Evidence for local anaesthetic transperineal biopsy versus transrectal prostate biopsy
BMJ 2024; 387 doi: https://doi.org/10.1136/bmj-2023-078175 (Published 02 December 2024) Cite this as: BMJ 2024;387:e078175
- Alastair D Lamb, Cancer Research UK clinician scientist fellow, honorary consultant urologist1 2,
- Filipa Landeiro, senior researcher3,
- Ioana R Marian, senior medical statistician4,
- Steve Tuck, emeritus chairman5,
- Richard J Bryant, associate professor of urology, honorary consultant urologist12
- 1Nuffield Department of Surgical Sciences, University of Oxford, UK
- 2Department of Urology, Oxford University NHS Foundation Trust
- 3Nuffield Department of Population Health, University of Oxford
- 4Oxford Clinical Trials Research Unit (OCTRU) Centre for Statistics in Medicine (CSM), University of Oxford
- 5Oxford Prostate Cancer Support Group, Oxford
- Correspondence to A Lamb alastair.lamb{at}nds.ox.ac.uk
What you need to know
Prostate biopsy under local anaesthetic can be performed via the transrectal (TRUS) or transperineal (LATP) routes. Both use transrectal ultrasound
Each prostate biopsy technique has pros and cons, including differences in targeting multiparametric MRI visible lesions, potential complications, patient tolerability, expense, and time to undertake the procedure in the outpatient clinic
Three randomised controlled trials show no difference for infection or overall cancer detection between TRUS and LATP. However, these trials were underpowered to detect a difference, mainly because of the better than expected performance of TRUS in both categories. A further larger trial is awaited.
Prostate cancer is usually diagnosed using image guided needle biopsy. Approximately 70 000 such biopsies are performed annually in the UK,1 but these numbers have fallen since the widespread introduction of prostate multiparametric magnetic resonance imaging (mpMRI) scanning as a pre-biopsy investigation for men suspected to have prostate cancer.23 Initial suspicion normally arises following blood test results that show a raised level of prostate specific antigen (PSA) and/or an abnormal prostate examination, which are usually undertaken as part of case finding or opportunistic screening.4 However, prostate biopsies are an expensive intervention and have significant side effects for patients, and uncertainty persists on the need for further biopsies in the case of negative results.
Over the past three decades, prostate biopsy techniques have been increasingly refined, centring around transrectal ultrasound (TRUS), image guidance of biopsy needle placement, use of pre-biopsy mpMRI, and needle guidance access systems. The past five years have seen a gradual trend away from transrectal biopsy towards local anaesthetic transperineal biopsy (LATP), precipitated primarily by concerns about the infection risk of transrectal biopsy, along with the perceived superiority of transperineal biopsy in targeting mpMRI visible lesions.5 Transperineal access systems have removed the need for either a large fixed stepper system or “double free-hand” approaches, as the needle position can be fixed relative to the ultrasound probe in a “single free-hand” manner (fig 1), making the biopsy technically easier and less cumbersome. Additionally, in the UK, partly in response to raised public awareness of the diagnostic process in prostate cancer,6 there has been central funding for training and leadership to facilitate a transition from transrectal to transperineal biopsy.
(A) Transrectal ultrasound (TRUS) guided prostate biopsy and (B) Local anaesthetic transperineal (LATP) prostate biopsy differ by route of entry, being either transrectal (TRUS) or transperineal (LATP). Both involve a transrectal ultrasound probe and insertion of core biopsy needles into the prostate for diagnosis of prostate cancer
In England, figures from Hospital Episode Statistics show that LATP rates have been gradually increasing since 2014 (fig 2).17 The covid-19 pandemic accelerated the transition from TRUS to LATP when early evidence suggested presence of the virus in faeces.8 These factors have contributed to LATP exceeding TRUS in 2020. Despite this, prior to 2024 no randomised control trial (RCT) evidence found in favour of either technique, with all publications presenting observational data.9 In this article, we outline the current uncertainty regarding LATP prostate biopsy.
Changes in numbers of prostate biopsies performed since 2014. Hospital Episode Statistics data for England only, accessed from National Prostate Cancer Audit. Shaded areas correspond to external events influencing biopsy numbers, such as the ‘Fry/Turnbull’ effect6
What is the evidence of uncertainty?
A summary of the recommendations from existing international guidelines is presented in table 1. Several observational cohort studies initially suggested that LATP might be superior to TRUS biopsy in detecting clinically significant prostate cancer, while reducing infection risk.9 We highlight the ongoing uncertainty in some key areas and evidence related to RCTs in table 2.
