The Influence of Music on Perceived Pain and Levels of Anxiety While Undergoing Transperineal Prostate Biopsy: The VIVALDI Trial

Take Home Message

Music listening during transperineal prostate biopsy significantly reduces pain and distress, lowers sedation requirements, and improves patient satisfaction, representing a simple, safe, and effective nonpharmacological strategy to enhance comfort in outpatient prostate cancer diagnostics.

Abstract

Background

Music has been shown to reduce pain and anxiety during invasive procedures such as transrectal ultrasound-guided prostate biopsy, but its role during transperineal prostate biopsy (TPBx) has not yet been investigated.

Objective

To evaluate the effect of music listening on pain perception, anxiety, and patient satisfaction in men undergoing TPBx in an outpatient setting.

Design, setting, and participants

This was a prospective, monocentric, randomized controlled trial including 103 men with suspected prostate cancer enrolled between March and October 2025. Participants were randomized 1:1 to either a music intervention group (+MUSIC, n = 52) or a control group (–MUSIC, n = 51). Baseline clinical, radiological, and demographic characteristics were collected.

Intervention

Patients in the +MUSIC group listened continuously to self-selected music during TPBx, while the control group underwent the same standardized procedure without music.

Outcome measurements and statistical analysis

Pain was assessed at predefined procedural time points using a visual analog scale (VAS). Distress was measured pre- and post-procedure using the NCCN Distress Thermometer. Secondary outcomes included satisfaction with pain management, willingness to repeat biopsy, anesthetic requirements, and physiological parameters. Between-group comparisons were performed using the Mann–Whitney U test or Fisher’s exact test. Multivariable linear regression models were used to identify independent predictors of pain and satisfaction.

Results and limitations

Median age was 69 years, and 44% of patients had a Charlson Comorbidity Index ≥1. The +MUSIC group showed significantly lower postprocedural distress (median 1 vs. 2, p = 0.01). Pain scores were significantly lower in the +MUSIC group during local anesthesia (3 vs. 4.5, p < 0.01), periprostatic anesthesia (3 vs. 5, p < 0.01), first biopsy core (3 vs. 5, p = 0.01), and last biopsy core (3 vs. 5, p = 0.02), with no difference in post-micturition pain. The +MUSIC group required less additional sedation (37% vs. 57%, p=0.03) and lower anesthetic doses (p = 0.02). Satisfaction with pain management (5 vs. 3.5, p < 0.001) and willingness to repeat biopsy (4 vs. 3, p < 0.01) were significantly higher in the +MUSIC group. On multivariable analysis, music remained independently associated with reduced pain and increased satisfaction (p ≤ 0.03). Limitations include the single-center design and relatively small sample size.

Conclusions

Music listening during TPBx is a safe, simple, and effective non-pharmacological intervention that significantly reduces pain and anxiety while improving patient satisfaction and procedural experience.

ADVANCING PRACTICE.

What does this study add?

Bleomycin-induced pulmonary toxicity (BPT) is a common finding in computed tomography of the thorax (CT-T) after two cycles of combination chemotherapy (Cx). BPT is associated significantly with reduced pulmonary function tests (PFTs). Interestingly, all patients with reduced PFTs during long-term follow-up showed bleomycin-associated pulmonary changes on CT-T. Therefore, routine CT-T during Cx might aid clinicians in identifying patients at risk for long-term deterioration of their pulmonary function.

Clinical Relevance

Music has clear clinical relevance as a low-risk, cost-effective adjunct that can meaningfully reduce patient-reported pain during transperineal prostate biopsy. Its ability to lower anxiety and improve overall comfort may enhance patient cooperation and procedural tolerance, potentially leading to smoother workflows and better procedural outcomes. Given its ease of implementation and absence of side effects, music can be readily integrated into routine practice to improve patient experience without increasing clinical burden. Associate Editor: Roderick van den Bergh.

Patient Summary

Metastatic testicular germ cell tumors are typically treated with chemotherapy, which may lead to life-threatening pulmonary alterations. We found that pulmonary changes were frequently observed in computed tomography of the chest with decreased lung function after two cycles of chemotherapy. Most patients, but not all, recovered from reduced pulmonary function. However, those patients who had long-term changes in pulmonary function also had changes during chemotherapy on CT. Therefore, CT scans of the chest might help identify patients at risk of long-term pulmonary dysfunction.

