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11/04/14 1 Peter Grimm, DO Prostate Cancer Center of Seattle Comparing Treatment Results Of PROSTATE CANCER Prostate Cancer Results Study Group 2012

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The purpose of this work is to do a complete review study of the current literature on prostate cancer treatment

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Page 1: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 1

Peter Grimm, DOProstate Cancer Center of Seattle

Comparing Treatment Results Of PROSTATE CANCER

Prostate Cancer Results Study Group 2012

Page 2: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 2

Problem: Patients need a simple means to compare the cancer control rates of modern prostate cancer treatment methods.

11/04/14 2

Page 3: Comparing Treatment Results Of PROSTATE CANCER

11/04/14

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

11/04/14 3

Page 4: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 4

Ignace Billiet, MD F.E.B.U., Urologist Kortrijk, Belgium David Bostwick, MD Bostwick Laboratories David Crawford, MD Univ Colorado, Denver 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

Page 5: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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 Irvine California Stacy Wentworth, MD Piedmont Radiation Oncology Greensboro , NC Robyn Vera, DO Medical College of Virginia Richmond Virginia

Page 6: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 6

21,000+ prostate studies were published between 2000 and 2011

917 of those studies featured treatment results

145 of those met the criteria to be included in this review study.

Some treatment methods are under-represented due to failure to meet criteria

ABOUT THIS REVIEW STUDY

Page 7: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 7

“Will I be cured?” or “Will my treatment make me cancer free?” are valid patient questions. However, PSA numbers (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.

Page 8: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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.

Page 9: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 9

Brachy = Seed implantation either permanent or temporary seeds

IMRT = Intensity Modulated Radiation Therapy a form of External Radiation

RP = Standard open radical prostatectomyRobot RP = Robotic Radical ProstatectomyHIFU = High frequency Ultrasound Cryo= Cryotherapy Protons = form of External Radiation using ProtonsEBRT= External Beam Radiation Therapy ADT= Hormone Therapy

Page 10: Comparing Treatment Results Of PROSTATE CANCER

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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

11/04/14 10

Criteria for Inclusion of Article*

* Expert panel consensus

Page 11: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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] 11/04/14 11

Page 12: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 12

RP

EBRT/IMRT

Cryo Brachy/HDR

Robot RP

Proton HIFU

7.4% 10% 16% 19% 3.2% 23% 3%

20/272 26/241 2/32 44/236 2/62 3/13 1/31

Total of 917 Treatment Articles. Some articles addressed several treatments and were counted as separate articles for each treatment.

11/04/14 12

Page 13: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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. 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 do not indicate 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 27

How to Interpret the Results

Page 14: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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

*Next Slide

Page 15: Comparing Treatment Results Of PROSTATE CANCER

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

Page 16: Comparing Treatment Results Of PROSTATE CANCER

11/04/14BJU Int, 2012, Vol. 109(Supp. 1)

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

← 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

23 23

HIFU

% P

SA

Progression F

ree

1111

1515

Protons

21 21

4 4

1818

9 9

10 10

EBRT & Seeds

2525

Robot RP 26 26

Prostate Cancer Center of Seattle

27 27

HDR

28282929

3030

313132323333

34 34

1919 36 36

37 37

3838

LOW RISK RESULTST

reatment S

uccess

3 3 3939

35

4040

100100

101101

1313

16

103103

102 102

66

16 16

104104

105105

Page 17: Comparing Treatment Results Of PROSTATE CANCER

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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

← 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

23 23

HIFU

% P

SA

Progression F

ree

1111

1515

Protons

21 21

4 4

1818

9 9

10 10

EBRT & Seeds

2525

Robot RP

26 26

Prostate Cancer Center of Seattle

27 27

HDR

28282929

3030

313132323333

34 34

1919 36 36

37 37

3838

LOW RISK RESULTS Weighted

3 3 3939

35

4040

100100

101101

1313EBRT

Brachy

Surgery

Tre

atm

ent

Suc

cess

103103

102 102

66

16 16

104104

105105

Page 18: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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?”

Page 19: Comparing Treatment Results Of PROSTATE CANCER

11/04/14BJU 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

← 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

23 23

HIFU

% P

SA

Progression F

ree

1111

1515

Protons

21 21

4 4

1818

9 9

10 10

EBRT & Seeds

2525

Robot RP 26 26

Prostate Cancer Center of Seattle

27 27

HDR

28282929

3030

31 3132323333

34 34

1919 36 36

37 37

3838

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

Treatm

ent Success

3 3 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

838383834747

6161

96 96

103103

102 102

97 97

989860 60 66

16 16

104104

105105

Page 20: Comparing Treatment Results Of PROSTATE CANCER

11/04/14BJU 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

← 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

23 23

HIFU

% P

SA

Progression F

ree

1111

1515

Protons

21 21

4 4

1818

9 9

10 10

EBRT & Seeds

2525

Robot RP 26 26

Prostate Cancer Center of Seattle

27 27

HDR

28282929

3030

31 3132323333

34 34

1919 36 36

37 37

3838

LOW RISK RESULTS Weighted

>40 months follow-up or less than 100 patients

Treatm

ent Success

3 3 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

838383834747

6161

BrachyEBRT

Surgery

Hypo EBRT

96 96

103103

102 102

97 97

9898

60 60 66

16 16

104104

105105

Page 21: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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

Page 22: Comparing Treatment Results Of PROSTATE CANCER

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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 1919

