Off‐clamp partial nephrectomy: Level 1 data regarding real‐world utility (or futility)

Abstract

Antonelli et al. [1] address a longstanding controversy in our field that relates to the impact of ischaemia on functional recovery after partial nephrectomy (PN). Direct measurement of the percentage of parenchymal volume preserved in large cohorts of patients managed with PN has been performed and has demonstrated strong correlation with functional outcomes [2, 3]. In contrast, a correlation between ischaemic interval and functional recovery has not been observed, as long as parenchymal volume changes have been accounted for [2]. An important observation was that parenchymal volume preserved correlated strongly with ischaemia time. More complex PN, such as for a centrally located tumour, typically requires longer ischaemia time, and yields substantially reduced vascularised parenchymal volume. In contrast, an easy PN, e.g. for a small exophytic tumour, requires only a short ischaemic interval and associates with almost complete parenchymal volume preservation. When parenchymal volume preservation is not integrated into the analysis, duration of ischaemia appears to be a significant determinant of functional recovery, leading to the common refrain of a decade ago, ‘Every Minute Counts’ [2, 3]. When parenchymal volume changes are incorporated, ischaemia loses all significance, and it is the quantity and a quality of nephron mass preserved that prove to be the main determinants of functional recovery (Fig. 1) [2-4]. However, most such studies, while compelling, were retrospective and thus potentially subject to various biases. A randomised trial of on-clamp vs off-clamp PN has been reported and failed to show a functional difference, although the numbers were limited (71 patients) [5]. In this analysis, Antonelli et al. [1] present an interesting and important randomised trial of on-clamp vs off-clamp robotic PN in 324 patients with two kidneys, normal baseline renal function, anatomically normal contralateral kidney, and R.E.N.A.L. (Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location) nephrometry score of ≤10. The authors randomised 160 and 164 patients to the two different groups. The median tumour size was <3.0 cm and the median R.E.N.A.L. scores were 6 and 7 in the off-clamp and on-clamp cohorts, respectively. The primary end-point was the absolute change in the GFR at 6 months. Several other functional outcomes were also explored including absolute change in GFR at later time-points, significant change in the split renal function of the operated kidney, and whether the relative change in GFR was above a pre-defined threshold level of 25%. The analyses were done both intent-to-treat and per protocol, but in all instances significant functional differences were not observed. The median ischaemia time in the on-clamp group was only 15 min, so this trial was really evaluating limited warm ischaemia vs no ischaemia, and prolonged ischaemia was not under investigation [1]. The trial was designed with only one experienced and dedicated robotic surgeon participating at each centre to optimise surgical quality. Despite this, cross-over was substantial, including 69 cases (43%) in the off-clamp group who ended up with vascular occlusion. In 14 of these patients the surgeon decided preoperatively to clamp due to tumour complexity, but in the great majority (55 patients, 35% of the off-clamp cohort) conversion occurred due to intraoperative bleeding [1]. A previous report from this trial demonstrated that safe outcomes were obtained despite these conversions, and perhaps timely conversion may have contributed to this [6]. This study is well designed and provides Level 1 data, and the authors are to be congratulated for their efforts [1]. It confirms that limited warm ischaemia has minimal or no effect on functional recovery after PN in most patients with small renal masses, and it demonstrates that off-clamp approaches can lead to potential challenges, albeit manageable, even in this relatively low-risk population. No