1. Introduction

Prostate biopsy is a cornerstone in the diagnosis of prostate cancer [1]. Despite its widespread use, little is known about patients’ subjective experiences of transrectal ultrasound-guided biopsy (TRUSB), although it is recognized that the procedure can cause significant discomfort [2]. Patients frequently report preprocedural anxiety and fear, exacerbated by the sensations of pain and distress [2]. In recent years, transperineal prostate biopsies (TPBx) have gained popularity due to concerns over infection risks associated with the transrectal route and due to their improved accuracy [3]. However, compared with TRUSB, TPBx has traditionally been associated with a greater risk of significant pain or discomfort, often necessitating the use of more intensive anesthesia, due to the fact that the transperineal approach requires the biopsy needle to penetrate highly innervated layers of the pelvic floor [4].

Numerous studies have highlighted the effectiveness of music as a nonpharmacological intervention for reducing perceived pain and discomfort during invasive medical procedures [2], [3], [5], [6]. Specifically, listening to music during TRUSB has been shown to alleviate pain perception and improve patient satisfaction [2], [6]. In a study by Chang et al, music supplementation during TRUSB was found to be a safe, cost-effective, and efficient strategy for improving patient comfort and reducing pain, anxiety, and dissatisfaction, highlighting the role of music as therapeutic support for this procedure [2]. These results were also confirmed by a subsequent meta-analysis, although the limited number and quality of the included studies prevent definitive conclusions [6].

However, the impact of music in the context of TPBx remains unexplored. This is particularly relevant, since TPBx is generally associated with higher levels of pain and anxiety compared with the transrectal approach, highlighting an even greater need for effective nonpharmacological strategies to enhance patient comfort [7], [8].

To fill this gap in the literature, our study aims to evaluate, through a randomized controlled design, the effect of music listening on pain perception and anxiety in men undergoing TPBx in an outpatient setting.

2. Materials and methods

We conducted a monocentric, nonblinded randomized controlled trial, investigating the role of music on perceived pain and anxiety during TPBx. The study was registered on ClinicalTrials.gov (NCT07234097). Men referred to our center for suspected prostate cancer (PCa) and scheduled for fusion TPBx between March 2025 and October 2025 were enrolled after providing written informed consent, including acceptance of data publication. At the time of enrollment, participants were randomized with a 1:1 allocation ratio by means of a computer-generated random list into two groups: intervention (+MUSIC) and control (−MUSIC). Simple randomization was applied without the use of blocks, and the allocation sequence was concealed using Research Electronic Data Capture (REDCap), which ensured that group assignment was not revealed until after participant enrollment.

The primary endpoints of the study were pain perception and overall procedural experience, while pain at specific time points was analyzed to provide a detailed characterization of patients’ discomfort throughout the intervention.

2.1. Inclusion and exclusion criteria

We included all adult men with suspicious PCa, based on prostate-specific antigen (PSA) values and/or abnormal digital rectal examination (DRE) and multiparametric magnetic resonance imaging (mpMRI) findings, scheduled for fusion TPBx according to guidelines [1].

Participants were excluded if they had a previous prostate biopsy (any approach), if they reported hearing impairment or any problems with the anorectum, or if they were under chronic pain management therapy.

2.2. Patient assessment and data collection

All participants were assessed with a thorough medical history. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI) [9]. Likewise, weight and height were measured, calculating body mass index (BMI) for each participant. Educational level was investigated and then categorized into two groups, as follows: primary/secondary school and high school/university degree. Preprocedural PSA values were collected, and all participants underwent a standard pelvic examination to assess abnormal findings on DRE. Prostate volume and Prostate Imaging Reporting and Data System (PI-RADS) characteristics were evaluated through mpMRI images. PI-RADS version 2.1 was used in all cases [10].

2.3. TPBx procedure and evaluation of pain and anxiety

To psychometrically quantify pre-TPBx distress severity, all participants completed the National Comprehensive Cancer Network (NCCN) distress thermometer [11]. The instrument is a screening tool to assess and address psychological distress in patients with cancer over the past week. It is a single-item tool using a 0 (no distress) to 10 (extreme distress) point Likert scale resembling a thermometer.

In group +MUSIC, patients listened to music continuously, played through a speaker, from entry into the preoperative holding area until the end of the TPBx. Patients were allowed to freely choose the music to listen to during the procedure, ensuring that the auditory stimulus was personally preferred and familiar.

In group −MUSIC, patients underwent the same biopsy procedure without listening to music.

The fusion TPBx procedure was standardized for all patients. Patients were placed in the lithotomy position, and mild sedation using 1 mg of intravenous midazolam was performed approximately 10 minutes before local anesthesia. Local anesthesia of the perineum with 10 mL of 2% lidocaine was injected subcutaneously, and the 4.0–14.0 MHz endosonic biplane transducer probe (BK Medical, Burlington, MA, USA, Type E14C4t) was then introduced per rectum. An additional 10 mL of 2% lidocaine was injected in the periprostatic area. The fusion procedure of ultrasound (US) and mpMRI images was performed with the MIM software, fully integrated in the bk5000 ultrasound scanner. During fusion-guided TPBx, a perineal template grid with a coordinate system was used in combination with a stepper. The TPBx procedure involved both targeted and random biopsies, with three targeted and an additional 14 random cores collected per patient, sampling the base, mid-gland, and apex in both the medial and lateral segments bilaterally. All biopsy samples were collected using an 18-G spring-loaded disposable needle. In case of uncontrolled pain, patients were allowed to ask for additional midazolam administration. Operative time was defined as starting from the introduction of the US probe per rectum until the completion of the last biopsy core. It did not include preprocedural MRI segmentation or intravenous midazolam administration, which were performed beforehand.

Patients were asked to rate the level of perceived pain at different time points of the procedure (local and periprostatic anesthesia, at the first and last biopsy core, after micturition) with a visual analog scale (VAS) ranging from 0 to 10, with 0 representing no pain and 10 representing the worst pain imaginable. Additionally, systolic blood pressure and heart rate were recorded before and immediately after the procedure. After TPBx, patients underwent a monitoring period of approximately one hour. In the absence of any observed complications, they were then cleared for discharge.

Before discharge, patients were asked to complete the NCCN Distress Thermometer, rating their level of distress related to the TPBx. In addition, patients reported their overall satisfaction with pain management during the procedure (1—highly unsatisfied to 5—highly satisfied) and ability to tolerate a repeat biopsy (1—very unlikely to 5—very likely). The entire procedure was performed in an outpatient setting. Postprocedural histological data and oncologic results were recorded.

During the study period, 152 patients were considered, of whom 48 were excluded due to a history of previous prostate biopsy, hearing impairment (n = 1), anorectal stenosis (n = 1), and chronic pain therapy (n = 1). Ultimately, 104 men were randomized in the +MUSIC (n = 52) and −MUSIC (n = 52) groups. One patient in the −MUSIC group was excluded since the procedure was not performed due to persistent high blood pressure after local anesthesia requiring cardiological examination.

2.4. EthXXXical approval

Data collection followed the principles outlined in the Declaration of Helsinki. All participants signed an informed consent agreeing to share their own anonymous information for future studies. The study was approved by our hospital ethics committee (Prot. 2025).

2.5. Statistical analysis

The sample size was calculated based on a two-sample (independent) Student t test for comparison of mean VAS scores between groups. The calculation was based on data from a previous study in patients undergoing TRUSB, which reported a mean reduction of 1.6 points in VAS pain scores (standard deviation = 2.0) in patients who listened to music during the procedure compared with controls [2]. Assuming a true difference in means of 1.62, a common standard deviation of 2.0, a two-sided alpha level of 0.05, and a statistical power of 80% (β = 0.20), a minimum of 30 participants per group was required. Sample size estimation was performed using the Russ Lenth Piface (Power and Sample Size) applet [12].

Data are presented as medians (interquartile range [IQR]) or frequencies (proportions). First, descriptive statistics were used to detail the demographic and clinical characteristics of the entire cohort without statistical testing, as randomization ensures comparability. Second, procedural outcomes, including psychometric scores and pain at predefined procedural time points, were compared between the +MUSIC and −MUSIC groups using the Mann–Whitney U test. The change in distress level from pre to postprocedure was compared within groups using the Wilcoxon signed−rank test. Moreover, the magnitude of the post versus predifference in distress level between groups was tested with the Mann–Whitney U test. Multivariable linear regression models were used to assess predictors of pain during TPBx and patient satisfaction with pain management. Models were adjusted a priori for age, CCI, PSA level, prostate volume, baseline distress score, and procedural time, based on their clinical relevance. Statistical tests were performed using SPSS version 28 (IBM Corp., Armonk, NY, USA). All tests were two-sided, with a significance level set at 0.05.

