Cryotherapy for the Treatment of - PowerPoint Presentation

Slide1

Cryotherapy for the Treatment of Prostate Cancer

C. Ryan Barnes, MD

Virginia Urology

Slide2

Active SurveillanceHormone therapyRadical prostatectomyOpenLaparoscopic (with or without a robot)Brachytherapy (seed implantation)

External beam radiation

Cryotherapy (Cryoablation, Cryosurgery)

Localized Prostate Cancer Management Options

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Slide3

Prostate Cryotherapy

Slide4

AUA Best Practice StatementAugust 2008

A review of the historical evolution of cryosurgery provides two overriding messages, the first being that there is evidence of therapeutic benefit, and the second, that treatment-associated morbidity has been reduced as technological refinements have emerged.

Babbian

et al. J

Urol

2008; 180

(5):1993-2004

4

Slide5

Cryotherapy RefinementsTransrectal Ultrasound (TRUS)

Argon and helium

Thermocouple monitoring

Urethral warmingVariable ice lengths (short ice)Multiple cryoprobe controls

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Slide6

Ice formation ruptures and destroys cellsDestruction occurs at time of treatmentTumor blood supply damaged beyond repairHarmless scar tissue left behind

How Ice Destroys Cancer

Baust

, et al.

Curr

Opin

Urol

2009

Slide7

Cryotherapy History19th Century

Ice used for local control of cervical cancer

1960’s

Closed metal tube with tissue contact for Parkinson’s disease1960’s to 1980’s

Evolution of urologic application from open approaches to transurethral to

transperineal

Ahmed L, et al. J

Endouro

2006; 20(7):471-474.

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Slide8

Today: Endocare, Inc

Integrated or external ultrasound

Fold-down keyboard

Probe holder and testing rack

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Slide9

Cryoprobes produce various

iceballs

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These isotherms represent measurements collected using gelatin formula which approximates performance (±5mm) in soft tissue at 100%

gas for 10 minutes. The actual isotherms may vary.

Slide10

Cryotherapy ApplicationsPrimary Treatment

Salvage Treatment for Post-Radiotherapy Recurrence

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Slide11

Primary Cryotherapy

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Slide12

Primary Cryotherapy Patient Selection

2008 AUA Best Practice Statement:

Any patient with biopsy proven localized prostate cancer.

Ideal patients:

Reasonable size gland

(Consider

neoadjuvant

reduction for large glands)

No prior TURP

PSA < 10 ng/mLPatients with high risk of positive margins Non-surgical candidates Patients for whom potency is low priority

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Babbian

et al. J

Urol

2008; 180

(5):1993-2004

Slide13

Primary Cryotherapy Data HighlightsTimeframes up to 10 years

3

Over 6,000 patients studied

1-8Overall BDFS = 73%-90%1-8Return to potency as high as 51% after 4 years3

Utilized active rehabilitation

Rectal injury ≤ 0.5%

1,3,5-8

Incontinence < 8%

1,4-8

1Dhar et al, J Urol 2010; 183(4 Supl):e184 Abstract 467. 2Donnelly et al, Cancer 2010; 116(2):323-30. 3Cohen et al, Urology 2008; 71(3):515-8. 4DiBlasio et al, IBJU 2008; 34:443-50. 5

Ellis et al, Urology 2007; 69(2):306-10.

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Prepelica et al, Cancer 2005; 103(8):1625-30.

7

Bahn et al, Urology 2002; 60(

Supl

2A):3-11.

8

Long et al, Urology 2001; 57(3):518-23.

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2010: Patients Followed Over 10 Years

Cancer Specific Survival = 92%

(Only 8% died due to prostate cancer)

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Primary Cryotherapy Efficacy Comparison

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Cryoablation versus EBRTCancer 2010; 116:323-330

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“Significantly fewer positive biopsies were documented after cryoablation than after radiotherapy.”

Slide17

PSA Stability for low-risk cancer

Graph and references from Katz and

Rewcastle

, Current

Onc

Reports 2003; 5:231-238. Used with permission

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PSA Stability for moderate-risk cancer

Graph and references from Katz and

Rewcastle

, Current

Onc

Reports 2003; 5:231-238. Used with permission

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PSA Stability for high-risk cancer

Graph and references from Katz and

Rewcastle

, Current

Onc

Reports 2003; 5:231-238. Used with permission

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Slide20

Primary Cryotherapy Morbidity Comparison

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Slide21

Radical

Prostatectomy

External

Beam RT

0

10

20

30

40

50

Cryo

Brachy

IMRT

8%

3

1%

4

49%

1

7%

2

10%

5

1%

6

7%

7

4%

8

15%

9

0%

10

Occurrence (%)

1

Steineck et al, NEJM 2002; 347(11):790-6;

2

Walsh et al, J

Urol

2000; 163(6):1802-7.

3

Long et al, Urology 2001; 57(3):518-23.

4

Donnelly et al, Urology 2002; 60(4):645-9.

5

Reis et al,

Int

Urol

Nephrol

2004; 36(2):187-90.

6

Feigenberg et al,

Int

J

Radiat

Oncol

Biol

Phys

2005; 62(4):956-64.

7

Matalinska et al, J

Clin

Oncol

2001; 19(6):1619-28.

8

Potosky et al, J NCI 2000; 92(19):1582-92.

9

Zelefsky et al,

Int

J

Radiat

Oncol

Biol

Phys

2002; 53(5):1111-6.

10

Brabbins et al,

Int

J

Radiat

Oncol

Biol

Phys

2005; 61(2):400-8.

Range of Incontinence Rates (2000-05)

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Slide22

1

Matalinska

et al

,

J

Clin

Oncol

2001; 19(6):1619-28.

