CAMPROBE: Improving the Safety and Tolerability of Local Anaesthetic Outpatient Transperineal Prostate Biopsies - Beyond the Abstract
In the UK alone, tens of thousands of TRUSBx are performed annually, and this number will rise as the rate of suspected prostate cancer is set to increase by 69% by 20302. While TRUSBx are generally well tolerated, they are associated with a significant risk of infection because the biopsy needle has to repeatedly traverse the rectal wall. A recent paper from the UK ProtecT prostate cancer study has reported post-TRUSBx biopsy fever and shivers in 12% of men and severe sepsis in about 1% despite antibiotics 3. Post-biopsy sepsis was again reported to be 1-2% in a recent review of nearly 200,000 biopsies performed in England4. More worryingly, these rates are rising and there is evidence of increasing antibiotic resistance as a primary driver5,6. Costs associated with UK hospitalization episodes for biopsy-related sepsis alone are estimated to be £7–11 million annually. These costs and risks will be amplified by increasing referral trends and by worrying rises in antibiotic resistance of up to fourfold.5,6
Transperineal (TP) biopsy (TPBx) has significantly lower infective risks as needles traverse the sterilised perineum, and in fact, TPBx predate TRUSBx.7,8 Techniques using a perineal brachytherapy template grid under general anesthesia (GA) or a free-hand ‘fan technique’ under local anesthesia (LA) are both well established, although significant regional variations in practice exist9. The use of GA and specialised equipment for grid-based TPBx limits its utility as a routine replacement for TRUSBx. Attempts at doing grid-based biopsies without GA have reported use of 50–60 ml of LA, additional analgesia and/or significant patient pre-preparation, which is not compatible with routine out-patient or office-based practice10,11. The free-hand LA TPBx technique is appealing as it requires only two perineal punctures and no specialist equipment. However, the procedure is not standardized nor commonly performed in UK centres. We sought a way to enable wider uptake of LA TPBx as a viable, cost-neutral and routine replacement for TRUSBx by developing the CAMbridge PROstate Biopsy DevicE (CAMPROBE).
The CAMPROBE is a cannulated TP access system based on the co-axial concept but bespoke to the context of prostate biopsies. The integrated device allows for synchronous device insertion and LA infiltration under ultrasound guidance, negating the need for separate punctures, nerve blocks or sedation. Once in position, standard 18G core-needle biopsies can be taken through the retained cannula. Videos of the procedure can be seen here:
No specialized equipment is required except a couch suitable for lithotomy and a linear array ultrasound probe. Because the CamPROBE is an integrated device, LA is delivered under vision, which allows precise deployment of LA and hence reduced dosages. In addition, the free-hand approach makes the probe position much more comfortable for men, negating the need for anal sphincter relaxants or rectal LA gel. Compared to other approaches, the CamPROBE method is much safer as an outpatient technique and requires minimal staffing (akin to the standard TRUSBx). The method exploits already existing equipment and consumables available in any urology unit and will thus be easy to adopt. Future device costs are projected to be low and equivalent to current costs for disposable needle guides used for TRUSBx. This is crucial given than many millions of biopsies are performed world-wide. The developing world has the most prevalent incidences for TRUSBx-related infections and sepsis12. These developing countries have scarce resources to fund expensive biopsy alternatives. The low-cost of CamPROBE makes it feasible to adopt the safer TPBx world-wide.
In terms of the accuracy of cancer detection, many studies have shown that the free-hand transperineal approach has equivalent cancer detection compared to TRUSBx 13-15. The CamPOBE approach is also highly suitable for the modern era of image guidance as it can already be used for cognitive guided biopsies. The technology for image-guided free-hand TP biopsy is already here with two recent small studies demonstrating the feasibility and suggesting superiority to systematic biopsy alone in detecting significant cancer 16,17. We found that after device insertion, there was no association with increasing numbers of biopsies taken and patient discomfort. Thus, we foresee no issues with obtaining both targeted biopsies and systematic sectoral biopsies using our method. In contrast, recent reports of grid-based TP approaches under LA for cognitive image-guided biopsies have only performed targeted biopsies, presumably to try and limit patient discomfort 10.
In summary, the CamPROBE is a simple, cheap but disruptive technology that appears to be a good outpatient LA alternative, using the safer TP route. The simplicity and standardisation of the procedure should allow widespread uptake, with significant safety and cost benefits for health service delivery. Our current UK NIHR i4i funded work to develop a cheap, disposable version of the device will accelerate the journey from the prototype in the current study to a single use, low-cost disposable device.
Written by: Professor Vincent J Gnanapragasam, BMedSci MA Ph.D. FRCS FRCSEdUrol, University of Cambridge and Department of Urology, Cambridge University Hospitals NHS Foundation Trust
University Lecturer in Uro-oncology & Honorary Consultant Urologist, Academic Urology Group, Department of Surgery & Oncology, University of Cambridge, Co-lead Urological Malignancies Programme, CRUK, Cambridge Cancer Centre, University of Cambridge, Urology Clinical trials and Research Lead, Cancer Directorate, Cambridge University Hospitals Trust
Read the Abstract
References
1. Cancer Research UK.
2. Mistry M, Parkin DM, Ahmad AS, Sasieni P. Cancer incidence in the United Kingdom: projections to the year 2030. Br J Cancer. 2011 Nov 22;105(11):1795-803.
3. Rosario DJ, Lane JA, Metcalfe C, Donovan JL, Doble A, Goodwin L, Davis M, Catto JW, Avery K, Neal DE, Hamdy FC. Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study. BMJ. 2012 Jan 9;344:d7894.
4. Anastasiadis E, van der Meulen J, Emberton M. Hospital admissions after transrectal ultrasound-guided biopsy of the prostate in men diagnosed with prostate cancer: a database analysis in England. Int J Urol. 2015 Feb;22(2):181-6.
5. Batura D, Gopal Rao G. The national burden of infections after prostate biopsy in England and Wales: a wake-up call for better prevention. J Antimicrob Chemother. 2013 Feb;68(2):247-9.
6. Carignan A, Roussy JF, Lapointe V, Valiquette L, Sabbagh R, Pépin J. Increasing risk of infectious complications after transrectal ultrasound-guided prostate biopsies: time to reassess antimicrobial prophylaxis? Eur Urol. 2012 Sep;62(3):453-9
7. Barringer B. Carcinoma of the prostate. Surg Gynecol Obstet 1922; 34: 168–176.
8. Grummet JP, Weerakoon M, Huang S, et al. Sepsis and ‘superbugs’: should we favour the transperineal over the transrectal approach for prostate biopsy? BJU Int 2014; 114: 384–388.
9. Galfano A, Novara G, Iafrate M, et al. Prostate Biopsy: The Transperineal Approach. European Association of Urology and European Board of Urology. EAU-EBU Update Series 2007; 5: 241–249.
10. Bass EJ, Donaldson IA, Freeman A, et al. Magnetic resonance imaging targeted transperineal prostate biopsy: a local anaesthetic approach. Prostate Cancer Prostatic Dis 2017; 20: 311–317.
11. Smith JB, Popert R, Nuttall MC, et al. Transperineal sector prostate biopsies: a local anesthetic outpatient technique. Urology 2014; 83: 1344–1349.
12. Bennett HY, Roberts MJ, Doi SA, Gardiner RA. The global burden of major infectious complications following prostate biopsy. Epidemiol Infect. 2016 Jun;144(8):1784-91. doi: 10.1017/S0950268815002885. Epub 2015 Dec 9.
13. Guo L-H, Wu R, Xu H-X, et al. Comparison between Ultrasound Guided Transperineal and Transrectal Prostate Biopsy: A Prospective, Randomized, and Controlled Trial. Scientific Reports. 2015;5:16089. doi:10.1038/srep16089
14. Takenaka A. et al. A prospective randomized comparison of diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy. Prostate Cancer Prostatic Dis. 11, 134–8 (2008).
15. Hara R. et al. Optimal approach for prostate cancer detection as initial biopsy: prospective randomized study comparing transperineal versus transrectal systematic 12-core biopsy. Urology. 71, 191–5 (2008).
16. Zhang Q, Wang W, Yang R, et al. Free-hand transperineal targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and transrectal ultrasound: single-center experience in China. Int Urol Nephrol 2015; 47: 727–733.
17. Lian H, Zhuang J, Wang W, et al. Assessment of free-hand transperineal targeted prostate biopsy using multiparametric magnetic resonance imaging-transrectal ultrasound fusion in Chinese men with prior negative biopsy and elevated prostate-specific antigen. BMC Urol 2017; 17: 52.