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Neuromodulation for Genito-Urinary Disorders

Steven W. Siegel, MDSteven W. Siegel, MD

Centers for Continence CareCenters for Continence Care and Female Urologyand Female Urology

Metropolitan Urologic SpecialistsMetropolitan Urologic SpecialistsSaint Paul, MinnesotaSaint Paul, Minnesota

Disclosure

– Medtronic, AMS, Uroplasty, Allergan

• Consultant, lecturer, proctor, grant/research support

– Medical Advisor, Board Member or Equity Partner

• Uroplasty, Allergan, GT Medical, QIG

– Off Label Usage:

• Interstim for pelvic pain, neurogenic disorders

• BoNT for OAB

Neuromodulation in Urology

• Sacral (InterStim)• Tibial (Urgent PC)• Spinal (VoCare)• Chemodenervation (Botox)

Neuromodulation for GU Disorders

• Refractory OAB– Failed drugs and behavioral therapy

• Urinary Retention– Idiopathic non-obstructive

• Non-neurogenic etiology• Fecal Incontinence

Current treatments for Overactive Bladder

• Behavioral therapies & Physical Therapy

• Drugs, anitcholinergic

• Intravesical Botox

• Neuromodulation– Sacral

– PTNS

• Surgery– Augmentaton cystoplasty

– Urinary diversion

How Likely Are Patients To Continue With Their Drug Therapy?

Prescription persistency rates of OAB medications

among patients new to market (n=21,362)

• 56% of patients chose not to refill their prescription a second time

• Only 15% of patient continued with their therapy through the first year

History of Sacral Neuromodulation

1981 Tanagho and Schmidt UCSF1994 European CE Mark1997 FDA approves for Urge Incontinence1999 FDA approves for UF and NOUR2002 FDA approves for OAB2002 Wide use of fluoro, staged implant/tined lead2006 Small stimulator2011 FDA approval for bowel indication

InterStim Therapy Cumulative Use World-wide

100,000 patients have received InterStim Therapy

Technique Change – 2002 Percutaneous Tined Lead Placement

Num

ber

of P

atie

nts

(in 1

,000

s)

Additional SNM Applications

• Pediatric patients/Dysfunctional elimination syndrome• IC/Pelvic pain• Bowel Dysfunction– Present indications*

» Fecal incontinence» Fecal urgency-frequency (IBS)» Idiopathic chronic constipation

– Many patients have both GU/GI symptoms– Often GI improvements most meaningful to patients

Hoebeke P, JOU 2004De Gennaro M, JOU 2004Humphreys M, JOU 2006Roth abstract 823, AUA 2007

Siegel S, JOU 2001Comiter C, JOU 2003Feler C, Anesth Clin NA 2003Peters K, BJU 2004Everaert K, Eur Urol 2004

Mechanism of Action

• Not a bladder specific therapy• Central afferent modulation

– Targets reflex centers in cord and pons

• Treats both OAB and retention– Blocks ascending sensory pathway inputs

• Turns on voiding reflexes by suppressing the guarding reflex pathways

• ‘Human Software’ Analogy

Leng WW - Urol Clin North Am - 01-FEB-2005; 32(1): 11-8

Peripheral Neuroanatomy

• Parasympathetic– S2 – S4 afferent and efferent (Pelvic Nerve)– Excites bladder, inhibits urethra

• Sympathetic– T12 – L1 afferent and efferent (Hypogastric Nerve)– Excites urethra, inhibits bladder

• Somatic– S2 – S4 afferent and efferent (Pudendal Nerve)– Excites external urethral sphincter

Pelvic Floor Innervation Schematic

OAB Response (ITT and As Treated)

Targets

S3, S4

Pudendal N

Dorsal Genital N

Anatomy: Sacral Canal

Relate Sacral Anatomy to Lead Location

Lateral SacrumPosterior Sacrum

Trial Stimulation: PNE

• Insulated Needle with exposed tip placed at S3– nerve location & function

• Sensory Response– Genital/anal sensation

– Patient comfort

• Motor Response– Bellows & toe

Trial Period Criteria

Success equals >

50% improvement

• number of leaks/day

• number of voids/day

• voided volume/void

• degree of urgency

Implantable Pulse Generator IPG Implantation

• Based on success of trial• Outpatient procedure under local/sedation• Patient unchanged if therapy denied/discontinued• Can modulate stimulation parameters externally• Permanent devices last up to 10 years (Interstim I)

Patient Selection

• Abnormal Voiding– May include other symptoms

• Pain• Bowel dysfunction

• Younger (typical age 45-55)• Non-neurogenic• High tone pelvic floor muscle

dysfunction

Poor Candidates for SNM

• Nerve damage– Peripheral neuropathy– Future need for MRI

• Pelvic malignancy• Intrinsic abnormality of bladder

– XRT– Fibrosis– Decompensation

• Pain without voiding complaints• Very elderly

SNM: Clinical Efficacy

Urge Incontinence1

45% completely dry34% experienced > 50% reduction

in leaking episodes

Urgency Frequency2

31% returned to normal voids (4 to 7 voids/day)

33% experienced > 50% reduction in voids

Retention3

61% eliminated use of catheters16% experienced > 50% amount of

urine emptied from catheter usage

N=33N=38 N=38

SNS Study Group 1JOU 1999;162 ,2JOU 2000;163, 3JOU 2001;165

• Brazelli, M. et al. Efficacy & Safety of Sacral Nerve Stimulation for the Treatment of Urinary Urge Incontinence: A Systematic Review. Journal of Urology. Vol. 175 835-841, Mar. 2006

Systematic Review: Urge Incontinence

% of patients achieving continence or > 50% improvement in their symptoms

Randomized Controlled Trials vs. Case Series Reports

Investigation of 1,827 implants from 34 clinical trials

SNM shown to be effective for the treatment of urinary urge incontinence1

Results of a prospective, randomized, multicenter study evaluating the safety and efficacy of InterStim

Therapy at 6-month follow-up in subjects with symptoms of overactive bladder

Frequency-UrgencyUrge Incontinence

Siegel, et al AUGS 2012

Urgency-Frequency

0

25

50

75

100

PFP < 0.0001

RPP = 0.01

BPP = 0.01

GHP = 0.003

VP = 0.01

SFP = 0.002

REP = 0.17

MHP = 0.01

% o

f Pati

ents

Control (n=20) Implant (n=23) US Norm

PF - Physical Functioning BP - Bodily Pain V - Vitality RE - Role EmotionalRP - Role Physical GH - General Health SF - Social Functioning MH - Mental Health

Improvement in Quality of Life, 6-Month SF-36 Scores

Janknegt RA, Hassouna MM, Siegel SW, Schmidt RA, Gajewski JB, Rivas DA: Patient satisfaction and complications following sacral nerve stimulation for urinary retention, urge incontinence and perineal pain: A multicenter evaluation. Int Urogynaecol J, 11: 231, 2000

Five year results of SNM for voiding dysfunction: Outcomes of a prospective, worldwide clinical study

• 17 centers– 163 patients, mean age 44.7, 87% females

• Success rate 5 years post implant– 68% UI– 56% UF– 71% Retention

• If success at 1 year, rate of success at 5 years– 89% UI– 71% UF– 78% Retention

Van Kerrebroeck et al, JOU 2007

Complications

• Reoperation rate <20% – Loss of efficacy– Pain at lead or IPG site– Infection

* Starkman, NUU 2007; van Voskuilen, BJU 2007; Kessler, Eur. Urol 2006

BehavioralBehavioral

PFM RehabPFM Rehab

DrugsDrugs

How Should We Treat OAB How Should We Treat OAB Patients?Patients?

PTNS, SNMPTNS, SNM

BoNT, Other surgeryBoNT, Other surgery

Discussion