Timo Soeterik

92 CHAPTER 5 DISCUSSION In this study, we explored the association between side-specific nerve sparing RP and the risk of ipsilateral positive margins using a large, multi-institutional, real-world patient cohort. On multivariable logistic regression analysis nerve sparing was associated with significantly higher odds of positive margins compared with non-nerve sparing (OR 1.42, 95% CI 1.14 – 1.82). Our study results call into question the classic assumption that nerve sparing is not associated with an increased risk of positive surgical margins. Our main findings are relevant for clinical practice as patients and their urologists need to be aware of the fact that nerve sparing does increase the risk of positive margins. This effect was masked in previous studies, apparently due to methodological limitations and insufficient unadjusted residual confounding by indication. Also, as nerve sparing does not guarantee preservation of erectile function, 10 patients unlikely to benefit from nerve sparing should not be unnecessarily exposed to its risks. Several studies on this topic have been performed previously, reporting conflicting results. Coelho et al reported comparable positive margin rates of 876 patients regardless of nerve sparing type. 15 For bilateral, unilateral and non-nerve sparing, respectively, the positive margin rates in pT2 tumours were 8.2%, 6.1% and 8.5% ( p = 0.93) and 27.7%, 26.7% and 30.8% ( p = 0.93) in pT3. Comparable findings were reported in a study by Moore et al, including 945 patients. 16 The authors reported no significant differences in positive margin rates between nerve sparing groups on multivariable analysis adjusting for age, PSA, Gleason score, percentage of positive biopsy cores and clinical stage. The reported relative risks were 0.58 (95% CI 0.30 - 1.40, p = 0.11) for unilateral nerve sparing and 0.64 (95% CI 0.35 - 1.17) for bilateral nerve sparing. Choi et al evaluated functional outcomes and positive margin rates in their series of 602 consecutive RARPs. 17 Nerve sparing improved 24-month urinary control without an increase in positive margin rates compared to non-nerve sparing RARP. Lastly, a study on the SEARCH (Shared Equal Access Regional Cancer Hospital) database including 1018 cases echoed the previously stated findings, and reported that neither bilateral nor unilateral nerve sparing techniques were associated with a higher risk of a positive margin. 18 Our findings are inconsistent with those reported in previous studies, for which we have two possible explanations. The potential confounders adjusted for during analysis in previous studies were prostate-specific and not prostate side-specific. To determine causality between a nerve sparing approach and ipsilateral positive margins, each prostate lobe should be considered as a separate case. For example, it is likely that among patients in whom unilateral nerve sparing was performed the ipsilateral side had favourable tumour characteristics compared to the contralateral side. Disregarding the side-specific factors in the analysis limits the ability to evaluate the causality between nerve sparing and an ipsilateral positive surgical margin and, therefore, the effects of side-specific covariates remain masked. The second reason regards the type and number of covariates for which was adjusted during multivariable analysis in previous studies. In this study, the large sample size and side-specific nature of the majority of covariates