High Intensity Focused Ultrasounds for the treatment of Prostate Cancers Clinical update November D. Maruzzi - L. Ruggera

Transcription

1 High Intensity Focused Ultrasounds for the treatment of Prostate Cancers Clinical update November 2014 D. Maruzzi - L. Ruggera

2 HIFU development Second prototype Integrated Imaging First prototype: ABLATHERM Maxis Focal One 2013

3 Long term Clinical Results First line Treatment by EDAP TMS 3 report 10 year outcomes of Ablatherm HIFU from large patient populations followed years

4 by EDAP TMS Long-term Clinical Results First-line Treatment Ganzer et al Regensburg, Germany Thüroff et al Munich, Germany Crouzet et al Lyon, France 10 Year Cancer Specific Survival 10 Year Metastasis Free Survival Ablatherm HIFU Prostatectomy Ablatherm HIFU Prostatectomy Low % %* % 99%* Intermediate 96-98% 96-97%* 94-95% 94%* High 92% 92-95%* 86% 89%* *Boorjian et al J Urol Apr;179(4): ; Stephenson et al J Clin Oncol Sep 10;27(26):4300-5

5 by EDAP TMS Inclusion criteria: #localized PCa, clinical stage T1M0 T2M0 #PSA <30 ng/ml, #no previous radical therapy for PCa None of the patients were candidates for surgery because of age, comorbidity, or patient refusal.

6 Fig. 1 Influence of pre high intensity focused ultrasound (HIFU) risk group on biochemical free survival rates (Phoenix criteria) following HIFU therapy. D Amico risk group 5 yr BFSRs 8 yr BFSRs LOW 86% 76% INTERMEDIATE 78% 63% HIGH 68% 57% p < Biochemical recurrence (Phoenix definition) was observed in 205 patients (21.2%). ( p < 0.001) The 8 yr BFSRs in patients with and without previous ADT were 70% and 66%, respectively ( p = 0.992)

7 Fig. 2 Overall, prostate cancer (PCa) specific, and metastasis free survival rates following highintensity focused ultrasound (HIFU) treatment. 10 yr metastasis free survival rate low : 99% inter: 95% high: 86% Overall survival rate : 80%

8 PCa specific survival rate low : 99% inter: 98% high: 92%

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10 Nadir PSA (median 7.9 wk[range 1 52]) was a significant predictive factor for biochemical failure. PSA nadir 5 yr BFSRs 10 yr BFSRs < 0.3 ng/ml 88% 75% ng/ml 72% 32% 1.0 ng/ml 50% 23% p < 0.001

11 by EDAP TMS SALVAGE TREATMENT AFTER HIFU 371 pts (37.1 %) with rising PSA (Phoenix definition) 13.9% SRT alone 10.7% SRT plus ADT and/or CT 12.1% ADT alone 0.4% ADT plus CT ADDITIONAL TREATMENT BIOCHEMICAL FREE SURVIVAL RATE D Amico risk group 5 yr BFSRs 8 yr BFSRs LOW 81% 68% INTERMEDIATE 66% 53% HIGH 47% 38% SRT ADDITIONAL TREATMENT BIOCHEMICAL FREE SURVIVAL RATE D Amico risk group 6 yr BFSRs LOW 97% INTERMEDIATE 89% HIGH 63%

12 by EDAP TMS

13 by EDAP TMS Thüroff et al Munich, Germany

14 by EDAP TMS 80% OVERALL SURVIVAL Similar to current local Bavarian population survival statistics 95% 10-year metastasisfree survival rate NO CORRELATION BETWEEN OVERALL SURVIVAL AND RISK GROUP BDFS: 68% low risk 62% interm. risk 60% high risk < % Cancer specific survival rate >

15 SALVAGE TREATMENT FREE SURVIVAL by EDAP TMS 10 YEARS SALVAGE THERAPY-FREE RATE 98 % low risk 72% interm. risk 68% high risk

16 by EDAP TMS

17 Salvage publications Gelet et al. Urology 2004 Murat et al. European Urology 2008 Baco and Berge. Scan J of Urol and Nephrol 2010 & International J of Urology 2011 Crouzet et al. European Urology 2012

18 by EDAP TMS Salvage publications 290 patients 5 yr cancer specific survival rate: 80% 5 yr metastasis free rate: 79.6% specific post-radiation treatment parameters Side effects (Post-radiation parameters) Urinary incontinence Grade I 25% Grade II 11% Grade III 8% BOO 12% Uretrorectal fistula 0.4% Pubic bone osteitis 2.5%

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20 Focal Therapy Rationale Focal therapy could represent the perfect balance between Active Surveillance and Over treatment Focal Therapy could be the future of prostate cancer therapies Focal therapy relies on accurate imaging to target the area to be treated Focal Therapy needs controlled energy to treat the designated area Focal therapy needs precise tools to evaluate the treated area

21 The 3 pillars of Focal Therapy 1. Localization 2. Treatment 3. Validation

22 The 3 pillars of Focal Therapy 1. Localization 2. Treatment 3. Validation

23 Focal Imaging 1. Localization MR images reading Identification and Record of Tumors Image registration Software tools

24 The 3 pillars of Focal Therapy 1. Localization 2. Treatment 3. Validation

25 Focal Treatment 2. Treatment Position Accurately energy to be delivered Precise energy delivery Ability to follow precisely a contour

26 The 3 pillars of Focal Therapy 1. Localization 2. Treatment 3. Validation

27 Focal Control 3. Validation Immediate validation of effective treatment Compare effectively treated areas with planning Ability to complete treatment if necessary

28 Focal HIFU publications Hemiablation treatments Two strategies Multi-focal treatments

29 Focal HIFU publications 41 patients treated by focal HIFU 92% free from clinically significant PCa 100% continence preservation QOL preservation 89% erection sufficient for penetration

30 Focal HIFU publications 31 patients treated by HIFU Hemiablation 11% positive controlateral biopsy 100% continence preservation 75% erection sufficient for penetration Our study suggests that hemiablation HIFU is a valid focal therapy strategy, feasible in dayto day practice with good promising results

31 Salvage Focal HIFU patients treated by Hemi salvage HIFU 80% negative Biopsy 93% continence preservation QOL preservation

32 Focal One Proof of concept study 10 patients Stage T1-T2a Max PSA 10 ng/ml Gleason 6 or 7 (3+4) One single visible tumor on MRI targeted biopsy Safety margin of 6mm around the tumor Contrast enhanced US control at the end of the procedure Courtesy of Dr S. Crouzet (Edouard Herriot Hospital, Lyon, France)

33 Focal One Proof of concept study Patients characteristics Mean age : 65.8±5.5 years old Stage : T1= 9 patients T2a= 1 patient Gleason score: 6= 7 patients 7(3+4) = 3 patients PSA : 4.47± 3.7 ng/ml Mean prostate volume : 50±23 cc Courtesy of Dr S. Crouzet (Edouard Herriot Hospital, Lyon, France)

34 Focal One Proof of concept study Results Treated volume: 14cc ( ) : 28% Nadir PSA : 3.46 ±2ng/ml 2 infections after control biopsy No urinary retentions and no dysuria No incontinence Potency preserved (IEEF score >17) on 9 patients at 3 months on 10 patients at 6 months Courtesy of Dr S. Crouzet (Edouard Herriot Hospital, Lyon, France)

35 Focal One Proof of concept study Pathological results at 1 month CEUS guided biopsy: 2 in the treated area 3 around the treated area 100% of negative biopsy Courtesy of Dr S. Crouzet (Edouard Herriot Hospital, Lyon, France)

36 Focal One Proof of concept study Conclusions Very promising pathological results Very low side effects Imaging is essential Non answered questions Definition of failure Follow up modalities Courtesy of Dr S. Crouzet (Edouard Herriot Hospital, Lyon, France)

37 Publications In 2015 Focal results will be published: Hemiablation trial publication Focal HIFU from 4 French centers Focal One proof of concept study (10 focal patients) Two Match-paired studies should be published: HIFU vs RP HIFU vs RTx