1/26/20141 Peter Grimm, DO Prostate Cancer Center of Seattle Comparing Treatment Results Of PROSTATE...

04/10/23 1

Peter Grimm, DOProstate Cancer Center of Seattle

Comparing Treatment Results Of PROSTATE CANCER

Prostate Cancer Results Study Group 2013

04/10/23 2

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

04/10/23 2

04/10/23

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

04/10/23 3

04/10/23 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

04/10/23 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

04/10/23 6

25,000+ prostate studies were published between 2000 and 2012

1,066 of those studies featured treatment results

218 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

04/10/23 7

“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.

04/10/23 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.

04/10/23 9

Brachy = Seed implantation, either permanent or

temporary seedsEBRT= External Beam Radiation Therapy

(includes IMRT- Intensity Modulated Radiation) RP = Standard open radical prostatectomyRobot RP = Robotic Radical ProstatectomyHIFU = High frequency Ultrasound Cryo= Cryotherapy Protons = form of External Radiation using

ProtonsADT= Hormone Therapy

04/10/23 10

1. Patients should be separated into Low, Intermediate, and High Risk groups

2. Success must be determined by PSA analysis

3. All Treatment types considered: Seeds (Brachy), Surgery (Standard or Robotic), EBRT (External beam radiation therapy & IMRT (Intensity Modulated Radiation therapy), HIFU (High Frequency Ultrasound), CRYO (Cryo Therapy), Protons, HDR (High dose Rate Brachytherapy)

4. Article must be in a Peer Reviewed Journal

04/10/23 10

Criteria for Inclusion of Article*

* Expert panel consensus

04/10/23 11

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: [email protected]

04/10/23 11

04/10/23 12

RP

EBRT/IMRT

Cryo Brachy/HDR

Robot RP

Proton HIFU

9% 12% 6% 20% 6% 25% 3%

26/303 34/284 2/34 60/299 4/70 4/16 1/36

Total of 1,066 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.

04/10/23 12

04/10/23 13

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 reference number. The article references can be found in the notes section below the slides (Click on the “view” tab in upper left corner of PowerPoint and select notes page, you can then scroll down to see all the references below the graphs)

Treatment Success % = Percent of men, whose PSA numbers indicate no cancer progression (progression free) at a specific point in time

The bottom line of the graph indicates the number of years the study is out. An example, the blue dot with #27 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 27

How to Interpret the Results

04/10/23 14

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 (cont.)

*Next Slide

04/10/23 15

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

04/10/23BJU Int, 2012, Vol. 109(Supp. 1)

77

5 5

22 22

← Years from Treatment →

CRYO

• Prostate Cancer Results Study Group • Numbers within symbols refer to references

11 12 12

24 24

14 14 8 8

22

HIFU

% P

SA

Pro

gres

sion

Fre

e

1111

1515

Protons

4 4

1818

9 9

10 10

EBRT & Seeds

2525

Robot RP 26 26

Prostate Cancer Center of Seattle

27 27

HDR

28282929313132323333

34 34

1919 36 36

37 37

LOW RISK RESULTST

reat

men

t S

ucce

ss

3939

35

4040

100100

101101

1313

16

103103

102 102

66

16 16

104104

105105

106106107107

108 108

Update of z

2020109109

109109

110110

111111111111112 112

113 113

114 114

115 115

04/10/23BJU Int, 2012, Vol. 109(Supp. 1)

17

77

60

70

80

90

100

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Seeds

Surgery

EBRT

5 5

22 22


CRYO


11

12 12 24 24

14 14

8 8

22

HIFU

% P

SA

Pro

gres

sion

Fre

e

1111

1515

Protons

4 4

1818

9 9

10 10

EBRT & Seeds

2525

Robot RP

26 26


27 27

HDR

28282929313132323333

34 34

1919 36 36

37 37

LOW RISK RESULTS Weighted

3939

35

4040

100100

101101

1313EBRT

Brachy

Surgery

Tre

atm

ent

Suc

cess

103103

102 102

66

16 16

104104

105105

106106107107

108 108

Update of

2020109109

110110

111 111 112 112

113 113

114 114

115 115

04/10/23 18

“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?”

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

19

77

60

70

80

90

100

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Seeds

Surgery

EBRT

5 5

22 22


CRYO


11 12 12

24 24

14 14 8 8

22

HIFU

% P

SA

Pro

gres

sion

Fre

e

1111

1515

Protons

4 4

1818

9 9

10 10

EBRT & Seeds

2525

Robot RP 26 26


27 27

HDR

28282929 31 3132323333

34 34

1919 36 36

37 37

LOW RISK RESULTS >40 months follow-up or less than 100 patients

Tre

atm

ent

Suc

cess

3939

35

4040

4141

100100

101101

1313

6565

4949

7676

8080

5656

59 59

63 63

4141

75 75

51 51

71717272

90 90

7373

7474

7070

4242

5757

85 858484

6666

43436464

44 44EBRT & ADT

5353

82828181 6262

5454

7979

Hypo EBRT

86 86

8787

8888

4545

5858

6969

78787878

77 77

46464646

48484848

91 91

++ Seeds & ADT

93938989

5050

6767

68 68

95959494

555552525252

83838383

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96 96

103103

102 102

97 97

989860 60 66

16 16

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105105

106106

9999

107107

108 108

Update of

2020109109

110110

201201

202 202

111 111 112 112

113 113

114 114

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

20

77

60

70

80

90

100

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Seeds

Surgery

EBRT

5 5

22 22


CRYO


11 12 12

24 24

14 14 8 8

22

HIFU

% P

SA

Pro

gres

sion

Fre

e

1111

1515

Protons

4 4

1818

9 9

10 10

EBRT & Seeds

2525

Robot RP 26 26


27 27

HDR

28282929 31 3132323333

34 34

1919 36 36

37 37

3838

LOW RISK RESULTS Weighted

>40 months follow-up or less than 100 patients

Tre

atm

ent

Suc

cess

3939

35

4040

4141

100100

101101

1313

6565

4949

7676

8080

5656

59 59

63 63

4141

75 75

51 51

71717272

90 90

7373

7474

7070

4242

5757

85 858484

6666

43436464

44 44EBRT & ADT

5353

82828181 6262

5454

7979

86 86

8787

8888

4545

5858

6969

78787878

77 77

46464646

48484848

91 91

++ Seeds & ADT

9393

9292

8989

5050

6767

68 68

95959494

555552525252

83838383

47476161

BrachyEBRT

Surgery

Hypo EBRT

96 96

103103

102 102

97 97

9898

60 60 66

16 16

104104

105105

106106

9999

107107

108 108

Update of

2020109109

110110

201201

202 202

111 111 112 112

113 113

114 114

115 115

04/10/23 21

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

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

22

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 29

2222

2121

5 5

% P

SA

Pro

gres

sion

F

ree

1818

12 12

2828 17 17

10 10

99

88 2 2 1 1

13 13

Protons

EBRT & Seeds

HDR



1515

443636


37 37

EBRT, Seeds + ADT

3838

++

Seeds Alone

Seeds + ADT40 40

Robot RP

4141

42 42

44 44

4343

4545

46 46

Hypo EBRT

INTERMEDIATE RISK RESULTST

reat

men

t S

ucce

ss

77

11 11

14 14

2020

35 35

34 34

39 39

23232424

1616

66

2626

3030

27 27 47 47

48 48

49 49

150150

151151

31 31

Update of

152152

152152

153153

154154155155

155155

156156

157 157

157 157

EBRT + ADT

158 158

159 159

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

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 29

2222

2121

5 5

% P

SA

Pro

gres

sion

F

ree

1818

12 12

2828

3 3 17 17

10 10

99

88 2 2 1 1

13 13

Protons

HDR



1515

443636

37 37

3838

++

Seeds Alone

Seeds + ADT40 40

Robot RP

4141

42 42

44 44

4343

4545

46 46

INTERMEDIATE RISK RESULTS Weighted

77

11 11

14 14

2020

35 35

34 34

39 39

23232424

1616

66

2626

EBRT & Seeds

EBRT Surgery

Brachy

EBRT & Seeds

Hypo EBRT

EBRT, Seeds + ADT

Tre

atm

ent

Suc

cess


3030

27 27 47 47

48 48

49 49

150150

151151

31 31

Update of

152152

152152

153153

154154155155

155155

156156

157 157

158 158

159 159

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

24

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 29

2222

2121

5 5

% P

SA

Pro

gres

sion

F

ree

1818

12 12

2828

3 3 17 17

10 10

99

88 2 2 1 1

13 13

Protons

EBRT & Seeds

HDR



151544

3636


37 37

EBRT, Seeds + ADT

3838

++

Seeds Alone

Seeds + ADT40 40

Robot RP

4141

42 42

44 44

4343

4545

46 46

INTERMEDIATE RISK RESULTS>40 months follow-up or less than 100 patients

Tre

atm

ent

Suc

cess

77

11 11

14 14

2020

35 35

34 34

39 39

23232424

1616

6 6

2626

8282

6666

8888

6767

7070

9797

6363

6565

102102103103

101 101

8686

87878585

58586868

717181815050

EBRT + ADT

9494

9393

9292

7777

919151

6969

Hypo EBRT99 99

7575

9090

8989

5656

5555

5454

8080

5757

8383

60 60

7373

7272

9898

5353

5252

7979

95956464

100100

8484

7878

5959

62 62

7474

9696

7676

1041045959

5959

1051053030

27 27 47 47

48 48

49 49

150150

151151

106106 107 107 31 31

109109

108108

Update of

152152

152152

153153

154154155155

155155

156156

11

0 1

10

157 157

158 158

159 159

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

25

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 29

2222

2121

5 5

% P

SA

Pro

gres

sion

F

ree

1818

12 12

2828

3 3 17 17

10 10

99

88 2 2 1 1

13 13

Protons

HDR



151544

3636


37 37

3838

++

Seeds Alone

Seeds + ADT40 40

Robot RP

4141

42 42

44 44

4343

4545

46 46

INTERMEDIATE RISK RESULTS weighted


77

11 11

14 14

2020

35 35

34 34

39 39

23232424

1616

6 6

2626

8282

6666

8888

6767

7070

9797

6363

6565

102102103103

101 101

8686

87878585

58586868

717181815050

EBRT + ADT

9494

9393

9292

7777

919151

6969

Hypo EBRT99 99

7575

9090

8989

5656

5555

5454

8080

5757

8383

60 60

7373

7272

9898

5353

5252

7979

95956464

100100

8484

7878

5959

62 62

7474

9696

7676

EBRT

Brachy

Surgery

EBRT & Seeds

EBRT, Seeds +ADT

Tre

atm

ent

Suc

cess

104104

1051053030

27 27 47 47

48 48

49 49

150150

151151

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109109

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Update of

152152

152152

153153

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155155

156156

11

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157 157

158 158

159 159

04/10/23 26

Zelefsky definition 2 or more factors

Gleason > 7 PSA 10-20 Clinical Stage T1c- T2b

D'Amico Gleason Score 8-10 PSA >20

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

27

66 11 11

25 25

15 15

55

EBRT Seeds +ADT

19 19

3030

16 16 20 20

18 18

2929

% P

SA

Pro

gres

sion

Fre

e

17

21 21

8824 24

26 26

37 37

4141

1212

Protons

EBRT & Seeds

HDR

EBRT & ADT




4242

43 43

4646

47 47

Robot RP

48 48

4949

101101

102102

103103

104 104

105 105

106106

Hypo EBRT

107 107

109 109

HIGH RISK RESULTST

reat

men

t S

ucce

ss

2323

3535

108 108 44

22

3131

39393333

3434

77

11

110110

2727

33

1313

1414

28 28

4040

10 10

111 111

112112

113113

114 114

115115

Surg & ADT

116 116

118118

117 117 119 119 121121

122122

Hypo EBRT +ADT

123123

124124

120 120 120 120

HDR + ADT

120120

Update of

125125

125

126126

127 127

128128

129129

130130

131 131

Surg & EBRT

132 132 133133

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

28

66 11 11

25 25

15 15

55

EBRT Seeds +ADT

19 19

3030

16 16 20 20

18 18

2929% P

SA

Pro

gres

sion

Fre

e

17

21 21

88

22 22

24 24

26 26

37 37

4141

1212

Protons

HDR




4242

43 43

4646

47 47

Robot RP

48 48

4949

101101

102102

103103

104 104

105 105

106106

107 107

109 109

HIGH RISK RESULTSWeighted

2323

3535

108 108 44

