Reassessment of approaches to prostate biopsy in the era of magnetic resonance imaging-targeted biopsy: insights from the ProBE-PC study

Prostate biopsy (PB) is essential for the diagnosis of prostate cancer (PCa). Two main approaches are used for PB: transrectal prostate biopsy (TR-PB) and transperineal prostate biopsy (TP-PB). As urologists, we choose the appropriate approach based on the merits and demerits of each method. In many institutions, TR-PB has been adopted owing to its simplicity, especially in terms of anesthesia (1,2). However, these two biopsy methods have been the subject of ongoing debate regarding infection rates and diagnostic accuracy.

For instance, TR-PB has been associated with a higher incidence of infection compared with that of TP-PB (3,4). This is mainly attributed to the fact that TR-PB involves accessing the prostate via the rectum, thus increasing the risk of infection owing to the presence of bacteria in feces. In contrast, TP-PB, which is performed through the perineum, has been shown in studies to carry a lower infection risk (3,4). However, recent studies have shown that the infection rates between TR-PB and TP-PB are not significantly different, suggesting that the topic of ongoing debate is the occurrence of infections after biopsy (5-7). From a diagnostic standpoint, regarding the clinically significant PCa (csPCa) detection rate, various studies have reported the superiority of TP-PB, whereas others indicated no significant differences between the two (3,8-10). One notable disadvantage of the TR-PB approach, especially during the era of systematic biopsies, is its lower efficacy in detecting cancer located in the anterior regions of the prostate (11). This is attributed to its limited ability to adequately sample these regions.

Recently, the use of magnetic resonance imaging (MRI) in the diagnostic workflow for PCa has been increasingly standardized. Specifically, MRI is now typically performed before PB, and the biopsy procedure is guided based on MRI findings. MRI has the potential to reduce the overdiagnosis of clinically insignificant PCa while improving the detection of csPCa (12). In MRI-targeted biopsy, both transrectal and transperineal approaches are utilized. With the incorporation of MRI into the diagnostic process, a reevaluation is needed regarding previously recognized challenges, such as the undersampling of PCa in the anterior regions when using the transrectal approach.

In this issue of the Journal of Urology, Mian et al. conducted a randomized controlled trial to compare the diagnosis of csPCa between TR-PB and TP-PB (ProBE-PC study). In the ProBE-PC study, 840 patients were enrolled and randomly assigned in two groups at a 1:1 ratio. Following the exclusion of patients not meeting the inclusion criteria, 384 patients underwent TR-PB and 398 patients underwent TP-PB. Among them were included those who underwent MRI-targeted biopsy, with 287 patients (75%) in the TR-PB group and 295 patients (74%) in the TP-PB group. No significant differences in the distribution of Prostate Imaging-Reporting and Data System (PI-RADS) scores were observed between the two groups. The primary outcome of this study was the proportion of csPCa diagnosed with Gleason grade group ≥2. csPCa was detected in 47.1% [95% confidence interval (CI): 42.2%, 51.1%] of men in the TR-PB group and 43.2% (95% CI: 35.4%, 48.1%) in the TP-PB group. The use of the TP-PB approach was not associated with a higher detection rate of csPCa [odds ratio (OR) =0.72; 95% CI: 0.50–1.04]. Factors such as age, prostate-specific antigen (PSA) density, previous biopsy, and PI-RADS score were linked to an increased detection of csPCa, whereas family history and the presence of anterior regions were not associated with an improved detection rate of csPCa. The secondary outcome, that is, the detection rate of csPCa by MRI-targeted fusion biopsy, was 56% and 53% in the TR-PB and TP-PB groups, respectively. Interestingly, in men with anterior regions identified on multiparametric MRI, the csPCa detection rates for TR-PB and TP-PB were 44.5% and 39.3%, respectively. Furthermore, an increasing PI-RADS score was associated with a higher likelihood of detecting csPCa. However, no significant difference in the detection rates of PCa across any Gleason grade group for any PI-RADS score was observed between the TR-PB and TP-PB groups.

