Review Reports - Transition from Transrectal Systematic to Transperineal Lesion-Focused Prostate Biopsy: A Real-World Comparative Analysis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

I read with extreme interest this nicely written manuscript and nicely designed study. This is a retrospective study but the size of the series is adequate. Methods are well described and results well presented. All the biopsies were performed by a single urologist and all specimens evaluated by a single pathologist dedicated. Limitations of the study are well declared.

I would strengthen the discussion by inserting a few concepts more: you may discuss if this transition may have same results in newbies or not very experienced urologists (especially residents who seems to be much more exposed to transrectal doi: 10.1111/bju.15935. ). You also may discuss if there is a transperineal technique that may be easier to be performed for the transition ( i.e. free hand vs template vs fan technique - i.e. doi: 10.1007/s00345-018-2599-6. )

Comments on the Quality of English Language

Well written

Good English

Author Response

Reviewer Comment

I would strengthen the discussion by inserting a few concepts more: you may discuss if this transition may have same results in newbies or not very experienced urologists (especially residents who seem to be much more exposed to the transrectal approach; doi:10.1111/bju.15935). You also may discuss if there is a transperineal technique that may be easier to be performed for the transition (i.e. free-hand vs template vs fan technique; doi:10.1007/s00345-018-2599-6).

Response

We thank the reviewer for this very positive and encouraging evaluation of our manuscript.

In response to this comment, we have strengthened the Discussion to address the potential impact of operator experience on the generalizability of our findings. We now explicitly acknowledge that all biopsies in the present study were performed by a single experienced urologist, ensuring procedural consistency, but that results may not be directly extrapolated to less experienced operators or trainees, who have historically been more exposed to the transrectal approach. The reviewer’s suggested reference has been incorporated to support this point.

In addition, we have expanded the Discussion to address technical considerations related to the transition toward the transperineal approach. We now discuss that simplified free-hand or fan-based transperineal techniques may represent more accessible options during the early learning phase compared with template-based approaches, while acknowledging that comparative data on diagnostic performance and learning curves remain limited. The second suggested reference has been added accordingly.

These revisions have been incorporated into the Discussion section (Limitations paragraph) of the revised manuscript and are highlighted using track changes.

Reviewer 2 Report

Comments and Suggestions for Authors

The study retrospectively compares an earlier, larger cohort undergoing transrectal biopsy with combined targeted and systematic cores (TBx + SBx) with a more recent cohort in which isolated but spatially extended targeted biopsies (TBx + PBx) were performed via a transperineal approach. Using extensive statistical adjustment, the authors report a higher detection rate of clinically significant prostate cancer together with a reduced detection of insignificant disease in the more recent cohort. From a clinical perspective, this interpretation is plausible, and the authors’ conclusion that the observed effect is primarily driven by sampling geometry rather than by the biopsy route itself is supported by the cited literature.

The manuscript is clearly structured, well written, and easy to follow. The research question is clinically highly relevant and addresses a timely topic in MRI-guided prostate biopsy. The statistical methodology is sophisticated and appropriate for a retrospective real-world design, including propensity score weighting, IPTW, and sensitivity analyses. Overall, the results are presented transparently and supported by up-to-date literature.

In my opinion, this is a methodologically sound and clinically relevant real-world analysis. The manuscript would benefit from improved contextualization of the reported effect size and from a clearer discussion of the clinical implications of the findings. The authors might consider whether the following points could be addressed in the final version:

1. A direct comparison of absolute detection rates of clinically significant prostate cancer with large prospective MRI-based studies, particularly the Göteborg cohort, is missing. As these studies suggest that modern MRI-guided strategies already detect a substantial proportion (approximately 80%) of clinically significant cancers, contextualizing the absolute csPCa detection rates observed in the present study would be helpful. In my view, even a brief descriptive comparison would allow readers to better judge the incremental diagnostic yield. Without this comparison, it remains difficult to assess the magnitude of the additional diagnostic yield relative to established reference data, especially as the manuscript predominantly reports relative effect measures.

2. The authors clearly and transparently discuss the limitations inherent to their retrospective before–after design. In this context, it would be valuable if they could explicitly comment on whether their data provide any indication as to clinical scenarios in which omission of systematic biopsies might be considered reasonable. In addition, it would be informative to know whether there were subgroups within their cohort in whom the authors would still favor the classical combination of targeted and systematic biopsies (TBx + SBx). Such clarification would be helpful for daily clinical decision-making, without overstating the evidentiary strength of the study.

Author Response

Reviewer Comment 1

A direct comparison of absolute detection rates of clinically significant prostate cancer with large prospective MRI-based studies, particularly the Göteborg cohort, is missing. As these studies suggest that modern MRI-guided strategies already detect a substantial proportion (approximately 80%) of clinically significant cancers, contextualizing the absolute csPCa detection rates observed in the present study would be helpful. In my view, even a brief descriptive comparison would allow readers to better judge the incremental diagnostic yield. Without this comparison, it remains difficult to assess the magnitude of the additional diagnostic yield relative to established reference data, especially as the manuscript predominantly reports relative effect measures.

Response

We thank the reviewer for this insightful comment. We agree that contextualizing the absolute detection rates of csPCa is essential to better interpret the magnitude of the observed effect beyond relative measures.

In response, we have added a descriptive contextualization of the absolute csPCa detection rates observed in our weighted cohorts. We now report these absolute rates and interpret them in light of large prospective MRI-based reference studies, including the Göteborg-2 cohort. While explicitly acknowledging the limitations of direct comparisons due to differences in study design, population, and biopsy indications, this addition provides readers with a practical reference framework to better appreciate the incremental diagnostic yield associated with optimized sampling geometry.

These changes have been incorporated into the Discussion section, immediately following the opening paragraph reporting the main results, and are highlighted using track changes.

Reviewer Comment 2

The authors clearly and transparently discuss the limitations inherent to their retrospective before–after design. In this context, it would be valuable if they could explicitly comment on whether their data provide any indication as to clinical scenarios in which omission of systematic biopsies might be considered reasonable. In addition, it would be informative to know whether there were subgroups within their cohort in whom the authors would still favor the classical combination of targeted and systematic biopsies (TBx + SBx). Such clarification would be helpful for daily clinical decision-making, without overstating the evidentiary strength of the study.

Response

We thank the reviewer for this important and clinically relevant suggestion. We agree that readers would benefit from clearer guidance regarding the potential clinical implications of our findings, while avoiding overinterpretation of retrospective data.

Accordingly, we have expanded the Discussion to explicitly address clinical scenarios in which omission of SBx might be considered reasonable, as well as situations in which the classical combination of TBx + SBx would still be favored. We now emphasize that our data do not support universal omission of SBx but may provide hypothesis-generating signals within a lesion-focused framework, particularly in carefully selected patients with a single MRI-visible lesion and concordant clinical and radiological risk profiles. Conversely, we explicitly discuss scenarios where SBx may remain appropriate, including clinical–radiological discordance, equivocal MRI findings, suspected multifocal disease, or when broader gland sampling is required for risk stratification. These considerations are supported by relevant prospective MRI-based studies and are framed cautiously in light of the retrospective before–after design and limited subgroup sizes.

These revisions have been incorporated into the Discussion section, in a dedicated paragraph following the biopsy template discussion and preceding the limitations paragraph, and are highlighted using track changes.