Alessandro Veccia

MP49-02 PERIOPERATIVE MORBIDITY OF CLAMP VS OFF-CLAMP ROBOTIC PARTIAL NEPHRECTOMY: PRELIMINARY RESULTS FROM A MULTICENTRE RANDOMIZED CLINICAL TRIAL (THE CLOCK STUDY)

INTRODUCTION AND OBJECTIVES: To assess the significance of mannitol used as renal protective agent during nephronsparing surgery (NSS) on renal functional outcomes after NSS. METHODS: A prospective, randomized, placebo-controlled, double-blind, phase 3 trial (ClinicalTrials.gov identifier NCT01606787) designed to detect a 5% difference between treatment arms with a power of 90%. Patients were randomized 1:1 to receive mannitol (12.5 g) or normal saline solution placebo intravenously within 30 min prior to renal vascular clamping. Eligibility criteria included age >18 yr, renal artery clamping during NSS, and preoperative estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m. Intraoperatively, a standardized fluid management algorithm was used to maintain hemodynamic stability and urine output 0.5 mL/kg/h. Postoperatively, eGFR was obtained at 6 wk and 6 mo. A renal scan was obtained pre operatively and at the 6-mo endpoint. An ANCOVA model was used to assess the differences in eGFR at 6 wk and 6 mo, and in renal scan at 6 mo after NSS. Differences in grade 3-5 complications were assessed using Fisher0s exact test. At the interim analysis on the first 88 patients, the O0Brien-Fleming stopping boundaries requiring a significance level of 0.0031 were not met (p 1⁄4 0.6). RESULTS: A total of 105 patients per treatment arm were enrolled. After excluding 11 patients (7 in the placebo and 4 in the mannitol arm) who did not undergo NSS; 2 patients (1 in each arm) converted to radical nephrectomy, and 1 patient from the mannitol arm who never received the study drug, 98 and 101 patients in the placebo and mannitol arms, respectively, were evaluated. Median age was 56 yr (interquartile range [IQR] 48, 63) and 60 yr (IQR 50, 66) in the placebo and mannitol arm, respectively. Comparing placebo to the mannitol arm, the adjusted difference of 0.2 eGFR units at 6 mo after NSS was not significant (95% confidence interval [CI] -3.1, 3.5; p1⁄4 0.9). The adjusted difference of -2.6 eGFR units at 6 wk after NSS was not significant (95% CI -5.8, 0.7; p 1⁄4 0.12). No significant differences were detected between treatment arms in median split function on 6-mo renal scan (difference -1.7; 95% CI -3.8, 0.4; p 1⁄4 0.11), or in grade 3-5 complication rates within 90 days of NSS (difference 3.2%; 95% CI -4.1%, 11%; p 1⁄4 0.4). CONCLUSIONS: This randomized prospective trial provides evidence against the use of mannitol as renal protective agent during NSS since no clinical or statistically significant advantage to the use of intravenous mannitol in patients undergoing NSS was found.

MP11-02 OUTCOMES OF A PHASE III RANDOMIZED CONTROLLED TRIAL COMPARING PREVENTIVE VERSUS DELAYED LIGATION OF DORSAL VASCULAR COMPLEX DURING ROBOT-ASSISTED RADICAL PROSTATECTOMY

Primary endpoint was estimated blood loss (EBL); considering significant a difference 330 ml, a sample size of 226 patients were calculated (two-sided α of 0.05 and 80% power). Secondary endpoints were: transfusion rate, positive surgical margins (PSMs), apical PSMs and 1-month PSA and continence (0-1 security pad/day). Differences were compared using Pearson chi-square test or MannWhitney test as appropriate (p<0.05 was considered statistically significant).

Positive Surgical Margins Predict Progression-free Survival After Nephron-sparing Surgery for Renal Cell Carcinoma: Results From a Single Center Cohort of 459 Cases With a Minimum Follow-up of 5 Years

Background The role of positive surgical margins (PSMs) on the recurrence of renal cell carcinoma (RCC) after partial nephrectomy (PN) is debated, and available evidence lacks long‐term data. The aim of this study was to evaluate the predictive role of PSMs on progression‐free survival (PFS) in a large cohort followed for at least 5 years. Methods This study was a retrospective analysis of a prospectively compiled single‐institution database collecting complete information on more than 2700 patients who had undergone surgery for renal tumor. The data of all the patients submitted to PN for RCC and with least 5 years follow‐up were extracted. Surgical specimens were examined at the time of surgery only by 2 expert uro‐pathologists. A PSM was defined as the presence of cancer cells at the inked surface of the specimen. The role of PSMs on survival was estimated by Cox regression models adjusted for influent covariates. Results A total of 459 patients fulfilled the inclusion criteria and were evaluated. PSMs were observed in 27 (5.9%) cases. No differences in preoperative and pathologic data were found comparing patients with and without PSMs. At a median follow‐up of 96 months (interquartile range, 74‐131 months), a clinically evident relapse of RCC was diagnosed in 36 (7.8%) patients at a median interval of 36 months from PN. Among these, 6 had a PSM for an incidence of relapse of 22.2% in the PSM group, whereas 30 had negative margins, for an incidence of 6.9% (P = .013). The sites of relapse were distant organs in 18 cases, and the kidney underwent PN in 21. The patients with PSMs showed a borderline significantly higher incidence of distant metastasis (11.1% vs. 3.5%; P = .071) and a significantly higher incidence of renal relapses (14.8% vs. 3.9%; P = .029). Multivariable Cox models confirmed that the presence of PSMs was an independent predictor of PFS (odds ratio, 3.127; P = .013). Conclusions PSMs are an independent predictor of PFS in patients who underwent PN for RCC, owing to a higher incidence of distant and local relapses. Surveillance in presence of PSMs should be intensified and extended for a long time. Micro‐Abstract The presence of positive surgical margins (PSMs) after partial nephrectomy has been associated with an increased risk of disease recurrence, but conclusive evidence is lacking. The aim of this study is to examine the prognostic role of PSMs in a large retrospective cohort with long‐term follow‐up. PSMs were associated with disease recurrence, both local and distant, and decreased progression‐free survival. Patients with PSMs should undergo a more intense follow‐up.

External Validation of the Arterial-Based Complexity Score and First Head-to-Head Comparison With the R.E.N.A.L. and PADUA Scores and C-index

&NA; The aim of the present study was to prove the arterial‐based complexity (ABC) score validity by comparing it with the R.E.N.A.L. (radius, exophytic/endophytic tumor properties, nearness of tumor to deepest portion of collecting system or sinus, anterior/posterior descriptor, location relative to the polar line), PADUA (preoperative aspects and dimension for anatomic classification of renal tumors), and C‐index scores. We performed a retrospective analysis of pre‐ and postoperative data from 234 patients who had undergone open and robot‐assisted partial nephrectomy. An external urologist who was unaware of the outcomes reviewed all computed tomography scans to assign the nephrometry scores and determine tumor complexity. We found no statistically significant superiority for the ABC system. Introduction: We performed an external validation of the arterial‐based complexity (ABC) score using a head‐to‐head comparison with the R.E.N.A.L. (radius, exophytic/endophytic tumor properties, nearness of tumor to deepest portion of collecting system or sinus, anterior/posterior descriptor, location relative to the polar line), PADUA (preoperative aspects and dimension for anatomic classification of renal tumors), and C‐index scores for the prediction of surgical outcomes after partial nephrectomy. Materials and Methods: The data from a series of consecutive open or robot‐assisted partial nephrectomies performed from January 2014 to July 2016 by 4 expert surgeons at a tertiary academic institution were reviewed. After dedicated training, 1 urologist not involved in the surgical procedures evaluated the cross‐sectional imaging studies and assigned the nephrometry score using the 4 nephrometry scoring systems. The predictive performance of the ABC and other scoring systems was tested in univariate and multivariable fashion. Results: Overall, 234 patients were recruited (148 men and 86 women; age, 63 ± 10.9 years). The scores were all related to the estimated blood loss, use of hilar clamping, ischemia time, operative time, length of stay, and MIC (margin status, ischemia time, complications) score. They were not related to the occurrence of postoperative complications or, for the C‐index and ABC score, the length of stay. In a head‐to‐head comparison, the ABC was not inferior only to the C‐index relative to the occurrence of complications and MIC score, with borderline statistical significance. On multivariate analysis, the ABC score provided significant improvement only for the prediction of the operative and ischemia times. However, its performance was inferior to that of the other scoring systems. In addition, only the PADUA score improved the prediction of artery clamping and MIC score, and only the R.E.N.A.L. score showed an advantage for the prediction of the estimated blood loss. Conclusion: The predictive ability of ABC was inferior to that of well‐established existing nephrometry scoring systems, such as the PADUA and R.E.N.A.L. scores.