% P

SA

Progression F

ree

1818

12 12

2828

3 3 17 17

10 10

32 32

99

88 2 2

2525

1 1

13 13

Protons

EBRT & Seeds

HDR

← Years from Treatment →

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

1515

443636

Prostate Cancer Center of Seattle

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

reatment S

uccess

77

11 11

14 14

2020

35 35

34 34

39 39

23232424

1616

66

2626

3333

3030

27 27 47 47

Page 23: Comparing Treatment Results Of PROSTATE CANCER

11/04/14BJU 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 1919

% P

SA

Progression F

ree

1818

12 12

2828

3 3 17 17

10 10

32 32

99

88 2 2

2525

1 1

13 13

Protons

HDR

← Years from Treatment →

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

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

3333

EBRT & Seeds

EBRT Surgery

Brachy

EBRT & Seeds

Hypo EBRT

EBRT, Seeds + ADT

Tre

atm

ent

Suc

cess

Prostate Cancer Center of Seattle

3030

27 27 47 47

Page 24: Comparing Treatment Results Of PROSTATE CANCER

11/04/14BJU 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 1919

% P

SA

Progression F

ree

1818

12 12

2828

3 3 17 17

10 10

32 32

99

88 2 2

2525

1 1

13 13

Protons

EBRT & Seeds

HDR

← Years from Treatment →

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

151544

3636

Prostate Cancer Center of Seattle

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

Treatm

ent Success

77

11 11

14 14

2020

35 35

34 34

39 39

23232424

1616

6 6

2626

3333

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

9595

6464

100100

8484

7878

5959

62 62

7474

9696

7676

1041045959

5959

1051053030

27 27 47 47

Page 25: Comparing Treatment Results Of PROSTATE CANCER

11/04/14BJU 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 1919

% P

SA

Progression F

ree

1818

12 12

2828

3 3 17 17

10 10

32 32

99

88 2 2

2525

1 1

13 13

Protons

HDR

← Years from Treatment →

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

151544

3636

Prostate Cancer Center of Seattle

37 37

3838

++

Seeds Alone

Seeds + ADT40 40

Robot RP

4141

42 42

44 44

4343

4545

46 46

INTERMEDIATE RISK RESULTS weighted

>40 months follow-up or less than 100 patients

77

11 11

14 14

2020

35 35

34 34

39 39

23232424

1616

6 6

2626

3333

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

9595

6464

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

Page 26: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 26

Zelefsky definition 2 or more factors

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

D'Amico Gleason Score 8-10 PSA >20

Page 27: Comparing Treatment Results Of PROSTATE CANCER

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27

66 11 11

3636

25 25

15 15

55

EBRT Seeds +ADT

19 19

3030

16 16 20 20

18 18

2929% P

SA

Progression F

ree

17

21 21

88

99

22 22

24 24

26 26

37 37

4141

1212

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

4242

43 43

4444

45 45

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

reatment S

uccess

10 10

2323

3535

108 108 44

22

3131

3939

3232

3333

3434

38

77

11

110110

2727

33

1313

1414

28 28

4040

Page 28: Comparing Treatment Results Of PROSTATE CANCER

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28

66 11 11

3636

25 25

15 15

55

EBRT Seeds +ADT

19 19

3030

16 16 20 20

18 18

2929% P

SA

Progression F

ree

17

21 21

88

99

22 22

24 24

26 26

37 37

4141

1212

Protons

HDR

← Years from Treatment →

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

Prostate Cancer Center of Seattle

4242

43 43

4444

45 45

4646

47 47

Robot RP

48 48

4949

101101

102102

103103

104 104

105 105

106106

107 107

109 109

HIGH RISK RESULTSWeighted

10 10

2323

3535

108 108 44

22

3131

3939

3232

3333

3434

38

EBRT, 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

Page 29: Comparing Treatment Results Of PROSTATE CANCER

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29

66 11 11

3636

25 25

15 15

55

EBRT Seeds +ADT

19 19

3030

16 16 20 20

18 18

2929% P

SA

Progression F

ree

17

21 21

88

99

22 22

24 24

26 26

37 37

4141

1212

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

4242

43 43

4444

45 45

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

Treatm

ent Success

10 10

2323

3535

108 108 44

22

3131

3939

3232

3333

3434

38

5050

5151

5252

53

5454

55

HIFU

5656

8686 8787

57

5858

5959

6060

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

Page 30: Comparing Treatment Results Of PROSTATE CANCER

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30

66

11 11

3636

25 25

15 15

55

19 19

3030

16 16 20 20

18 18

2929% P

SA

Progression F

ree

17

21 21

88

99

22 22

24 24

26 26

37 37

4141

1212

Protons

← Years from Treatment →

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

4242

43 43

4444

45 45

4646

47 47

48 48

4949

101101

102102

103103

104 104

105 105

106106

107 107

109 109

HIGH RISK RESULTS Weighted

>40 months follow-up or less than 100 patients

Treatm

ent Success

10 10

2323

3535

108 108 44

22

3131

3939

3232

3333

3434

38

5050

5151

5252

53

5454

55

HIFU

5656

8686 8787

57

5858

5959

6060

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

Prostate Cancer Center of Seattle

11

77

9090

9191

110110

2727

33

1313

1414

28 28

4040

9292

Page 31: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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

11/04/14 31

OBSERVATIONS

Page 32: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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

Page 33: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 33

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

++

Page 34: Comparing Treatment Results Of PROSTATE CANCER

11/04/14 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 6Gleason Score 7 or Gleason 6PSA < 10 PSA 10-20PSA < 10 PSA 10-20

High Risk High Risk Stage T2c or T3 Gleason score ≥ 8 PSA > 20 ng/mL

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

Page 35: Comparing Treatment Results Of PROSTATE CANCER

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Peter Grimm, DO [email protected]

Lisa Grimm, Research Coordinator [email protected] Or ProstateCancerTC.com

Or contact PCRSG member Prostate Cancer Treatment Center website

www.Prostatecancertreatmentcenter.com