK RESULTS weighted
>40 months follow-up or less than 100 patients
7
11
14
20
35
34
39
24 23
16
6
26
82
66
88
67
70
97
63
65
103 102
101
86
85 87
68 58
81 71 50
EBRT + ADT
94
93
92
77
51 91
69
Hypo EBRT
99
75
90
89
56
55
54
80
57
83
60
73
72
98
53
52
79
95
64
100
84
78
59
62
74
96
76
EBRT
Brachy
Surgery
EBRT & Seeds
EBRT, Seeds +
ADT
Treatment Success
104
105
30
27
47
48
49
150
151
107
31
109
108
Update of
152
152
153
154
155
155
156
110
157
158
159
19
25
32
160
161
156

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28
Zelefsky definition
 2 or more factors
Gleason > 7
PSA 10-20 Clinical Stage T1c- T2b
D'Amico
Gleason Score 8-10
PSA >20

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6
11
25
15
5
EBRT Seeds +
ADT
19
30
16
20
18
29
% PSA Progression Free
17
21
8
24
26
37
41
12
Protons
EBRT & Seeds
HDR
EBRT & ADT
← Years from Treatment →
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
Prostate Cancer Center of Seattle
42
43
46
47
Robot RP
48
49
101
102
103
104
105
106
Hypo EBRT
107
109
HIGH RISK RESULTS
Treatment Success
23
35
108
4
2
39
33
34
7
1
110
27
3
13
14
28
40
10
111
112
113
114
115
Surg & ADT
116
118
117
119
121
122
Hypo EBRT +ADT
123
124
120
120
HDR + ADT
120
Update of
125
125
126
127
128
130
131
Surg & EBRT
132
133
9
32
32
36
36
44
31
45
134
135
136
136
9
22
112

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6
11
25
15
5
EBRT Seeds + ADT
19
30
16
20
18
29
% PSA Progression Free
17
21
8
22
24
26
37
41
12
Protons
HDR
← Years from Treatment →
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
Prostate Cancer Center of Seattle
42
43
46
47
Robot RP
48
49
101
102
103
104
105
106
107
109
HIGH RISK RESULTS
Weighted
23
35
108
4
2
39
33
34
EBRT, Seeds & ADT
Brachy
EBRT
Surgery
EBRT & ADT
EBRT & Seeds
Hypo EBRT
Treatment Success
1
7
110
27
3
13
14
28
40
10
111
112
112
113
114
115
116
Surg & ADT
118
117
119
121
HDR + ADT
122
123
124
120
120
Update of
125
125
126
127
128
130
131
132
Surg & EBRT
133
9
32
32
36
36
44
31
45
134
135
136
136
9

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6
11
25
15
5
EBRT Seeds +
ADT
19
30
16
20
18
29
% PSA Progression Free
17
21
8
24
26
37
41
12
Protons
EBRT & Seeds
HDR
EBRT & ADT
← Years from Treatment →
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
Prostate Cancer Center of Seattle
42
43
46
47
Robot RP
48
49
101
102
103
104
105
106
Hypo EBRT
107
109
HIGH RISK RESULTS
>40 months follow-up or less than 100 patients
Treatment Success
35
108
4
2
39
33
34
50
51
52
53
54
55
HIFU
56
86
87
57
58
59
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
88
79
80
81
89
84
83
82
85
1
7
90
91
110
27
3
13
14
28
40
92
10
23
111
112
112
113
114
115
116
Surg & ADT
118
117
119
119
121
60
122
123
124
120
120
HDR + ADT
Update of
125
125
93
126
127
128
94
95
96
97
98
130
131
132
Surg & EBRT
133
9
32
32
36
36
44
31
45
134
135
99
136
136
22
9

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6
11
25
15
5
19
30
16
20
18
29
% PSA Progression Free
17
21
8
22
24
26
37
41
12
Protons
← Years from Treatment →
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
42
43
46
47
48
49
101
102
103
104
105
106
107
109
HIGH RISK RESULTS Weighted
>40 months follow-up or less than 100 patients
Treatment Success
10
23
35
108
4
2
39
33
34
50
51
52
53
54
55
HIFU
56
86
87
57
58
59
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
88
79
80
81
89
84
83
82
85
Surgery
Brachy
EBRT
EBRT & ADT
EBRT & Seeds
Hypo EBRT
HDR
EBRT Seeds +
ADT
Robot RP
Prostate Cancer Center of Seattle
1
7
90
91
110
27
3
13
14
28
40
92
111
112
112
113
114
115
116
Surg & ADT
118
119
60
122
123
123
124
120
HDR + ADT
Update of
125
125
93
126
127
128
94
95
96
98
130
131
132
Surg & EBRT
133
9
32
32
36
36
44
31
45
134
135
99
136
136
9

33. 4/15/2014
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For most low risk patients, most therapies will be successful.
There appears to be a higher cancer control success rate for Brachy over EBRT and Surgery for all groups. Patients are encouraged to look at graphs and determine for themselves
 Serious side effect rates must be considered for any treatment
 Relaxing the report selection criteria doesn’t seem to impact the results substantially
OBSERVATIONS

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= Seeds alone
= EBRT & Seeds
= Surgery = Standard Radical Prostatectomy
= “Robot” =Robotic Prostatectomy
= “HIFU” = High Frequency Ultrasound
= “HDR”= High Dose Rate Brachytherapy +/-EBRT
= EBRT alone
= Hypo EBRT
= Protons

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= “CRYO” Cryo Therapy
= EBRT, Seeds, & ADT
= Seeds & ADT
= EBRT & ADT
= Surgery & ADT
= “Brachy” = all seed implant treatments
= all Surgery treatments
= all EBRT treatments
= all EBRT & Seeds
= all EBRT, Seeds & ADT
+

36. 4/15/2014
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Intermediate Risk
Stage T1 or T1-2 Stage T1-2
Gleason Score 7 or Gleason 6
PSA < 10 PSA 10-20
High Risk
Stage T2c or T3
Gleason score ≥ 8
PSA > 20 ng/mL
Low Risk
Stage: T1 or T2a,b Gleason Sum < 6 PSA < 10 ng/ml

37. 4/15/2014
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Peter Grimm, DO
peter@grimm.com
Lisa Grimm, Research Coordinator
lisa@prostatecancertc.com
Or ProstateCancerTC.com
Or contact PCRSG member
Prostate Cancer Center of Seattle website
www.Prostatecancertreatmentcenter.com