All the truth about Cryotherapy and HIFU for LPca Francois-Joseph Murat, MD Lyon, France
1rst Generation  2nd Generation 3rd Generation 1964   1980‘s   1990‘s Cryotherapy :Historical considerations
Prototypes  1rst Generation 2nd Generation 1993-2000   2000-2005   2006- HIFU: Historical considerations
<ul><li>Transperineal approach. Urethral warmer </li></ul><ul><li>Cryo probe nber depending on prostate volume </li></ul><...
<ul><li>Transrectal approach </li></ul><ul><li>Elementary lesion nber depending on prostate volume </li></ul><ul><li>Real-...
1. Thermal effects Intra/extra cellular ice formation Endothelial damages: ischemia rupture of cell walls 2. Mechanical ef...
1. Thermal effects 2. Mechanical effects fast temperature rise  (>80°C) generation of gas bubbles collaps of cavities: cav...
coagulation necrosis Early feedback (M3) on treatment efficacy 2 treatments but a unique histological aspect
ONCOLOGICAL RESULTS
Local Control: Negative Biopsy Rate « the strongest predictor of biochemical failure was post treatment biopsy status » Ze...
Local Control: Negative Biopsy Rate Cryotherapy: 76.5% - 88%* control biopsies not performed systematically  after cryo * ...
1. Gelet et al, J Endourol. 2000; 2. Gelet et al, Eur Urol. 2001; 3. Poissonnier et al Prog Urol. 2003; 4. Poissonnier et ...
Warnings biochemical Disease Free Survival (bDFS): No validated definition  ASTRO or Phenix +++ PSA thresholds (<0.2ng/ml,...
5-year bDFS for  Low risk  prostate cancer  (range in the literature since 2000/all definitions of bDFS) 0 40 80 100 HIFU ...
5-year bDFS for  Low risk  prostate cancer   (range in the literature since 2000/all definitions of bDFS) 0 40 80 100 HIFU...
5-year bDFS for  Intermediate risk  prostate cancer   (Range in the literature since 2000/all definitions of bDFS) 0 40 80...
0 40 80 100 87% 1 77% 2 89% 3 71% 4 bDFS (%) 87% 7 72% 8 94% 5 40% 6 60 20 1. Robertson et al J Endourol 2009. 2. Blana et...
TOXICITY ?
Incontinence 0 10 20 30 7% 1 2.3% 2 49% 3 5% 4 Incidence (%) 1% 12 8% 11 † excluding grade I, ‡pad rate. 1. Ficarra et al,...
Rectal Complications  0 1 2 3 4 5 RT Occurence (%) 0 10 20 30 40 50 HIFU RT 43% 0% Occurence (%) None  reported Severe (fi...
Bladder Outlet Obstruction 1. Uchida et al, BJU Int. 2006; 2. Poissonier et al, Eur Urol. 2007; 3. Elliot et al, J Urol. 2...
Impotence ?
Impotence 1. Blana et al Urology. 2004. 2. Thuroff et al. J Endourol. 2003. 3. Langenhuisen et al Eur Urol 2008. 4. Finley...
Take Home messages   <ul><li>HIFU and Cryo   </li></ul><ul><li>effective in full gland ablation for LPca </li></ul><ul><ul...
<ul><li>Is full gland ablation the future of localized prostate cancer treatment ??? </li></ul>
EAU Guidelines <ul><li>« Although focal therapy is currently not the standard treatment for men with organ-confined Pca, i...
Different Focal strategies Cryo or HIFU allow different kind of focal strategies Hemiablation Nerve Sparing Zonal
Focal therapy : From Outsiders to winners ! Effective in tissue destruction Ability to partial treatment Minimally invasiv...
Focal therapy: the winner is ???? Cryo ? HIFU ?
1. Bahn et al. J Endourol, 2006; 2. Onik et al. Urol Oncol, 2008; 3. Truesdale et al. Cancer Journal, 2010; 4. Van Velthov...
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ECCLU 2011 - F.J. Murat - Prostate cancer: All the truth about local treatment options T1-T2 - High-intensity focused ultrasound and cryotherapy

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ECCLU 2011 - F.J. Murat - Prostate cancer: All the truth about local treatment options T1-T2 - High-intensity focused ultrasound and cryotherapy

  1. 1. All the truth about Cryotherapy and HIFU for LPca Francois-Joseph Murat, MD Lyon, France
  2. 2. 1rst Generation 2nd Generation 3rd Generation 1964 1980‘s 1990‘s Cryotherapy :Historical considerations
  3. 3. Prototypes 1rst Generation 2nd Generation 1993-2000 2000-2005 2006- HIFU: Historical considerations
  4. 4. <ul><li>Transperineal approach. Urethral warmer </li></ul><ul><li>Cryo probe nber depending on prostate volume </li></ul><ul><li>Real-time US and thermal monitoring </li></ul>Cryotherapy : a minimally invasive therapy
  5. 5. <ul><li>Transrectal approach </li></ul><ul><li>Elementary lesion nber depending on prostate volume </li></ul><ul><li>Real-time US monitoring </li></ul>HIFU : a minimally invasive therapy
  6. 6. 1. Thermal effects Intra/extra cellular ice formation Endothelial damages: ischemia rupture of cell walls 2. Mechanical effects freezing (-40°C) and thawing process Cryotherapy: Physical aspects
  7. 7. 1. Thermal effects 2. Mechanical effects fast temperature rise (>80°C) generation of gas bubbles collaps of cavities: cavitation High Intensity Focused Ultrasound: Physical aspects
  8. 8. coagulation necrosis Early feedback (M3) on treatment efficacy 2 treatments but a unique histological aspect
  9. 9. ONCOLOGICAL RESULTS
  10. 10. Local Control: Negative Biopsy Rate « the strongest predictor of biochemical failure was post treatment biopsy status » Zelefsky et al. J Urol, April 2008
  11. 11. Local Control: Negative Biopsy Rate Cryotherapy: 76.5% - 88%* control biopsies not performed systematically after cryo * Bahn et al, 2002/ Cohen et al , 2008/ Jones et al, 2008 / Caso et al, 2010. HIFU: 73% - 93% control biopsies systematic 3-6 mo after HIFU
  12. 12. 1. Gelet et al, J Endourol. 2000; 2. Gelet et al, Eur Urol. 2001; 3. Poissonnier et al Prog Urol. 2003; 4. Poissonnier et al Eur Urol. 2007; 5. Thuroff et al J Endourol. 2003; 6. Chaussy et al Curr Urol Rep. 2003; 7. Urology. 2004; 8. Ficarra et al BJU Int. 2006;98(6):1193-8; 9. Prostate Cancer Prostatic Dis. 2006;9(4):439-43; 15. Blana et al Urology 2008;72:1329-33:Urol. 2006 Mar;13(3):228-33; 14. Blana et al European Urol 2008; 53 1194-1203;10. Blana et al Urology 2008;72:1329-33; 16. Mearini et al J Urol. 2009;181:105-112. 17. Scardino et al, NCI Monogr. 1988;(7):95-103; 18. Borghede et al, Br J Urol. 1997 Aug;80(2):247-55. 19. Crook et al, Int J Radiat Oncol Biol Phys. 2000 Sep 1;48(2):355-67; 20. Zelefsky et al, J Urol. 2001 Sep;166(3):876-81; 21. Pollack et al, Int J Radiat Oncol Biol Phys. 2002 Nov 1;54(3):677-85; 22. Zelefsky et al, J Urol. 2008 Apr;179(4):1368-73 Local Control: Negative Biopsy Rate
  13. 13. Warnings biochemical Disease Free Survival (bDFS): No validated definition ASTRO or Phenix +++ PSA thresholds (<0.2ng/ml, <0.5 ng/ml, <1ng/ml)
  14. 14. 5-year bDFS for Low risk prostate cancer (range in the literature since 2000/all definitions of bDFS) 0 40 80 100 HIFU Cryo 92% 1 77% 2 85% 3 76% 4 bDFS (%) 60 20 1., Robertson et al J Endourology 2009. 2. Blana et al Urology 2008. 3. Jones et al J Urol 2008. 4. Long et al Urology 2001.
  15. 15. 5-year bDFS for Low risk prostate cancer (range in the literature since 2000/all definitions of bDFS) 0 40 80 100 HIFU Cryo 92% 1 77% 2 85% 3 76% 4 bDFS (%) Beam RT RP 94% 7 84% 8 100% 5 55% 6 60 20 1., Robertson et al J Endourology 2009. 2. Blana et al Urology 2008. 3. Jones et al J Urol 2008. 4. Long et al Urology 2001. 5. De Meerleer et al Radiother Oncol. 2007. 6. Goldner et al Strahlenther Onkol. 2006. 7. Stokes et al Int J Radiat Oncol Biol Phys. 2000. 8. Ciezki et al Int J Radiat Oncol Biol Phys. 2004.
  16. 16. 5-year bDFS for Intermediate risk prostate cancer (Range in the literature since 2000/all definitions of bDFS) 0 40 80 100 87% 1 77% 2 89% 3 71% 4 bDFS (%) 60 20 1. Robertson et al J Endourol 2009. 2. Blana et al Urology 2008. 3. Bahn et al Urology 2002. 4. Long et al Urology 2001. HIFU Cryo
  17. 17. 0 40 80 100 87% 1 77% 2 89% 3 71% 4 bDFS (%) 87% 7 72% 8 94% 5 40% 6 60 20 1. Robertson et al J Endourol 2009. 2. Blana et al Urology 2008. 3. Bahn et al Urology 2002. 4. Long et al Urology 2001. 5. De Meerleer et al Radiother Oncol. 2007. 6. Goldner et al Strahlenther Onkol. 2006. 7. Stokes et al Int J Radiat Oncol Biol Phys. 2000. 8. Ciezki et al Int J Radiat Oncol Biol Phys. 2004. HIFU Cryo Beam RT RP 5-year bDFS for Intermediate risk prostate cancer (Range in the literature since 2000/all definitions of bDFS)
  18. 18. TOXICITY ?
  19. 19. Incontinence 0 10 20 30 7% 1 2.3% 2 49% 3 5% 4 Incidence (%) 1% 12 8% 11 † excluding grade I, ‡pad rate. 1. Ficarra et al, BJU Int. 2006 Dec;98(6):1193-8. 2. Chaussy and Thuroff Curr Urol Rep. 2003;4(3):248-52. 3. Steineck et al, N Engl J Med. 2002 Sep 12;347(11):790-6; 4. Abou-Elela et al, Eur J Surg Oncol. 2007; 33:96-101; 5. Reis et al, Int Urol Nephrol. 2004;36(2):187-90; 6. Feigenberg et al, Int J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):956-64; 7. Matalinska et al, J Clin Oncol. 2001 Mar 15;19(6):1619-28; 8. Potosky et al, J Natl Cancer Inst. 2000 Oct 4;92(19):1582-92; 9. Zelefsky et al, Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1111-6; 10. Brabbins et al, Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):400-8. 11. Long et al, Urology. 2001 Mar;57(3):518-23; 12. Donnelly et al, Urology. 2002 Oct;60(4):645-9; 10% 5 1% 6 7% 7 4% 8 0% 10 15% 9 HIFU RP Cryo Brachy EBRT IMRT
  20. 20. Rectal Complications 0 1 2 3 4 5 RT Occurence (%) 0 10 20 30 40 50 HIFU RT 43% 0% Occurence (%) None reported Severe (fistula – requiring surgery) Minor (blood, diarrhea…) ≤ 0.6 % 2 0% ≤ 0.5 % 1 HIFU Cryo Cryo 0% ≤ 0.5 % 3 None reported 1. Poissonnier et al Prog Urol. 2003; 2. Chrouser et al J Urol 2005; 3. Bahn et al,Urology. 2002.
  21. 21. Bladder Outlet Obstruction 1. Uchida et al, BJU Int. 2006; 2. Poissonier et al, Eur Urol. 2007; 3. Elliot et al, J Urol. 2007; 4. Benoit et al, Urology. 2000; 5. Zefelsky et al, J Clin Oncol 1999; 6. Zefelsky et al, J Urol. 2006; 7. Shelley et al, Cochrane Database Syst Rev. 2007. 0 20 40 60 80 100 Incidence (%) 27% 1 6% 2 25.7% 3 2.7% 3 2% 7 55% 7 12% 4 8% 5 1.73 3 / 3% 6 Not reported HIFU RP Cryo Brachy EBRT IMRT
  22. 22. Impotence ?
  23. 23. Impotence 1. Blana et al Urology. 2004. 2. Thuroff et al. J Endourol. 2003. 3. Langenhuisen et al Eur Urol 2008. 4. Finley et al Urol Clin N Am 2010. 5. Matalinska et al, J Clin Oncol. 2001. 6. Walsh et al, J Urol. 2000. 7. Incrocci et al, Acta Oncol. 2005. 8. Incrocci et al, Acta Oncol. 2005. 9 Potosky et al, J Natl Cancer Inst. 2000. 10. Matalinska et al, J Clin Oncol. 2001. 0 20 40 60 80 100 Incidence (%) 53% 1 13% 2 91% 5 14% 6 50% 4 90% 3 51% 7 5% 8 63% 9 41% 10 Not reported HIFU RP Cryo Brachy EBRT IMRT
  24. 24. Take Home messages <ul><li>HIFU and Cryo </li></ul><ul><li>effective in full gland ablation for LPca </li></ul><ul><ul><li>oncological outcomes equivalent to other treatment options, </li></ul></ul><ul><ul><li>Morbidity equivalent or better than the other treatment options. </li></ul></ul><ul><li>Lg-term Fup and randomized controlled trials are still missing. </li></ul>
  25. 25. <ul><li>Is full gland ablation the future of localized prostate cancer treatment ??? </li></ul>
  26. 26. EAU Guidelines <ul><li>« Although focal therapy is currently not the standard treatment for men with organ-confined Pca, it is the therapeutic approach with the most important future potential. » </li></ul>
  27. 27. Different Focal strategies Cryo or HIFU allow different kind of focal strategies Hemiablation Nerve Sparing Zonal
  28. 28. Focal therapy : From Outsiders to winners ! Effective in tissue destruction Ability to partial treatment Minimally invasive treatment No dose limitation: perfect repeatability The lower the treated volume, the lower the complication rate HIFU Cryo HIFU Brachy Cryo HIF U Brachy Cryo HIFU Surgery/EBRT Brachy/HIFU Cryo/PDT Proven partial Treatment capacity Minimal invasiveness Repeatability
  29. 29. Focal therapy: the winner is ???? Cryo ? HIFU ?
  30. 30. 1. Bahn et al. J Endourol, 2006; 2. Onik et al. Urol Oncol, 2008; 3. Truesdale et al. Cancer Journal, 2010; 4. Van Velthoven personnal communication. 5. French association of urology, current multicenter trial. FOCAL THERAPY CRYO HIFU Study 1 2 3 4 5 Pts 31 48 77 24 140 Fup (Mo) 70 54 24 20 9 bDFS 93% 94% 73% 82.6% NA Potency (%) 89 90 93 NA 100 Continence (%) 100 100 100 100 100

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