Comparing outcomes of transperineal to transrectal prostate biopsies performed under local anaesthesia

Abstract Objectives To compare and review the outcomes of transperineal (TP) prostate biopsies with transrectal (TR) biopsies performed under local anaesthesia (LA). A review of the relevant published literature is presented. Patients and methods We prospectively analysed 212 consecutive patients who underwent TP prostate biopsy using the PrecisionPoint™ access system under LA, at our institution from October 2018 to March 2020. We compared the morbidity and cancer detection rates using this approach with our historical cohort of 178 patients who underwent the TR biopsy method under LA. Results The mean age of the TP biopsy group was 69 years, and median prostate specific antigen (PSA) was 13.17 ng/ml. Mean prostate volume was 45.1 ml with a median of 12 cores taken per patient. Patient demographics were similar to our TR biopsy cohort, with mean age of 68 years, median PSA of 10.76, mean prostate volume of 49.6 ml and a median of 12 cores taken per patient. The TP biopsy group had 0% sepsis rate compared with 2.2% in the TR group. Haematuria in the TP versus transrectal ultrasonography (TRUS) cohort was 0.9% versus 1.7%, respectively. The TP biopsy‐naïve group had a cancer detection rate of 63.5% (127 of 200 patients), of which 84% were ≥Grade Group 2 (GG2). The TR biopsy‐naïve group had cancer detection rate of 50% (86 of 172 patients), of which 87.2% was ≥GG2. Conclusion TP prostate biopsy had less urinary infectious and septic complications compared with the TR approach. Our data suggest at least comparable diagnostic accuracy between both biopsy approaches.

(TP) or the transrectal (TR) route. The recent systematic review and meta-analysis by Xiang et al. 2 comparing TP and TR prostate biopsies revealed comparable diagnostic accuracies between the two routes.
TR route of prostate biopsies remains the most common approach. One major drawback is the uncommon but serious risk of sepsis. 3 Infective complications may be severe and contribute to increased hospital admissions. In an analysis by Jiang et al.,4 38% of patients who presented with sepsis had received correct prophylactic antibiotics, highlighting the inherent difficulty in predicting or preventing this potentially disastrous complication. As the use of prophylactic antibiotics becomes routine, the emergence of fluoroquinolone-resistant organisms has also increased. 5 The TP route of prostate biopsy greatly reduces this risk of infection as the needle traverses the perineal skin rather than the rectal mucosa. 6 Contemporary series have reported infective complications as low as 0-1%, even without the use of prophylactic antibiotics. 7,8 The peripheral zone (PZ) contains the majority of prostatic glandular tissue. The PZ is mostly located at the back of the gland, closest to the rectal wall, and extends to the apical portion of the gland. About 70-80% of prostate cancers originate in the PZ. Earlier studies 9,10 have shown improved cancer detection rate in the apical and anterior region of the prostate with the TP route. The Victorian Transperineal Biopsy Collaboration 11 showed that up to 75% of cancers involved the anterior region on second biopsy, whereas 25% were confined exclusively within the anterior region. In this study, we compare the outcomes of our centre's experience with TP prostate biopsies under local anaesthesia (LA) and compare it with our prior series of TR biopsies. We also present a review of current literature on the outcomes of a contemporary series of TP biopsies under LA.

| PATIENTS AND METHODS
The primary objective of this study was to evaluate the safety and efficacy of the TP biopsy under LA. Study ethics was obtained and approved through our institutional review board. We prospectively evaluated 212 consecutive patients who underwent TP biopsy under LA at our institution from October 2018 to March 2020. We compared the complications and cancer detection rates using this approach with our historical cohort of 178 patients who underwent traditional TR biopsy from July 2017 to January 2019. As upfront prostate magnetic resonance imaging (MRI) was not yet a standard recommendation for biopsy-naïve men at the point of initiation of our study, our patients were given the option of either going for prostate biopsy versus having a prostate MRI first.
The TP biopsies were performed with the PrecisionPoint™ Transperineal Access System with a BK Medical ® Endocavity 8848 transrectal probe. Our patients were routinely given a dose of oral cephalexin 500 mg on the day of the TP biopsy. Twelve patients (5.6%) were not given prophylaxis, and this was based on surgeon preference. The PrecisionPoint™ Transperineal Access System has a rail/clamp subassembly, a needle carriage with 4 apertures and a 15-gauge access needle (Figure 1). This is a single-use item and is disposed after use. The assembled device is then clamped to the BK Medical ® Endocavity 8848 transrectal probe. We wrapped the proximal end of the TR probe with adhesive Coban™ bandage before attaching the clamp of the PrecisionPoint™ TP access system ( Figure 2). The bandage improves the grip of the clamp onto the probe, thereby minimising rotational movement of the PrecisionPoint™ TP access system during the biopsy. We marked the 12 o'clock position on the bandage with a marker to guide alignment with the ultrasound transducer.
The patients are placed in lithotomy position with heel stirrups.
The scrotum is lifted away from the perineum with tape. The perineum is cleaned with povidone iodine and the ultrasound probe is inserted into the rectum to visualise and measure the prostate. We injected 1% lignocaine superficially at the perineal skin on both sides prior to inserting the access needle sheath. Further, 10-ml 1% lignocaine was given on each side as periprostatic nerve block ( Figures 3 and 4). Systematic 12 core biopsies were taken based on a template ( Figure 5). Additional target cores were taken at the discretion of the physician. Saturation biopsy, if done, was performed based on the Ginsburg protocol. 11 Procedural pain score was recorded using visual analogue scores (VAS) from patients immediately after the procedure.
In our TR biopsy cohort, we gave prophylactic oral fluroquinolones 1 day before and up to 3 days after the biopsy, with an additional single intramuscular gentamicin injection preprocedure.   (Table 1).

