3 Committee discussion

The diagnostics advisory committee considered evidence on local anaesthetic transperineal (LATP) prostate biopsy, with or without the following freehand needle positioning devices:

EZU-PA3U (Hitachi)
PrecisionPoint (BXTAccelyon)
SureFire Guide (Delta Surgical)
Trinity Perine Grid (KeboMed)
UA1232 (BK Medical)
the double freehand CamPROBE device (JEB Technologies).

Evidence was considered from several sources, including a diagnostics assessment report and an overview of that report. Full details are in the project documents for this guidance.

Risk of infection, possible adverse events, pain and embarrassment are important patient concerns about prostate biopsy

3.1 Patient experts explained the main issues and concerns around prostate biopsy from a patient perspective. These included the importance of getting clear and accurate information about the procedure and possible adverse events. They highlighted risk of infection as a major concern for patients. They were also worried about the severity and duration of side effects such as urinary retention and haematuria. A patient expert explained the importance of receiving early results to reduce the anxiety of waiting for a biopsy result. The committee heard that prostate biopsies using any method can be undignified and embarrassing for patients. Alongside pain, this may be a factor in some patients preferring to have a general anaesthetic. This may be more of an issue for LATP biopsies because patients need to be in a lithotomy position. Patient experts said that unpleasant prostate biopsy experiences can stop people going to any more biopsy appointments.

Clinical effectiveness

The evidence on cancer detection rates is limited and suggests no significant difference between different biopsy methods

3.2 The evidence on cancer detection rates of the different prostate biopsy approaches was limited. The clinical effectiveness review included 23 studies and the strength of evidence was mixed. Six studies were randomised controlled trials (RCTs), but most were observational. Six studies were only available as conference abstracts and 1 (Bojin 2019) was an unpublished slide set. The external assessment group (EAG) said that there was a high risk of reporting bias in these studies because of the limited information that they included. Most studies did not report whether a prebiopsy multiparametric MRI (mpMRI) had been done and some did not report the number of biopsy cores taken. In studies that did report the number of cores, these varied from around 12 to 24 cores. The committee noted that studies that used an mpMRI image to take targeted biopsy samples and those that took more cores may result in higher cancer detection rates regardless of the biopsy technique used. Eight of the studies used the PrecisionPoint device, 4 used a coaxial needle and 1 used a grid and stepper (for LATP compared with general anaesthetic transperineal [GATP] biopsy). There were 4 single arm studies (1 on CamPROBE and 3 on the UA1232 device). The rest did not report what device was used. There was no comparative evidence on the CamPROBE, EZU-PA3U, UA1232, SureFire or Trinity Perine Grid devices. The committee noted that of the 23 included studies, a single RCT available as a conference abstract was the only study used in the network meta-analysis of cancer detection rates for LATP using a freehand needle positioning device. The committee said that there was limited evidence on cancer detection rates and that caution should be used when interpreting the results. It also noted that the ongoing trial of transrectal compared with LATP biopsy (TRANSLATE; see section 3.7) RCT will provide further evidence on detection rates of clinically significant prostate cancer. The committee concluded that, because there was generally no significant difference between LATP using any method, LATP using a freehand needle positioning device, local anaesthetic transrectal ultrasound (LA-TRUS) or GATP, it could not say if one technique was better than the others.

Cancer detection rates and adverse events are likely to be similar between the different freehand needle positioning devices

3.3 All the comparative clinical evidence for freehand needle positioning devices was on the PrecisionPoint device. However, a clinical expert explained that the different freehand devices were all used in a similar way, with a needle positioning guide that attaches to the ultrasound probe. This keeps the needle and ultrasound probe in phase during the procedure. The clinical experts said they would not expect significant differences in cancer detection rates and adverse event rates between the devices. No studies directly compare the individual devices so there was no evidence that one performs better than any other. The committee concluded that the clinical effectiveness in terms of cancer detection and adverse events was likely to be similar for all the freehand needle positioning devices, although this was uncertain.

The evidence is not generalisable to double freehand prostate biopsy

3.4 A clinical expert explained that double freehand prostate biopsy approaches should be considered separately to the freehand approach that uses a needle positioning guide. CamPROBE is a double freehand device and therefore is not attached to the ultrasound probe. Clinical experts said that this was a more difficult technique because one hand guides the ultrasound probe while the other guides the needle, and they need to be kept in phase manually. They said that it may be more challenging to target small areas accurately using this technique, and that it takes longer to train someone to the required level of competency. The committee concluded that, because of these differences, double freehand techniques such as CamPROBE cannot be assumed to have the same clinical effectiveness in terms of cancer detection and adverse events as freehand needle positioning devices. Comparative studies of the CamPROBE biopsy device are needed to assess its clinical effectiveness (see section 4.1).