3. Results

Table 1 details the clinical and demographic characteristics of the study cohort (n = 103). The median (IQR) age was 69 (63–75) yr, and 45 (44%) patients had a CCI ≥ 1. A high school or university degree (74%) was the most frequently reported educational status. The median PSA value was 6.2 (4.4–8.2) ng/mL, and abnormal DRE findings were rare (5.8%). Median prostate volume was 48 (36–72) mL, and a PI-RADS score of 3, 4, and 5 was found in 41 (40%), 42 (40%), and 20 (20%) patients, respectively.

Table 1.

Clinical characteristics and descriptive statistics of the whole cohort of patients (No. = 103)

	Overall
No. of patients [No. (%)]	103 (100)
Age (years)
Median (IQR)	69 (63–75)
BMI (kg/m2)
Median (IQR)	25.4 (23.3–28.5)
CCI ≥1 [No. (%)]	45 (44)
Educational status [No. (%)]
Primary/secondary school	27 (26)
High school/university degree	76 (74)
Family history of PCa [No. (%)]	15 (14)
PSA (ng/mL)
Median (IQR)	6.2 (4.4–8.2)
Abnormal findings on DRE [No. (%)]	6 (5.8)
Prostate Volume (ml)
Median (IQR)	48 (36–72)
Maximum PIRADS score [No. (%)]
3	41 (40)
4	42 (40)
5	20 (20)
Single PIRADS [No. (%)]	70 (68)
Operative time (min)
Median (IQR)	28 (23–34)
Positive biopsy for PCa [No. (%)]	64 (62)
ISUP Grade Group [No. (%)]
I	14 (22)
II	25 (39)
III	13 (20)
IV	7 (11)
V	5 (8.0)
EAU Risk Group [No. (%)]
Low	15 (23)
Intermediate	37 (58)
High	12 (19)

Keys: BMI = body mass index; CCI = Charlson Comorbidity Index; PCa = Prostate Cancer; iPSA = Index Prostate Specific Antigen; DRE = Digital Rectal Examination; PIRADS = Prostate Imaging-Reporting and Data System; ISUP = International Society of Urological Pathology; EAU = European Association of Urology

The median operative time was 28 (23–34) minutes, and PCa was diagnosed in 62% of biopsies (Table 1). Most patients were in International Society of Urological Pathology (ISUP) grade group II (39%) and had intermediate European Association of Urology (EAU) risk category (58%). Supplementary Table 1 details clinical characteristics of patients as segregated in the study groups.

Table 2 details psychometric and procedural data in +MUSIC and −MUSIC groups. The change in distress scores (pre–post) was significantly greater in the +MUSIC group compared with the −MUSIC group (3 [1−4] vs 1.5 [0−3]; p = 0.014), indicating a more pronounced improvement among participants exposed to music.

Table 2.

Psychometric and procedural data in the whole cohort (No. = 103)

	+Music	−Music	p-value*
Distress
Median (IQR)	5 (2–6)	4 (2–6)
Postoperative distress level			0.012
Median (IQR)	1 (1–2)§	2 (1–4)§
Delta distress level (pre-post)			0.014
Median (IQR)	3 (1–4)	1.5 (0–3)
Vital signs
Preoperative
Heart rate (beats/min)
Median (IQR)	71 (62–81)	71 (65–76)
Systolic blood pressure (mmHg)
Median (IQR)	120 (107–171)	119 (105–167)
Postoperative
Heart rate (beats/min)
Median (IQR)	72 (63–84)	71 (66–77)
Systolic blood pressure (mmHg)
Median (IQR)	116 (103–163)	120 (108–172)
Pain (VAS Score)
Local anesthesia, median (IQR)	3 (2–4)	4.5 (3–6)	<0.013
Periprostatic anesthesia, median (IQR)	3 (2–4)	5 (3–6)	<0.014
First biopsy core, median (IQR)	3 (2–4)	5 (3–6)	0.011
Last biopsy core, median (IQR)	3 (2–5)	5 (2–7)	0.021
Post micturition, median (IQR)	1 (1–2)	1 (1–2)
Need for more sedation [No. (%)]	19 (37)	29 (57)	0.034
Added midazolam (mg)			0.021
Median (IQR)	0 (0–1)	1 (0–2)
Satisfaction for pain management
Median (IQR)	5 (4–5)	3.5 (3–5)	<0.001
Willingness to undergo a new procedure
Median (IQR)	4 (4–5)	3 (2–4)	<0.012

Keys: VAS = Visual analog Scale.

