Title: A randomised controlled trial of TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation (TRANSLATE) of potential clinically significant prostate cancer
Funder: Department of Health and Social Care

Abstract: Background & Aims:_x000D_ _x000D_ Prostate cancer is the most commonly diagnosed male cancer in the UK. During investigation for suspected prostate cancer, men are referred by their GP to receive an MRI scan followed by a prostate biopsy, which involves taking small samples of tissue from the prostate gland to check for cancer. Currently, most prostate cancers are diagnosed using a type of biopsy called a “TransRectal UltraSound-guided” (TRUS) biopsy, which is performed in clinic. However, evidence shows that TRUS biopsies can miss approximately one third of significant prostate cancers, and also has a risk of causing severe infection due to the needle passing through the rectum. The alternative option is to take prostate samples through skin behind the scrotum, known as a “transperineal biopsy”, which may be better at detecting cancer by allowing the needle to be directed more accurately and result in less infection. Until recently, this type of biopsy required a general anaesthetic and a one day stay in hospital, but advances in anaesthetic techniques now allow us to perform this procedure in the outpatient setting, known as a "Local Anaesthetic Transperineal Prostate" (LATP) biopsy. _x000D_ LATP biopsy is gaining popularity in the UK as an alternative biopsy method to TRUS, but we currently do not know if it is better than TRUS. The aim of this study is to determine whether LATP biopsies are better than TRUS biopsies at detecting significant cases of prostate cancer, and reducing infection rates. We will also be looking at the tolerability of the two biopsies, complication rates (such as bruising and pain), admissions to hospital, the need for a repeat biopsy, and whether use of the LATP biopsy will save the NHS money compared to the TRUS biopsy._x000D_ _x000D_ Trial design:_x000D_ _x000D_ This is a randomised controlled trial to compare the TRUS biopsy with the LATP biopsy. This means that men who agree to take part will be allocated by chance (like tossing a coin) to one of the two biopsy techniques and will be aware of which biopsy they receive. The trial aims to recruit 1042 men over an 15-month period from a minimum of nine NHS hospitals in the UK. Men are eligible if they have been referred for a biopsy with a new suspicion of prostate cancer based on an abnormal prostate-specific antigen (PSA) blood test or finger examination of the prostate, and have already received a pre-biopsy MRI scan. Every participating NHS centre will have the necessary skills to perform either the LATP or TRUS biopsy procedure, making them uniquely placed to undertake such a study, as most other centres exclusively use one or other technique._x000D_ _x000D_ Patient involvement & dissemination:_x000D_ _x000D_ Consultation with patients has taken place during the planning of the study (with the Oxford Prostate Cancer Support Group, and NCRI Prostate Group) and patients will continue to be involved throughout the conduct of the study. The findings will be presented at national and international urology meetings, and will be published in a suitable high-impact scientific journal. Men taking part in the study will be informed of the findings via the study website. _x000D_ _x000D_ We anticipate that the results of the study may have significant practice-changing impact, with the potential to affect over 100,000 men in the UK annually, given the number of men currently undergoing a prostate biopsy each year. The findings from this study are likely to extend beyond the UK given the ubiquitous nature of prostate cancer.

Lay abstract: Research Hypothesis: LATP biopsy improves detection of clinically significant PCa, and decreases infection rates, compared to TRUS biopsy._x000D_ _x000D_ Background: Prostate cancer (PCa) is the commonest cancer in men in the United Kingdom (UK), with ~45,000 cases diagnosed per year. 100,000 men each year in the UK are referred for biopsy for suspected PCa based on prostate-specific antigen (PSA) testing and/or abnormal digital rectal examination (DRE). The optimal method of clinic biopsy to detect significant PCa, and limit infection risk, is uncertain. _x000D_ _x000D_ Aims / Objectives: To assess the efficacy of LATP versus TRUS biopsy in detecting clinically significant PCa; and to provide evidence-based information about the differences in biopsy-related complications, cost-effectiveness and patient-reported outcomes between these two biopsy options._x000D_ _x000D_ Methods: A prospective, multi-centre, open-label RCT of LATP versus TRUS biopsy; the setting will be a minimum of nine large Urology departments across UK NHS hospitals. We aim to recruit 1042 biopsy-naïve men referred with suspected PCa based on an elevated age-specific PSA or abnormal DRE, suitable for investigation with pre-biopsy magnetic resonance imaging (MRI) and prostate biopsy. Men will be randomised 1:1 to LATP prostate biopsy, performed with an average of ~12 systematic biopsy cores in 6 sectors depending on prostate size, with an additional ~4 target biopsy cores for each radiologically significant lesion seen on pre-biopsy MRI, using an LATP device according to local centre practice, versus TRUS prostate biopsy, performed according to each hospital’s standard practice, with an average of ~12 systematic biopsy cores in two sectors depending on prostate size, with an additional ~4 target biopsy cores. The primary outcome is detection rates of clinically significant PCa, defined by presence of any Gleason pattern 4 disease; secondary outcomes will assess rates of infection (to include: all symptoms of infection, general practitioner (GP) prescribed treatment for infection, readmissions to hospital for infection, and microbiologically proven infection), Health related quality of life (HRQoL), patient reported tolerability of the procedure, patient reported biopsy-related complications (including bleeding, bruising, pain, loss of erectile function), number of subsequent prostate biopsy procedures, cost-effectiveness and histological parameters. Men will be followed up at baseline, 7 days, 35 days and 4 month post-randomisation._x000D_ _x000D_ Timelines for delivery: The total length of the trial is 31 months. Recruitment will last for 15 months. There will be a formal stop/go review of the internal pilot in month 12 of the project (after 6 months of recruitment) to ensure a minimum of 140 patients have been randomised and 4 centres have been opened to recruitment. If the target is met, the trial will continue to recruit for a further 9 months. Data from the patients in the internal pilot phase will be included in the final analysis._x000D_ _x000D_ Anticipated impact and dissemination: We anticipate that the study results have potential to affect over 100,000 men in the UK annually, given the number of men undergoing prostate biopsies. The findings are likely to extend beyond the UK and dissemination will be through publications, presentations and appropriate use of media. A full patient and public involvement (PPI) programme is included.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS