Tips and implementation of 3rd line therapies for

refractory OAB

Kathleen Kobashi, MD, FACSViriginia Mason Medical Center

DisclosuresAllergan

Medtronic

AUA/SUFU OAB Guidelines

1st line 2nd line 3rd line

Behavioral therapyDietary modification

Physical therapy

AntimuscarinicsBeta-3 agonists

OnabotulinumtoxinAPosterior tibial nerve

stimulationSacral neuromodulation

Gormley EA, et al.,: J Urol 2012;188(6 Suppl):2455-63.

Format overview

Case-based discussion

Virtual

Encourage questions and discussion!

Cases

• Female patient with refractory OAB

• Male patient with refractory OAB

• Dual incontinence

• Neurogenic bladder

Take homes• When do we introduce 3rd line therapies?

• Counseling tips

• Is one 3rd line therapy better than another?

• Optimizing clinic/ASC/OR flow

• Engaging and empowering staff

• Minimizing hassle factor

• Optimizing lead placement

• Troubleshooting

Case #1

• 54-year-old healthy woman with OAB

• Failed conservative measures

• Not enthusiastic about medications

Medications

• Do you HAVE to do meds?

• Efficacy, side effects, cost

• How many meds?

This Photo by Unknown Author is licensed under CC BY-NC-ND

Counseling

When should we introduce 3rd line therapies?

Is there “typical” scripting?

Which therapy in this patient?

Scripting

WHEN TO INTRODUCE?

PATIENT EXPECTATIONSGOAL SETTINGTREATMENT OPTIONS

Which one?Does data help you

choose?

This Photo by Unknown Author is licensed under CC BY-NC

Take homes• Getting to 3rd line

therapies sooner

• Introduce options early in algorithm

• It’s all in the presentation

• Friendly language

• Goal setting and establishing expectations

This Photo by Unknown Author is licensed under CC BY-ND

Case #2• 62-year-old male with OAB symptoms

• Urgency with occasional close calls

• Frequency q1.5 hours; nocturia x3

• Very mild obstructive symptoms

• PVR: 20 cc

• Failed mirabegron and declines antimuscarinic

Caveats for a male?

• Counseling

• How do you choose?

• Minimum work up before 3rd lines?

• If you do onabotulinumtoxin, technique?

• What about PTNS?

Considerations

Specific considerations

in menAny further workup?

How do you choose?

OptionsConsider pros and cons of each

PTNS: What is it?

• Peripheral neuromodulation technique

• Equivalent to Stoller afferent nerve stimulation (SANS)

• Technique originates from traditional Chinese medicine

• Acupuncture over posterior tibial nerve

• Often combined with sacral or pubic sites for pelvic disorders

Tibial Nerve for OAB

• PTNS (percutaneous tibial nerve stimulation)

• Once weekly for 12 weeks, and then monthly

• Data is good

• Requires travel and frequent visits

Technique

Technique

• Treatment leg is elevated• 34-gauge needle placed at posterior tibial nerve two fingers

above medial malleolus• Needle should be near, but not on nerve• Grounding electrode over medial aspect of calcaneus• Low voltage (9V) stimulation, fixed frequency of 20 Hz

Contraindications: Cardiac pacemakers/defibrillatorspregnancy, those seeking pregnancy, nerve damage

What to expect…

• Well tolerated?

• General success rates?

• Durability?

• Do you have to keep doing it?

• Why don’t we do more?

PTNS Outcomes

• Success rates

• Better efficacy combined with meds

• Should complete full 12 weeks of treatment

• Need maintenance

Unknowns…

• Can we achieve a therapy that allows better patient compliance?

• Can this therapy have better results if administered more often?

PTNS Summary

• Pros and cons

• THE most minimally invasive option

• Practicality may be an issue

• Must complete 12 weeks

• Need monthly maintenance

Case #3

• 46-year-old woman with dual incontinence

• Failed 1st and 2nd line therapies for OAB

• Fecal incontinence in spite of high fiber intake and PT

Best option…Sacral neuromodulation

SNS an easy option

• PNE or staged?

• Flow in your clinic

• Staff engagement, assistance, empowerment

• Programming, educating, interrogating

• Lean on you reps!!

Optimizing lead placement

But are we doing our best?

Aims for placement

Achieve stimulation in all 4 electrodes under 2 V

Optimal lead placement superomedial in S3 foramen

• How is that even possible?!

• (IS it?!!)

Objective: The lead should follow the nerve

The S3 nerve

emerges in the upper

medial quadrant.

Use landmarks• Fluoroscopy to localize target points

• Position patient so that C-arm can image sacrum and coccyx

• Drape so buttocks are visible

• Target: superior and medial

• Goal: “bellows” and great toe plantarflexion

AP sacrumTo locate medial edge of foramina

Lateral film

To locate S3

Needle placement

Stimulation

S2: Rotation

S3: Bellows and great toe plantarflexion

S4: Bellows only

All wrong

Important message

Don’t judge earlier placement by what we know today

Considerations

• SUI

• Programming

• Combination therapy

Take homes• It IS absolutely possible to get:

• All 4 electrodes to stimulate under 2

• Know landmarks and use them!

• Practice makes ”perfect!”

• Give your patients the best you can give them

Take homes• Engage your staff

• Consider batching

• PTNS ties up room but not staff

• If PNE ties things up, do staged in OR

• Lean on industry representatives (they want to help you!)

• We all get better with time

Case #4

• 46-year-old woman with multiple sclerosis and OAB

• Failed 1st an 2nd line therapies

• Detrusor overactivity on urodynamics

Some thoughts…

MINIMAL EVALUATION? UDS NECESSARY? ANYTHING NOT AN OPTION?

Botulinum Toxin Prep

• 50 mL vial of 1% lidocaine into the bladder

• Lidocaine jelly to the urethra• Betadine prep to urethra• Botulinum toxin diluted

• OnabotulinumtoxinA – 10 mL NS

• Don’t shake the vial!

• Needle out and ready to use• Antibiotics

All done by the nursing staff

Botulinum Toxin Prep• 100-200 units of BoNT-A

• Dilute with sterile NS

• Don’t shake vial

• Lidocaine gel/fluid – allows for injection in office

• Cystoscope – flex or rigid

• Needle - depends on scope used

Botulinum Toxin Injection

• 0.5 - 1 ml/injection site

• 5-10 units per site

• 10-20 sites

• Trigone?

• Injection depth – suburothelial vs. intradetrusor

CystoscopeRigid

• Easier for women

• Cheaper needles

• Easier to stay on template

• Lateral wall more of a challenge

• Two hands sufficient

Flexible

• Easier for men

• More expensive

• Needle

• Damage to working channel

• Template?

• Need three hands!

Injection NeedlesFlexible Cystoscope

• Olympus

• Cook

• Laborie

Rigid Cystoscope

• Williams• Most expensive

• Needle within protective sheath• No impact on deflection of scope

• Sharp needle

Injection Template

Injection Template

• Efficacy comparable to phase 3 trials

• 73 patients – none required CIC

• Related to afferent target as opposed to detrusor?

MacDiarmid et al, SUFU, 2020

OnobotulinumtoxinA for NDO Catheterization

• de novo CIC rate (for those not on CIC at baseline)

• 200 U – 30.6%

• Placebo – 6.7%

• No definition of retention/when to start CIC

• Consider 100 U for pts not on CIC at baseline

Ginsberg, et al, J Urol, 2012Cruz, et al, Eur Urol, 2011

Tullman, et al, Neurology, 2018

MS patients, CIC rate with 100 U• BoNT-A – 15.2%• Placebo – 2.6%

NGB/NDO – 100 vs 200 U onabotA

100 U

• Volitional void

• Low PVR

• Wants to avoid CIC

• What if unable to CIC?

200 U

• Already on CIC

• Able to CIC

• Wants max efficacy

CIC Post-Injection• Back in two weeks

• All about symptoms

• Do not need to base on arbitrary PVR volume

• Diabetics a bigger concern

• CIC with diabetes (81) – 12.3%

• CIC w/o diabetes (526) – 6.3%Collins et al, Int Urogynecol J, 2017

Right and Wrong Patient

Optimal

• OAB/UUI

• Urodynamic DO

• Able and willing to CIC

• Neurogenic

Suboptimal

• Can’t or won’t consider CIC

• Looking for bowel help

• High PVR at baseline

• BOO at baseline

BTX after SNS failure

• 76 patients after failed SNS (62F)

• 43% success

• 36-month persistence – 48.1%

• Primary cause of discontinuation – failure (42%)

Baron et al, Neururol Urodyn, 2020

Take homes• Can do in office

• Patients tolerate well

• Use the scope that works for you

• Protect your fiberoptics!

• No aminoglycosides

• If not better, check PVR and UA

• Use with caution in patients with BOO

The future is here…

StimGuard® Implantable Tibial

• Wireless Microimplant

• Office Based Procedure

63

Courtesy of Ken Peters, MD

Advanced Technologies

eCoinValencia Technologies

• Only fully-implantable tibial nerve stimulator subQ above fascia• Leadless design• Size and shape of a US nickel• Experience implanting unilaterally in 46 subjects in the lower leg for

overactive bladder; and bilaterally in 48 subjects in the forearm for hypertension

• 15 minute office or outpatient procedure using local

“eCoin”Electroceutical Coin

BlueWindImplantable unit in proximityof tibial nerve

External stimulator30 minutes daily stimulation

ICS 2016: 71% of patients had >50% improvement

Bioness

Treatment 3-7 days per week30 minute durations

In multicenter trials now

Final points

PTNS

From a practical standpoint...

“Pros” “Cons”

SNSBattery life 5-15 years

No retentionGlobal effects on pelvic floor

Implanted devicePotential complications

2-staged surgeryNot for “neurogenic bladder”

BTXNothing implanted

Local anesthesia in officeWell-tolerated

Risk of retentionRisk of UTI

Durability of response

Take home messages

• Successful options exist

• Know the tricks

• Practice helps!

• We must keep learning

• As technique improves and technology advances, so must we…