Rates of infection and sepsis are higher for TRUS biopsies than transperineal biopsies

3.5 Clinical experts said sepsis can happen after a prostate biopsy. It is rare but serious, and can result in death. In the EAG's clinical effectiveness review, relatively few studies reported post-biopsy sepsis. In the studies that did report sepsis, it only occurred after LA-TRUS biopsy and not after transperineal biopsy. An analysis of recent hospital episode statistics (HES) data (from 2017 to 2019) by Tamhankar et al. (2020) showed that there was a difference in rates of infection and sepsis between TRUS biopsies and transperineal biopsies. Rates of infection were 1.50% in people who had a TRUS biopsy and 0.67% for a transperineal biopsy. Similarly, rates of sepsis were higher for TRUS biopsies (1.12%) than for transperineal biopsies (0.42%). The committee concluded that LATP biopsies may reduce the risk of infection and sepsis compared with TRUS biopsies.

There are some differences between LATP and TRUS biopsy approaches

3.6 Clinical experts explained the key differences between LA-TRUS and LATP biopsy approaches. An LA-TRUS biopsy tends to take fewer cores (usually 12), whereas centres that use the Ginsburg protocol for LATP may take 24 cores or more (2 LATP protocols are used in the UK: the RAPID protocol and the Ginsburg technique). However, some centres may also take 12 cores for LATP plus additional targeted cores based on mpMRI results. A clinical expert said that mpMRI may identify anterior lesions of the prostate and these can be more difficult to reach using LA-TRUS biopsy than LATP. However, the committee heard that there was no evidence to assess the clinical effectiveness of the different biopsy approaches in people with anterior lesions. Clinical experts said that LATP may be less tolerable because of the lithotomy position and if numerous skin punctures were needed, when using a grid and stepper for example. LATP biopsies also take slightly longer than TRUS biopsies, particularly when clinicians are training or first start using the technique. However, a clinical expert said that when practitioners are trained equally in the techniques, the difference is minimal. Less experienced clinicians may find it easier to use a grid and stepper. Clinical experts explained that, in a minority of cases, LATP might be contraindicated, for example in people who have had gender reassignment. There are also some patient groups with a higher risk of infection (for example, immunocompromised people) who would prefer LATP because of the lower risk of sepsis with LATP than LA-TRUS. Clinical experts explained that there is a move towards using LATP nationally and that some centres no longer do TRUS prostate biopsies.

Participation in the ongoing TRANSLATE RCT is encouraged to generate further evidence to help refine clinical practice

3.7 The ongoing TRANSLATE RCT will provide further comparative evidence on LA-TRUS biopsy and LATP biopsy using a freehand needle positioning device. The trial aims to recruit 1,042 men over 15 months from 9 NHS hospitals in the UK. The protocol says that an average of around 12 systematic biopsy cores will be taken, depending on prostate size, with an additional 4 target biopsy cores for each significant lesion seen on prebiopsy MRI. The primary outcome is detection rates of clinically significant prostate cancer. Secondary outcomes include rates of infection, health related quality of life, patient reported tolerability of the procedure, patient reported biopsy-related complications, number of subsequent prostate biopsy procedures, cost effectiveness, and histological parameters. The trial will last for 31 months and is expected to end in October 2023. The committee concluded that centres should be encouraged to participate in the TRANSLATE RCT to generate more evidence to help understand the effects of differences between the LATP and LA-TRUS biopsy approaches and refine clinical practice.

Cost effectiveness

The committee prefers the new assumptions used in the EAG's revised analysis

3.8 The committee considered the original and revised base case analyses and noted that in the revised analysis the key differences with the largest effect on the incremental cost effectiveness ratios (ICERs) were:

studies that used spinal anaesthesia were excluded
overnight hospitalisation data from the Berry et al. (2020) study was excluded.

A clinical expert said that studies that used spinal anaesthesia were more closely aligned with general anaesthetic approaches and so could not be used to assess LATP. A clinical expert explained that the Berry et al. (2020) study used older data from when transperineal biopsy was frequently done under general anaesthetic and more cores were taken. Overnight stays after this type of biopsy were more common, but this does not reflect current clinical practice. Clinical experts agreed that excluding the spinal anaesthesia studies and the Berry et al. overnight stay data was appropriate, and the committee concluded that it preferred the EAG's revised base case.

LATP using a double freehand coaxial needle technique does not appear to be a cost effective use of NHS resources

3.9 In the analysis in which most studies did LATP prostate biopsy using a double freehand coaxial needle (LATP-other), this group was dominated by LA-TRUS in most analyses. ICERs for PrecisionPoint compared with LA-TRUS were generally cost effective at below £30,000 per quality-adjusted life year (QALY) gained. This was driven by cancer detection rates. The clinical experts said that studies that used a coaxial needle approach may have lower cancer detection rates because it is a more difficult technique. They said that therefore it is not appropriate to pool freehand data with double freehand coaxial needle data because they did not expect the clinical effectiveness to be the same (see section 3.4). The committee concluded that LATP using a double freehand coaxial needle technique did not appear to be cost effective, but this was very uncertain and more evidence was needed.

Using the cost of the PrecisionPoint device in a scenario analysis increases the ICERs

3.10 The EAG did a scenario analysis using the PrecisionPoint device cost instead of an average cost of all the freehand devices. In this scenario the ICER for LATP using PrecisionPoint compared with LA-TRUS remained below £20,000 per QALY gained for people having a first biopsy, but was higher than £30,000 per QALY gained in people having a repeat biopsy. However, clinical experts explained that the proportion of people having a first biopsy is much greater than the proportion of people having a repeat biopsy. The EAG did not model alternative scenarios using the costs of the other freehand devices but the committee noted that the PrecisionPoint device was the most expensive device. The committee concluded therefore that all the freehand needle positioning devices, including PrecisionPoint, had the potential to be cost effective in first and repeat biopsies.

Histopathology costs may be overestimated in the revised model

3.11 The EAG's model results were very sensitive to changes in the number of cores taken during the biopsy. It said that this was because of the histopathology cost per core. In the revised base case a higher histopathology cost was used, increasing from £107.50 for 12 cores in the original model to £438.96 for 12 cores in the revised model. The EAG explained that this had little effect on the base case ICERs because the histopathology costs cancel each other out when it is assumed that 12 cores are taken for each biopsy approach. However, if the number of cores differs between biopsy approaches, then there is a bigger effect on the results. The committee noted that the incremental QALYs were very small, which made the ICERs sensitive to changes in cost. Increasing the number of cores from 12 to 24 for LATP biopsy resulted in a very large increase in the ICERs, taking the results above what is generally considered to be cost effective by NICE. A clinical expert said that the average number of cores taken by a centre depended on which LATP biopsy protocol it used. Two LATP protocols are used in the UK: the RAPID protocol and the Ginsburg technique. Centres using the RAPID protocol take around 12 to 15 cores, whereas centres using the Ginsburg protocol take 24 or more. A clinical expert explained that the model may have overestimated the likely increase in histopathology costs in the 24 core scenario, because increasing from 12 to 24 cores increases histopathology costs only minimally. Histopathology costs only increase substantially if more than 24 cores needed analysing. The committee concluded that the histopathology costs are likely to be overestimated in the revised base case, and that moving from 12 to 24 cores is unlikely to have a substantial effect on the ICERs.

The freehand needle positioning devices have the potential to be cost effective and are recommended as an option for LATP biopsy

3.12 The committee noted that in most analyses, freehand needle positioning devices were cost effective, with ICERs well below £20,000 per QALY gained. Although there was some uncertainty in the model results around cancer detection rates and biopsy costs (see section 3.2), there was no evidence to suggest that LATP biopsy using a freehand needle positioning device was any less effective than LA-TRUS biopsy. The ongoing TRANSLATE study will provide comparative data that may help reduce this uncertainty. The reduced rates of infection and sepsis were an important benefit of LATP biopsy (see section 3.5). Cost effectiveness modelling suggests that using a freehand needle positioning device for transperineal biopsy is more cost effective than other methods such as the double freehand coaxial needle technique (see section 3.9). The committee therefore concluded that the freehand needle positioning devices have the potential to be cost effective and should be recommended as an option for LATP biopsy.

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Transperineal biopsy for diagnosing prostate cancer