The ProBE-PC study had several strengths (13). One notable strength was its robust methodology, as it was a randomized controlled trial. In this context, the ProBE-PC study was able to demonstrate that the detection rates of csPCa between TR-PB and TP-PB did not differ (13). For instance, a previous study reported that TP-PB had a higher detection rate of csPCa compared with that of TR-PB (14). However, given the retrospective nature of that study (14), a possibility of selection bias exists. Conversely, in the recently reported randomized controlled trial, the PERFECT trial, which utilized a similar study design to the ProBE-PC study, the noninferiority of TP-PB compared with TR-PB in MRI-targeted biopsy was not demonstrated (7) (Table 1). One potential mechanism for the discrepancy in the results between these two randomized controlled trials may lie in the differences in the study design. Specifically, the PI-RADS score criteria for MRI-targeted biopsy varied between the two studies. In the ProBE-PC study, MRI-targeted biopsy was performed for PI-RADS ≥3 (13), whereas in the PERFECT trial, the procedure was conducted for PI-RADS ≥4 (7) (Table 1). Previous meta-analysis demonstrated that cancer detection rates were 16% for PI-RADS 3, 59% for PI-RADS 4, and 85% for PI-RADS 5 (15). Whether or not to include PI-RADS 3 as a target for biopsy could significantly affect the diagnostic rate. Second, the biopsy procedures were performed using a software-based fusion technique in the ProBE-PC study (13). As the ProBE-PC study was conducted at a single institution rather than multiple centers, the accuracy of MRI-targeted biopsy was well-maintained. Third, not only TR-PB but also TP-PB were performed under local anesthesia. This can be considered as evidence supporting the feasibility of TP-PB under local anesthesia.

However, the ProBE-PC study is not without areas for improvement. First and importantly, this study reported findings from a single expert center where software-assisted MRI-targeted biopsy is routinely performed. Specifically, results obtained from a single expert center may not fully reflect outcomes in broader, multicenter settings, where variations in expertise and resources may influence the results. Results from multiple centers would likely enhance the potential for broader applicability of the findings. Therefore, further research, including multicenter studies, is warranted to strengthen the external validity of the results. Second, although the study concludes that no significant difference exists in csPCa detection rates between TR-PB and TP-PB, it does not fully explore the clinical implications of this equivalence. The lack of statistical significance does not imply practical equivalence, and this nuance is not adequately discussed. The third consideration regards the definition of csPCa. In the ProBE-PC study, csPCa was defined as Gleason grade group ≥2, based on previous study (16). Using GG2 as a threshold for csPCa remains a reasonable approach. However, recent guidelines and clinical trials have highlighted that PCa with a small tumor volume of Gleason grade group 2 may be eligible for active surveillance (17-19). This raises the question of whether Gleason grade group 2 should truly be classified as csPCa. Of the Gleason pattern 4 cancers, the cribriform pattern is particularly concerning, and its inclusion has been reported to affect prognosis (20). In addition, although not included in Gleason grading, the presence of intraductal carcinoma of the prostate (IDC-P) is also of significant importance. IDC-P is recognized as a poor prognostic factor (20,21) and should be considered a defining characteristic of csPCa. Future studies may be required to incorporate csPCa factors, including cribriform pattern and IDC-P. Fourth, one important consideration in the choice of the biopsy approach is the effect on the quality of life (QOL) of the patient. The ProBE-PC study also reported on complications, revealing no significant difference in the incidence of infectious or noninfectious complications between patients subjected to TR-PB and those undergoing TP-PB (6). Hence, when selecting the biopsy method, patient-reported outcomes, such as QOL, should be regarded as crucial factors and must be factored into the clinical decision-making process. Including patient-reported outcomes or other metrics would have strengthened the discussion and practical applicability of the findings. Fifth, this study followed the methodology and objectives of previous trials, such as the PERFECT study. Therefore, it presents no novel findings or data that would significantly contribute to progress in this area. Furthermore, the discussion does not address the broader impact of MRI, particularly its potential role in reducing overtreatment and enhancing patient management strategies. Sixth, both biopsy methods (TR-PB and TP-PB) demonstrate similar efficacy regarding csPCa detection. Factors such as cost, resource availability, and patient comfort may influence the choice of biopsy method in clinical practice. Patient preferences regarding the invasiveness associated with each approach are important aspects that warrant further investigation in future studies.

Undoubtedly, the ProBE-PC study reflected the effect of MRI on the accuracy of the PCa diagnostic workflow. Previous studies have suggested differences in the detection rates of csPCa and cancer in the anterior regions of the prostate between TR-PB and TP-PB (3,8-11). However, the ProBE-PC study, a randomized controlled trial, demonstrated that the detection rates of csPCa do not significantly differ between the two approaches. It had been reported that by performing targeted-PB only in patients with elevated PSA levels and visible lesions on MRI, half of the diagnoses of clinically insignificant PCa could be avoided, while the detection rate of advanced or high-risk cancers remains extremely low (22). In this context, a future perspective for PCa diagnostic workflows could involve performing targeted biopsies exclusively for visible lesions on MRI, regardless of the biopsy approach, in cases of elevated PSA levels. The ability to visualize lesions with MRI may have removed the need for choosing between biopsy approaches in the accuracy of PCa diagnosis, highlighting the significant contribution of this study to advancing clinical practice.

Acknowledgments

None.

Footnote

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