Focal Therapy for Localized Prostate Cancer Future directions

Transcription

1 Smilow Comprehensive Prostate Cancer Center Focal Therapy for Localized Prostate Cancer Future directions Samir S. Taneja, MD The James M. and Janet Riha Neissa Professor of Urologic Oncology Professor of Urology and Radiology Director, Division of Urologic Oncology Co-Director, Smilow Comprehensive Prostate Cancer Center GU Program Leader, New York University Cancer Institute

2 Disclosures Consultant: Hitachi-Aloka Biobot Royalties: Elsevier Sponsored Scientific Studies: Trod Medical

3 Acknowledgements Funding/Support Joseph and Diane Steinberg Charitable Trust MyFifident Foundation Tisch Family NYU CTSI Department of Defense NYU Andrew Rosenkrantz Fang Ming Deng Ming Zhou Jonathan Melamed Henry Rusinek Graham Wiggins Herbert Lepor William Huang Trainees/Students James Wysock, NYU Marc Bjurlin, NYU Susan Marshall, NYU Basir Tareen, NYU Clement Orczyk, Lille, Fr Julien Lenobin, Lille, Fr Antonio Derosa, Brazil Xiasong Meng, NYU Neil Mendhiratta, NYU Michael Fenstermaker, NYU

4 Challenges of the Focal Therapy Paradigm Candidate Selection Method of Delivery Image guided Biopsy guided Treatment Planning Extent Adequacy of Margin Outcome Measures How do we prove benefit Cost QOL Survival

5 Available Energy Sources for Focal Ablation Laser Electroporation Radiofrequency (bipolar) Photodynamic Therapy High-intensity Focused Ultrasound Cryosurgery Radiation (focal/interstitial) Surgery

6 Available Energy Sources for Focal Ablation Laser Electroporation Radiofrequency (bipolar) Photodynamic Therapy High-intensity Focused Ultrasound Cryosurgery Radiation (focal/interstitial) Surgery

7 Key Concepts Balance of focal treatment vs. adequacy of treatment Confluence of tissue destruction Inaccuracy of localization Can be overcome by increasing tissue treated Dispersion of thermal energy Contributes to toxicity

8 Early Outcomes Early outcomes with cryosurgical hemiablation quite good Robust declines in PSA Negative biopsy in approximately 75% Low rates of incontinence/urinary dysfunction Modest reduction in erectile function Efforts to improve more targeted treatment (laser), less thermal dispersion (VTP-PDT) result in lower toxicity, higher rates of residual cancer

9 Potential Reasons for Focal Therapy Failure Poor localization by imaging Inadequate detection Incomplete demonstration of tumor Poor staging biopsy Implies disease missed by MRI and biopsy Under-sampling at baseline Inadequate treatment Under-treatment of target zone Inadequate margin

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11 Non-confluent Undertreatment

12 Lenobin et al, J Urology, 2015

13 100.00% 80.00% High SS 9 mm 60.00% 63.22% % Max Hausdorff 40.00% 20.00% 0.00% % 29.30% % % %Max HD Mean % Tumor Diameter on T2WI (+)SD (-)SD Lenobin et al, J Urology, 2015

14 Co-Registration guided focal ablation Biopsy targeting by co-registered biopsy Concordance of MRI, targeted biopsy, and systematic biopsy Lesion size and focality limited to favorable treatment plan Ablation by cognitive ultrasound based planning using cryo, RF Follow-up co-registered biopsy Fusion using pre and post treatment MRI

15 msr Right posterolateral mid-apex: Gleason 6 (3/4 cores) Standard core -Right medial mid: Gleason 6 (1 core)

16 Ablation planning sequence Basal extent Apical extent Widest diameter

17 Focal Ablation - Cryo

18 NYU cryoablation experience 39 men underwent focal cryosurgical ablation (median follow-up 18.4 mo) 32 men with no previous radiation therapy (median follow-up 17.6 months) 7 men with previous radiation therapy (median follow-up 20.5 months)

