Reply to Drs. Bayraktar and İşler's Letter to the Editor re: Basadonna LM, Passarelli F, Graps G, et al. Music During Transperineal Prostate Biopsy (The VIVALDI Trial): A Few Questions on the Gap Between Self-reported Benefit and Objective Findings

We thank Drs. Bayraktar and Işler [1] for their letter to the editor and for raising several points about our trial that merit clarification.

Regarding the divergence between patient-reported outcomes and objective physiological parameters, we would first note that heart rate (HR) and systolic blood pressure (SBP) in our trial were recorded only immediately before and after the procedure, as standard in an outpatient transperineal biopsy setting, rather than continuously, as would be possible with continuous arterial pressure monitoring. A single pre- and post-snapshot is unlikely to capture the brief autonomic fluctuations that may occur during the most stimulating phases of the procedure and may therefore underestimate any transient anxiolytic effect of music. We would also emphasize that pain and distress, as experienced and reported by the patient, rather than autonomic parameters used as surrogate markers, represent the clinically relevant outcomes in an outpatient procedure of this kind. In this context, patient-reported pain remains a key end point for assessing the effectiveness of the intervention. It is also worth noting that, although Chang et al. [2] reported statistically significant differences in HR (70.7 ± 8.91 means and SD vs 75.1 ± 6.30 bpm; p = 0.01) between the music and no-music groups, the magnitude of this difference was small and its clinical relevance is likely limited. Moreover, patients allocated to the intervention group had higher SBP during biopsy (126.1 ± 12.20 means and SD vs 118.4 ± 13.26 mm Hg; p = 0.01), further highlighting the limited value of autonomic parameters as surrogate markers of patients’ procedural experience. Finally, the concomitant use of midazolam may have affected autonomic parameters in both groups and should therefore be considered when interpreting physiological data [3].

Regarding the second comment, we would clarify that all patients received an identical baseline dose of intravenous midazolam, irrespective of group allocation. Additional doses were administered only upon explicit patient request during the procedure and were not based on the operators’ discretion. The lower rate of supplemental sedation of patients in the music group therefore reflects their perceived need rather than variation in the operators’ threshold for administering additional sedation. Nevertheless, we acknowledge that operator awareness of group assignment cannot be entirely excluded as a potential source of bias, as the reviewers correctly pointed out.

Regarding statistical methodology, we agree that the ordinal nature of the patient-reported outcomes deserves consideration when selecting the multivariable analytical approach. Although Visual Analogue Scale (VAS) pain scores and satisfaction scores are ordinal/bounded measures, linear regression is frequently applied to patient-reported scales when treated as approximately continuous variables. Nevertheless, we recognize that an ordinal regression approach would represent a more conservative and methodologically appropriate alternative for this specific end point. Regarding the distributional assumptions, these were considered in the context of the regression analyses, particularly the distribution of residuals and homoscedasticity.

Regarding the fourth point, we fully agree with the authors’ assessment that the between-group difference in pain scores, although statistically significant, was modest and close to the commonly reported minimal clinically important difference for the VAS score. Therefore, we have maintained a cautious interpretation of the magnitude of this effect and acknowledge that its clinical relevance should not be overstated.

In conclusion, future studies could also investigate immersive virtual reality. In this regard, a recent preliminary study evaluated the HypnoVR system during prostate biopsy and reported promising results in terms of feasibility and patient comfort, although the very small sample size limits definitive conclusions [4]. Larger randomized studies comparing music, immersive virtual reality, and standard care could clarify whether these interventions provide additional benefits in reducing procedural pain and distress during transperineal prostate biopsy.



Conflicts of interest: The authors have nothing to disclose.