22

3131

39393333

3434

EBRT, Seeds & ADTEBRT, Seeds & ADTBrachy

EBRT Surgery

EBRT & ADT

EBRT & Seeds

Hypo EBRT

Tre

atm

ent

Suc

cess

11

77

110110

2727

33

1313

1414

28 28

4040

10 10

111 111

112112

112112

113113

114 114

115115

116 116

Surg & ADT

118118

117 117 119 119 121121

HDR + ADT

122122123123

124124

120 120 120120

Update of

125125

125

126126

127 127

128128

129129

130130

131 131

132 132

Surg & EBRT

133133

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

29

66 11 11

25 25

15 15

55

EBRT Seeds +ADT

19 19

3030

16 16 20 20

18 18

2929% P

SA

Pro

gres

sion

Fre

e

17

21 21

88

99

22 22

24 24

26 26

37 37

4141

1212

Protons

EBRT & Seeds

HDR

EBRT & ADT




4242

43 43

4646

47 47

Robot RP

48 48

4949

101101

102102

103103

104 104

105 105

106106

Hypo EBRT

107 107

109 109

HIGH RISK RESULTS>40 months follow-up or less than 100 patients

Tre

atm

ent

Suc

cess

3535

108 108 44

22

3131

39393333

3434

5050

5151

5252

53

5454

55

HIFU

5656

8686 8787

57

5858

5959

6161

6262

6363

6464

65

6666

6767

6868

6969

7070

7171

7272

7373

74

7576

77

78

8888

79

80

81

8989

8484

8383 8282

85

11

77

9090

9191

110110

2727

33

1313

1414

28 28

4040

9292

10 10

2323 111 111

112112

112112

113113

114 114

115115

116 116

Surg & ADT

118118

117 117 119 119 119 119 121121

6060

122122123123

124124

120 120 120120

HDR + ADT

Update of

125125

125

93126126

127 127

128128

129129

94

95 95

96 96

97 979898

130130

131 131

132 132

Surg & EBRT

133133

04/10/23BJU Int, 2012, Vol. 109(Supp 1)

30

66

11 11

25 25

15 15

55

19 19

3030

16 16 20 20

18 18

2929% P

SA

Pro

gres

sion

Fre

e

17

21 21

88

22 22

24 24

26 26

37 37

4141

1212

Protons



4242

43 43

4646

47 47

48 48

4949

101101

102102

103103

104 104

105 105

106106

107 107

109 109

HIGH RISK RESULTS Weighted


Tre

atm

ent

Suc

cess

10 10

2323

3535

108 108 44

22

3131

39393333

3434

5050

5151

5252

53

5454

55

HIFU

5656

8686 8787

57

5858

5959

6161

6262

6363

6464

65

6666

6767

6868

6969

7070

7171

7272

7373

74

7576

77

78

8888

79

80

81

8989

8484

8383 8282

85

Surgery

Brachy

EBRT

EBRT & ADT

EBRT & Seeds

Hypo EBRT

HDR

EBRT Seeds +ADT

Robot RP


11

77

9090

9191

110110

2727

33

1313

1414

28 28

4040

9292

111 111

112112

112112

113113

114 114

115115

116 116

Surg & ADT

118118119 119

6060

122122123123

123123

124124

120120

HDR + ADT

Update of

125125

125

93126126

127 127

128128

129129

94

95 95

96 96 9898

130130

131 131

132 132

Surg & EBRT

133133

04/10/23 31

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

04/10/23 31

OBSERVATIONS

04/10/23 32

= 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

04/10/23 33

= “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

++

04/10/23 34

Intermediate Risk Intermediate Risk Stage T1 or T1-2 Stage T1-2 Stage T1 or T1-2 Stage T1-2

Gleason Score 7 or Gleason Score 6Gleason Score 7 or Gleason Score 6PSA < 10 ng/ml PSA 10-20 PSA < 10 ng/ml PSA 10-20

ng/mlng/mlHigh Risk High Risk Stage T2c or T3Stage T2c or T3 Gleason Score ≥ 8 Gleason Score ≥ 8 PSA > 20 ng/mLPSA > 20 ng/mL

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

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Peter Grimm, DO [email protected]

Lisa Grimm, Research Coordinator [email protected]

Or contact a PCRSG member Prostate Cancer Center of Seattle

(website & email)

www.Prostatecancertreatmentcenter.com [email protected]

1/26/20141 Peter Grimm, DO Prostate Cancer Center of Seattle Comparing Treatment Results Of PROSTATE...

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