P value according to the Wilcoxon Signed Rank Test.

^*P value according to the Mann-Whitney U test.

^§p < 0.01 vs. baseline.

Pain perception, assessed by the VAS, was consistently lower in the +MUSIC group throughout all stages of the procedure. Specifically, during local anesthesia, the +MUSIC group had a median pain score of 3 (2–4), compared with 4.5 (3–6) in the −MUSIC group (p < 0.013). Similar differences were observed during periprostatic anesthesia (3 [2−4] vs 5 [3−6]; p < 0.014), at the first biopsy core (3 [2−4] vs 5 [3−6]; p = 0.011), and at the last biopsy core (3 [2−5] vs 5 [2−7]; p = 0.021). A lower proportion of patients in the +MUSIC group required additional sedation compared with the −MUSIC group (37% vs 57%, p = 0.034). Among those who received additional sedation for bothersome pain, a lower dose of midazolam was administered to patients in the +MUSIC group compared with those in the −MUSIC group (0 [0−1] vs 1 [0−2]; p = 0.021). Patients in the +MUSIC group reported significantly higher satisfaction scores with pain management compared with those in the −MUSIC group (5 [4−5] vs 3.5 [3−5], p < 0.001). Similarly, patients in the +MUSIC group showed higher willingness to undergo a repeat biopsy compared with participants in the −MUSIC (4 [4−5] vs 3 [2−4], p < 0.012).

Table 3 reports linear regression analysis predicting pain during TPBx in the whole cohort. The multivariable model showed that prostate volume was positively correlated with pain (p = 0.012), while the presence of music during the procedure was significantly associated with reduced pain (p = 0.011), even after accounting for patients’ age.

Table 3.

Linear regression models predicting pain during TPBx

	beta	p-value	95% IC
MVA model
Age	−0.1	0.7	−0.12 to 0.92
Prostate volume	0.02	0.012	0.01–0.05
Music during procedure	−1.8	0.011	−2.53 to −0.30

Keys: TPBx = Transperineal prostate biopsy; MVA = Multivariable model; CI = confidence interval.

Similarly, in multivariable linear regression analysis, the presence of music during the procedure was significantly associated with higher satisfaction (p < 0.011), even after accounting for patients’ age, preoperative distress, and procedural time (Table 4).

Table 4.

Linear regression models predicting patient’s satisfaction with pain management during TPBx

MVA model	beta	p-value	95% CI
Age	−0.03	0.8	−0.04 to 0.03
Preoperative distress	0.07	0.5	−0.07 to 0.14
Procedural time	0.04	0.7	−0.02 to 0.03
Music during procedure	0.3	0.011	0.18–1.27

Keys: TPBx = Transperineal prostate biopsy; MVA = Multivariable model; CI = confidence interval.

4. Discussion

The role of music in reducing pain perception and enhancing patient satisfaction during outpatient urological procedures has gained growing interest in recent years, with multiple studies exploring its impact across different interventions. Our study was designed to investigate the role of music in alleviating pain and enhancing patient comfort during TPBx.

In our cohort, patients in the +MUSIC group reported significantly lower pain scores than those in the −MUSIC group. Pain levels were consistently lower at every stage of the procedure in the +MUSIC group, from the administration of local anesthesia through the final core biopsy sampling. Moreover, patients in the +MUSIC group required less additional sedation and expressed higher satisfaction with pain management. The presence of music during the procedure emerged as a relevant clinical predictor of reduced pain and improved TPBx satisfaction, even after accounting for clinical confounders.

A systematic review by the EAU highlighted consistent evidence showing that music significantly reduces both pain and anxiety across a range of outpatient urological procedures [13]. Specifically, music was found to lower pain scores in all studies involving TRUSB and play a key role in reducing anxiety levels in many other procedures, including shock-wave lithotripsy (SWL), cystoscopy, and nephrostomy tube placement. The literature also underscored music’s ability to reduce physiological stress markers, such as heart rate and systolic blood pressure, during TRUSB and SWL [2]. Furthermore, music significantly increased patients’ willingness to repeat procedures and overall satisfaction, which is vital for enhancing patient compliance and improving their experience during outpatient urological treatments.

Focusing on TRUSB, a study by Tsivian et al demonstrated that music could effectively reduce pain and anxiety [14]. In a randomized controlled trial of 88 patients, those assigned to the music group reported significantly lower pain scores and greater overall comfort. These findings indicate that music may function as a simple, nonpharmacologic intervention capable of modulating pain perception and anxiety, likely through attentional distraction and the promotion of relaxation. These effects are especially valuable in outpatient settings, where enhancing the overall patient experience is a priority.

These results are also confirmed by Chang et al, suggesting that music can be a valuable tool for enhancing patient comfort during invasive procedures like TRUSB [2]. Music helped reduce pain and anxiety, improved overall satisfaction, and encouraged greater cooperation for future interventions. In this context, music therapy can be considered an effective and cost-efficient strategy to optimize the patient experience during a prostate biopsy.

Recent evidence and updated clinical guidelines now endorse the TPBx approach as the preferred method for prostate biopsy [1]. This shift is supported by comparable detection rates of clinically significant PCa between the two techniques, an improved safety profile with significantly lower infection and sepsis rates in TPBx, and its feasibility under local anesthesia [15]. However, TPBx is generally associated with higher levels of pain and distress compared with the transrectal approach [7], [8], highlighting an even greater need for effective nonpharmacological strategies to enhance patient comfort.

To the best of our knowledge, this is the first study to investigate the impact of music on both pain and anxiety specifically during TPBx, reflecting current clinical practice. Consistent with previous studies that have assessed patient-reported outcomes after TRUSB using numerical rating scales for pain, discomfort, and anxiety [11], we asked patients to rate their perceived pain on a 0–10 VAS at defined time points during TPBx, including during local and periprostatic anesthesia, at the first and last biopsy cores, and prior to discharge. This real-time, subjective assessment allowed us to capture patients’ physical and emotional responses throughout the procedure. In our cohort, patients exposed to music (+MUSIC) consistently reported lower VAS scores across all time points compared with those without music (−MUSIC), confirming the analgesic effect of music during TPBx. Moreover, we showed that postoperative distress was significantly lower in the +MUSIC group compared with the −MUSIC group and that patients in the +MUSIC group were more satisfied with pain management and showed higher willingness to undergo a repeat biopsy compared with participants in the −MUSIC group.

Such methods reflect a broader clinical emphasis on recognizing distress as a key component of patient experience, often referred to as the sixth vital sign in oncology, given its proven impact on quality of life and treatment outcomes [11].

Previous studies, such as the ProBE-PC and NORAPP trials, have explored patient-reported pain during prostate biopsy, although not focusing specifically on transperineal approaches only [16], [17]. In the NORAPP trial, for instance, local anesthesia was administered using 40 mL of lidocaine, compared with 20 mL in our protocol [17]. These differences in study design, anesthetic volume, and patient populations may partly explain the higher pain scores observed in our cohort. In the ProBE-PC trial, which compared transrectal and transperineal biopsy without music, transperineal biopsy was associated with higher pain scores, particularly during local anesthesia and on the evening of the procedure [16]. In contrast, our study focused exclusively on transperineal biopsy and evaluated the effect of music, which significantly reduced pain at all stages, including local anesthesia and each biopsy core. This underscores the difficulty of directly comparing patient-reported outcomes across studies with differing methodologies and procedural approaches.

At present, our standard practice involves performing TPBx with both targeted and random sampling for the diagnosis of PCa. However, a transition to targeted and perilesional biopsy is expected in the near future, in accordance with current guideline recommendations [16]. This approach is expected to reduce the number of biopsy cores required [18], thereby likely decreasing the duration of the procedure, the associated pain, and the amount of anesthesia requested. Evidence suggests that perilesional biopsy can enhance the detection of clinically significant PCa while minimizing overdiagnosis, ultimately improving the efficiency of the biopsy process [19]. Focusing on the anesthesia protocol, in our institution, mild sedation with 1 mg midazolam and local lidocaine is administered before TPBx in all cases, allowing for additional midazolam, if needed, during the course of the procedure. We showed that a lower proportion of patients in the +MUSIC group required additional sedation and that among those who received additional midazolam, a lower dose was administered. Therefore, we further stress the important role of music during TPBx also in reducing the burden of intravenous sedation.

