Rezum for treating lower urinary tract symptoms secondary to benign prostatic hyperplasia

4.1 The committee concluded that the evidence from the Rezum II study demonstrated the effectiveness of Rezum in relieving lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) with a sustained benefit up to 4 years after the procedure. The committee noted that this is supported by the results of the observational studies. The committee noted that there are no studies that directly compare Rezum with other treatments in relieving symptoms in people with BPH, but considered an indirect comparison between Rezum and UroLift, which was drawn from analogous trial data. This suggests that Rezum is at least as effective as UroLift over 4 years. The clinical experts explained that these 2 minimally invasive procedures are used in similar cohorts of populations in clinical practice and that, in their experience, both procedures provide a similar degree of symptom relief. They also noted that Rezum is versatile in treating different shapes of prostate.

4.2 The committee noted that there is 1 pivotal study that provides the evidence for the efficacy of Rezum. The clinical experts explained that Rezum II was a US study and designed to meet US Food and Drug Administration eligibility criteria. Its major inclusion criteria were: men aged 50 or over who have symptomatic BPH with an International Prostate Symptoms Score (IPSS) of 13 or greater, and with a prostate volume, measured by transrectal ultrasound, of 30 cm³ to 80 cm³. The committee concluded that there is limited evidence on the efficacy of Rezum in men outside this cohort. The clinical experts confirmed that, in their clinical practice, this cohort of patients corresponds closely to those that they treat with Rezum and that this encompasses approximately 75% to 85% of the overall population that need treatment to relieve LUTS. The clinical experts also explained that, for people with mild LUTS (IPSS less than 8), first-line treatment is medication or lifestyle change. For people with an estimated prostate volume 120 cm³ and greater, more invasive surgical interventions are recommended.

4.3 The clinical experts explained that loss of sexual function is an important concern for people undergoing invasive treatment for LUTS because the invasive procedure is likely to damage nerves on the external surface of the prostate. They also explained that Rezum involves injecting steam into carefully directed and localised areas of the prostate from the inner, urethral surface of the prostate, and this may avoid possible damage to surrounding nerves. The committee considered that the published evidence suggests that sexual function is retained after treatment with the Rezum procedure. It did note, however, a high incidence of sexual inactivity in people included in the Rezum II study and that overall sexual function showed a tendency to decline during study follow up. The experts explained that there are different types of sexual dysfunction. They said that after treatment with Rezum erectile dysfunction is rare, but ejaculatory dysfunction has been reported. Overall, the committee concluded that the risk to sexual function is low with Rezum, and that this may be particularly important to people who are sexually active at the time of treatment. The committee was uncertain, however, about the impact of Rezum on longer-term sexual function because no data are available for longer than 4 years.

4.4 The evidence from the Rezum II study and observational studies indicated that treatment with Rezum with significant relief of LUTS is associated with a significant improvement in quality of life, which persists for up to 4 years of follow up. The clinical experts confirmed that, in their experience, people who underwent Rezum express a high level of satisfaction after the procedure.

4.5 The clinical experts advised that complications after the Rezum procedure are similar to those after other procedures for LUTS because of BPH and include urinary tract infections (UTIs), bleeding, epididymitis and abscess. The clinical experts also explained that, after the Rezum procedure, a urinary catheter is left in place for 5 to 7 days to allow the dead prostate tissue to drain away. The need for catheterisation, combined with the presence of necrotic tissue, are considered by the clinical experts to be predisposing factors for developing UTIs and, more rarely, urosepsis. This risk is higher for Rezum than UroLift, which usually does not need a post-operative urinary catheter. The clinical experts estimated that the risk of UTIs associated with a urinary catheter is around 5% to 7%, so a short course of prophylactic antibiotics may be prescribed after the procedure. The committee heard that post-procedure UTI rates associated with Rezum may be difficult to record because patients may present to their GP for treatment. It also noted that antibiotic use was not reported in the Rezum II study. The committee concluded that UTI is a common complication after Rezum but the risk of UTI can be reduced using prophylactic antibiotics.

4.6 The committee noted that the Rezum II study reported a 4.4% rate of surgical retreatment after Rezum over 4 years of follow up. The LIFT study reported a 13.6% rate of surgical retreatment after UroLift over 5 years of follow up. The clinical experts suggested that the average retreatment rate in their experience is low after Rezum, and that retreatment is most likely in the first year after the procedure. The clinical experts explained that, because there is no direct view of the prostate cavity during the Rezum procedure, additional transurethral resection of the prostate (TURP) is sometimes needed to remove residual prostate tissue after Rezum. Overall, the committee concluded that the retreatment rate with Rezum is low and compares favourably with similar treatments like UroLift.

4.7 The clinical experts explained that Rezum is currently done in some NHS trusts and that there has been an increased demand by people for this procedure in some centres. The committee noted that the published evidence for Rezum is from studies that were done outside the UK. Nonetheless, the clinical experts explained that the study population included in the Rezum II study is similar to the people that they treat with Rezum in their own practices in the NHS. The committee concluded that the evidence is generalisable to UK NHS practice.

4.8 The clinical experts said there are currently 8 different treatments, including Rezum, available in the NHS for people with significant LUTS that have not responded to conservative therapy including medication and lifestyle changes. The clinical experts considered TURP to be the standard of care for LUTS secondary to BPH, but emphasised that treatments need to be offered to people on an individual basis guided by their individual circumstances. Key factors for consideration include: the availability of procedures in their local hospitals, age, prostate gland size and characteristics, and comorbidities. Rezum's advantages over some other technologies are that it is a minimally invasive procedure that can be done under local anaesthesia with sedation, and it takes only around 20 minutes. Despite this, the clinical experts estimated that around two thirds of procedures done in the NHS are under general anaesthetic. People usually do not need an overnight stay in hospital, however. The clinical experts said that Rezum should be avoided in people with prostatitis or confirmed prostate cancer, in people for whom day case treatment is impractical or unsafe, and if there's a risk of increased bleeding, for example if they're having anticoagulant treatment.

4.9 The clinical experts said that an enlarged prostate that causes LUTS as a result of prostatic obstruction is caused by prostatic hyperplasia, which is a benign histopathological diagnosis. The clinical experts explained that there is currently no consensus on how prostate size should be estimated or measured in UK clinical practice. They considered that normally imaging would be used to estimate prostate size before surgically invasive treatment. The clinical experts said that imaging modalities could complement information from rectal digital examination of the prostate. Common imaging tools include transrectal ultrasound, cystoscopy and MRI. On the basis of these measurements, the committee heard that Rezum is usually offered to people with moderate prostatic enlargement with a prostate that is typically estimated to be 30 cm³ to 80 cm³.

4.10 The clinical experts explained that urologists need specialist training to do the Rezum procedure. This training is provided by the company and includes lectures and simulation training. The clinical experts suggested that Rezum is relatively easy to learn and that the training requirement is minimal. The committee concluded that the amount of training needed to carry out the Rezum procedure is reasonable.

4.11 The committee noted that the external assessment centre's (EAC) cost modelling results showed that Rezum is likely to be cost saving compared with TURP and holmium laser enucleation of the prostate (HoLEP) by £569 and £651 per patient respectively over 4 years. The committee noted, however, that there are some limitations in the model, including the assumption that all treatments are equally effective in relieving LUTS. Indirect comparative data from the trials suggest that the technologies may not all reduce the IPSS score to the same extent. The clinical experts confirmed that more invasive procedures such as TURP, which removes prostate tissue, would be expected to have greater IPSS improvements. It's uncertain to what extent this impacts the need for retreatment. The committee identified other limitations in the cost model, including the fact that no consideration was given to the impact of urinary catheterisation and removal, or the need for antibiotics after Rezum. The EAC said that the key drivers of the cost savings for Rezum over standard treatments such as TURP and HoLEP are the length of hospital stay and procedure time. Adding the cost of catheter removal to the modelling for Rezum does not substantially affect its cost savings compared with standard treatments. The EAC also noted that prophylactic antibiotics are likely to be common to all treatments, as well as Rezum. The committee concluded that the costs of catheter and prophylactic antibiotic use were unlikely to substantially affect Rezum's cost savings.

4.12 The committee noted that the base-case results, which are based on published data sources, suggested that Rezum saves £497 per person compared with UroLift over 4 years. The committee also noted, however, the results of the EAC's additional analyses, which included parameters that may better reflect current use of UroLift. The committee noted that 1 of the parameter changes was to include the cost of catheter removal for Rezum but not for UroLift. Based on the expert advice received, the committee agreed with this parameter change. The committee also noted the uncertainty about the current cost of the UroLift technology and its impact on the cost modelling results. Overall, the committee concluded that there are currently too many uncertainties to be able to draw any firm conclusions about the costs of using Rezum compared with UroLift.

4.13 The committee heard from the clinical experts that Rezum is commonly done as day surgery and people are not usually admitted to hospital after the procedure. The EAC considered that this was a key driver in the estimated cost savings when Rezum is compared with standard treatments such as TURP. The company's model showed that the cost of consumables for Rezum such as a delivery device was estimated to be around £1,348 per person. The company provides the generator and servicing such as maintenance free of charge. The cost of consumables relative to competitor treatments also influenced the cost modelling results. The company representatives confirmed that they do not anticipate any changes to this cost model for the foreseeable future. The committee concluded that the main driver for cost savings in the model is that Rezum is done as day surgery and people do not stay overnight at hospital.

4.14 The EAC did deterministic sensitivity and probability sensitivity analyses that varied parameters in the cost models, and the results showed that Rezum remained cost saving compared with standard treatments such as TURP and HoLEP. The committee concluded that, based on the published evidence, cost modelling and expert opinion, using Rezum is likely to lead to a cost saving of £569 compared with TURP, and £651 compared with HoLEP, for every person treated over a 4‑year time horizon.

4.15 Further evidence to address the efficacy of Rezum when directly compared with other treatments such as TURP would be welcome, including their relative impact on symptom relief, quality of life, short and long-term sexual function, and their possible benefits in people with urinary retention and with large prostate glands. More information is also needed on the number of steam injections needed with Rezum in normal clinical practice, and whether more injections are harmful.