2Walsh et al, J Urol

2000; 163(6):1802-7.

3

Bahn

et al

,

Urology

2002; 60(

Supl

2A):3-11.

4

Donnelly

et al

,

Urology

2002; 60(4):645-9.

5

Incrocci

et al

,

Acta

Oncol

2005; 44(7):673-8.

6

Incrocci

et al

,

Acta

Oncol

2005; 44(7):673-8.

7

Potosky

et a

l,

JNCI

2000; 92(19):1582-92.

8

Matalinska

et al

,

J

Clin

Oncol

2001; 19(6):1619-28.

9

Zelefsky

et al

,

J

Urol

2006; 176(4):1415-9.

10

Skala

et al

,

Int

J

Radiat

Onco

Biol

Phys

2007; 68(3):690-8.

0

20

40

60

80

100

Radical

Prostatectomy

Cryo

Brachy

External

Beam RT

IMRT

93%

3

53%

4

91%

1

14%

2

51%

5

5%

6

63%

7

41%8Occurrence (%)49%9

32%

10

Range of Impotence Rates (2000-05)

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Slide23

 

Severe

(fistula)

Moderate

(bleeding, urgency, diarrhea)

Radical Prostatectomy

1-19%

1,2

Cryotherapy

< 0.5%

3

0%

4

Brachytherapy

< 0.5%

5

“Rare”-27%

6,7

Beam radiation

 

12-43%

1,2

 

IMRT

 

 0-25%

8,9

 

1

Shrader-Bogen et al, Cancer 1997; 79:1977-86.

2

Talcott et al, J

Clin

Oncol

1998; 16(1):275-83.

3

Dhar et al, J

Urol

2010; 183(4

Supl

):e184 Abstract 467.

4

Donnelly et al, Urology 2002; 60(4):645-9.

5

Theodorescu et al, Cancer 2000; 89(10):2085-91.

6

Ragde et al, Cancer 1997; 80(3):442-52.

7

Merrick et al,

Int

J

Radiat

Oncol

Biol

Phys 2000; 48(3):667-74.

8

Zelefsky et al,

Radiother

Oncol

; 55:241-9.

9

Brabbins et

al,Int

J

Radiat

Oncol

Biol

Phys. 2005; 61(2):400-8.

Rectal Morbidity

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Slide24

Primary Cryotherapy Summary

Efficacies appear to be similar across treatments

Cryoablation may be better for high risk patients

Morbidities differ across treatments

Urinary function may be better for cryoablation over surgery

Bowel function may be better for cryoablation over radiation

Impotence is likely after primary cryoablation

May be reduced with active rehabilitation

Patients must discuss specific circumstances and possible risks and benefits of cryoablation with their urologist

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Salvage Cryotherapy for Post-Radiotherapy Recurrence

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46,870 localized CaP, XRT/brachy

32% biopsy proven failures =

15,000

Reported treatments for radiation failures:

Hormone therapy 93.5 %

Radical prostatectomy 0.9 %

Cryotherapy 3.0 %

Radiation Therapy Failure

Agarwal

PK et al. Cancer 2008; 112:307

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Slide27

Salvage Cryotherapy Patient Selection

2008 AUA Best Practice Statement

Men with organ confined disease with positive biopsy

confirming disease in prostate.

Ideal Patient

PSA < 10

ng

/mL* (≤ 4

ng/mL is optimal**)Long PSA doubling timeNo evidence of seminal vesicle invasionLife expectancy > 10 yearsNegative metastatic evaluation

*Definition of Low Risk

**More detail on next slides

Babbian

et al. J

Urol

2008; 180

(5):1993-2004

27

Slide28

Salvage Cryotherapy Data HighlightsTimeframes up to 7 years

5

Over 1,000 patients studied

1-7Overall bDFS = 42%-69%1-7

42%

bDFS

study still showed 96% disease-specific survival

2

Return to potency for largest study = 40%

1Rectal injury ≤ 2.2%1,3,4,7Incontinence ≤ 13%1,3,4,71Dhar et al, J Urol 2010; 183(4 Supl):e184 Abstract 467. 2Pisters et al, J Urol

2009; 182(2):517-27.

3

Ismail et al, J

Urol

2008; 179(4

Supl

):184 Abstract 525.

4

Donnelly et al, Pros Can Pros

Dis

2005; 8(3):235-42.

5

Bahn et al,

Clin

Pros Can 2003; 8(3):111-4.

6

Izawa et al, J

Clin

Oncol

2002; 20(11):2664-71.

7

Katz et al, Rev in

Urol

2002; 4(

Supl

2):S18-23.

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Salvage Cryotherapy Efficacy Comparison

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Failure-Free Survival (5 Years)

Parekh A, et al.

Semin

Radiat

Oncol

2013; 23: 222-234

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Slide31

Salvage Cryotherapy Morbidity Comparison

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Slide32

Morbidities

Parekh A, et al.

Semin

Radiat

Oncol

2013; 23: 222-234

32

Slide33

1

Pisters LL, et al. J Urology 1997; 157(3): 921-5

Salvage Cryotherapy Summary

Efficacies appear to be similar for CA, RP and BT

Morbidity risk for RP is significantly higher

Formidable operation with risk of blood loss, rectal injury and significant postoperative complications

1

Stricture and fistula rates for brachytherapy are higher

Incontinence rate for brachytherapy is lower

Patients must discuss specific circumstances and possible risks and benefits of cryoablation with their urologist

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Prostate Cryotherapy SummaryShould be offered as an option to men seeking treatment

Any grade, non-metastatic disease

Less invasive than surgery

Can be performed with spinal block

Efficacy comparable to other therapies

Minimal morbidity except for potency

Salvage for radiation recurrence

Lower morbidity than radical prostatectomy

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Questions?