Optilume for treating recurrent bulbar urethral strictures

The committee noted that the clinical evidence showed Optilume to be effective in improving clinically relevant outcomes including anatomical success, peak flow rate and international prostate symptom score (IPSS) at 2 years. The single-arm study data suggested that Optilume remains effective at 4 years (unpublished data from ROBUST 1). The committee considered that the studies of Optilume seemed to be well conducted and that the results were plausible. It concluded that the results to date are promising, although long-term comparative evidence was needed to see if the short-term benefits would be sustained at 5 years.

The committee had some concerns about the generalisability of the evidence to clinical practice in the NHS. None of the ROBUST studies included any centres in the UK. Optilume is proposed for second-line treatment after stricture recurrence, but people in ROBUST 3 had more than 2 endoscopic treatments before having Optilume. The clinical experts noted that this reflects NHS practice. In ROBUST 3, strictures were predilatated in the entire Optilume group and in 58% of the control group. The clinical experts confirmed that this is not standard practice for either procedure in the NHS but that using a guidewire could dilate the stricture slightly. The company stated that, from the available evidence, predilatation does not appear to have affected Optilume's effectiveness. The clinical experts also agreed that predilatation is unlikely to affect Optilume's drug delivery and the overall results of ROBUST 3. The committee concluded that the evidence is broadly generalisable to NHS practice.

The most common adverse events reported in the literature were urinary tract infection and acute urinary retention. Biological, haematological and serological studies in ROBUST 1 and 3 identified no significant effects on health. The external assessment centre (EAC) considered Optilume to be safe based on the evidence and expert feedback. The company stated that paclitaxel is locally delivered and washed out with urine. There is very little systemic exposure, and paclitaxel is mostly cleared within a day and cannot be detected. The company also noted that it is in the process of collecting safety data for up to 5‑year follow up in ROBUST 3. The committee concluded that the data provided reasonable assurance that Optilume is safe to use and understood that longer-term safety data will be collected in ROBUST 3.

The committee acknowledged that the presence of paclitaxel in semen may potentially affect semen quality, testicular function and fertility. It queried how the clinical experts counsel people about fertility. The clinical experts advised that they tell people that there is a theoretical risk of altered semen characteristics. They explained that it is up to the person having Optilume whether to continue with the treatment. The clinical experts advise them to abstain from sexual activity for 2 weeks and use barrier contraception for 3 months. They noted that so far, this has not affected the decision making of the people who have had treatment with Optilume. A postmarket study (STREAM PMS) to assess semen characteristics after treatment with Optilume in men younger than 55 is currently enrolling participants.

The clinical experts agreed that there is no single outcome measure for recurrence that is used consistently. ROBUST 3 is collecting both objective (anatomical success, freedom from repeat intervention, postvoid residual and maximum flow rate) and subjective outcomes for recurrence (IPSS and IPSS quality of life). The clinical experts noted that subjective symptom outcomes are the easiest way to assess whether there is a stricture. The objective outcomes need more invasive assessments. They are not measured until someone presents with symptoms. IPSS, maximum flow rates and postvoid residual outcomes can be used because they are indicators that there is reasonable bladder emptying. The clinical experts noted that IPSS is not a disease-specific patient-reported outcome for strictures but that it has relevance because strictures also affect flow rates. It assesses how bothered people are about their symptoms. The committee concluded that all the outcomes in ROBUST 3 are clinically relevant. It also concluded that the results from the ROBUST studies are in line with what the clinical experts have seen in clinical practice.

Optilume has been available in the UK since June 2021. The company stated that 10 NHS trusts have adopted Optilume and 82 procedures have been completed. It also stated that several NHS trusts have put in a business case for it, and more NHS trusts are looking to do so. The committee concluded that there is clinical interest in, and a rise in the adoption of, Optilume within the NHS.

The clinical experts stated that, before the COVID‑19 pandemic, waiting times for routine urethroplasty were 7 to 8 months. Waiting times are now more than 2 years. Standard endoscopic treatments are typically done as day cases under general anaesthesia, but some may incorporate a short inpatient stay. Optilume can be done more routinely in an outpatient setting under local anaesthesia. After the procedure, people empty their bladder and can go home. The clinical experts confirmed that no changes are needed to the existing infrastructure because urology units would already be set up to do flexible cystoscopy and urethrograms. Using Optilume in an outpatient setting could reduce the waiting lists substantially. The committee recognised that the NHS is under severe pressure post the pandemic. It concluded that Optilume has the potential to reduce waiting lists, and that this may not be fully captured in the cost analysis.

The clinical experts noted that trans women, with or without gender reassignment, have a bulbar urethra. If a bulbar stricture occurs, this is managed in the same way as for cisgender men. They considered that the evidence is generalisable to this group.

The EAC accepted the model structure from the company but graphically redesigned the model diagram to provide a clearer presentation of the structure. The committee agreed that the model reflected NHS practice but noted that there should be a clearer distinction between what is an event compared with a health state. The health states labelled 'cured' have been amended to 'asymptomatic' because strictures can recur and people then move into the 'symptomatic' health state. The committee concluded that the rationale for the model was sensible and that the model structure was now clearer.

The company's base case assumed that 50% of procedures would be done as a day case and 50% in an outpatient setting. The initial EAC's base case was amended to 100% of day-case procedures. The clinical experts confirmed that Optilume is also being used in an outpatient setting. The EAC's base case was amended to 50% of day-case and 50% of outpatient procedures. The clinical experts noted that this was a reasonable assumption and that there is a high likelihood of more procedures being done in an outpatient setting in the future. The committee accepted the EAC's base-case assumption and recognised this may be a conservative estimate with a trend toward increasing outpatient procedures.

The EAC's base case showed that Optilume was cost saving compared with standard endoscopic methods. The key cost driver was the probability of recurrence. Using deterministic one-way sensitivity analysis, this was the only variable that could make the base-case cost incurring at 5 years. However, the probabilistic sensitivity analysis for the EAC's base case showed that 94% of the iterations were cost saving. Scenario analysis, including using different clinical outcomes for recurrence rates, also showed that Optilume was cost saving. The committee concluded that the results were robust and suggested that Optilume is likely to be cost saving. However, long-term comparative data on recurrence is needed to improve the certainty of the cost saving associated with Optilume at 5 years and beyond.

One-year data from ROBUST 3 has been published but the trial is ongoing with a 5‑year follow up. The committee understood that the planned follow up will include patient-reported outcomes. But the committee also considered it important to request further evidence to be collected in the NHS. It considered that real-world evidence and observational studies are important to assess clinical and operational effectiveness alongside ROBUST 3. The committee noted that outcomes should include:

• patient-reported outcome measures including IPSS and quality of life

• objective outcome measures indicating stricture-free success such as reintervention rates.
  
  The clinical experts noted that a large European registry has been set up to collect objective outcomes for stricture recurrence prospectively for several technologies, including Optilume. This registry includes NHS trust hospitals and NHS patients.