C. Palumbo

Below Safety Limits, Every Unit of Glomerular Filtration Rate Counts: Assessing the Relationship Between Renal Function and Cancer-specific Mortality in Renal Cell Carcinoma

BACKGROUND The hypothesis that renal function could influence oncological outcomes is supported by anecdotal literature. OBJECTIVE To determine whether estimated glomerular filtration rate (eGFR) is related to cancer-specific mortality (CSM) in patients who had undergone surgery for renal cell carcinoma (RCC). DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis of 3457 patients who underwent radical (39%) or partial nephrectomy (61%) for cT1-2 RCC between 1990 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. CSM was analyzed in a multivariable competing-risk framework, estimating the subdistribution hazard ratio (SHR) accounting for deaths from other causes. The relationship between eGFR and CSM was investigated from multiple statistical approaches-extended Cox regression with eGFR incorporated as a time-dependent covariate, landmark analysis, and joint modeling. Other predictors were selected by competing-risk random forest method and backward elimination. RESULTS AND LIMITATIONS The relationship between eGFR and CSM was graphically described by a linear spline, i.e. a continuous piecewise linear function with two lines joined by a knot. For eGFR treated as a time-dependent covariate, the knot was located at 65ml/min; at landmark analysis with eGFR at the baseline, 12 mo, and last functional follow-up, the knots were 85, 60, and 65ml/min, respectively. In multivariable competing-risk analysis, CSM was associated with eGFR only for values of eGFR below these cutoffs, with SHRs for every 10ml/min of reduction in eGFR of 1.25 (p=0.003), 1.16 (p=0.028), 1.44 (p=0.02), and 1.16 (p=0.042), corresponding to time-dependent eGFR, and eGFR at baseline, 12 mo, and last functional follow-up, respectively. Joint modeling confirmed these results. A retrospective design with inherent biases in data collection represents a limitation. CONCLUSIONS In patients undergoing surgery for RCC, renal function should be preserved in order to improve cancer-related survival. PATIENT SUMMARY The relationship between renal function and probability of dying due to renal cancer is complex. The present study found a correlation between glomerular filtration rate and cancer specific mortality that could reconsider the oncological role of renal function in patients undergoing surgery for renal cancer.

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.

Positive surgical margins and early oncological outcomes of robotic vs open radical prostatectomy at a medium case-load institution.

BACKGROUND The aim of this study was to analyze the rates of positive surgical margins (PSM) after radical prostatectomy in patients undergoing robotic surgery (robot assisted laparoscopic prostatectomy [RALP]) compared with those undergoing open surgery (radical retropubic prostatectomy [RRP]), at an institution with medium case load. METHODS Retrospective consultation of a perspectively-maintained database that stores the data of all the patients submitted to radical prostatectomy at our institution since 1/2008. The indication to RRP vs. RALP was based almost exclusively on the period of the study: RRP was the sole available option between 1/2008 and 3/2010 and afterwards RALP become the standard of treatment, once a learning curve of 50 cases was concluded. A PSM was defined as the presence of cancer at the inked surface of prostate. A univariate and multivariate binary logistic regression estimated which factors were related to PSMs. RESULTS The data of 576 patients (285 RRP, 291 RALP) were evaluated. The overall PSM rate was 28.1% (162/414 patients; 20.6% for pT2 stage, 51.8% for pT>2); overall PSM rate for RRP vs. RALP was 31.9% vs. 24.4 % (P=0.044). At multivariable analysis the factors related to the risk of PSM were stage pT>2 (RR 2.979, P=0.001), Gleason Score >6 (RR 1.662, P=0.026), the volume of tumor (RR 1.019, P=0.008) and the surgical technique (RALP vs. RRP, RR 0.647, P=0.039). CONCLUSIONS In a series from a medium case-load institution, once data are adjusted for local staging, tumor volume and Gleason score, the risk of PSM is lower for RALP than RRP. This evidence could be of support for health-care practitioners to introduce robotic systems.

MP05-01 MANAGEMENT AND PROGNOSIS OF POSITIVE SURGICAL MARGINS AFTER RADICAL PROSTATECTOMY: RETROSPECTIVE ANALYSIS OF A CONTEMPORARY COHORT

INTRODUCTION AND OBJECTIVES: Positive surgical margins (PSM) after RP are a known factor associated with BCR. Radiation therapy (RT) currently represents an established option for metastasis-free patients. However, the timing of administration is not univocal. The aim of this study is to identify factors related to the indication to adjuvant radiation therapy (aRT) vs salvage (sRT), taking a picture of the contemporary management and prognosis of patients with PSM after radical prostatectomy (RP) at an academic tertiary institution. METHODS: We retrospectively reviewed our perspectivelymaintained database. RP has been performed with an open retropubic approach until 2010, then with a robotic transperitoneal one.All the cases with PSM and adverse pathological features (stage pT3, GS 8) were submitted to a multidisciplinary discussion. The indication to sRT was given if biochemical recurrence (BCR, PSA 0.2 ng/ml), preferably before PSA >0.5 ng/ml. Logistic regression models were used to determine the factors associated with RT indication and BCR in univariate and multivariate analysis. The BCR-free survival was calculated using KaplanMeier method. RESULTS: Out of 789 patients, 197 had PSM (overall prevalence 25,2%), with monofocal involvement in 121 (60.8%) and multifocal in 78 (39.2%). An aRT was indicated in 40 patients (20.3%). Findings are summarized in table 1. Factors independently related to aRT indication were: pathological stage, number of sites of PSM and post-operative PSA. The median follow-up time was 51.1 months (IQR 30.9-69.3). Among the 157 patients for whom aRT was not indicated, 39 experienced a relapse of PSA (prevalence of BCR 24.8%, p not significant). 26 were then treated by sRT, 8 by androgen deprivation therapy, 5 underwent surveillance. Overall, a BCR was found in 46 patients (23.4%) after a median time of 24.0 months (IQR 18.0-36.0). At the last available control 176 patients (89.3%) had a PSA < 0.2 ng/ml (median value 0.02). Only pathological stage was significantly related to the risk of BCR. CONCLUSIONS: In a real-life scenario, the indication to aRT is more restrictive than what recommended by guidelines and is driven by the amount of PSM and a detectable post-operative PSA. No differences in BCR free survival are evident in patients with PSM submitted to aRT vs sRT. Source of Funding: none