19 Biopsy Outcomes 25/39 patients have undergone follow-up biopsy (median 8.31 mo) Median time last biopsy 8.31 months 21 had focal therapy no previous radiation treatment (15 negative; 3 with Gleason 6; 3 with Gleason >=7) 4/30 had focal therapy with previous radiation treatment (4 reported negative biopsy) 4 retreated (2 repeat cryoablation; 1 cyberknife; 1 radical prostatectom, 2 AS) Overall 19/25 biopsy negative Positive biopsies largely margin or distant recurrences

20 Median PSA/IPSS/SHIM Scores Baseline 3 month 6 month last visit 5 0 PSA IPSS SHIM

21 Phase II Trial of Bipolar RF for Co-Registration Guided Focal Cryoablation Single institution investigator init at NYU 21 men Concordant MRI, MRI fusion biopsy, systematic biopsy Gleason 3+4 PSA 10 Treatment planning by cryo fusion/planning software Repeat biopsy by co-registration at 6 months Primary endpoint negative biopsy Secondary endpoint QOL

22 Encage TM Working principle A Faraday cage deflects energy and prevents any damage inside

23 Encage TM Working principle The same happens when energy source is inside the cage (external environment is protected)

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26 RFA Helical Coil Radiofrequency ablation is carried out through radio waves, a form of electromagnetic energy, produced by an electrical generator (Stockert Neuro N50). Energy type used for the ablation procedure utilizes a frequency of 500 khz.

27 Sagittal Ultrasound Image of Coil During Ablation

28 Case 2 T2WI DCE High b ADC

29 Case 3 T2WI ADC DCE Subtraction No residual evidence of tumor Ablation cavity appears to encompass previously noted tumor No significant extraprostatic necrosis

30 T2WI and subtraction DCE at 3 days (top) and 7 days (bottom)

31 6 month Postop MRI Characteristics Patient 1: Ablation Cavity has significantly retracted in size Axial T2-weighted image and subtracted axial post-contrast T1-weighted image. Show small residual ablation cavity by 6 months postop. Patient 2

32 Effects on PSA PSA Baseline PSA 3 month PSA 6 mo 2 0 Pt * * Significant decrease, p=.004)

33 Effect on Urinary Function - IPSS Baseline IPSS 3 month 6 month 5 0 Pt * *NS

34 Effect on Sexual Function: SHIM Baseline SHIM 3 month 6 month 5 0 Pt * * *NS

35 Toxicity/Adverse Events 4/21 men had postop urinary retention requiring foley catheter, then successfully voided 3 days later 1 man with large pelvic hematoma following treatment, requiring hospital admission, but no intervention

36 Primary Endpoint: 6 month biopsy 16/21 men (20/25 lesions) with negative treatment zone biopsy (76%) 9/21 with negative biopsy (42.8%) 12/21 with residual cancer (56.2%) 7/21 with out of field residual disease 5/21 with in field residual disease 6/21 with in margin residual disease 3 men for re-treatment, 2 for RP, 1 for RT, 6 for AS

37 Case 3 T2WI DCE ADC b1500 PI-RADS 4/5 region, right mid posterolateral 10 x 10 mm Capsular bulge, no clear extracapsular extenstion

38 Cancer Detection Rates in 6 Month MRI Negative MRI Abnormal, likely post treatment 4 Abnormal, likely tumor Total Number Any Cancer In-field Cancer Gleason >=3+4

39 Spectrum of Energy Sources Laser Electroporation Bipolar RF VTP (PDT) HIFU Cryosurgery

40 Factors Affecting Choice of Energy Selection Extent of ablation Size of tumor/extent Method of tumor detection Image detected more focal Biopsy detected wider ablation Ability to achieve confluent destruction Location of tumor within the prostate Proximity to nerves Distance from rectum Apex

41 Future Directions Improving localization Integration of fusion software into treatment platforms Sonablate HIFU platform Improving confluence of treatment Real-time feedback regarding treatment Introduction of biologic adjuncts to ablation Improving margin control Better mapping tools Improving imaging platforms

42 Conclusions Focal therapy is evolving from fiction to fact Implementation is feasible, but the benefits remain to be validated Focal implies partial with adequate margin control Candidate selection and optimal method of guiding treatment will rely upon the goal of therapy Lesion ablative focal therapy requires validated, reliable cancer imaging strategies In the absence of image-detected disease, biopsy selection requires larger amounts of tissue be treated Long-term outcomes for validation will remain a challenge for the future