What's New in Surgery for BPH? - Grand Rounds in Urology

What’s New in Surgery for BPH?

Steven A. Kaplan, M.D. Professor of Urology

Director, Benign Urologic Diseases and The Men’s Health Program Icahn School of Medicine at Mount Sinai

Surgical Options

§ Minimally invasive options •  Office based •  Ambulatory based •  Minimal anesthestic •  High risk patients •  Low morbidity

§  Advanced Invasive Options •  Improved versions of prostatectomy

Technology Based Treatment of LUTS related to BPH

§  ALL surgical approaches based on removing bladder outlet obstruction1 (? Tissue)

§  Minimally Invasive Therapies1 §  Thermotherapies1 §  Novel hybrid therapies2

§  Surgical Debulking Procedures1 •  Vaporizers and Enucleators1

•  Robots Vs. Lasers Vs Electrosurgical Technologies3

1.  Kacker R, Williams SB. J Urol 2011: 8; 171-176. 2.  Hoffman RM et al. Cochrane Database Syst Rev 2009;(1):CD001987

3.  Lee N et al. AUA 2011. Abstract 2098.

LUTS: lower urinary tract symptoms BPH: benign prostatic hypertrophy

Minimally Invasive Therapies: Update

FDA APPROVED §  Prostatic Lifts1

•  Transurethral Suture Tacking

§  Robotic/Laparoscopic Technology •  Single Port2 and Transvesical Approaches3

§  Vapor Ablation (Steam)

Investigational §  Photodynamic Therapy4 §  Histotripsy (focused ultrasound) §  Prostatic Arterial Ablation §  WaterJet/Laser Technology §  Intraprostatic Injections5

•  Botox, NX 1207, ethanol and other compounds 1.  Woo, H. et al. BJU Int 2011;108: 82-8

2.  Fareed K, et al. BJU Int 2012: DOI: 10.1111/j.1464-410X.2012.10954.x 3.  Granberg CF, et al. J Endourol. 2009 May;23(5):747-52

4.  Tiwari A, et al. Exp Opin Invest Drugs 2005; 5.  Denmeade S, et al. Eur Urol 2011; 59:747-54. Epub 2010 Nov 24.

The Prostatic Urethral Lift

§  Compress encroaching lateral lobe §  Deliver UroLift® implant to hold in

place §  An average of 4.9 implants for

prostates ≤ 80cc

AnterolateralLoca,on

§  Mechanicallyopensprosta0curethra

§  Resultisvisibleundercystoscopy

§  Implantsareanterolateral,awayfromNVbundlesordorsalvenouscomplex

PRE POST

Prosta0cUrethralLiEProgress

PUBLISHED

RandomizedCrossoverStudy

Posi0veGuidance

N.I.C.E.PUBLISHED

2YearDurability

DeNovoApproval

HCPCSCoding

CoverageAETNA

PUBLISHEDRandomizedBlindedStudy

PUBLISHEDSexualFunc0on

Over2,000treated

PUBLISHED

2YearRandomizedDurability

PUBLISHED

BPH6Study:RandomizedtoTURP

Coverage

Medicare23statesSeveralprivates

PUBLISHED

‘Real-World’EuropeanRegistry

PUBLISHED

Safety&Feasibility

Category1CPTCodes[Effec0veJan’15]

PUBLISHED

LOCALStudy

Where does UroLift® fit?

§  Men with moderate to severe LUTS due to BPH who… •  Want to preserve sexual function •  Concerned about possible TURP/laser complications •  Want rapid return to daily life •  Unhappy with BPH drugs due to insufficient relief or

bothersome side effects

Widely Studied

Publications to Date §  J Urology USA randomized

(n=206, 1yr) §  J Sexual Medicine USA sexual function

(n=140, 1 yr) §  EU J Urology EU registration (n=102,

1yr) §  Urology J. 2 yr Multi-Center Study

(n=64,2 yr) §  J. Sexual Medicine Sexual Function (n=64,

1yr) §  British J. Urology First-in-Man (n=19,1 yr) §  Canadian J. Urology Technique §  Multiple small studies from France, Spain, Germany

•  Prospec0ve,1:1randomizedstudycomparingPULtoTURP

Design

• 80subjectsenrolledat10Europeancenters• UK,Germany,Denmark

Enrollment

•  50yearsold•  IPSS>12•  Qmax≤15ml/s,PVR≤350ml•  Prostatevolume≤60cc•  ISI<5•  Noac0veinfec0ons,urinaryreten0on,stones,obstruc0vemedianlobe

•  Sexuallyac0ve•  Ruledoutforprostatecancer• Washedoutfroman0coagulants

Criteria

BPH6RandomizedStudyOverview

Sonksenetal.EurUrol2015;DOI10.1016/j.eururo.2015.04.024

Pa0entcohortswerecomparable

Characteris,cs

PUL(N=44*) TURP(N=35)

Mean,SD[min-max],(n)Age(yrs) 63,6.8[50-84],(44) 65,6.4[51-78],(35)

Prostatevolume(cc) 38,11.6[16-59],(44) 41,13.4[17-68],(35)

Prostatelength(mm) 46,6.4[24-56],(43) 47,5.8[37-60],(34)

PSA 2.4,1.8[0.4–8.2],(43) 2.6,2.1[0.3–8.6],(33)

IPSS 22,5.7[12-33],(44) 23,5.9[13-34],(35)

Qmax(mL/s)† 9.2,3.5[3-15],(39) 9.5,3.2[3-15],(32)

PVR(mL) 86,71.6[0-344],(44) 102,86.9[0-328],(35)

ISI 1.8,1.0[1–4],(44) 2.0,1.0[1–4],(35)

SHIM 20,4.9[7–25],(44) 18,5.5[7–25],(35)

MSHQ-EjDfunc0on 11,2.7[4–15],(44) 9,2.3[4–13],(35)

MSHQ-EjDbother 1.7,1.8[0–5.0],(44) 2.0,1.5[0–4.0],(35)

*Onesubjectwasexcludedfromanalysisforviola0onofinclusioncriteria


SymptomImprovementsasExpected•  UroLiEshowsmorerapidimprovement,andTURPsurpassesat12months

(11.4vs15.4pointIPSSimprovements)

p=0.05


Peakflowrate(Qmax)improvesmorewithTURP

•  PULQmaxnormalizesto15mL/sec,whileTURPissuper-physiologicat22mL/sec.


AUA2015Update:3YearL.I.F.T.Durability

Mean,95%CI

Roehrborn.AUA2015

AUA2015Update:Secondaryendpointsstableto3years

3MonthChangefromBaseline

PULChangefromBaseline

PUL Control Difference

1Year 2Years 3Years

Qmax(mL/s) 4.28 1.98 p=0.005 4.0 4.2 3.5

QOL 2.2 1.0 p<0.001 2.4 2.2 2.3

BPHII 3.9 2.1 p<0.001 4.0 3.8 3.8

Roehrborn.AUA2015

AUA2015Update:Ejaculatoryanderec0lefunc0onpreserved•  Erec0lefunc0onunchanged,whileEjaculatoryfunc0onimprovedmodestly

**

*

*

***

**

*

*

*

*

Mean,95%CI*p<0.05

Roehrborn.AUA2015

AUA2015Update:Addi0onalfollowontreatment

•  10.7%requiredreinterven0onby3years:•  6(4.3%)receivedaddi0onalPULimplants•  9(6.4%)underwentTURPorPVP

•  14of642implants(2.1%)weredeployedsuchthatexposedtobladderandshowedencrusta0on:

•  Over3years,9implantswereremoved(endoscopicgraspers)

•  Importanttechniquepoint:Ifdeployedtooproximally,removeimplantduringindexprocedurewithendoscopicgraspersorscissors.

Roehrborn.AUA2015

Summary

§  Novel approach to BPH •  Symtom reduction •  Sexual function preserved

§  Concerns •  Retreatment rates high •  Encrustation •  Reproducibility

TIME WILL TELL !!!

Introduction: Convective WAVE™ Technology

A NEW Technology Platform for Tissue Ablation

Convective Water Vapor Energy (WAVE™)

A NEW Technology

CONVECTIVE Thermal Heat Transfer WATER VAPOR (STEAM) to Ablate Tissue

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Differences in Thermal Energy Transfer CONVECTION Conduction

Prostate Capsule

• Vapor rapidly disperses through interstices • Condensation releases stored thermal energy • Cell membranes are gently denatured, thereby

causing cell death

Vapor Injection

Heat Source

• Heat is conductively transferred from cell to cell • Conductive heating of prostate capsule occurs • Temp gradient results in cells near source being

heated substantially more than those far away

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Vapor Ablation (Steam) Rezum System: NxThera, Inc

510 K FDA Clearance in Sept 2015

Methods: Rezūm FIM and Pilot Treatment Summary

FIM Pilot

Mean ± SD Range Mean ± SD Range

Treatment Time per Injection (seconds) 8.9 ± 0.9 (7,10) 9 -

Calories/Treatment 218 ± 26 (190,289) 208 -

Total Treatments in Both Lateral Lobes 5.1 ± 1.6 (2,8) 3.8 ± 1.1 (2,6)

Treatments/Median Lobe 2.5 ± 0.6 (2,3) 1.8 ± 0.8 (1,3)

Total Treatments/Prostate 4.9 ± 1.9 (4,9) 4.4 ± 1.9 (2,9)

22

Results: MRI and 3D Renderings Analysis Volume Reduction From 1 Wk

Post Rx Time N Mean

(cm3) Mean ∆ (cm3)

Mean % ∆

Lesion Volume

1 Week 30 9.5

1 Month 29 3.3 -6.2 -65.3%

3 Months 28 0.7 -8.8 -92.6%

6 Months 28 0.3 -9.2 -96.8%

Transition Zone Volume

1 Week 30 44.3

1 Month 29 36.1 -8.2 -18.5%

3 Months 28 30.4 -13.9 -31.4%

6 Months 28 27.2 -17.1 -38.6%

Prostate Volume

1 Week 30 75.2

1 Month 29 64.1 -11.1 -14.8%

3 Months 28 55.8 -19.4 -25.8%

6 Months 28 50.7 -24.5 -32.6%

23

Results: IPSS

24

Baseline

N=30

Week 1 N=30

Month 1 N=30

Month 3 N=28

Month 6 N=28

Year 1 N=27

IPSS 23.0 ± 6.3 19.0 ± 8.7 13.2 ± 7.9 8.7 ± 6.9 8.3 ± 7.1 10.8 ± 6.7

IPSS ∆ (0) -4.0 ± 11.3

-10.8% -9.8 ± 10.8

-37.2% -14.7 ± 8.3

-61.9% -15.0 ± 8.7

-63.0% -12.8 ± 6.9

-54.3%

Rezūm II Study Design

TotalEnrolledN=197

Treatmentn=136

2WeekFollow-Up

Controln=61

1MonthFollow-Up

3MonthFollow-Up

2WeekFollow-Up

1MonthFollow-Up

3MonthFollow-Up

BLINDED

6MonthFollow-Up

12MonthFollow-Up

2,3,4,and5YearFollow-Up

OPEN

PRIMARY ENDPOINT 3 Month ITT Randomized Comparison Rezūm IPSS Reduction > 125% Control

1 Year Rezūm Durability

LongTermFollowUpto5Years

6MonthFollow-Up

SubjectCrossovern=53

25

Procedural Results Treatment (N=136)

Control (N=61)

Mean ± SD (n)

Mean ± SD (n)

Treatment Time (min) 5.3 ± 3.5 (135) 3.3 ± 1.3 (61)

% subjects with middle lobe treated or

identified

31.1%

(42/135) 18.0% (11/61)

Number of treatments total 4.5 ± 1.8

(135) N/A

TypeofMedica,on

#ofSubjects(N=196)

PercentageofSubjects

OralSeda0on 135 68.88%ProstateBlock 41 20.92%IVSeda0on 20 10.20%Procedural Pain

Management

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Primary Efficacy Endpoint – As Treated

Metpre-specifiedprimaryefficacyendpoint!

TreatmentArm ControlArm

Baseline 3Months Change Baseline 3

Months Change P-value

IPSSScore 22.0±4.8

10.7±6.5

-11.3±7.6

21.9±4.7

17.5±7.6 -4.3±6.9<0.0001

Improvement in LUTS as measured by IPSS change for subjects in the Treatment Arm as compared to those in the Control Arm at 3 months post-treatment.

27

IPSS - As Treated

N=61 N=135 N=59 N=130 N=61 N=132 N=61 N=134 N=129 N=77 28

Qmax - As Treated

N=61 N=135 N=61 N=133 N=61 N=133 N=125 N=75 29

1 Mo 3 Mo 6 Mo

Primary Safety Endpoint

Met primary safety endpoint!

Patients% (n/N)

Primary Safety Composite Endpoint: 1 0.7% (1/136) 3.40% <0.000

1Upper CI ≤ 12% Yes

1) Device perforation of rectum or GI tract 0 0.0% (0/136)

2) Device related formation of fistula between the rectum and urethra 0 0.0%

(0/136)3) De novo severe urinary retention lasting more than 21 consecutive days post treatment

1 0.7% (1/136)

1 One-sided 95% Exact Binomial CI

Treatment ArmEvents Upper

CI¹ P-value Endpoint Criteria

Endpoint Met?

Demonstrate that the composite observed rate of post-procedure device-related serious complications in the Treatment Arm is <12% at 3 months.

30

Safety Profile •  3 device or procedure-related SAEs (2 treatment subjects)

–  Subj. 1 – extended retention (significant intravesical lobe protrusion) –  Subj. 2 – allergic reaction to Xanax (nausea and vomiting)

•  12 unrelated SAEs (9 treatment subjects) –  3 bowel obstructions; 1 hemorrhoid; 1 UTI, 1 syncope; 1 injury, Other; 1 pneumonia; 1

spinal stenosis; 1 pulmonary embolism; 1 pyelonephritis, 1 cancer •  Most common AEs

–  Mild-to-moderate, typically resolved by 2 weeks (% subjects per arm)

TreatmentSubjects(N=136)

ControlSubjects(N=61)

Dysuria 23(16.9%) 1(1.6%)

Hematuria,Gross

17(12.5%) 0(0%)

Hematospermia

10(7.4%) 0(0%)

UrinaryFrequency

9(6.6%) 2(3.3%)

UrinaryUrgency

8(5.9%) 1(1.6%)

31

Goals of Less Invasive BPH

§  Rapid Results •  Feeling better within days •  Symptoms improve > Rx

§  Minimal Adverse Effects •  No serious adverse events •  No ED, EjD •  No Post Op Foley

§  Tolerable In-Office Treatment

Goals of Less Invasive BPH

§  Predictable §  Reproducible §  Reliable §  Durable §  Positive Economic Drivers

•  Patient, Urologist, Insurers

Offer a Procedural Treatment that

Reduces Obstruction AND Competes with

Palliative MEDICAL Therapy

Medi Tate TIND Temporary Implantable Nitinol Device (TINDTM)


§  5 minutes to deploy – The device can be deployed in any clinical setting that has standard rigid cystoscopy equipment. The deployment procedure is intuitive and does not require a post-procedure catheter. Once the device is deployed, the patient is free to return to normal activities immediately.

§  5 days in position – TIND remains in position for 5 days. When deployed in the prostatic urethra, the device clears obstructive tissue by exerting pressure on prostate tissue from the inside, clearing the urethral path and enabling improved urination immediately following the procedure. The long-term effect is achieved by the reshaping of the prostate: channels are formed that permanently expand the cross-sectional area along the entire prostatic urethra.

§  5 minutes to remove – 5 days later, the device is removed in just a few minutes.

Complications •  1 UTI •  1 Prostatic Abcess •  1 Transient Incontinence •  1 Urinary Retention


§  Devices were implanted between May 2010 and July 2012, within a mean operative time of 5.8±2.9 min, and retrieved five days thereafter, within a mean operative time of 2.8±1.1 min.

§  No intra-procedural complications were recorded during implantation or retrieval procedures. •  One case of urinary tract infection and one case of

temporary acute urinary retention were recorded and resolved.

§  All patients reported significant symptomatic improvement and terminated BPH medicinal regimens within 3 months of implantation, with an improvement of 51.96±19.16% and 51.79±68.66% in IPSS and Qmax, respectively, by that time point

Prostate Arterial Embolization

§  Reliance on image based reduction in prostate volume

§  Naïve prostato – centric concepts of LUTS •  Lack of controls

§  Definitions of clinical improvement •  ? Placebo effect

§  Tends to ignore LUTS / bother metrics

§  ..\2014 01 31- 2 PCP 2014\ProArc.wmv

HowItWorks?

Step3:Inaverysimpleandquickprocedure,theurologist

performsacircularincisionintheprostate0ssue,andsimultaneouslyplacestheimplantinsideofit

HowItWorks?

Step4:Thedeliverysystemisretracted,leavingtheimplantsto

expandthepreviouslyobstructedarea

SuccessfulPre-ClinicalTrials

•  Theprocedurehasbeenfoundtobesafe:o  Goodclinicalcondi0onsofanimalsduringtheen0refollow-upperiod

o  Nosignificantadverse0ssueresponse

o  Normalblood/urineparameters

o  Normalbehavior

ExpandedareaBladder

Prostate

Significantenlargementoftheurethra90dayspostprocedure

•  Preliminaryproofthattheprocedureissafeandfeasible

•  Post12monthsreports(3pa0ents):

o  Pa0entsarefeelinggoodwithnocomplaints

o  Majorsymptomsimprovements

o  Sexualfunc0onwaspreserved

•  Strongefficacyindica0ons

•  Nounexpectedsafetyissues

•  Procedure0meislessthanfiveminutes

SuccessfulFirstinManTrial

VORTX RX Histotripsy Technology §  Histotripsy applies high

intensity acoustic energy to fragment and homogenize cellular tissues through a process known as cavitation.

§  Cavitation appears as a “bubble cloud” on ultrasound imaging and is easily tracked and monitored by the surgeon throughout the procedure.

§ Once treated, tissues change in ultrasound appearance from bright to dark, enabling the surgeon to easily track the treatment as it progresses.

§  The VORTX RX is an investigational device and is limited by law to investigational use by qualified investigators in the United States and Canada.

47

THE AQUABEAM® System Conformal Planning Unit

•  Surgical planning & mapping •  Controlled depth of resection •  Integrated TRUS display

Aquablation •  Submerged high velocity

saline jet •  Tissue selectivity & depth

control •  Non-thermal (room

temperature)

Handpiece •  24 Fr, precise sapphire nozzle •  Cystoscopic visualization •  Aspiration for tissue collection

NotavailableforsaleintheUnitedStates

48

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100

Depth(m

m)

PowerLevel(0-100inincrementsof5)

DEPTHCONTROLAQUABEAMTECHNOLOGY

49

ANGLEPLANNING–TRANSVERSEVIEW

50

CONTOURPLANNING–SAGITTALVIEW

51

AQUABLATIONTREATMENT

52

Pa,entDemographics(n=21)

Age 70+5.1yrs(62–78yrs)

Prostatesize

57+19.4ml(30–102ml)

Medianlobe

57%(12/21pa0ents)

PrimaryEndpoints(Safety&Feasibility) TechnicalSuccess 100% Opera0veTime 38+9min(23–56min) Resec0onTime 5.0+2.9min(1–22min) Haemoglobin (post op)

5.7% reduction (143 to 135 g/l)

21SUBJECTSPHASEII–12MONTHFOLLOWUP

v  Post-opera0vedysuriawasminimalv  Nointra-op.complica0onsv  Adverseeventsweretypicallymildandtransient

53

SecondaryEndpoints(Symptoms,UrinaryFlowRate,QOL)

Mediancatheterwithdrawal0me

One(1)day(1–7)

Pdet@Qmaxchange 40%reduc0on(65to39ml/cmH2O)

ProstateVolume 39%reduc0on(57to35ml)

v  Nocasesofurinaryincon0nence,retrogradeejacula0onorerec0ledysfunc0onwerereported


*p<0.05;†p<0.01;‡p<0.001;§p<0.0001

23.0

10.7

7.0 7.1 6.8

0

5

10

15

20

25

30

0 13 26 39 52WEEKS

IPSSMEAN&95%CI

§ §§

§

8.6

14.816.6

18.9 18.3

0

5

10

15

20

25

0 13 26 39 52WEEKS

Qmax(ml/s)MEAN&95%CI

‡

§ §‡

54

*p<0.05;†p<0.01;‡p<0.001;§p<0.0001

5.0

2.31.8 1.7 1.7

0

1

2

3

4

5

6

0 13 26 39 52WEEKS

QoLMEAN&95%CI

§§ §§

143

84

5239

54

0

40

80

120

160

200

0 13 26 39 52

PVR(ml)MEAN&95%CI

*

†

†

†


55

WATERNCT02505919

•  Prospec0vemul0centerrandomizedcontrolledtrial–  Aquabla0onvs.TURP

•  Targetpa0entpopula0on:moderate-to-severeBPH–  Age45-80withLUTSduetoBPH–  IPSS≥12–  Prostatevolume30-80byTRUS–  Qmax<15mL/s

•  Randomiza0onPhase–  2:1randomiza0on,blockedbycenterandIPSS>20vs.<20

56

PrimaryEndpoints

•  Safety•  Clavien-Dindograde2orabovesurgicalcomplica0on

•  Effec,veness•  DecreaseinIPSS•  Non-inferiorityapproach

Summary

§ All procedures do well in the hands of the specialized committed expert

§  Energy-based surgical techniques require comprehension of their unique tissue effects with specific technology

Summary

§  Small glands tend to do well with any technology •  Large glands more difficult to do -- not for novice •  No matter the surgical technology, surgeon attain

hemostasis

Technology Opportunities

§ We are drowning in data and starving for intelligence

§ Most of our metrics are static and not dynamic § Our ability to capture data is not fully realized §  Science must direct analyses with objective

measures and NOT soft marketing measures

Artificial Intelligence

winningAlgorithms | Portsmouth, NH | @winningAlgs

Webscraping à Event Matching àMobile Interface

•  Scrape unstructured data from the Internet •  Combine attributes with events •  iOS mobile application for iPad and iPhone •  Support real-time decisions with data

healthDeck healthDeck is a predictive engine used by

healthcare professionals to determine a patient’s risk and inform physician treatments

healthDeck

Cancer Alzheimer’s Diabetes Multiple Sclerosis HIV/AIDS Arthritis Heart

Disease

healthDeck Heart Disease is the tool that doctors will use for specific patients

healthDeck healthDeck is a predictive engine used by

healthcare professionals to determine a patient’s risk and inform physician treatments

healthDeck

Cancer Alzheimer’s Diabetes Multiple Sclerosis HIV/AIDS Arthritis Prostate

Disease

healthDeck Pprostate Disease is the tool that doctors will use for specific patients

healthDeck: Prostate Disease Algorithms

winningAlgorithms | Portsmouth, NH | @winningAlgs

Pa0entDataMedicalandUnstructured

Data

Pa�ernRecogni0on

ErrorHighly

AccurateProstateDisease

Predic0on

1 2 3Pa0entrecordsareusedtodevelopapredic0vealgorithm

Alearningalgorithmadjuststheformulaun0litdiscoversacollec0onofemergingpa�ernsthatpredictprostatedisease

Theoutputsareprostatediseaseriskpredic0on,discoveryanalysis,andthoughtprocessassistance

What's New in Surgery for BPH? - Grand Rounds in Urology

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