Authors' objectives: People with suspected prostate cancer are usually offered either a local anaesthetic transrectal ultrasound-guided prostate biopsy or a general anaesthetic transperineal prostate biopsy. Transperineal prostate biopsy is often carried out under general anaesthetic due to pain caused by the procedure. However, recent studies suggest that performing local anaesthetic transperineal prostate biopsy may better identify cancer in particular regions of the prostate and reduce infection rates, while being carried out in an outpatient setting. Devices to assist with freehand methods of local anaesthetic transperineal prostate may also help practitioners performing prostate biopsies. To evaluate the clinical effectiveness and cost-effectiveness of local anaesthetic transperineal prostate compared to local anaesthetic transrectal ultrasound-guided prostate and general anaesthetic transperineal prostate biopsy for people with suspected prostate cancer, and local anaesthetic transperineal prostate with specific freehand devices in comparison with local anaesthetic transrectal ultrasound-guided prostate and transperineal prostate biopsy conducted with a grid and stepping device conducted under local or general anaesthetic. Prostate cancer accounts for 30% of all cancers diagnosed in men in the UK and the incidence is rising. It is more common in men over 45 years of age. Symptoms that cannot be attributed to other health conditions include lower back or bone pain, lethargy, erectile dysfunction, haematuria, weight loss and lower urinary tract symptoms. National Institute for Health and Care Excellence (NICE) guideline NG12 advises on recognition and referral of people presenting with possible prostate cancer. A prostate-specific antigen (PSA) test and digital rectal examination should be performed. If PSA levels are raised above normal or if the prostate feels malignant, then the person should be referred for suspected cancer. NICE guideline NG131 advises on diagnosis and management. It recommends a multiparametric magnetic resonance imaging (mpMRI) test with the results reported using a five-point Likert scale to indicate how likely the presence of prostate cancer is. The Likert scale score, or alternatively the Prostate Imaging Reporting and Data System (PI-RADS score, not mentioned in the NICE guideline), is used to assess whether the person is offered a prostate biopsy. People with a score of 3 or above should be offered a multiparametric magnetic resonance imaging (mpMRI)-influenced prostate biopsy. People with a score of 1 or 2 will discuss risks and benefits with a clinician and if a prostate biopsy goes ahead, it should be a systematic biopsy. Two main options for biopsy are transrectal ultrasound prostate biopsy under local anaesthetic (LATRUS) and transperineal prostate biopsy under general anaesthetic (GATP). Biopsies can be either targeted (based on mpMRI findings) or systematic (samples are taken according to a predefined scheme) or both. Recent studies suggest that performing transperineal prostate biopsy under local anaesthetic (LATP) could better identify cancer in particular regions of the prostate and could have lower infection rates than transrectal biopsies while also being able to be carried out in an outpatient setting. Transperineal prostate biopsy is usually carried out under general anaesthetic due to pain caused by the procedure and tolerability is a key issue. Various freehand devices to assist with LATP prostate biopsy are being introduced to the market. The six specific freehand devices specified in the NICE scope for this review are: Cambridge Prostate Biopsy Device (CamPROBE) (JEB Technologies Ltd, Suffolk, UK); EZU-PA3U (Hitachi Ltd, Tokyo, Japan); PrecisionPoint™ Transperineal Access System (BXTAccelyon Ltd, Burnham, UK); SureFire Guide (LeapMed, Jiangsu, China); Trinity® Perine Grid (KOELIS®, NJ, USA); UA1232 puncture attachment (BK Medical, MA, USA). The aim of this review is to evaluate the diagnostic yield, clinical effectiveness and cost-effectiveness of LATP prostate biopsies performed with or without available specialist devices and equipment, in people with suspected prostate cancer. Two decision questions were prioritised by NICE for this assessment, with input from relevant stakeholders: Decision question 1. Do LATP prostate biopsies in patients with suspected prostate cancer represent a clinically and cost-effective use of National Health Service (NHS) resources? Decision question 2. Do freehand transperineal biopsy devices for LATP prostate biopsies in patients with suspected prostate cancer represent a clinically effective and cost-effective use of NHS resources? There are five comparisons required to address the two decision questions in the NICE scope: LATP-any (using coaxial needle or grid and stepping device or freehand device) versus LATRUS LATP-any (using coaxial needle or grid and stepping device or freehand device) versus GATP LATP-freehand (freehand device only) versus LATRUS LATP-freehand (freehand device only) versus GATP LATP-freehand (freehand device only) versus LATP-grid and stepping device.

Authors' results and conclusions: We included 19 comparative studies (6 randomised controlled trials and 13 observational comparative studies) and 4 single-arm studies of freehand devices. There were no statistically significant differences in cancer detection rates for local anaesthetic transperineal prostate (any method) compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.00, 95% confidence interval 0.85 to 1.18) (n = 5 randomised controlled trials), as was the case for local anaesthetic transperineal prostate with a freehand device compared to local anaesthetic transrectal ultrasound-guided prostate (relative risk 1.40, 95% confidence interval 0.96 to 2.04) (n = 1 randomised controlled trial). Results of meta-analyses of observational studies were similar. The economic analysis indicated that local anaesthetic transperineal prostate is likely to be cost-effective compared with local anaesthetic transrectal ultrasound-guided prostate (incremental cost below £20,000 per quality-adjusted life-year gained) and less costly and no less effective than general anaesthetic transperineal prostate. local anaesthetic transperineal prostate with a freehand device is likely to be the most cost-effective strategy: incremental cost versus local anaesthetic transrectal ultrasound-guided prostate of £743 per quality-adjusted life-year for people with magnetic resonance imaging Likert score of 3 or more at first biopsy. Transperineal prostate biopsy under local anaesthetic is equally efficient at detecting prostate cancer as transrectal ultrasound-guided prostate biopsy under local anaesthetic but it may be better with a freehand device. local anaesthetic transperineal prostate is associated with urinary retention type complications, whereas local anaesthetic transrectal ultrasound-guided prostate has a higher infection rate. local anaesthetic transperineal prostate biopsy with a freehand device appears to meet conventional levels of costeffectiveness compared with local anaesthetic transrectal ultrasound-guided prostate. Systematic review of diagnostic test evaluation and clinical effectiveness The literature searches identified a total of 1969 references of which 111 references were subjected to full-text screening. Twenty-seven publications reported 23 studies meeting the inclusion criteria for this review: 19 comparative studies of which 6 were RCTs and 13 were observational studies (1 of which is unpublished); and 4 single-arm studies for LATP-freehand devices where no comparative evidence was identified. There were no statistically significant differences in cancer detection rates for LATP (any method) compared to LATRUS with RR = 1.00 [95% confidence interval (CI) 0.85 to 1.18] (n = 5 RCTs). A single randomised trial estimated a non-significant difference in cancer detection rates in favour of LATP using a freehand device (PrecisionPoint) compared to LATRUS RR = 1.40, 95% CI 0.96 to 2.04. This finding was supported by meta-analysis of observational comparative studies RR = 1.21 (95% CI 1.08 to 1.34) (n = 4 studies). There were no statistically significant differences in cancer detection rates in meta-analyses comparing other biopsy methods. Evidence from the systematic review for other clinical outcomes, biopsy-related complications and patient-reported outcomes was sparse. Transperineal prostate biopsy under local anaesthetic is equally efficient at detecting prostate cancer as transrectal ultrasound-guided prostate biopsy under local anaesthetic but evidence from one RCT, supported by observational studies, suggests that it might be better when using a freehand device. Local anaesthetic transperineal prostate biopsy is associated with urinary retention-type complications, whereas local anaesthetic transrectal ultrasound-guided prostate biopsy has a higher infection rate. Economic evaluation suggests that LATP with a freehand device is likely to be cost-effective compared with LATP with other methods, LATRUS and GATP for patients with no previous biopsy at high risk of having prostate cancer indicated by previous MRI results. This result is sensitive to the estimated cost of the freehand device, the number of and cost of core samples taken, and the sources for biopsy complication rates. Recommendations for research Evidence for freehand devices. There was no comparative evidence for several of the freehand devices in the NICE scope. The TRANSLATE study is expected to help address this question, as it is evaluating the PrecisionPoint, UA1232 and ‘any ultrasound probe-mounted needle guidance device’. Outcomes not covered in included available evidence. We suggest that incidence of defined complications (standardised for grading of severity and length of follow-up), health-related quality of life and longer-term clinical outcomes could be defined in a core outcome set. LATP versus GATP. Evidence for this comparison is sparse (we identified one RCT reporting cancer detection rates). Repeat biopsy population. There is a need for separate reporting of results for this subgroup, or a separate prospective RCT. UK NHS setting. The three UK studies included in our review were single-centre observational studies with a limited set of outcomes. The TRANSLATE study is expected to remedy this; it is a multicentre randomised study across nine NHS Trusts in England.

Authors' recommendations: Evidence for freehand devices. There was no comparative evidence for several of the freehand devices in the NICE scope. The TRANSLATE study is expected to help address this question, as it is evaluating the PrecisionPoint, UA1232 and ‘any ultrasound probe-mounted needle guidance device’. Outcomes not covered in included available evidence. We suggest that incidence of defined complications (standardised for grading of severity and length of follow-up), health-related quality of life and longer-term clinical outcomes could be defined in a core outcome set. LATP versus GATP. Evidence for this comparison is sparse (we identified one RCT reporting cancer detection rates). Repeat biopsy population. There is a need for separate reporting of results for this subgroup, or a separate prospective RCT. UK NHS setting. The three UK studies included in our review were single-centre observational studies with a limited set of outcomes. The TRANSLATE study is expected to remedy this; it is a multicentre randomised study across nine NHS Trusts in England.

Authors' methods: We conducted a systematic review of studies comparing the diagnostic yield and clinical effectiveness of different methods for performing prostate biopsies. We used pairwise and network meta-analyses to pool evidence on cancer detection rates and structured narrative synthesis for other outcomes. For the economic evaluation, we reviewed published and submitted evidence and developed a model to assess the cost-effectiveness of the different biopsy methods. There is limited evidence for efficacy in detecting clinically significant prostate cancer. There is comparative evidence for the PrecisionPoint™ Transperineal Access System (BXTAccelyon Ltd, Burnham, UK) but limited or no evidence for the other freehand devices. Evidence for other outcomes is sparse. The cost-effectiveness results are sensitive to uncertainty over cancer detection rates, complication rates and the numbers of core samples taken with the different biopsy methods and the costs of processing them. Systematic review of diagnostic test evaluation and clinical effectiveness A systematic review of diagnostic and clinical effectiveness evidence was conducted following a peer-reviewed protocol. Searches were based on a comprehensive search strategy. Bibliographic databases, including MEDLINE, EMBASE, Web of Science, The Cochrane Library and the International HTA database, were searched for English-language references in July 2021, and these searches were updated at the end of October 2021. Urology conferences and freehand-device company submissions were hand-searched, and reference lists of identified systematic reviews and meta-analyses were checked. Relevant studies were sought through contact with study authors and NICE Specialist Committee members. Studies were eligible if they included people with suspected prostate cancer with an indication for prostate biopsy and reported diagnostic yield, for example, cancer detection rates, or other clinical or patient-reported outcomes. The eligible interventions were any LATP biopsy (of which LATP-freehand biopsy is a subset) and the eligible comparators were LATRUS and GATP; the LATP-grid and stepping device was an eligible comparator when compared with the LATP-freehand intervention. The Cochrane risk of bias tool (version 1) was used to assess risk of bias for the included randomised controlled trials (RCTs) and The Joanna Briggs Institute critical appraisal checklists were used to assess the included observational studies. Two reviewers carried out study selection, data extraction and critical appraisal, with any disagreements resolved through discussion and referred to a third reviewer for resolution as necessary. We conducted meta-analysis of the cancer detection rate outcomes for which sufficient comparative data were available. Pairwise meta-analysis was conducted for the above comparisons, with randomised and non-randomised studies analysed separately. Network meta-analysis was conducted for the two decision questions specified in the NICE scope. We synthesised the data for other outcomes narratively, as evidence was too sparse for meta-analysis.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR134220

Year Published: 2024

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/ZKTW8214

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/ZKTW8214

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