3 Committee discussion

The diagnostics advisory committee considered evidence on MRI fusion biopsy systems using Artemis, Biojet, BiopSee, bkFusion, Fusion Bx 2.0, FusionVu, iSR'obot Mona Lisa, KOELIS Trinity and UroNav from several sources, including a diagnostics assessment report and an overview of that report. Full details are in the project documents for this guidance.

Benefits of the technology for people with suspected prostate cancer

3.1 Patient experts explained that technologies that help correctly diagnose prostate cancer could reduce the number of missed cancers and repeat biopsies. Overtreatment was highlighted as a particular issue and concern for patients. During consultation on the draft guidance, a stakeholder further highlighted concerns that higher rates of overdiagnosis from using MRI fusion could lead to potentially higher levels of overtreatment. Any reduction in the number of samples taken during the biopsy could lower the likelihood of biopsy-related complications. Any reduction in the need for further biopsies would help avoid some of the stress and anxiety associated with this. The external assessment group (EAG) stated that there is no evidence of a significant difference in safety outcomes between biopsies done with MRI fusion and cognitive fusion, but that the evidence is limited by poor reporting and at high risk of confounding because of differences in biopsy routes and anaesthesia methods. The patient experts also highlighted that a shorter procedure time could help to preserve dignity and minimise stress and anxiety during the biopsy. During consultation on the EAG's report, stakeholders highlighted the importance of minimising the biopsy procedure time and pain or discomfort, particularly for biopsies under local anaesthetic. They added that stress and anxiety over the biopsy can lead to a poor experience for the person, which can deter them from having additional procedures.

Clinical effectiveness

Benefits of MRI fusion biopsy systems from the trials

3.2 The committee agreed that the evidence for MRI fusion technology looked promising, but that there was a lot of uncertainty around the performance of the technology when compared with cognitive fusion. The EAG's network meta-analyses used pooled data from different MRI fusion technologies for its base-case analysis. The results suggested that MRI fusion, compared with cognitive fusion, may detect more International Society of Urological Pathology (ISUP) grade 2 or higher prostate cancer. But whether MRI fusion truly detected more higher-grade cancer, and if so by how much, was very uncertain. The EAG explained that few studies in the meta-analysis included people with higher-grade cancer, and few cases were detected in these studies.

3.3 The committee discussed the limitations of the clinical evidence included in the EAG's meta-analyses. None of the studies were done in the UK. The EAG judged all studies used in the meta-analysis to be at high risk of bias, and it stated that no high-quality randomised controlled trials have been published. The meta-analyses also showed moderate heterogeneity that could not be explained by differences in individual MRI fusion biopsy systems.

Performance differences between the different MRI fusion biopsy systems

3.4 The committee was uncertain how appropriate it was to use data generated using 1 system to show the performance of others. There was limited data directly comparing the different systems, and evidence levels varied across the different MRI fusion technologies. The EAG combined data from different technologies in its base-case analysis, based on advice from clinical experts. The committee noted that there are fundamental differences between the MRI fusion biopsy systems, which may influence outcomes. Only 2 MRI fusion systems had more than 1 study included in the meta-analysis. For 1 of these (KOELIS Trinity), all studies used a previous version of the software included in the current device. The company commented that the KOELIS Trinity uses an updated version of the same software included in the KOELIS Urostation (which is now discontinued). The EAG did not identify any evidence for Fusion Bx 2.0 or FusionVu, and none of the identified studies for the bkFusion or ISR'obot Mona Lisa met the inclusion criteria for the meta-analysis. The EAG stated that evidence was insufficient to conclude whether any MRI fusion biopsy systems were superior to others.

Potential impact on waiting times of adopting MRI fusion biopsy systems

3.5 The committee considered that adopting MRI fusion biopsy systems could prolong waiting time for prostate biopsies, and that this was not captured in the cost-effectiveness estimates. The clinical experts explained that radiologist services are at full capacity in the NHS. Clinical experts with experience using MRI fusion biopsy systems highlighted that more preparatory time is needed per biopsy with MRI fusion than with cognitive fusion, although this does decrease with more experience in using the technology. This lowers the number of biopsies that can be done in a day. In its economic model, the EAG assumed that additional procedure time for MRI fusion use would be 10 minutes in a high throughput centre (5 minutes radiologist time to import and obtain appropriate MRI sequences and 5 minutes during the biopsy), based on expert advice. It was suggested that this would be longer when the technologies were first used, because of lack of experience. The additional time was added to the cost of doing MRI fusion biopsy in the model (for example, for staff time), but the model did not include any impact of this on slowing biopsy throughput. The clinical experts commented that MRI fusion could improve patient throughput if it reduced the repeat biopsies needed (for example, if there was more confidence in a negative biopsy). The EAG commented that how much MRI fusion increases wating times would depend on whether the capacity constraint was access to the biopsy procedure or to the initial MRI (which would be the same for MRI fusion and cognitive fusion biopsy). The committee was also concerned about how adopting software fusion technology could potentially impact how many biopsy procedures can be done per day, and consequently the effect on waiting times for this procedure.

Cost effectiveness

Improving detection of higher-grade prostate cancer makes the technology more cost effective in the model

3.6 The cost-effectiveness estimates for MRI fusion biopsy systems (with or without systematic biopsy), compared with cognitive fusion, were generally favourable, but uncertain. Potential adverse impacts on the capacity of services to do biopsies (see section 3.5) were not considered in the model. The EAG's analysis showed that cost effectiveness was most affected by the improved detection of localised or locally advanced higher-grade cancers (ISUP 2 or higher). When targeted fusion was combined with systematic biopsy, there were more cost savings and health benefits in the long-term model for MRI fusion than for cognitive fusion.

3.7 The EAG cautioned that the uncertainties in the clinical evidence should be considered alongside the overall cost effectiveness, because the evidence used in its network meta-analysis underpinned its economic model. The committee recalled that although the data suggested that MRI fusion may detect more higher-grade cancers, this was very uncertain (see section 3.2). It noted that a scenario analysis done by the EAG in which any benefit to detecting cancer for MRI fusion was removed from the model, the incremental cost-effectiveness ratios (ICERs) increased to over £500,000 per quality-adjusted life year (QALY) gained. The committee concluded that the uncertainty about how much better MRI fusion is at detecting higher-grade cancers means that the cost effectiveness of these technologies, while potentially favourable, is also very uncertain.

Benefits to less experienced health professionals

3.8 The committee acknowledged that the technology could benefit less experienced healthcare professionals, and help to standardise care across different centres and improve accessibility. The clinical experts noted that biopsies are done by various healthcare professionals including urologists, radiologists and nurse specialists. The level of experience in doing biopsies varies, and specialist centres are more likely to have professionals with more experience. They suggested that the accuracy of cognitive fusion is highly dependent on the operator. The EAG identified 1 study that reported cancer biopsy positivity rates by operator experience (Stabile et al. 2018). It reported an increase in the biopsy positivity rates in the first 60 procedures, where it plateaued, regardless of the biopsy approach. Operator experience predicted the biopsy positivity rate of targeted biopsies, particularly for transrectal MRI fusion biopsy compared with transrectal cognitive fusion or transperineal MRI biopsy fusion.

3.9 The clinical experts suggested that using MRI fusion biopsy systems could help standardise biopsy quality. They said that this could minimise geographical variation in procedure standard caused by the variation in operator expertise. Improving the ability of less experienced operators to do the procedure may allow it to be available more widely, improving accessibility.

MRI fusion biopsy systems show promise, but better-quality evidence is needed

3.10 The committee recognised that MRI fusion biopsy systems show promise, could help improve standards across the NHS and patient access (see section 3.9), and may be cost effective. But it felt there was too much uncertainty about how much it would improve detection of prostate cancer to recommend its use for routine adoption (see sections 3.6 and 3.7). Further research is needed to reduce this uncertainty, and so also reduce the uncertainty about the cost effectiveness. The committee was also concerned about how adopting MRI fusion technology could potentially impact how many biopsy procedures can be done per day, and consequently the effect on waiting times for this procedure (see section 3.5). Further data on this would help reduce concerns about the impact of adopting MRI fusion biopsy systems.

Research considerations

An ongoing study may fill some evidence gaps

3.11 The ongoing IP7-PACIFIC trial (see trial NCT05574647 on the ClinicalTrials.gov website, accessed 14 November 2022) is likely to provide further, potentially high-quality, data on MRI fusion biopsy systems for detecting clinically significant prostate cancers, compared with cognitive fusion biopsy. The primary outcome of the trial is the proportion of clinically significant cancers (defined as ISUP 2 or above) detected in people who had a biopsy with a suspicious MRI (MRI score 3, 4 or 5 on either the Likert or Prostate Imaging-Reporting and Data System [PI-RADS] schema). The EAG commented that the study aims to recruit 3,600 people with suspected prostate cancer in the UK, but that not all of these people will provide data on MRI fusion performance (the study includes 2 linked randomised controlled trials, and is also comparing biparametric and multiparametric MRI to detect clinically significant prostate cancers). The EAG emphasised that to help inform cost-effectiveness estimates from its model, the numbers of cancer detected by ISUP grade should be reported (rather than just the number of ISUP grade 2 or higher). During consultation on the draft guidance, a stakeholder further highlighted the importance of collecting data on the effect of MRI fusion technologies on detecting clinically insignificant prostate cancer, as well as higher-grade cancers. Given the uncertainty about the generalisability of data generated using 1 MRI fusion technology to others (see section 3.4), it would be beneficial if data was reported separately for each MRI fusion biopsy system. The committee concluded that this will be a useful trial for reducing uncertainty about MRI fusion biopsy performance, but noted that the estimated study completion data is not until 2026. It stated that people should be encouraged to participate in the trial.

Existing data and resources to collect data

3.12 The clinical experts highlighted that professional bodies such as the British Association of Urological Surgeons and the Royal College of Radiologists may have data that could contribute to a future assessment. They also suggested that establishing further registries may help data collection. The committee suggested that centres should consider contributing to existing audit tools such as the National Prostate Cancer Audit when possible.

  • National Institute for Health and Care Excellence (NICE)