| Complications
There was no reported case of urosepsis (Table 2) in the TP compared with the TR group (0% vs. 2.2%, p = 0.04). The rate of nonseptic urinary tract infection (UTI) complications in the TP biopsy group was also lower than the TR group (0.9% vs. 2.2%). Of the two patients in the TP group who reported UTI symptoms, one had a previous background of chronic bacterial prostatitis. One patient (0.9%) in the TP group had symptomatic hypotension, which was attributed to vasovagal in nature. He did not show signs of sepsis, had a normal urine microscopy and urine culture yielded no growth. He was hospitalised for monitoring and discharged after 1 day. Two patients in the TP group (0.9%) reported mild gross haematuria but did not require hospitalisation or intervention. The urinary retention rate was 3.8% for the TP group compared with 4.5% in the TR group (p = 0.8).
The mean VAS score was 3.67 AE 2.57 (0-9) in the TP group.

| Use of MRI prostate
Sixty-three of 212 (29.7%) patients who underwent TP biopsy had an MRI prostate done before the biopsy ( for TP compared with TR biopsy (0.9% vs. 2.2%). This is comparable with other centres' UTI rate, ranging from 0% to 2.2% in Huang's study (Table 6). Given the low risk of septic complications, some centres have even moved to omission of peri-procedural prophylactic antibiotics. Ristau et al. 8 reported 1000 patients in his series, giving a single-dose cephalexin in the first 600 patients and no antibiotics in the next 400 patients with no culture proven UTIs and no hospital admissions for sepsis. Another report by Meyer et al. 9 showed that no patients experienced an infectious complication despite omission of peri-procedural antibiotics in all cases following a TP biopsy. The reduction in use of prophylactic antibiotics would help to limit the development of fluoroquinolone-resistant organisms worldwide.
There was a higher overall detection rate (63.5% vs. 50%, p = 0.012) and a trend towards more clinically significant prostate cancers (53.5% vs. 43.6%, p = 0.062) being detected when comparing our TP versus TR biopsy-naïve cohort. Our TP biopsy cancer detection rate is comparable with other international centres (Table 7), showing cancer detection ranges of 35.0-76.0% and clinically significant cancer detection ranges of 33.0-60.1%. The cancer detection rate for 6% of our TP biopsy patients who had saturation biopsy was 50%. Hence, our increased prostate cancer detection rate in the TP cohort was unlikely confounded by patients who underwent saturation biopsies. Of note, none of the patients with clinically significant cancers with a PSA < 10 had a saturation biopsy performed. We postulate that this increase in detection rate could be, in part, due to a higher pick up rate in anterior zone cancers.
However, we also recognise certain limitations on the comparison of cancer detection rates between our TP and TR cohorts. For example, the use of MRI prostate and number of cores sampled could not be controlled for. To assess the feasibility of this technique under LA, we also assessed patients' peri-procedural pain score using the VAS. We started recording VAS scores after our initial learning curve. In total, we analyzed the VAS score of 112 of 212 patients. This was taken immediately after the patient had completed the TP biopsy and was asked to rate a pain score for the entire procedure. The mean VAS score was 3.67 AE 2.57 (0-9).  25 This could be in part due to the penetration of the TP biopsy gun through the sensitive perineal skin and the surrounding neurovascular bundles encasing the prostatic capsule, unlike penetration of the rectal mucosa, which has been shown to have a lower sensitivity to pain. 26 However, there have been more recent studies 27 suggesting that the majority of patients who had previously undergone TR biopsy rated the TP approach more tolerable and some reporting no difference in perceived discomfort.
Given the described benefits, the TP approach has been gaining presence. However, it has yet to gather widespread adoption. Some barriers may be that most urologists were trained in TR biopsy and are not familiar with the transition to TP biopsy. Proper training is needed for urologists to learn TP biopsy under LA. In addition, there is additional capital cost in procuring the PrecisionPoint™ Transperineal Access System. However, the eventual shift towards TP biopsy seems to help drive overall cost down, with lower infectious-related admissions. 28 In the United Kingdom, the TRexit initiative, 29 which comprises six London hospitals, have successfully ceased all TR biopsies and converted to a pure TP under LA biopsy service since March 2019. Our institution has also moved away from TR biopsies since October 2018 and is now exclusively performing TP biopsies.
In conclusion, TP biopsy under LA is safe and well tolerated.
There is a lower complication rate, in particular sepsis, as compared with TR biopsy. There is an at least comparable cancer detection rate with TP compared with TR biopsies.