S Crouzet, O Rouvière, JY Chapelon, F Mege, X martin, A Gelet

S Crouzet, O Rouvière, JY Chapelon, F Mege, X martin, A Gelet

Why HIFU? Efficacy demonstrated Real time control of the target Early control of the necrosis area is possible with MRI or TRUS using contrast agents (Sonovue) Repeatability demonstrated HIFU is not a therapeutic impasse Salvage EBRT is efficient after HIFU with few side effects :Rivière et all (Eur Urol 2010) Salvage Radical surgery is feasible : Lawrentschuk et all (J of Urol 2011)

HIFU treatment can be modulate «Standard» HIFU HIFU «nerve sparing» HIFU Hémi-ablation Focal HIFU

Focal treatment with HIFU in 69 patients 2002 2004 : 37 nerve sparing procedures 2009 2011 : 32 hemi ablation procedures Primary care : 11 Salvage post EBRT or BRACHY : 21

Nerve sparing HIFU Inclusion criteria: T1/T2 localized PC PSA < 15 Gleason 7 Positive biopsies in one lobe (6 core biopsies) IIEF 5 > 17 Procedure: 6 mm safety margin

Follow up Serial PSA measurements Control biopsies 3 months after the HIFU session Second HIFU session or EBRT in case of positive biopsy after the first or the second HIFU session Progression definition : Phoenix criteria or additional therapy

Treatment characteristics TURP before HIFU (during the same anesthesia) ABLATHERM : Maxis device HIFU sessions : 1.35 per patient one HIFU session : 25 pts (68%) two HIFU sessions : 12 pts (32%) Median Follow up : 66 months (12 98)

Results Mean nadir value : 1.25 ng/ml Median nadir value : 0.14 ng/ml Nadir value 0.3 : 26 pts (70%) Prostate volume : 8.5 ± 6 cc Salvage EBRT : 10 patients (27%)

Results Control biopsies after the first HIFU session: Negatives: 20/37 (64%) Positives :17/37 (46%) Ipsi lateral : 10 (27%) Contra lateral : 5 (19%) Bilateral : 2 (5%) Control biopsies after the second HIFU sessions : negative 8/12 patients (66%)

Results Survival rates at 60 months Overall survival rate : 100% Cancer specific survival rate : 100% Metastasis free survival rate : 100% Progression free survival rate : 68% [49 82]

Results Progression Free Survival rates at 60 months low risk : 79% [54 92} intermediate risk : 50% [29 81] p = 0.07

Results IIEF 5 score development after the first HIFU session (37 pts) median IIEF5 score before HIFU 22 after HIFU 16 A significant decrease of potency was observed after the first NS HIFU session A score IIF5 17 was achieved in only 54% of patients

Oncologic outcome : Conclusion High rate of positive control biopsies : 46% 32% of patients received a second HIFU session Progression free survival rate : 79% in low risk patients 27% of salvage EBRT IIEF5 score : Significant decrease after the NS HIFU session : IIF5 17 was only achieved in 54% of patients

HIFU hemiablation 2009 2011 : 32 hemi ablation Primary care : 11 Salvage post EBRT or BRACHY : 21

HIFU hemiablation : Primary care Low risk patients (d Amico) Patients selection using multimodalities MRI and biopsies (12 randomized cores + 2 cores in each area of interest identified on MRI) Unilateral disease 2 adjacent positive sextant Safety distance between apex and urethra and the MRI abnormal area: 6 mm from the apex, >5 mm from the urethra and distance from posterior capsule <26mm

HIFU hemiablation : Primary care No associated TURP ABLATHERM Integrated Imaging 4mm safety margin from the apex Treaded area 4 mm safety margin from the apex

HIFU hemiablation : Primary care Follow up Serial PSA measurement Control biopsies after MRI : 12 randomized biopsies + 2 cores in each area of interest Questionnaires IPSS ICS IIEF QLC 30

HIFU hemiablation : Results A 50% decrease in PSA value was seen at 3 months Median PSA before HIFU 4.25 nadir value 2.46

HIFU hemiablation : Results Control biopsy available : 9 pts Negatives : 6 pts (77.7% in the treated lobe) Positives : 3 pts Ipsi lateral lobe :1 Contra lateral lobe:1 Ipsi lateral lobe and contra lateral lobe :1

HIFU hemiablation : Results IPSS and Continence IPSS Before HIFU 8 After HIFU 5 ICS Before HIFU 0 After HIFU 0

HIFU hemiablation : Results QLC 30 median before HIFU 31 after HIFU 30

HIFU hemiablation : Pathological outcome at 6 months Apex Middle part Base

Recurrence in the non treated 12 month after treatment lobe: MRI Before HIFU PO day 2

HIFU hemiablation : Conclusion Work in progress: long term outcome? Selection of patients is difficult and expensive (MRI) Preliminary results seems similar to the results of Ahmed & Emberton on 20 patients (J Urol:2011.185,1246 1255) low rate of side effects (continence and potency) PSA value reduced by only 50% (Ahmed study 80%)

Salvage HIFU hemiablation Salvage HIFU after EBRT or Brachytherapy failure is feasible and efficient Total salvage HIFU induces side effects: Incontinence grade 2/3 : 20% Bladder outlet obstruction : 15% Early identification of local recurrence is possible using MRI and targeted biopsies

Salvage HIFU hemiablation : Inclusion criteria Local recurrence after EBRT or Brachytherapy No metastasis (bone scan, CT scan, pet cholin scan) Recurrence demonstrated with MRI Unilateral proven disease : MRI Randomized biopsies (12 + seminal vesicles) and MRI guided biopsies

Salvage HIFU hemiablation : Treatment Unilateral associated bladder neck incision ABLATHERM Integrated Imaging : specific parameters Urethra included in the treated area 0 4 mm safety margin from the apex Treaded area 0-4 mm safety margin from the apex

Salvage HIFU hemiablation : Follow up MRI at day 2 Serial PSA measurement At 6 months : MRI and 12 randomized biopsies + 2 cores in each area of interest Questionnaires IPSS ICS QLC 30

Salvage HIFU hemiablation 21 patients included After EBRT: 14 After Brachytherapy: 7 Mean age 66±5 years (median 65) PSA 3.56±2.2 ng/ml (median 3) Prostate volume : 15.7cc (median 16 ) Number of positive core: 3.5 per patient

Salvage HIFU hemiablation : Results A 90% decrease in PSA value was seen at 3 months Median PSA Before HIFU 3.06 Nadir value 0.34

Salvage HIFU hemiablation : Control biopsy available: 10 pts Negatives : 8 pts (80 %) Positives : 2 pts Ipsi lateral lobe :1 Contra lateral lobe : 1 Only 3 patients needed an androgen deprivation for biochemical failure without local relapse One metastasis Results

Salvage HIFU hemiablation : Recto urethral fistula: 0 Continence No pads :18 (85%) Incontinence grade 1 : 2 (10%) Incontinence grade 2 : 1 (5%) Results Incontinence grade 3 (AUS needed): 0 Bladder outlet obstruction:1 Potency : partial loss of potency (IPF5 inhibitor use) in 3 out of 8 potent patients (37%)

Salvage HIFU hemiablation after ERBT failure PSA 4.68 before salvage HIFU 23/04/2009 Nadir 1,09 05/10/2009 Negative control biopsies 13/10/2009 Last PSA value 1.52 12/04/2011 Before HIFU Day 2 after HIFU one year after HIFU

Salvage HIFU hemiablation after brachytherapy failure MRI before HIFU MRI after HIFU

Salvage HIFU hemiablation after brachytherapy failure Initial PSA : 4 ng, Apical relapse : 2 positives biopsies No side effect. Nadir PSA : 0.3ng/ml PSA at 7 years 1.1ng/ml

Feasible Salvage HIFU hemiablation: Selection of patients is easy using MRI and targeted biopsies High efficacy conclusion The rate of side effect (incontinence) is low compared to standard salvage HIFU Early identification of local relapse is needed

Nerve sparing HIFU :+/ Conclusion High rate of re treatment or salvage EBRT Significant decrease of potency HIFU hemi ablation for selected low risk patient : + low rate of side effects lack of long term outcomes Salvage HIFU hemiablation : +++ low rate of side effects local control