The Role of Freehand Transperineal Prostate Biopsy Under Local Anesthesia Without Antibiotics in Outpatient Settings

Abstract

The objectives of this study were to evaluate and compare the application of freehand transperineal prostate biopsy (FTPB) under local anesthesia (LA) versus systematic transperineal prostate biopsy (STPB) in an outpatient setting without antibiotics. A total of 218 biopsy-naive patients with suspicion of prostate cancer (PCa) based on multiparametric magnetic resonance imaging (mpMRI) were retrospectively analyzed. Suspicious areas on mpMRI were graded using the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1). FTPB was performed for each suspicious lesion, followed by a 12-core STPB under LA. Histopathological outcomes, complications, and tolerability were recorded. The results showed that PCa was detected in 129 (59.17%) patients, with 104 (47.71%) being clinically significant prostate cancer (csPCa). There was agreement between FTPB and STPB in 94 (72.88%) patients. FTPB diagnosed fewer PCa cases but more csPCa cases than STPB. LA-FTPB was well-tolerated with no severe complications. The conclusions suggest that FTPB under LA in an outpatient setting without antibiotics is safe, feasible, and efficient.

Background

Prostate cancer (PCa), the second most prevalent cancer among men globally, poses a significant health challenge in contemporary societies (Kensler & Rebbeck, 2020). Historically, prostate biopsies have been conducted using the transrectal ultrasound (TRUS)-guided method (Moe & Hayne, 2020). Nevertheless, TRUS biopsies present inherent drawbacks, such as low accuracy of detecting clinically significant prostate cancer (csPCa), high rates of false-positive results and high infectious complications (Ahdoot et al., 2020; Wagenlehner et al., 2013).

Given the limitations of TRUS biopsy, magnetic resonance imaging (MRI)-guided targeted biopsies (TBs) have been explored due to the superior image quality provided by MRI. In comparison to non-targeted TRUS-guided biopsies, TB is capable of identifying more clinically significant PCa (Siddiqui et al., 2013). Currently, three main types of MRI-based targeted prostate biopsies exist: MRI in-bore-guided biopsy, MRI-TRUS fusion TB (FUS-TB), and MRI-cognitive TB (COG-TB; Exterkate et al., 2020; Liang et al., 2020). To date, none has definitively proven its superiority over the others (Bass et al., 2022). Theoretically, considering economic factors and accessibility, COG-TB, also known as freehand TB, may be the most advantageous given its reduced need for additional equipment and specialized software (Verma et al., 2017).

The advancements in local anesthetic (LA) technologies for transperineal prostate biopsy (TPB) have facilitated a transition from the traditional TRUS approach to a transperineal method (Omer & Lamb, 2019). This standard transperineal technique exhibits a reduced infection rate compared with its predecessor, a crucial factor in mitigating antibiotic resistance (Xiang et al., 2019). In addition, the transperineal route has demonstrated enhanced diagnostic sensitivity for csPCa (Pepe et al., 2017). However, the conventional disadvantage of transperineal biopsies has been the requirement for general anesthesia, rendering it unsuitable for outpatient procedures (Smith et al., 2014). Recently, there have been promising reports regarding the application of LA in transperineal biopsies. Considering these factors, we aim to assess the viability and safety of freehand transperineal prostate biopsies (FTPBs) in an outpatient setting using LA without antibiotics in this study (Kum et al., 2020; Setia et al., 2022; Smith et al., 2014).

Method

Patients Selection

In this retrospective study, 218 patients underwent FTPB from January 2020 to September 2021 with informed written consent at the Affiliated Yantai Yuhuangding Hospital of Qingdao University. All patients underwent a prostate-specific antigen (PSA) blood test, digital rectal examination (DRE) and multiparametric magnetic resonance imaging (mpMRI; Ingenia CX 3.0T, Philips, The Netherlands) before the biopsy. Exclusion criteria included those men (a) with a previous history of PCa or prostate biopsy, (b) with symptoms of urinary tract infected disease (which demand the use of antibiotic), (c) negative MRI image, or (d) coagulation disorders. All patients were not routinely given prophylactic antibiotics. The T2-weighted axial and coronal, axial diffusion-weighted coefficient (DWI) and high b-value, as well as T1-weighted dynamic contrast enhancement (DCE) images were assessed by two radiologists with over 10 years of MRI experience based on the PI-RADS v2.1. At most, two suspicious lesions would be selected for target biopsy. For patients with more than two suspicious lesions, lesion(s) with higher PI-RADS score would be chosen for subsequent analysis. The csPCa was defined as high-grade PCa (Gleason ≥ 3 + 4).

Procedures

All prostate biopsies were conducted in an outpatient setting and completed solely under LA. Patients were positioned in the lithotomy position. A total of 40 ml of 1% lidocaine was injected into either side of the midline of the perineum to raise a wheal on the skin. The scrotum was elevated, and the buttocks were taped laterally to stretch the perineum. The sagittal and transverse views of the prostate were simultaneously visualized and displayed on the screen using a bk3000 ultrasound unit with a model E14CL4b biplanar transducer (BK Ultrasound, Peabody, MA). Subsequently, an additional 10–12 ml of 1% lignocaine was injected into the neurovascular bundles on both sides under ultrasound guidance. Further LA could be administered to areas anterior and distal to the bilateral apical regions based on the operator’s decision (Chiu et al., 2021).

After LA, biopsies were performed using a biopsy gun (Bard Medical, Karlsruhe, Germany) equipped with a biopsy needle (18G, 130; Bard) by two independent experienced urologists, refusing the help of templates or any other auxiliary tools. A maximum of two cancer-suspicious lesions identified on the mpMRI image were selected and subsequently underwent the FTPB procedure. The total number of target cores was four for each patient. Subsequently, a standard 12-core systematic transperineal biopsy (STPB) was performed by another operator who was blinded to the mpMRI image. The biopsy region protocol for the STPB was mapped as shown in Figure 1.

Figure 1.

The Biopsy Region Protocol of STPB

A standard validated visual analog scale (VAS) between 0 and 10 was used to record patients’ tolerability (Figure 2). The 0 represents no pain and 10 represents the worst. Discomfort caused by probe (VAS-1), LA injections (VAS-2) and biopsies (VAS-3) were assessed immediately after biopsy using a VAS questionnaire. Complications, including urinary tract infection, urinary retention, hematuria, and sepsis were recorded. All samples were examined and analyzed by two senior pathologists. The csPCa was defined as Gleason score ≥ 3 + 4.

Figure 2.

The Standard Validated Visual Analog Scale: 0–2 Comfortable, 3–4 Mild Discomfort, 5–6 Moderate Discomfort, 7–8 Severe Discomfort, 9–10 Extreme Discomfort

Statistical Analysis

Continuously coded variables were presented as medians with its interquartile ranges (IQRs) or means with its standard deviations. Categorical variables were recorded as frequency with its proportion. Descriptive statistics were underwent by SPSS Statistics v26 (IBM, Armonk NY). Categorical data were compared using McNemar’s test. A p value < .05 was considered to be statistically significant.

Results

A total of 218 patients were included in the study. The patient demographics and a summary of the biopsy findings are presented in Table 1. For all patients, an FTPB consisting of four cores per patient, was performed along with an additional STPB consisting of 12 cores. Of the 218 suspected patients, 129 (59.17%) were diagnosed with PCa, with 25 (19.38%) classified as insignificant and 104 (80.62%) as significant cancers. No significant complications from the prostate biopsy were observed, and the biopsy was well-tolerated and successfully performed on every patient.

Table 1.

Patient Demographics and Biopsy Findings

Variable	All patients	Men with PCa
Men included, n	218	129 (59.17%)
Age (year)	68.00 (63.00–74.00)	70.00 (64.50–75.00)
tPSA (ng/ml)	9.38 (6.01–19.08)	16.80 (9.47–22.40)
Prostate volume (ml)	44.85 (32.34–68.49)	39.35 (29.36–50.24)
Suspicious lesion per patient, no.
1	82 (37.61)	38 (29.46)
2	136 (62.39)	91 (70.54)
PI-RAD score, no. (%)
3	90 (41.28)	12 (9.30)
4	64 (29.36)	53 (41.09)
5	64 (29.36)	64 (49.61)
Target cores per patients	4	4
ciPCa, no. (%)	—	25 (19.38)
csPCa, no. (%)	—	104 (80.62)
Gleason score, no. (%)
6	—	25 (19.38)
7 (3 + 4)	—	28 (21.71)
7 (4 + 3)	—	29 (22.48)
8 or higher	—	47 (36.43)
Median VAS score
Probe insertion	3.06 ± 0.88	3.05 ± 0.85
LA	3.39 ± 0.91	3.39 ± 0.90
Biopsy	3.19 ± 1.01	3.29 ± 1.20
Positive predictive value	59.17%
Complication
Urinary tract infection	2 (0.92%)	1 (0.78%)
Urinary retention	3 (1.38%)	1 (0.78%)
Hematuria	9 (4.13%)	5 (3.88%)
Sepsis	0	0

Note. Data are median (IQR) or n (%) or M (SD). tPSA = total prostate-specific antigen; MRI = magnetic resonance imaging; PCa = prostate cancer; csPCa = clinically significant prostate cancer; VAS = visual analog scale; LA = local anesthesia; IQR = interquartile range; SD = standard deviation; ciPCa = clinically insignificant prostate cancer.

The overall detection rate of PCa between the STPB and the FTPB did not differ significantly (52.75 vs. 49.54%; 115 vs. 108 cases, p = .311; Table 2), while the clinically significant PCa detection rate with FTPB was higher than the STPB (42.66 vs. 33.94%, 93 vs. 74 cases, p < .001). The overall rate of PCa increased to 59.17% when combined the two methods, including 25 (19.38%) insignificant and 104 (80.62%) significant cancers, and an additional 14 cases of PCa were diagnosed (115 vs. 129).

Table 2.

Comparison of Pathology From STPB and FTPB

		csPCa (Gleason ≥ 7)
FTPB	STPB	7 (3 + 4)	7 (3 + 4)	8 or higher	ciPCa (Gleason < 7)	No cancer	Total
csPCa	7 (3 + 4)		63		20	10	23
	7 (3 + 4)						27
	8 or higher						43
ciPCa			1		10	4	15
No cancer			10		11	89	110
Total		22	20	32	41	103	218

For patients diagnosed with PCa, a subgroup analysis was performed to assess the performance of the systematic biopsies (Figure 3). Twenty-one (16.28%) and one (0.78%) patients were diagnosed with PCa and upgraded to csPCa, respectively, by the combination of systematic biopsies.

Figure 3.

Cross-Tabulation of Histology (Gleason Score) of Targeted and Systematic Biopsy Among Patients Diagnosed With PCa. 21 Patients Were Diagnosed With Prostate Cancer by Addition of systematic Biopsies (Yellow Box). In addition, 1 Patients Were Upgraded to CsPCa by Addition of Systematic Biopsies (Red Box). GS = Gleason Score

Discussion

With the application of mpMRI, precise needle biopsy of the prostate can be achieved, leading to the emergence of TB. Given its device-friendliness and operator-centric nature, cognitive biopsy significantly enhances procedural efficiency. Rigorous preoperative screening, which includes assessing PSA levels, conducting DRE, and utilizing both ultrasound and MRI, is conducive to the smooth progression of the biopsy procedure and ensures definitive diagnosis. However, a notable drawback of transrectal biopsy is the potential contamination from intestinal flora, which may elevate the risk of infection and antibiotic resistance. The transperineal approach offers a new research avenue for the diagnosis of PCa, especially csPCa (Ristau et al., 2018), prompting us to explore the potential for further refining the biopsy process using novel biopsy methods and in an outpatient setting under LA without antibiotics.

Our findings indicate that the combined biopsies detected 129 cases of PCa, with 104 of these cases being csPCa. If relying solely on the target biopsy, 21 cases of PCa and one case of csPCa would be missed. Although FTPB detected a greater number of csPCa cases, systematic biopsy remains a crucial tool in the evaluation of patients referred for prostate biopsy. Borkowetz et al. reported a higher cancer detection rate (CDR) for csPCa (44%) when combining systematic transrectal biopsy with transperineal FUS-TB, compared with using either (Borkowetz et al., 2018). Neale et al. suggested performing systematic biopsy alongside cognitive freehand-guided transperineal biopsy, as it remains justified in equivocal cases or patients with small but suspicious MRI lesions, and provides additional information for clinical decision-making (Neale et al., 2020). In a large prospective study, Elkhoury et al. found that combining targeted and systematic biopsy offers the best chances of detecting cancer, thereby enhancing the utility of a 12-core systematic approach (Elkhoury et al., 2019). Furthermore, the current European Association of Urology (EAU) guidelines recommend that in biopsy-naive patients with a positive mpMRI, a combination of systematic and targeted biopsies should be performed (Cornford et al., 2024). In some cases, the MRI-visible lesion may be falsely positive, with the tumor actually located elsewhere in the prostate. The discordance in tumor locations detected by different biopsy methods indicates that targeted and systematic biopsies may detect distinct tumors, and that combined biopsies effectively improve the CDR (Elkhoury et al., 2019; Neale et al., 2020). Therefore, a combination of systematic and targeted biopsies is deemed necessary.

Compared with the transrectal approach, transperineal biopsy has a well-documented lower risk of infection (Skouteris et al., 2018; Young et al., 2019). In recent years, TPB has gained increased adoption owing to its reduced associated infectious risk. As a relatively sterile procedure, limiting the use of antibiotics would be beneficial for avoiding adverse events and addressing the global antibiotic resistance crisis. The main reason why antibiotic prophylaxis is not necessary for TPB is that the biopsy needle does not traverse the rectum, making it more economical and practical compared with targeted antibiotic prophylaxis and carbapenem prophylaxis. Setia et al. discovered that antimicrobial prophylaxis may be safely omitted when utilizing the freehand TP approach (Setia et al., 2022). Islam et al. demonstrated that outpatient TPB without antibiotics is comparable with TRB with antibiotics in terms of safety and CDR (Islam et al., 2021). Similarly, Sigle et al. also found that TPB performed without antibiotic prophylaxis is a safe procedure (Sigle et al., 2021). Among the numerous published series reporting on TPB experiences, the incidence of sepsis is either zero or near-zero, and non-life-threatening urinary tract infections are rare. This finding is consistent with the results of our study (Islam et al., 2021; Kum et al., 2020; Setia et al., 2022; Sigle et al., 2021; Young et al., 2019). Considering the prevalence of antibiotic resistant organisms, resistance in rectal flora and occurrence of transrectal prostate biopsy sepsis, reducing antimicrobial use will be the next step to improve the efficiency of prostate biopsy.

Similar to other studies, pain scores for various steps in LA biopsies were reported to range from 2 to 4 of 10, with the LA injection being identified as the most painful part. Kum et al. evaluated the VAS scores for LA FTPB in the outpatient setting, and the pain scores for probe insertion, LA injection, and biopsies were 1.05, 3.75, and 2.8, respectively, which were lower than those in our cohort (3.06, 3.39, and 3.19, respectively; Kum et al., 2020). Smith et al. reported similar pain scores (mean 3.08, 3.29, and 2.88) for LA template-guided biopsies (Smith et al., 2014). Stefanova et al. conducted TPBs using LA in 1,287 consecutive patients at risk for PCa and reported a mean VAS pain score of 3.0 for the LA injection procedure (Stefanova et al., 2019). In our study, all patients were able to adopt the lithotomy position and experienced mild pain without severe complications during the procedure, indicating that TPB under LA is a promising method in an outpatient setting.

Several limitations of the study need to mention. First, there was a lack of a control group receiving standard systematic biopsy. Second, comparisons between biopsy results and whole-mount pathology from prostatectomy were not performed, necessitating further investigation into the value of the Gleason score. Third, the data were collected from a single center, and the sample size of this study was limited.

Conclusion

This clinical study indicates that performing FTPB under LA without antibiotics in outpatient settings is safe, feasible, and effective. It demonstrated a low infection rate and high patient acceptance. The combined use of FTPB and STPB facilitated the diagnosis of PCa.