Guideline recommendations on local anaesthetic transperineal prostate biopsy
Current level 1 evidence comparing LATP and TRUS biopsy
Diagnostic accuracy
Observational studies have suggested that LATP may have a higher cancer detection rate compared with TRUS biopsy, particularly for tumours located in the anterior or apical part of the prostate gland; however, meta-analyses from 2023 showed conflicting results,1617 and the magnitude of this potential advantage for different anatomical locations in the prostate remains unclear.
More research is needed to directly compare the diagnostic accuracy of the two biopsy methods in a randomised controlled population. Studies presenting LATP data represent practice from early adopters, who had a particular interest in prostate cancer diagnostics. It may therefore be inappropriate to compare these results with longer term TRUS biopsy series, which have often been performed by urological trainees, nursing colleagues, and general urologists. In 2024, one RCT (the Perfect trial) investigated diagnostic yield as a primary outcome and reported an inferior detection rate of clinically significant prostate cancer (csPCa) from biopsy of posterior lesions on MRI with LATP versus TRUS biopsy.14 A further RCT found no difference in detection of csPCa when investigated in a secondary outcome analysis.18
Infection risk
Transrectal biopsy requires passage of a needle biopsy through the rectal wall. In contrast, transperineal biopsies enter through the perineal skin. The rates of infection (such as urinary tract infection, prostatitis, gastrointestinal infections, and sepsis) resulting from the two biopsy approaches are variable and are dependent on the geographical location of the cohort, population demographics, and the local degree of antibiotic resistance, particularly to quinolones. This is largely because of increased use and higher rates of quinolone resistance in the Indian subcontinent. Outside metropolitan areas the infection rates with TRUS biopsy, particularly when clinicians use rectal swabs and antiseptic preparation such as iodine, may be much lower than the 5% rate quoted in some of the literature. Case series show low rates of demonstrable sepsis after LATP, at less than 1%.19202122 Importantly for antibiotic stewardship, LATP may enable equivalent or lower infection rates without the need for antibiotic prophylaxis.2324
The Probe-PC,13 Prevent (PCORI),18 and Perfect (CCAFU-PR1)14 randomised controlled trials did not show any difference in composite infection outcomes between the two approaches, although the studies were underpowered to detect sepsis, with minimal events in either group.1318
Patient tolerability
LATP biopsy has been reported to be less comfortable for patients compared with TRUS biopsy.2526 However, patient experiences vary, and factors such as expertise of the operator can influence overall patient experience. A prospective comparative study using a visual analogue pain scale found no overall difference between the two approaches, but highlighted increased pain during placement of local anaesthetic in LATP.25 This study also found no difference in urinary symptoms or retention. The Probe questionnaire was developed to provide a comprehensive assessment of patient acceptability of transrectal biopsy.27 To our knowledge, only one study has attempted comprehensively to assess patient tolerability following LATP. This highlighted an important minority of patients who described the procedure as a moderate or major discomfort, with some patients expressing preference for the left lateral position used for TRUS rather than the lithotomy position required for LATP (45% of men in this study had previously undergone TRUS).19 The Prevent trial also assessed tolerability using a Likert scale (0-10) and reported a 0.6 “adjusted increase” in peri-procedural pain with LATP. Patient tolerability needs to be assessed in a robust comparative study.28 Nevertheless, we believe that most of the physical discomfort experienced relates to the placement of the rectal ultrasound probe, which is common to both approaches, and we therefore await the comparative data.
Cost and resourcing
The cost effectiveness of LATP versus TRUS biopsy is important to consider. The availability of equipment, local expertise, time taken for the procedure, and healthcare resources may influence the practicality of adopting LATP on a broader scale. When using a transperineal access system (single freehand), LATP biopsy requires use of additional equipment and therefore costs more. Some evidence also suggests that LATP biopsy takes longer than TRUS biopsy.29 However, these extra investments in LATP may remain cost effective as this approach may reduce the need for antibiotics. The health economic analysis within the Translate trial28 will provide the first comprehensive evidence on this.
Is ongoing research likely to provide relevant evidence?
Five RCTs registered at clinicaltrials.gov (PROBE, PREVENT, PERFECT, TRANSLATE, and the Hong Kong trial) directly compare LATP with TRUS biopsy (tables 2 and 3). These have and will provide important data regarding key diagnostic and side effect outcomes, as well as cost effectiveness analysis of the two methods of prostate biopsy.
Ongoing randomised controlled trials comparing LATP and TRUS biopsy
What should we do in light of the uncertainty?
No high quality evidence favours either option; therefore it seems appropriate to maintain equipoise regarding the optimal technique for prostate biopsy until the full results of the current RCTs are available.3031 We need to be careful. There are high profile examples of the field moving towards a preferred option despite the absence of comprehensive data. For example, da Vinci robotics have been widely adopted in prostatectomy surgery, despite only one large RCT performed in over two decades of its use, which showed no evidence of a difference from open surgery in key patient related outcomes.32
When deciding which prostate biopsy technique to use, we suggest clinicians weigh the evidence and consider the technique familiar to their unit and the patient’s preferences. It is possible, as the evidence continues to emerge, that clinicians may choose to offer LATP for patients with a history of urinary sepsis or immune compromise as well as those with anterior prostate lesions on diagnostic MRI.
Recent guidance from the National Institute for Health and Care Excellence included a summary recommendation (Recommendation 1.410) for urology units in the UK to support recruitment to the Translate trial. Updates to guidance are likely in due course when we have evidence based answers to these important questions.
Search strategy
We searched Pubmed/Medline for [((local anaesthetic transperineal biopsy) OR (LATP)) AND Prostate] to identify recent publications. We also reviewed guidelines from the UK and international urological organisations (table 1). Otherwise, we relied on expert knowledge and literature review conducted as part of the NIHR Health Technology Assessment funding application (NIHR131233).
Recommendations for further research
Population: Men requiring diagnostic biopsy for prostate cancer after PSA, digital rectal examination, and mpMRI
Intervention: Local anaesthetic transperineal biopsy under transrectal ultrasound guidance
Comparison: Transrectal biopsy under transrectal ultrasound guidance
Outcomes: Diagnosis of clinically significant prostate cancer (primary); infection rates; urinary retention rate; sexual dysfunction; patient tolerability; need for repeat biopsy; health related quality of life; cost
How patients were involved in the creation of this article
The chairman of our local Oxford Prostate Cancer Support Group (OPCSG; https://www.opcsg.org/) is a prostate cancer survivor, a co-investigator in the Translate trial, and a co-author of this article. He helped with the design of the Translate trial, including the primary and secondary outcomes, and generating survey data about the key areas of concern for men undergoing prostate biopsy
What patients need to know
If referred for investigation of possible prostate cancer, most patients will require a prostate biopsy, usually after a pre-biopsy mpMRI scan
Transrectal and transperineal biopsies can both be performed under local anaesthetic in the outpatient clinic
The two different approaches have risks and benefits and, so far, no high quality evidence shows that either approach is definitively superior to the other
Education into practice
How would you communicate the risks and benefits of the different approaches to prostate biopsy?
What are the priorities for men undergoing the prostate cancer diagnostic process? (eg, ruling in/out cancer, avoiding infection, avoiding discomfort, etc)
Are there any other areas of practice where clinicians may advocate one diagnostic or treatment option over another in the absence of high quality evidence?
Health economic considerations of prostate biopsy
Currently it is more expensive to perform LATP than TRUS biopsy. The higher costs of LATP are mainly because of the cost of the freehand device, which is not required for TRUS
The Translate trial28 will include a robust health economic analysis, including assessing the cost effectiveness of the two devices used for LATP in this trial (PrecisionPoint and BK–UA1232) compared with TRUS biopsy. Other devices include Trinity, SureFire, CamPROBE, and standard venous cannulas. Prices range from £7.54 to £200,33 some of which are reusable while others are single use (fig 1
The prices of consumables (eg, biopsy gun, syringe and needles, co-axial needle, gloves, syringes, etc) are also different between LATP and TRUS, with estimates ranging from £81.07 to £107.66.33
Higher costs may be offset by differences in rate of re-biopsy and possibly lower readmission rates for sepsis. Re-admission for infection following TRUS biopsy reportedly resulted in 37 000 additional “bed days” in 2013, amounting to a cost of £7.7m to £11.1m per year to the NHS.34
Acknowledgments
Advisers to this series are Nai Ming Lai, Win Sen Kuan, Paula Riganti, and Juan Franco.
Footnotes
Provenance and peer review: commissioned; externally peer reviewed.
Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none.
Further details of The BMJ policy on financial interests are here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests