Authors' objectives: Magnetic resonance imaging localises cancer in the prostate, allowing for a targeted biopsy with or without transrectal ultrasound-guided systematic biopsy. Targeted biopsy methods include cognitive fusion, where prostate lesions suspicious on magnetic resonance imaging are targeted visually during live ultrasound, and software fusion, where computer software overlays the magnetic resonance imaging image onto the ultrasound in real time. The effectiveness and cost-effectiveness of software fusion technologies compared with cognitive fusion biopsy are uncertain. To assess the clinical and cost-effectiveness of software fusion biopsy technologies in people with suspected localised and locally advanced prostate cancer. A systematic review was conducted to evaluate the diagnostic accuracy, clinical efficacy and practical implementation of nine software fusion devices compared to cognitive fusion biopsies, and with each other, in people with suspected prostate cancer. Comprehensive searches including MEDLINE, and Embase were conducted up to August 2022 to identify studies which compared software fusion and cognitive fusion biopsies in people with suspected prostate cancer. Risk of bias was assessed with quality assessment of diagnostic accuracy studies-comparative tool. A network meta-analysis comparing software and cognitive fusion with or without concomitant systematic biopsy, and systematic biopsy alone was conducted. Additional outcomes, including safety and usability, were synthesised narratively. A de novo decision model was developed to estimate the cost-effectiveness of targeted software fusion biopsy relative to cognitive fusion biopsy with or without concomitant systematic biopsy for prostate cancer identification in biopsy-naive people. Scenario analyses were undertaken to explore the robustness of the results to variation in the model data sources and alternative assumptions. Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the UK. In the NHS people with suspected PCa are offered multiparametric magnetic resonance imaging (mpMRI). People with suspected PCa, according to MRI, are offered a biopsy procedure to confirm the presence and severity of cancer. Traditionally patients were offered a systematic transrectal, ultrasound-guided prostate biopsy (or systematic biopsy). Since the introduction of mpMRI, specific areas of abnormal tissue can be targeted, by combining (or fusing) the results of mpMRI and ultrasound imaging. Several methods for fusing MRI and ultrasound images exist, including cognitive fusion (CF), in which a region of interest is identified prior to biopsy and the biopsy operator estimates where it might be on an ultrasound image, and software fusion (SF), where regions of interest on magnetic resonace images are identified and contoured before biopsy and overlayed with the prostate contours on ultrasound images during the biopsy. Systematic biopsy may be used in addition to targeted biopsy. A number of SF technologies are available. However, the effectiveness and cost-effectiveness of SF compared with CF is uncertain. This study aimed to assess the clinical and cost-effectiveness of SF biopsy systems in people with suspected localised and locally advanced PCa.

Authors' results and conclusions: Twenty-three studies (3773 patients with software fusion, 2154 cognitive fusion) were included, of which 13 informed the main meta-analyses. Evidence was available for seven of the nine fusion devices specified in the protocol and at high risk of bias. The meta-analyses show that patients undergoing software fusion biopsy may have: (1) a lower probability of being classified as not having cancer, (2) similar probability of being classified as having non-clinically significant cancer (International Society of Urological Pathology grade 1) and (3) higher probability of being classified at higher International Society of Urological Pathology grades, particularly International Society of Urological Pathology 2. Similar results were obtained when comparing between same biopsy methods where both were combined with systematic biopsy. Evidence was insufficient to conclude whether any individual devices were superior to cognitive fusion, or whether some software fusion technologies were superior to others. Uncertainty in the relative diagnostic accuracy of software fusion versus cognitive fusion reduce the strength of any statements on its cost-effectiveness. The economic analysis suggests incremental cost-effectiveness ratios for software fusion biopsy versus cognitive fusion are within the bounds of cost-effectiveness (£1826 and £5623 per additional quality-adjusted life-year with or with concomitant systematic biopsy, respectively), but this finding needs cautious interpretation. Software fusion biopsies may be associated with increased cancer detection in relation to cognitive fusion biopsies, but the evidence is at high risk of bias. Sufficiently powered, high-quality studies are required. Cost-effectiveness results should be interpreted with caution given the limitations of the diagnostic accuracy evidence. The systematic review of clinical evidence included a total of 3733 patients who received SF and 2154 individuals with CF from 23 studies. Evidence was included for all devices specified in the protocol, except for Fusion Bx 2.0 and FusionVu. Overall, the evidence for all devices was at high risk of bias. Overall, biopsy-naive patients were under-represented. Fourteen studies were included in the meta-analyses. Diagnostic accuracy Across all analyses results must be interpreted with caution due to the high risk of bias in the evidence base and wide uncertainty over the results. The meta-analyses show that patients undergoing SF biopsy may have: (1) a lower probability of being classified as not having cancer, (2) similar probability of being classified as having non-clinically significant cancer [International Society of Urological Pathology (ISUP) grade 1], and (3) higher probability of being classified at higher ISUP grades, particularly ISUP 2. Similar results were obtained where both biopsy methods were combined with systematic biopsy. Additional meta-analyses of cancer detection rates suggest that, compared with CF biopsy, SF may identify more PCa (any grade) (OR 1.30; 95% CrI 1.06, 1.61). Adding systematic biopsy to cognitive or SF may increase the detection of all PCa and of clinically significant (CS) cancer, and from this evidence there is no suggestion that SF with concomitant systematic biopsy is superior to CF with systematic biopsy. Meta-analyses of cancer detection rates, by individual device, showed that compared with CF biopsy, BioJet and Urostation are associated with a higher detection of PCa overall. There was no evidence that any of the SF devices increased detection of CS cancer (except for BioJet, although this is based on one low-quality study), and overall, the evidence was insufficient to conclude whether any individual devices were superior to CF, or whether some SF technologies are more accurate than others. Compared to CF biopsy, patients undergoing SF biopsy may show a lower probability of being classified as not having cancer, similar probability of being classified as having non-CS cancer, and a higher probability of being classified at higher ISUPs, particularly ISUP 2. Both SF and CF biopsy can miss CS cancer lesions, and the addition of standard-systematic biopsy increases the detection of all PCa and CS cancer for both fusion methods. There is insufficient evidence to conclude on the relative accuracy and clinical effectiveness of different software devices. Cost-effectiveness estimates comparing software to CF were generally favourable to SF, except where the technologies were assumed to have the same diagnostic accuracy. The drivers of economic value of SF, comparative diagnostic accuracy and prevalence, are affected by unquantified uncertainty. Judgements on the economic value of SF require integration of the uncertainties over the clinical evidence with the overall cost-effectiveness. Recommendations for further research High-quality, sufficiently powered RCT evidence comparing SF biopsy with CF biopsy is required to address limitations from the existing evidence. Improved reporting of diagnostic accuracy outcomes would enable future syntheses to make use of a larger body of evidence.

Authors' recommendations: High-quality, sufficiently powered RCT evidence comparing SF biopsy with CF biopsy is required to address limitations from the existing evidence. Improved reporting of diagnostic accuracy outcomes would enable future syntheses to make use of a larger body of evidence.

Authors' methods: There was insufficient evidence to explore the impact of effect modifiers. Systematic review A systematic review of the diagnostic accuracy, clinical effectiveness, safety and practical implementation of nine SF systems compared with CF and with each other, in people suspected PCa according to MRI was conducted. Comprehensive bibliographic searches, including MEDLINE and EMBASE and supplementary sources, were conducted up to 2 August 2022 for published and unpublished literature. Studies of people with suspected PCa who have had a MRI scan that indicates a significant lesion [Likert or prostate imaging – reporting and data system (PI-RADS) score of 3 or more], including biopsy-naive and repeat biopsy patients with a previous negative prostate biopsy, and comparing SF with CF or with another SF device, were included. The following SF technologies were included: ARTEMIS (InnoMedicus ARTEMIS), BioJet (Healthcare Supply Solutions Ltd), BiopSee (Medcom), bkFusion (BK Medical UK Ltd and MIM Software Inc.), Fusion Bx 2.0 (Focal Healthcare), FusionVu (Exact Imaging), iSR’obot Mona LisaTM (Biobot iSR’obot), KOELIS Trinity (KOELIS and Kebomed) and UroNav Fusion Biopsy System (Phillips). Previous versions were also eligible. In-bore (or in-gantry) biopsies were excluded. Prospective, randomised and non-randomised comparative studies were included, and retrospective evidence where no prospective evidence could be found for an eligible SF device. To provide sufficient evidence for a network meta-analysis (NMA), within-patient comparisons or randomised controlled trials (RCTs) between SF and systematic biopsy, and between CF and systematic biopsy, were also eligible to inform indirect comparisons of diagnostic accuracy. Two researchers independently screened the titles and abstracts of all reports identified by the bibliographic searches and of all full-text papers subsequently obtained. Data extraction and quality assessment were conducted by at least one researcher and checked by a second. Risk of bias of diagnostic accuracy studies was assessed using quality assessment of diagnostic accuracy studies-comparative (QUADAS-C). For diagnostic accuracy outcomes, studies reporting sufficient data were included in network meta-analyses comparing SF and CF with or without concomitant systematic biopsy, and systematic biopsy alone, where odds of being categorised in each of different cancer grades were allowed to vary by biopsy type. Results were reported as odds ratios with 95% credible intervals (CrIs). Additional diagnostic accuracy results that could not be pooled in a meta-analysis and clinical effectiveness, safety and implementation outcomes were synthesised narratively.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR135477

Year Published: 2024

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/PLFG4210

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/PLFG4210

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk