Patient selection
This retrospective study collected data from 312 consecutive patients who underwent TRUS-guided prostate biopsies at single institution (Gangnam Severance Hospital, Yonsei University Health System) between January 2019 and August 2020. The indication for prostate biopsy was persistent clinical suspicion of prostate cancer due to an elevated prostate-specific antigen (PSA) level (> 2.5 ng/mL) and/or a positive digital rectal examination (DRE) and continuous rise in PSA level during the follow-up period. The exclusion criteria comprised the following: (1) hemorrhoid grade ≥ III (n = 3), which indicated that the hemorrhoid tissue prolapsed beyond the dentate line; (2) history of hemorrhoidectomy (n = 1); and (3) inability to communicate (n = 4; two were foreigners and two were old men with communication difficulties). None of the 312 patients had neurological disease such as paraplegia or hemiplegia and none routinely used analgesics for chronic pain or other reasons. Finally, a total of 304 (97.4%) patients were included in the analysis (Fig. 1). This study was approved by the institutional ethics committee (Yonsei University Health System, Seoul, Korea, 3-2019-0418), and all procedures were conducted in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments. The requirement for informed consent was waived for this study as it was based on retrospective, anonymous patient data and did not involve patient intervention or the use of human tissue samples.
Data collection
The collected patient data included age, PSA level, prostate volume, history of prostate biopsy, DRE (positive; hard surface, nodular lesions or mass-like lesion), pathologic results, time of PNB and biopsies, adverse events (vasovagal syncope, allergic reaction, acute urine retention, clot retention, fever), and visual analog scale (VAS; ranging from 0 [no pain] to 10 [worst pain]) score measured at various time points: probe insertion, PNB at base, PNB at apex, each of the 12 core biopsy sites, and 15 min after prostate biopsy.
TRUS-guided prostate biopsy technique
All patients were hospitalized for half a day. Antibiotics (third generation cephalosporin) were administered prophylactically via intravenous injection 1 h before the biopsy and upon discharge (100 mg orally, three times a day for 2 days).
The patients assumed a left lateral decubitus position during the biopsy. All biopsies were performed by the same experienced urologist. After povidone iodine rectal preparation, all patients received 10 cm3 of 2 % IRLG (Instillagel®, Farco-Farma GmbH, Köln, Germany). After 5 min, a transrectal probe was inserted to measure the prostate volume, and the PNB procedure was performed with a Chiba needle (A & A M.D. Inc., Seongnam, Korea).
Biopsies were performed with the BK 3000 ultrasound system (Analogic Corporation, Peabody, MA, USA) using a 7.5–12-MHz multiplanar probe at each of the 12 biopsy sites, in the following order: right lateral base, right lateral mid, right lateral apex, right medial base, right medial mid, right medial apex, left lateral base, left lateral mid, left lateral apex, left medial base, left medial mid, and left medial apex. A 20-cm, 18-gauge disposable core biopsy instrument (Max-Core®, CR Bard Inc., Covington, GA, USA) was used in all cases.
Site of injection
The two methods of local anesthesia (base PNB and base and apex PNB) were alternately administered—(1) odd days (base-only PNB group: the PNB was administered on both sides of the prostate base) and (2) even days (base and apex PNB group: an additional PNB was administered on both sides of the prostate apex). The site of base injections was aimed at the major neurovascular bundle, after confirming the triangular echogenic “Mount Everest sign” between the base of the prostate and seminal vesicle in the parasagittal longitudinal view of the TRUS [6]. PNB administration at this site was considered to have anesthetized a large portion of the prostate gland. The site for apex injections was aimed at a smaller triangular echogenicity between the puborectalis muscles and the apex of the prostate gland. Each PNB injection utilized 2.5 cm3 of 2% lidocaine [6]. The base and apex PNB group received the base injection before the apex injection.
Study endpoints
The primary study endpoint was the pain scale score for the two PNB methods in each of the 12 core biopsy sites. The secondary endpoint was the comparison of pain scores between the PNB methods.
Statistical analysis
VAS pain scores in the base and apex PNB were defined as the average of the VAS scores for base and apex injections, respectively. Average pain was defined as the mean (± standard deviation [SD]) of the individual VAS pain scores at the 12 sites. Average pain at the base, mid, and apex of the prostate was defined as the mean (± SD) of the individual VAS pain scores at the base, mid, apex sites, respectively.
Continuous variables are expressed as either the mean ± SD or median (interquartile range). Categorical variables were reported as the number of occurrences and frequency. Comparisons between the base-only PNB group and the base and apex PNB group were performed with the independent t-test for continuous variables, and the chi-square test (Fisher’s exact test) for two or more variables. The results were also analyzed using a linear mixed model and illustrated with a mean profile graph. The correlation matrix structure of the linear mixed model was used to determine the relationship between the measured data at various points in time via the application of compound symmetry. Statistical analyses were performed using SAS (version 9.4.; SAS Institute, Cary, NC, USA) and PASS (version 15; NCSS, LLC. Kaysville, Utah, USA). The level of statistical significance was set at p < 0.05.