Transvaginal mesh proved noninferior to native tissue repair for vaginal prolapse but missed the superiority target in an FDA-mandated, postmarket, prospective parallel-cohort study.

The 36-month composite treatment success rates were 89.3% with mesh repair and 80.2% with native tissue repair, falling within the prespecified 12% margin for noninferiority but not achieving superiority. However, mesh demonstrated superiority over native tissue repair for a secondary endpoint that excluded baseline anatomic measures from the definition of anatomic success.

Subjective success scores were similar with the two repair strategies, as were the rates of serious adverse events (AEs), but device and/or procedure-related AEs occurred more often with native tissue repair, reported Bruce Kahn, MD, of the Scripps Clinic in San Diego, and coauthors in Obstetrics & Gynecology.

“The data presented here, together with those reported in the SUPeR [randomized] trial, suggest that transvaginal mesh may be superior to native tissue repair, but a 3-year timeline to establish this may be too short,” the authors noted in their discussion of the findings.

“The study also showed that transvaginal mesh is not inferior to native tissue repair in safety outcome measures,” they added. “The outcomes reported here are comparable with those of the SUPeR trial at 36-months’ follow-up and add to existing evidence that transvaginal mesh provides a safe, durable treatment for POP [pelvic organ prolapse].”

The study added fresh evidence to a decades-old controversy about the safety and efficacy of transvaginal mesh for POP. The controversy came to a head in 2019 when an FDA advisory committee concluded that mesh should demonstrate superiority to native tissue repair at 36 months in order to have a favorable risk/benefit ratio. The FDA subsequently halted the sale and distribution of transvaginal mesh products.

Little Impact on Opinion?

With regulatory (approval) authority on its side, the FDA holds all the cards, and the findings reported by Kahn and colleagues are unlikely to sway opinions on either side of the controversy, according to the author of an accompanying editorial.

“Will this study change the minds of either side of this debate? Probably not,” wrote John O.L. DeLancey, MD, of the University of Michigan in Ann Arbor. “The two sides are deeply entrenched in their positions. One sees the glass half empty and the other half full. Both approaches get similar results.

“Another way to look at this is how an engineer would. They would see that the glass has 50% unused capacity. Neither operative approach is as good as we would like, and there remain opportunities for improvement that have not yet been developed.”

An individualized approach to POP is needed, as opposed to a “one-size-fits-all approach” pitting mesh versus no mesh, DeLancey continued.

“We need to understand, for each woman, what structural failures exist so that we can target our interventions to correct them,” he stated.

The recent history of the transvaginal mesh controversy dates back to 2008, when the FDA issued a public health notice advising clinicians and patients about AEs involving urogynecologic applications of surgical mesh and recommending risk-mitigation strategies. The agency subsequently identified 2,874 reports of injury, death, or malfunction of surgical mesh, including 1,503 involving POP and 1,371 related to stress urinary incontinence (SUI) repairs.

FDA staff performed a systematic literature review to gather additional information about the safety and efficacy of transvaginal mesh.

In 2011, the agency convened a panel of outside experts to discuss the findings and the types of studies necessary to perform better assessments of the risks and benefits of transvaginal mesh used for POP and SUI repair. The FDA then issued orders for postmarket surveillance studies to Boston Scientific and Coloplast, which marketed transvaginal mesh devices for POP.

Controversial Study Design

Kahn and colleagues reported findings from a postmarket study of the Boston Scientific Uphold LITE transvaginal mesh. In one arm of the parallel-cohort study, investigators at multiple sites in the U.S. enrolled patients with POP suitable for treatment with transvaginal mesh. Eligible patients had pelvic organ prolapse quantification (POP-Q) scores of Ba≥0 for prolapse of the anterior compartment alone, C≥0 for apical compartment alone, or C≥-1/2 total vaginal length and Ba≥0 for multicompartment prolapse. Additionally, patients reported a bothersome bulge they could see or feel, per the Pelvic Floor Distress Inventory-20 (PFDI-20) questionnaire.

Patients in the native tissue repair group came from a pool of shared controls from the Uphold LITE 522 study and an American Urogynecologic Society registry.

The primary endpoint was composite treatment success at 36 months, consisting of anatomic success by POP-Q criteria (Ba≤0 and/or C≤0), subjective success (PFDI-20), retreatment, and rates of serious device- or procedure-related AEs. Results were analyzed in a hierarchical manner for noninferiority and superiority.

Mandated by the FDA, the primary outcome was criticized for including anatomic outcome measures that were the same as the objective inclusion criteria. As a result, investigators included a secondary composite endpoint that required improvement in objective measure (prolapse at the introitus with POP-Q point Ba<0 and/or C<0). The remaining components were the same as for the primary composite endpoint.

Data analysis included 225 patients in the transvaginal mesh arm and 485 in the control group. The primary analysis showed that the 6.1% absolute difference (6.5% propensity-score adjusted) in the composite success rate for the mesh arm fell within the 12% margin for noninferiority. However, the difference fell just short of statistical significance for superiority (P=0.056). Analysis of the secondary endpoint yielded a propensity-score adjusted difference of 10.6% in favor of transvaginal mesh, which did achieve statistical significance (P=0.009).

Subjective success rates were 92.4% for transvaginal mesh and 92.8% for native tissue repair. Serious AEs occurred in 3.1% of the mesh group and 2.7% of the control arm. Both outcomes met statistical criteria for noninferiority. Device/procedure-related failure rates were 35.1% with transvaginal mesh and 46.4% with native tissue repair.

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