Prostate Focal Therapy: What s on the Horizon? Thomas J Polascik, MD FACS

Transcription

1 Prostate Focal Therapy: What s on the Horizon? Thomas J Polascik, MD FACS

2 Current State of Prostate Focal Therapy Patient Selection Focal Ablation Technology and Technique Follow-up/ Surveillance after Focal Therapy Long Term Outcomes

3 Patient Selection: Evolution in Consensus De la Rosette 2010 (48) Ahmed 2012 (49) Donaldson 2015 (50) Tay 2016 (51) Goal Eradication of all cancer Eradication of all cancer Eradication of clinically significant cancer Cancer Determination mpmri Can be recommended at state of art centers Disease Factors Eradication of clinically significant cancer Overall TMB TMB and mpmri TMB or systematic + mpmri mpmri + systematic biopsy Biopsy of suspicious lesion Biopsy of nonsuspicious area Recommended No clear recommendation Recommended as far as possible - To be studied Recommended Recommended, MRI-TRUS Fusion Biopsy - TMB Recommended Recommended, at least 12 core TRUS biopsy Risk Group Low to moderate risk - Intermediate Intermediate Maximum grade Maximum size Residual Disease Permissible Patient Factors Age/ Life Expectancy Sexual Function T2a clinically or T2b radiologically - No agreement Up to 1.5 ml or 3 ml if not crossing midline; up to 20% of prostate volume or 25% if crossing midline None None 3+3 up to core length 5mm 3+3 up to core length 1mm At least 10 year life expectancy Effect unknown, counselling recommended NA Not a primary determinant; best suited to life expectancy >10 years and not <5 years According to major guidelines. No upper or lower limit whereby focal is contraindicated NA NA Important, but not the only indication for choosing focal therapy

4 Patient Selection: today s pitfalls 12 Core Biopsy Selecting unilateral disease for hemi-ablation: 88.4% sensitivity, 34% specificity TTMB mpmri + Fusion Bx Higher detection rate Invasive Needs OR Complications Reader dependent Fusion biopsy has many moving parts High NPV but consensus still points towards need for systematic biopsy

5 mpmri Reader-dependent Lesion identification Excluding extra-capsular extension Fusion Biopsy Dependent on quality of fusion Tay KJ, Gupta RT, Brown AF, Silverman RK, Polascik TJ. Defining the Incremental Utility of Prostate Multiparametric Magnetic Resonance Imaging at Standard and Specialized Read in Predicting Extracapsular Extension of Prostate Cancer. Eur Urol. 2016;70(2):

6 6

7 7

8 Newer Imaging Modalities PSMA-linked small molecules for imaging Evolution of radiolabels: 68 G vs 18 F (lower positron emission energy leading to greater contrast/ resolution) Multiparametric Ultrasound Development of advanced elastography techniques

9 PSMA-PET-MRI Fusion 68 Ga-PSMA PET MRI of a 50-year-old patient who had a rising serum PSA value (16 ng/ml at imaging) and two tumour-negative previous biopsy samples Maurer, T. et al. (2016) Current use of PSMA PET in prostate cancer management Nat. Rev. Urol. doi: /nrurol

10 PSMA-PET-MRI Fusion 68 G-PSMA-PET-MRI with Fusion Biopsy 16 cases, 6 histologically confirmed PCa of 7 suspicious cases Storz et al 18 F-DCFBC CT-PET with MRI Fusion 13 cases, PET was less sensitive than MR (0.17 vs 0.39) but more specific (0.96 vs 0.89) Rowe et al

11 Acoustic Radiation Force Impulse (ARFI) Imaging Matched B-mode, acoustic radiation force impulse (ARFI) and histologic prostate images of patient A. The first row shows an axial view (regular imaging plane) of the prostate; the second and third rows are two parallel coronal views. The axial imaging... Liang Zhai, Thomas J. Polascik, Wen-Chi Foo, Stephen Rosenzweig, Mark L. Palmeri, John Madden, Kathryn R. Nightingale Acoustic Radiation Force Impulse Imaging of Human Prostates: Initial In Vivo Demonstration Ultrasound in Medicine & Biology, Volume 38, Issue 1, 2012,

12 Acoustic Radiation Force Impulse (ARFI) Imaging Early study suggests good correlation between ARFI Index of Suspicion (IOS) and PIRADS score. Liang Zhai, Thomas J. Polascik, Wen-Chi Foo, Stephen Rosenzweig, Mark L. Palmeri, John Madden, Kathryn R. Nightingale Acoustic Radiation Force Impulse Imaging of Human Prostates: Initial In Vivo Demonstration Ultrasound in Medicine & Biology, Volume 38, Issue 1, 2012,

13 Focal Ablation Technology Cryo HIFU Laser VTP IRE Brachytherapy SBRT 8 cohort studies, 1 registry report (COLD) 4 cohort studies Phase I/ II Phase I/ II,III Phase I/ II Gold nanoparticles Water Vaporization

14 Focal Ablation Technique

15 Comparison of Outcomes Between Preoperatively Potent Men Treated with Focal Versus Whole Gland Cryotherapy in a Matched Population Mendez, M.H., et al., J Endourol, 2015 FT vs. WG matched comparison of 634 men All D Amico low risk Median FU: 58.3 months Treatment Oncological outcomes(bcr free survival)* Erectile function (recovery of function)** Continence Urinary retention Fistula WG Phoenix: 80.1% ASTRO: 82.1% FT Phoenix: 71.3% ASTRO: 73% 46.8% 98.7% 6 months: 7.3% 12 months: 1.9% 24 months: 0.6% 68.8% 100% 6 months: 5% 12 months: 1.3% 24 months: 0.9% 1 1 * All P 0.1; ** P=0.01 Mendez, M.H., et al., Comparison of Outcomes Between Preoperatively Potent Men Treated with Focal Versus Whole Gland Cryotherapy in a Matched Population. J Endourol, (10): p

16 Matched comparison in intermediate risk prostate cancer Biochemical Progression Free Survival (ASTRO) analysis time Number at risk Whole Gland Partial Whole Gland Partial Biochemical Progression Free Survival (Phoenix) analysis time Number at risk Whole Gland Partial Whole Gland Matched 200 pairs of WG and partial ablation Intermediate risk PCa BPFS following partial ablation - not significantly inferior than BPFS post WG Better sexual fx at 12 months post partial ablation (successful intercourse) WG 26.6% Partial % Partial

17 Anterior Gland Ablation

18 Treatment Adjuvants Ablation Sensitizers Thermophysical adjuvants Chemotherapeutics Pro-inflammatory cytokines or vascular-based agents Immunomodulators Neutraceuticals 18

19 Thermo-physical adjuvants Altering the cell environment may enhance the efficacy of cryoablation due to eutectic crystal formation. Han B, Bischof JC. Direct cell injury associated with eutectic crystallization during freezing. Cryobiology. 2004;48(1):

20 Chemotherapeutic Adjuvants Lung Tumors grafted onto mice. Chemotherapeutic agent: Venorelbine ditartrate Forest V, Peoc'h M, Campos L, Guyotat D, Vergnon JM. Benefit of a combined treatment of cryotherapy and chemotherapy on tumour growth and late cryo-induced angiogenesis in a non-small-cell lung cancer model. Lung Cancer. 2006;54(1):

21 Immunomodulators TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) Directly activates apoptotic pathways at elevated subfreezing temperatures but not by freeze concentration. TNF-alpha Shown to destroy tumors at the edge of the freeze zone. 21

22 Neutraceuticals: Vit D as a cryosensitizer 22

23 Follow-up/ Surveillance Unaddressed issues Have we attained sufficient quality in imaging to omit systematic biopsies at follow-up? What is the necessary frequency/ follow-up schedule for mpmri/ fusion biopsy or systematic biopsy? What is the role of PSA at follow-up?

24 SIU-ICUD Consensus Statement 2015 Definitions of Failure: Treated zone: small volume PGG1 or very small volume PGG2 (<0.2ml) acceptable Untreated zone: any foci of clinically significant cancer PSA Insufficient long term data To be collected for research purposes 24

25 SIU-ICUD Consensus Statement 2015 mpmri 3T or 1.5T w/ ERC At least once 6-12 months after treatment Periodically thereafter Biopsy MRI/ Fusion Biopsy Systematic Biopsy Treated Area Untreated area Mandatory biopsy at 3-6 months - MRI at months and again at 5 years months and again at 5 years months and again at 5 years 25

26 SIU-ICUD Consensus Statement 2015 Retreatment Cause of cancer persistence or recurrence in the treated zone is multifactorial. Patients should not be precluded from any of the standard prostate cancer treatment options, including additional focal therapy if clinically appropriate. Focal therapy can be performed in the salvage setting when the reasons for initial failure can be clearly identified and corrected. 26

27 Long Term Outcomes Loading

28 Moving Forward Evaluation of long term oncological outcomes Recurrence on mandatory biopsy Mortality Failure/ need for salvage treatment Randomized Trials or development of a Multicenter Focal Therapy Registry to capture outcomes in a standardized manner? 28

29 » Thank You 29