Our study has several strengths: it is novel in assessing both pain and distress modulation through music during TPBx, a procedure increasingly adopted in current clinical practice. Second, the use of a randomized protocol strengthens the internal validity of the study by minimizing selection bias and ensuring a more reliable comparison between the music and no-music groups. Third, the study investigated pain at different timepoints, distress, need for additional sedation, satisfaction with pain management, and willingness to repeat the procedure, providing a holistic assessment of patient-centered outcomes. Of note, besides listening to music, prostate volume was also associated with perceived pain during the procedure. The association between larger prostate volume and higher pain scores may be explained by several factors, including wider needle trajectory and increased tissue displacement during transperineal biopsy, all of which may contribute to increased nociceptive stimulation.

Our study is not devoid of limitations. First, the administration of midazolam as sedation may represent a potential confounding factor. Nonetheless, sedation was applied uniformly across all participants following a standardized protocol, with the minimum effective dose administered in all cases. Dose adjustments were made only upon explicit patient request in cases of uncontrolled discomfort. This standardized approach helps to mitigate the potential bias introduced by sedation. Importantly, one of the aims of the present study was to explore whether the use of music during the procedure could reduce pain perception and, consequently, the need for additional intravenous sedation. In this regard, patients in the +MUSIC group required additional sedation less frequently and received lower doses of midazolam, suggesting that music may represent a simple, nonpharmacological strategy to reduce the reliance on intravenous anesthesia during transperineal prostate biopsy in future clinical practice.

Second, unlike many prior studies that employed headsets to deliver music [2], thereby enhancing patient immersion and potentially improving the overall procedural experience, we opted for speaker-based music delivery. Music was played continuously from the patient's entry into the preoperative holding area until the conclusion of the TPBx procedure. This choice enabled uninterrupted verbal interaction and real-time assessment of pain through VAS, although it may have reduced the immersive quality associated with headphone use. Furthermore, the use of a perineal template grid constitutes another potential limitation. This approach requires multiple transcutaneous needle entries, which may increase patient discomfort. Alternative techniques may reduce the number of skin punctures, thereby potentially shortening procedure duration and minimizing associated pain.

A further limitation of this study is the high proportion of participants with a high school or university degree, which may have introduced a selection bias and could limit the generalizability of the results to populations with different educational backgrounds. Another limitation of this study is the lack of operator blinding to music exposure, which may have influenced clinical decision-making regarding the administration of additional sedative medication. Although the initial dose of midazolam was standardized, the possibility of bias related to subsequent sedation cannot be completely excluded. Finally, while the absolute difference in pain scores between groups may appear modest yet statistically significant, we believe it is clinically meaningful in the context of an outpatient transperineal prostate biopsy. Notably, these differences were associated with a reduced need for additional sedation and significantly higher patient satisfaction, supporting their relevance in routine clinical practice.

5. Conclusions

This prospective, randomized study provides novel evidence that music, when integrated into the clinical setting of TPBx, serves as a safe and easily applicable nonpharmacological intervention that significantly reduces pain perception and anxiety while improving overall patient satisfaction. By evaluating pain at multiple time points and considering sedation requirements, our findings offer a comprehensive assessment of the analgesic and anxiolytic effects of music throughout the TPBx procedure. As clinical practice moves toward perilesional biopsy, an approach expected to reduce both the number of biopsy cores and associated procedural discomfort, music may represent a valuable adjunct to further enhance patient experience. Future research should focus on standardizing music-based interventions by investigating optimal timing, musical genre, delivery method, and individual patient preferences to maximize therapeutic benefit.



Author contributions: Luca Boeri had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.



Study concept and design: Boeri

Acquisition of data: Maria Basadonna, Passarelli, Graps, Ciamarra, Parolin, Lucignani, Ripa, Gadda, De Lorenzis, Albo.

Analysis and interpretation of data: Boeri.

Drafting of the manuscript: Maria Basadonna, Passarelli.

Critical revision of the manuscript for important intellectual content: Boeri, Montanari, Passarelli, Maria Basadonna.

Statistical analysis: Boeri.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Boeri, Montanari.

Other (specify): Writing of the manuscript: Maria Basadonna, Passarelli.



Financial disclosures: None of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.



Funding/Support and role of the sponsor: None.

Associate Editor: Roderick van den Bergh

Statistical Editor: Rod Dunn

Appendix A. Supplementary data

The following are the Supplementary data to this article: