Update on current practice in Urogynecology: Findings from the

NIH sponsored treatment networks in urinary incontinence and pelvic

floor disordersPeggy A. Norton, M.D.

Chief of Female Pelvic Medicine and Reconstructive Pelvic Surgery

University of Utah School of Medicine

Learning objectives

• Describe main findings from the Urinary Incontinence Treatment Network (UITN)

• Describe main findings from the Pelvic Floor Disorders Network (PFDN)

• Be able to identify at least one finding from the UITN and PFDN that could change practice in general gynecology in your own community.

1998: American Urogynecologic Society began lobbying Congress for NIH funding in urogynecology

1998: American Urogynecologic Society began lobbying Congress for NIH funding in

urogynecology

Several large clinical treatment networks emerged and took requests for funding 99-02

• Pelvic pain treatment network (NIDDK)• Urinary incontinence treatment network (NICHD*)– Urinary incontinence, both stress and urgency– Evaluation and treatment

• Pelvic floor disorders network (NICHD**)– Broader definition included pelvic organ prolapse,

urinary and fecal incontinence.– Evaluation and treatment

* additional funding by Office of Research in Women’s Health and NIDDK** additional funding by ORWH and NICHD

Urinary incontinence treatment network 2001-2014

• What’s the best tx for SUI in women?– Burch colposuspension versus autologous fascial sling (SISTEr

trial, Stress Incontinence Surgical Efficacy tRial). RCT, reported 2 and 5 year outcomes, n=655

– Strict composite definitions of success for SUI and for overall UI (including urgency incontinence)

• Success rate higher with fascial sling, but causes more problems with voiding, urgency and UTIs. Success rates decline over 5 years, but sling still more successful. Women with preoperative urgency less likely to have successful outcome

Albo et al NEJM 2007 (two year)Brubaker et al J Urology 2012 (five year)

• Complications of UI surgeries are minimal & transient.• After effective surgery, women with UI will spend less money on

UI-related expenses.• The majority of women undergoing surgery for SUI also have

urgency UI, which they expect will get better with the surgery.• Satisfaction w/ surgery is higher than what is reflected in

composite success rates.• Despite gradual decline in success of both surgeries over time,

improvements in quality of life continue.• Counsel that fascial sling has a higher rate of needing takedown,

Burch patients have higher rate of subsequent surgery.

Five year success in SISTER trial depends on the definition of success

UITN: what’s the best surgical treatment for SUI in women?

• Mid-urethral mesh slings: RCT retropubic versus transobturator (TOMUS trial) 2006-2009. One, two and five year outcomes, n=597

• At 1 year, same objective success, similar subjective success. At 2 years, similar but not equivalent. Complications different, but rare.

• By 5 years, objective success 8% higher in retropubic, subjective success 6% higher in transobturator, neither difference is significant

• Seven new mesh erosions by year 5-7

Some differences between RetropubicMUS and TransobturatorMUS

Complication RMUS TMUSIntraoperative: rateperforation of bladder

5% 0%

Immediate postop: rate ofvoiding problems

3.4% 2%

Long term: 2 year rateexposure of mesh

3% 2%

For midurethral slings overall voiding problems, counsel 6/2 rule: 6 percent of women need a catheter at 2 weeks, and 2 percent need a catheter at 6 weeks

What is the role of urodynamics (UDS) in the evaluation of women prior to SUI surgery?

• In SISTEr, we were able to standardize urodynamics and find some important norms, but we did not see correlation with outcomes.

• In TOMUS, we found that low leakpoint and low urethral pressures were associated with surgical failure.

• ValUE: Value of Urodynamic Evaluation was conceived and eventually went forward

ValUE trial: Nager et al NEJM 2012

• Women undergoing SUI surgery, randomized to basic office evaluation v. basic eval plus UDS

• UDS did not improve surgical outcomes in women with uncomplicated SUI: rarely changed the treatment plan, although this was in a group of subspecialist surgeons

• Compared to UDS utilization at the beginning of the trial, calculate saving somewhere between 10 million and 90 million dollars annually in preop evaluation that doesn’t improve outcome

What about urgency incontinence?Burgio et al; Ann Intern Med 2008

• Be_DRI (Behavior Enhances Drug Reduction of Incontinence) 307 women with urgency UI

• Randomized drug v drug + extensive behavioral therapy, outcome= 70% reduction of incontinent episodes

• Subjects were more satisfied with drug plus behavioral tx, but getting behavioral treatment did not improve our ability to discontinue drug treatment

• Measures such as adjusting fluids improved outcome

How do these studies affect your practice or patient counseling?

• Patients considering a sling for stress urinary incontinence can expect improvement in quality of life that exceeds objective cure

• Urodynamic testing is not necessary prior to surgery in women with uncomplicated SUI

• Women with urgency incontinence can be managed successfully with anticholinergic medications, but adding behavioral management does not lead to discontinuation of these drugs.

What didn’t the UITN network do?

• No randomized trial between mesh sling and a fascial sling

• No trial of Botox or neuromodulation (PFDN did these)

• Could not recruit for trial of mixed incontinence • Did not define a “best outcome” for SUI treatment

Pelvic Floor Disorders Network

• Should we add a continence procedure to major surgical procedures for pelvic organ prolapse?

• CARE trial 2003-2005 Brubaker et al NEJM 2006• 322 women undergoing abd sacrocolpopexy (ASC) for POP

without SUI were randomized to additional continence procedure (Burch) or not

• At three months, 23.8% of those undergoing ASC plus Burch met criteria for SUI postop, compared to 44.1% of those who underwent ASC alone. Similar findings at two years

• No significant increase in adverse events

CARE trial: five year follow-up (Nygaard et al 2013)

• ASC is not as good as we believed: by five years, almost a third of subjects met “failure” criteria, but only 5% underwent repeat surgery and most reported satisfaction w/ op.

• Prophylactic SUI surgery continued to show benefit long term, with no adverse consequences.

• Mesh erosions occur with ASC, too: approximately 10% by year five

Outcomes following vaginal prolapse repair and mid urethral sling (OPUS) trial: Wei NEJM

2012• 337 women undergoing vaginal surgery for

POP who were not incontinent: randomized to TVT or sham incision.

• At 3 mos, 23.6% of women undergoing TVT reported bothersome UI compared to 49.4% of women with sham incisions

• At 12 mos, 27.3% of women undergoing TVT reported bothersome UI compared to 43% of women with sham incisions.

Are there good alternatives to anticholinergics for treating urgency UI?

• ABC Trial: Anticholinergic txvs.onabotulinumtoxin A for UUIVisco et al NEJM 2012• Women with UUI randomizedto drug/sham bladder injection or placebo/Botox 200 units bladder injection.• Cure rates with Botox were twice that seen with Anticholinergic medications in double blind trial• Main AEs were UTI and voiding dysfx (10%)

What is the best surgery for vaginal vault prolapse?

• OPTIMAL trial: Barber et al, JAMA 2013 (Dr. Scott is reviewing this paper)

• Urogyn perspective: Uterosacral ligament suspension widely adopted by specialists after 2000 without good evidence. Using MICHIGAN modification of SSLF, we saw similar outcomes for both procedures in the OPTIMAL

What else have we found?

• Colpocleisis study n=152: there is high satisfaction (95%) after obliterative surgery for POP in selected women (Fitzgerald

• ATLAS study: Ambulatory Treatments for Leakage Associated with Stress. Women with SUI randomized to vaginal pessary versus pelvic floor muscle therapy versus combined pessary and muscle therapy. Combination treatment did not offer improvement over single therapy

How likely is a woman to develop SUI after surgery for POP? Jelovsek 2013

• Urinary reduction stress test is only 17-34% accurate• Factors that were found to affect SUI after POP surgery:

– Increased age at surgery– White race– Higher vaginal parity– Higher body mass index– Current smoker– Current diagnosis of diabetes– Higher preoperative POP quantification stage– Higher POP quantification point Aa measure– Positive preoperative prolapse reduction stress test– Performance of a concomitant retropubic midurethral sling– Participation in strenuous exercise– Presence of baseline urgency urinary incontinence symptoms

• Calculate risk from 15% to 70%, helps give numbers to discussion between surgeon and patient

www.r-calc.comClick on , agree, and then open female pelvic medicine….

http://www.r-calc.com/administrator/calculatorGridPreview.aspx?isGrid=1&mobile=0&isTemp=0&calculator_grid_id=b8aa31f8-6023-493f-87bd-7d5c6553af91

Weighted prevalence rates of pelvic floor disorders (PFDs) in nonpregnant US women from the NHANES study (Nygaard et al 2008)

variable N=1961 UI n=331 FI n= 176 POP n=58 >1 pfd

overall 1961 15.7% 9% 2.9% 23.7%

Age 20-39 641 6.9% 2.9% 1.6% 9.7%

Age 40-59 668 17.2% 9.9% 3.8% 26.5%

Age 60-79 488 23.3% 14.4% 3.0% 36.8%

> 80 150 31.7% 21.6% 4.1% 49.7%

p <.001 <.001 .14 <.001

How has the PFDN changed the way we counsel or treat our patients?

• Pelvic floor exercise and vaginal pessaries are options in the treatment of SUI, but success rates are lower than surgical options (ATLAS)

• A quarter of women has at least one pelvic floor defect (NHANES)

• Colpocleisis is an effective surgery with a high satisfaction rate for selected patients

How has the PFDN changed the way we counsel or treat our patients?

• Consider adding continence procedure in women undergoing POP procedures (CARE and OPUS), possibly using on line calculator

• Sacrospinous ligament suspension and uterosacral suspensions are good option for vaginal vault prolapse (OPTIMAL)

• Botox should be considered in the treatment of urgency incontinence, especially in women who do not respond to anticholinergics (ABC)

Ongoing PFDN studies

• Has tried to study fecal incontinence: CAPS for postpartum symptoms, ABBI for adaptive behaviors in women with FI, BOOST after anal sphincter injury w/ childbirth, AIM for determining important sx outcomes for FI, and CAPABLE loperamide v pelvic floor training for FI

• Ongoing trial of Botox versus neuromodulation (Interstim) for refractory urgency incontinence (ROSETTA trial)2012-2015

• Ongoing trial of TVH/native repair v mesh hysteropexy (SUPER trial)2013-2015

• Mixed UI: surgery versus surgery plus meds (ESTEEM trial) 2014-2016

UITN studies of interest• Albo M, Richter H, Brubaker L, et al. Burch colposuspension v fascial

sling to reduce urinary stress incontinence. NEJM 2007;356:2143-55• Brubaker L, Richter H, Norton P, et al. Five year continence rates,

satisfaction and adverse events of Burch urethropexy and fascial sling surgery for UI. J Urol.

• Burgio K, Kraus S, Menefee S, et al. Bwehavioral therapy to enable women with urge incontinence to discontinue drug tx: a randomized trial. Ann Intern Med 2008;149:161-9

• Nager C, Brubaker L, Litman H, et al. A randomized trial of urodynamic testing before Stress-incontinence surgery. NEJM 2012 May 24;366(21):1987-97

• Richter H, Albo M, Zyczynski H, et al. Retropubic v transobturator midurethral slings for SUI. NEJM 2010; 362(22):2066-76.

PFDN studies of interest• Barber M, Brubaker L, Burgio K, et al. Comparison of 2 transvaginal surgeries: the OPTIMAL trial.

JAMA 2014;311(10):• Brubaker L, Nygaard I, Richter HE,et al. Two-year outcomes after sacrocolpopexy with and without

burch to prevent SUI. Obstet Gynecol. 2008 Jul;112(1):49-55: 1023-34• Fitzgerald MP, Richter HE, Bradley CS, Ye W, Visco AC, Cundiff GW, Zyczynski HM, Fine P, Weber AM,

Pelvic Floor Disorders Network. Pelvic support, pelvic symptoms, and patient satisfaction after colpocleisis. Int Urogynecol J Pelvic Floor Dysfunct. 2008 Dec; 19(12): 1603-9

• Jelovsek JE, Chagin K, Brubaker L, et al. A model for predicting the risk of de novo SUI in women undergoing POP surgery. Obstet Gynecol. 2014 Feb;123(2 Pt 1):279-87

• Nygaard I, Barber MD, Burgio KL, et al. Prevalence of symptomatic pelvic floor disorders in US woman. JAMA. 2008 Sep 17;300(11):1311-6.

• Nygaard I, Brubaker L, Zyczynski HM, et al. Long term outcomes following abdominal sacrocolpopexy for pelvic organ prolapse. JAMA. 2013 May 15;309(19):2016-24

• Richter HE, Burgio KL, Goode PS, Borello-France D, Bradley CS, Brubaker L, Handa VL, Fine PM, Visco AG, Zyczynski HM, Wei JT, Weber AM, Pelvic Foor Desorders Network. Non-surgical management of stress urinary incontinence: ambulatory treatments for leakage associated with stress (ATLAS) trial. Clin Trials. 2007 Jan; 4(1): 92-101.

• Visco AG, Brubaker L, Richter HE, et al. Anticholinergic therapy vs. onabotulinumtoxin A for urgency urinary incontinence. N Engl J Med. 2012 Nov 8;367(19):1803-13.

• Wei JT, Nygaard I, Richter HE, et al. A midurethral sling to reduce incontinence after vaginal prolapse repair. N Engl J Med. 2012 Jun 21; 366(25):2358-67