Synthetic sling or artificial urinary sphincter for men with urodynamic stress incontinence after prostate surgery: the MASTER non-inferiority RCT

Stress urinary incontinence (SUI) is a prevalent and debilitating condition affecting men post-prostate surgery. While artificial urinary sphincter (AUS) implantation is the established surgical treatment, it's invasive, requires specialized skills, and necessitates potential revisions. The male synthetic sling presents a less invasive alternative, but lacks robust comparative data from randomized controlled trials (RCTs). This study, MASTER, aims to fill this evidence gap by comparing the clinical effectiveness and cost-effectiveness of male synthetic slings versus AUS in men experiencing persistent SUI after prostate surgery. The increasing number of prostatectomies, coupled with the limitations of AUS (invasiveness, cost, need for specialized skills, and potential revisions), necessitates investigation into alternative surgical approaches like the male sling. Although the male sling appears less invasive and potentially cheaper, high-quality comparative RCT data are lacking, making it crucial to evaluate its relative safety and efficacy against the established AUS. MASTER will address this by providing a comprehensive comparison, also incorporating qualitative data to understand patient and surgeon perspectives.

Existing literature reveals inconsistencies in defining "cure" and "improvement" in post-prostatectomy incontinence (PPI). Studies often emphasize quantitative measures like pad tests, neglecting the patient's perception of success. The limited number of high-quality RCTs comparing AUS to other treatments, including male slings, highlights a critical gap in the evidence base. The existing evidence indicates high rates of persistent incontinence post-prostatectomy despite conservative treatments. AUS implantation, while effective for many, still leaves a significant number of men with persistent incontinence, emphasizing the need for effective and less invasive alternatives. While the male sling is presented as a potential solution, the absence of robust RCT data prevents evidence-based comparisons with AUS. This lack of data impacts both clinicians' decisions and the ability of healthcare policy-makers to optimize service provision and resource allocation. Therefore, a high-quality RCT that includes patient-reported outcomes and economic evaluations is essential for informing practice.

MASTER employed a multicenter, non-inferiority RCT design with a parallel non-randomized cohort (NRC) and an embedded qualitative component. 380 men with USI post-prostate surgery were randomized (1:1) to receive either a male synthetic sling or AUS. Randomization was minimized based on prior prostate surgery type, radiotherapy, and center. Surgeons and participants were unblinded. The NRC accommodated men who declined randomization, offering an opportunity to investigate treatment preferences. Data were collected using questionnaires at baseline, 6, 12, and 24 months post-randomization, with 12-month clinical reviews for the RCT. Key outcome measures included participant-reported continence at 12 months (ICIQ-UI SF questions 3 and 4, with a non-inferiority margin of 15%), cost-effectiveness (incremental cost per QALY at 24 months), adverse events, and quality of life. The qualitative component involved five studies: a focus group to establish the importance of study outcomes, and studies to explore the experiences of PPI, the two surgical procedures, men requiring further surgery, and the surgeons' experiences. Data analysis involved generalized linear models (GLMs) for primary and secondary outcomes, accounting for center effects and baseline covariates. Economic evaluations used a cost-utility approach, considering both NHS and participant perspectives. Missing data were addressed through multiple imputation. A Markov cohort model was used for a longer-term cost-effectiveness analysis.

MASTER enrolled 380 men in the RCT (190 per group) and 99 in the NRC. At 12 months, the male sling was non-inferior to AUS in terms of continence (ITT absolute risk difference -0.034, 95% CI -0.117 to 0.048; p=0.003). Both interventions led to significant improvement in incontinence symptoms (ICIQ-UI SF). Serious adverse events were infrequent (male sling: 8; AUS: 15). Quality of life improved in both groups. Secondary outcomes consistently favored AUS over the sling. The male sling was less expensive but yielded fewer QALYs. The incremental cost-effectiveness ratio (ICER) for slings compared to AUS was £425,870 per QALY lost, with a 99% probability of cost-effectiveness at a £30,000 willingness-to-pay threshold. Qualitative findings highlighted the importance of reduced pad use and improved quality of life, not just complete continence, as successful outcomes. Surgeons emphasized the higher invasiveness and technical complexity of AUS but also its generally higher success rates in terms of dryness. Men and surgeons expressed treatment preferences influenced by lifestyle, symptom severity, and access to information. A 20-year cost-effectiveness model analysis showed cost savings but also lower QALYs with slings, emphasizing the need for longer-term follow-up to reduce uncertainties.

MASTER's findings provide the first robust evidence comparing male slings and AUS for PPI. The non-inferiority of the sling in terms of continence at 12 months, despite a lower success rate, offers a less invasive alternative for appropriately selected patients. The superior performance of AUS in secondary outcome measures, along with its higher cost, suggests a trade-off between invasiveness and efficacy. The high ICER for male slings underlines their cost-effectiveness, particularly if QALY gains are prioritized. Qualitative data provided crucial context, revealing the importance of patient perspectives, particularly concerning the convenience and quality of life aspects. The study's findings can guide shared decision-making between men and surgeons, enabling personalized choices based on patient needs and preferences and acknowledging the trade-offs between invasiveness, cost, and efficacy. The high probability of cost-effectiveness for slings and the long-term model analysis highlight the ongoing need for data from extended follow-up. This study acknowledges potential biases from treatment preferences, but the detailed investigation enhances generalizability of results and addresses limitations of previous studies. Future research focusing on extended follow-up, pain outcomes, and refining patient selection criteria is crucial for optimizing clinical practice and resource allocation.

MASTER provides crucial comparative data on male slings and AUS for PPI. While slings are non-inferior in terms of primary continence outcomes at 12 months, AUS consistently outperforms slings in secondary measures and yields better patient satisfaction. Slings offer a cost-effective alternative, especially when QALY gains are prioritized. Long-term follow-up and further research exploring pain outcomes are needed to strengthen the evidence base. The study's comprehensive approach, combining quantitative and qualitative data, provides a holistic understanding of PPI surgical management and emphasizes the importance of shared decision-making informed by robust evidence.

The 24-month follow-up period might not capture all long-term complications or changes in efficacy. The lack of blinding of surgeons and patients could introduce bias. The study did not capture specific details of surgical pain outcomes. The economic analysis relied on various assumptions and data sources that introduce uncertainties. The model is sensitive to the long-term failure and complication values for both groups, but there is insufficient data to predict these over time. Extended follow-up is needed to confirm the long-term cost-effectiveness and safety profiles. While the study included a non-randomized cohort, recruitment issues highlighted the challenge of recruiting enough patients for randomization, with some being influenced by prior opinions or their doctor's recommendations.