MP97-05 OUTCOMES OF PREVENTIVE VS DELAYED LIGATION OF DORSAL VASCULAR COMPLEX DURING RARP: PRELIMINARY RESULTS OF A RANDOMIZED TRIAL

INTRODUCTION AND OBJECTIVES: Little glucose metabolism is generally thought to occur in prostate cancer, leading to low diagnostic accuracy of 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT). Nevertheless, this modality is reportedly useful for identifying high-risk local cancers. We therefore investigated whether local FDG uptake by the prostate reflects the perioperative results of robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: Between November 2012 and August 2016, a total of 248 patients underwent RALP at our institution. Of these, subjects in this study comprised 116 patients in whom FDG-PET/CT was employed for preoperative staging. We retrospectively compared perioperative results between patients, stratified for local FDG uptake in the prostate. Patients who had received preoperative hormone therapy were excluded from the study. FDG uptake was rated based on clinical reports prepared by two radiation diagnosticians. Patient background characteristics, perioperative results and postoperative pathological results were compared between subjects divided into PET-positive and -negative groups. RESULTS: Participants comprised 40 PET-positive subjects and 76 PET-negative subjects. Among the patient background characteristics, mean age was slightly but significantly higher in the PETpositive group (66 years) than in the PET-negative group (64 years; p1⁄40.0485). No significant differences were seen in PSA level, clinical T stage or Gleason Score (GS). Operative time, console time and volume of blood loss also showed no differences between groups, and no patients in either group suffered rectal perforation or required blood transfusion. Postoperative urethral balloon retention time and urinary continence rate at 3 months postoperatively were comparable between groups. Postoperative pathological results showed significantly higher values for the following parameters in the PET-positive group than in the PET-negative group: extraprostatic invasion (45.0% vs 22.4%; p1⁄40.0185); positive margin (30.0% vs 13.2%; p1⁄40.0445); and GS 1⁄48 (52.5% vs 23.7%; p1⁄40.00343). Multivariate analysis also showed that PET positivity tended to be associated with positive margins (odds ratio (OR), 2.45; p1⁄40.0819) and extraprostatic invasion (OR, 2.34; p1⁄40.0529), while GS 1⁄48 was a significant predictor (OR, 3.08; p1⁄40.0208). CONCLUSIONS: In RALP, FDG uptake should be considered a predictor of high-grade disease and a risk factor for positive margins.

MP34-09 IS A DELAY IN THE TIMING OF RADICAL CYSTECTOMY REALLY DETRIMENTAL? A RETROSPECTIVE STUDY ON A SINGLE CENTRE COHORT

INTRODUCTION AND OBJECTIVES: EAU guidelines recommends radical cystectomy (RC) within a time span of 90 days from the diagnosis, to avoid an impairment in the prognosis, but the literature on this issue is not univocal. This study aims to evaluate if the latency between the diagnosis and cystectomy (LDC) could affect oncological outcomes. METHODS: Retrospective analysis of a perspectivelymaintained database that stores data of all the patients submitted to RC since 2009 at a tertiary academic institution. LDC was defined as the days between RC and the last TURBT. The primary outcome was overall survival (OS), the secondary were: relationship between clinical and pathological features and a LDC >90 days and relationship between LDC and pathological upstaging (pUS) (shift from cT1-2 to pT3-4). Statistical correlations were evaluated by univariate and multivariate Cox regression and binary logistic models, considering as significant p values <0.05. RESULTS: Overall, 226 patients were included from January 2009 to June 2016 (mean/median LDC 89/79 days). A LDC>90 days was observed for 84 patients (37.2%), while pUS in 48 patients (25.7%). After a median follow up time of 17 months, the overall mortality rate was 47.3% (98/226). Table 1 summarizes results. Factors independently related to LDC >90 days were: age (OR1⁄41.047), Charlson Comorbidity Index (CCI)1⁄40 (OR1⁄4 0.428), diagnosis of recurrent BC (OR1⁄4 3.390) and lack of detrusor infiltration at TURBT (OR1⁄4 0.490). Factors related to pUS were: age (RR1⁄41.045) and detrusor infiltration at TURBT (OR1⁄40.307), whereas no relationship was found with LDC (upstaging rate LDC<90 vs >90 days 25.5% vs 26%). OS was independently related to female gender (RR1⁄40.597), CCI>0 (OR1⁄41.377), advanced clinical and pathological staging, and lymph node invasion (OR1⁄42.096), but not to LDC (estimated 2 years OS rate LDC<90 vs >90 days 55% vs 59%). CONCLUSIONS: Elderly and healthier patients with recurrent or clinically NMIBC are more frequently submitted to RC after a longer interval. In daily practice at referral institutions a comprehensive evaluation of the patient could balance known and unknown prognostic factors making negligible the impact of a delay in RC. A threshold of LDC of 90 days seems to affect neither the risk of pUS nor OS and should be discussed in further editions of Guidelines. Source of Funding: None

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.