Timo Soeterik

93 Nerve Sparing and Risk of Positive Margins enabled inclusion of a large number of potential confounders in the multivariable analysis, including the influence of the individual surgeon (and, thus, experience) on the occurrence of positive margins. To our knowledge, none of the previous studies performed an analysis including all of the most important potential predictors, including MRI stage, for positive margins. In two previously performed studies on this subject comparable conclusions were reported. 19,20 Zorn et al reported significantly higher posterolateral positive margin rates among patients with pT3 tumours who underwent interfascial nerve preservation compared to patients with pT3 tumours undergoing non-nerve sparing RARP (73% vs 33%, p = 0.05). 19 Fact this study had comparable results may be explained by the methodological approach, as their analysis was also done on the prostate lobe-level. In addition, the nerve sparing technique performed was comparable to ours, as interfascial nerve sparing was performed. 19 Liss et al also reported nerve sparing to be associated with an increased risk of positive margins on multivariable analysis (OR 5.58, 95% CI 1.176 - 26.46). 20 However, the calculated ORs (and large corresponding 95% CIs) on multivariable analysis should be interpreted with caution as the number of events was relatively low (21) for the total number of covariates included (6). 20 The positive margin rates, especially those observed for pT2 tumours (23%), were relatively high compared to those reported in other series. In a recent meta-analysis by Nguyen et al an absolute risk of positive margins of 8.1% for any nerve sparing and 7.7% for non-nerve sparing was reported. 7 The higher rates of positive margins observed in this study may be explained by the selection of higher-risk patients for surgery, with relatively higher biopsy Gleason scores (65% Gleason 7 or higher) and relatively high pT3 rates (40%) compared to those reported in other series (42% Gleason 7 or higher and 19% pT3). 10 Surgeon experience was previously reported to be associated with positive margins after RARP, and could also explain the higher positive margin rates in our cohort. 21 Of all surgeons performing RARP in this study a large proportion were novice, with 8 of 14 (57%) having performed fewer than 50 RARPs. Our study has a number of strengths, as it is a multicentre study with a large sample size, enabling inclusion of a relatively large number of covariates into the multivariable logistic regression model. However, some potential limitations must be acknowledged. Our study lacks central review regarding histopathological findings on prostate biopsy and final pathology after RARP. However, we assume this has no large impact on our main findings as positive surgical margin interpretation by uropathologists generally shows a high degree of interobserver agreement. 22 In addition, data regarding the degree of interfascial nerve sparing were lacking in the surgery reports, which could have led to measurement bias. Finally, inclusion of the location of positive surgical margins was outside the scope of the present study. Evaluation of the specific locations of the positive margins should be the subject of future research as the association between location and nerve sparing remains poorly understood. 5

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