The role of warm ischemia time on functional outcomes after robotic partial nephrectomy: a radionuclide renal scan study from the clock randomized trial.

PURPOSE: To evaluate the relationship between warm ischemia time (WIT) duration and renal function after robot-assisted partial nephrectomy (RAPN). METHODS: The CLOCK trial is a phase 3 randomized controlled trial comparing on- vs off-clamp RAPN. All patients underwent pre- and postoperative renal scintigraphy. Six-month absolute variation of eGFR (AV-GFR), rate of relative variation in eGFR over 25% (RV-GFR > 25), absolute variation of split renal function (SRF) at scintigraphy (AV-SRF). The relationships WIT/outcomes were assessed by correlation graphs and then modeled by uni- and multivariable regression. RESULTS: 324 patients were included (206 on-clamp, 118 off-clamp RAPN). Correlation graphs showed a threshold on WIT equal to 10 min. The differences in outcome measures between cases with WIT < vs ≥ 10 min were: AV-GFR - 3.7 vs - 7.5 ml/min (p < 0.001); AV-SRF - 1% vs - 3.6% (p < 0.001); RV-GFR > 25 9.3% vs 17.8% (p = 0.008). Multivariable models found that AV-GFR was related to WIT ≥ 10 min (regression coefficient [RC] - 0.52, p = 0.019), age (RC - 0.35, p = 0.001) and baseline eGFR (RC - 0.30, p < 0.001); RV-GFR > 25 to WIT ≥ 10 min (odds ratio [OR] 1.11, p = 0.007) and acute kidney injury defined as > 50% increase in serum creatinine (OR 19.7, p = 0.009); AV-SRF to WIT ≥ 10 min (RC - 0.30, p = 0.018), baseline SRF (RC - 0.76, p < 0.001) and RENAL score (RC - 0.60. p = 0.028). The main limitation was that the CLOCK trial was designed on a different endpoint and therefore the present analysis could be underpowered. CONCLUSIONS: Up to 10 min WIT had no consequences on functional outcomes. Above the 10-min threshold, a statistically significant, but clinically negligible impact was found.

External validation of yonsei nomogram predicting chronic kidney disease development after partial nephrectomy: An international, multicenter study.

OBJECTIVE: To externally validate Yonsei nomogram. METHODS: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis. RESULTS AND LIMITATION: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study. CONCLUSIONS: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.

Is off-clamp robot-assisted partial nephrectomy beneficial for renal function? Data from the CLOCK trial.

OBJECTIVES: To compare the functional outcomes of on- vs off-clamp robot-assisted partial nephrectomy (RAPN) within a randomized controlled trial (RCT). MATERIALS AND METHODS: The CLOCK study (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy; NCT02287987) is a multicentre RCT including patients with normal baseline function, two kidneys and masses with RENAL scores ≤ 10. Pre- and postoperative renal scintigraphy was prescribed. Renal defatting and hilum isolation were required in both study arms; in the on-clamp arm, ischaemia was imposed until the completion of medullary renorraphy, while in the off-clamp condition it was not allowed throughout the procedure. The primary endpoint was 6-month absolute variation in estimated glomerular filtration rate (AV-GFR); secondary endpoints were: 12, 18 and 24-month AV-GFR; 6-month estimated glomerular filtration rate variation >25% rate (RV-GFR >25); and absolute variation in ipsilateral split renal function (AV-SRF). The planned sample size was 102 + 102 cases, after taking account crossover of cases to the alternate study arm; a 1:1 randomization was performed. AV-GFR and AV-SRF were compared using analysis of covariation, and RV-GFR >25 was assessed using multivariable logistic regression. Intention-to-treat (ITT) and per-protocol analyses (PP) were performed. RESULTS: A total of 160 and 164 patients were randomly assigned to on- and off-clamp RAPN, respectively; crossover was observed in 14% and 43% of the on- and off-clamp arms, respectively. We were unable to find any statistically significant difference between on- vs off-clamp with regard to the primary endpoint (ITT: 6-month AV-GFR -6.2 vs -5.1 mL/min, mean difference 0.2 mL/min, 95% confidence interval [CI] -3.1 to 3.4 [P = 0.8]; PP: 6-month AV-GFR -6.8 vs -4.2 mL/min, mean difference 1.6 mL/min, 95% CI -2.3 to 5.5 [P = 0.7]) or with regard to the secondary endpoints. The median warm ischaemia time was 14 vs 15 min in the ITT analysis and 14 vs 0 min in the PP analysis. CONCLUSION: In patients with regular baseline function and two kidneys, we found no evidence of differences in functional outcomes for on- vs off-clamp RAPN.

External validation of the Palacios' equation: a simple and accurate tool to estimate the new baseline renal function after renal cancer surgery.

PURPOSE: To externally validate the Palacios' equation estimating the new baseline glomerular filtration rate (NB-GFR) after partial or radical-nephrectomy (PN, RN) for Renal cancer carcinoma (RCC). MATERIALS AND METHODS: Our research group recently published two studies that investigated the association between renal function and cancer-specific survival in RCC. The first one included 3457 patients undergone RN or PN for a cT1-2 RCC coming from five high-volume centers; the second one considered 1767 patients undergone RN or PN for a cT1-4 RCC in a single high-volume center. From such datasets, available complete patients' data were used to calculate the predicted NB-GFR through the Palacios' equation: predicted NB-GFR = 35.03 + 0.65 ∙ preoperative GFR - 18.19 ∙ (if radical nephrectomy) - 0.25 ∙ age + 2.83 ∙ (if tumor size > 7 cm) - 2.09 ∙ (if diabetes). The observed NB-GFR was calculated by the CKD-EPI equation on serum creatinine at 3-12 months after surgery. Concordance between observed and predicted NB-GFR was evaluated by Lin's concordance correlation coefficient and Bland-Altman analysis. RESULTS: 2419 patients were included (1210, cohort #1; 1219, cohort #2). The median observed NB-GFR value in cohorts #1 and #2 was 73.0 ml/min/1.73 m2 (IQR 56.1-90.1) and 64.2 ml/min/1.73 m2 (IQR 49.6-83); the median predicted NB-GFR was 71.1 ml/min/1.73 m2 (IQR 58-81.5) and 62.6 ml/min/1.73m2 (IQR 47.9-75.9). The concordance line showed a slope of 0.80 and 0.86, and an intercept at 11.02 and 5.41 ml/min/1.73 m2 in the cohort#1 and #2, respectively. The Palacio's equation moderately over-estimated and under-estimated NB-GFR, for values below and above the cut-off of 50 ml/min/1.73 m2 and 35 ml/min/1.73m2 in cohort#1 and #2. The Lin's concordance correlation coefficient was 0.79 (95% CI 0.77-0.81) and 0.83 (95% CI 0.82-0.85). CONCLUSIONS: We confirm the predictive performances of Palacios' equation, supporting its utilization in clinical practice.

Impact of Resection Technique on Perioperative Outcomes and Surgical Margins after Partial Nephrectomy for Localized Renal Masses: A Prospective Multicenter Study.

PURPOSE: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury). MATERIALS AND METHODS: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement. RESULTS: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement. CONCLUSIONS: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.

Safety of on- vs off-clamp robotic partial nephrectomy: per-protocol analysis from the data of the CLOCK randomized trial.

PURPOSE: To compare the safety of on- vs off-clamp robotic partial nephrectomy (RAPN). METHODS: 302 patients with RENAL masses ≤ 10 were randomized to undergo on-clamp (150) vs off-clamp (152) RAPN (CLOCK trial-ClinicalTrials.gov NCT02287987) at seven institutions by one experienced surgeon per institution. Intra-operative data, complications, and positive surgical margins were compared. RESULTS: Due to a relevant rate of shift from the assigned treatment, the per-protocol analysis only was considered and the data from 129 on-clamp vs 91 off-clamp RAPNs analyzed. Tumor size (off-clamp vs on-clamp, 2.2 vs 3.0 cm, p < 0.001) and RENAL score (5 vs 6, p < 0.001) significantly differed. At univariate analysis, no differences were found regarding intra-operative estimated blood loss (off- vs on-clamp, 100 vs 100 ml, p = 0.7), post-operative complications rate (19% vs 26%, p = 0.2), post-operative anemia (Hb decrease > 2.5 g/dl 26% vs 27%, p = 0.9; transfusion rate 3.4% vs 6.3%, p = 0.5; re-intervention due to bleeding 1.1% vs 4%, p = 0.4), acute kidney injury (4% vs 6%, p = 0.8), and positive surgical margins (3.5% vs 8.2%, p = 0.1). At multivariate analysis accounting for tumor diameter and complexity, considering the on-clamp group as the reference category, a significant difference was noted in the off-clamp group exclusively for blood loss (OR 0.3, 95% CI 0.09-0.52, p = 0.008). CONCLUSIONS: The on-clamp and off-clamp approaches for RAPN showed a comparable safety profile.

Partial versus radical nephrectomy in very elderly patients: a propensity score analysis of surgical, functional and oncologic outcomes (RESURGE project).

PURPOSE: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor. PATIENTS AND METHODS: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM). RESULTS: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis. CONCLUSIONS: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

Predictors of the Transition from Off to On Clamp Approach during Ongoing Robotic Partial Nephrectomy: Data from the CLOCK Randomized Clinical Trial.

PURPOSE: We sought to identify predictive factors of the transition from off clamp to on clamp robotic partial nephrectomy following an intraoperative decision. MATERIALS AND METHODS: In the multicenter, randomized, prospective CLOCK (CLamp vs Off Clamp the Kidney during robotic partial nephrectomy) trial 152 and 149 of the 301 patients with a localized renal mass were assigned to undergo off clamp and on clamp robotic partial nephrectomy, respectively. Surgery was done at a total of 7 referral institutions by 1 surgeon per institution. A localized renal mass was defined as having a R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior, location relative to polar lines, hilar) score less than 10. Surgeons had similar experience with at least 100 previous robotic partial nephrectomies. All patients underwent a preoperative and a 6-month renal scan. The current study deals with one of the secondary end points of the trial, comparing cases finalized as clampless (off robotic partial nephrectomy group) with those which were converted (shift robotic partial nephrectomy group). RESULTS: Of the 152 patients randomized to off clamp 61 (40%) were shifted to clamp with a median ischemia time of 15 minutes. In the shift robotic partial nephrectomy group the masses were larger (3.5 vs 2.2 cm) and more complex (R.E.N.A.L. score 7 vs 6). A significant association with transition was found for tumor diameter (OR 1.4) and the R.E.N.A.L. score continuously (OR 1.4) and when recoded in groups, including 4-no risk (referent OR 1), 5-6-low risk (OR 1.8), 7-8-intermediate risk (OR 3.6) and 9 or greater-high risk (OR 6.6). The shift robotic partial nephrectomy group had longer operative time, higher blood loss and increased performance of 2-layer renorrhaphy. No significant differences were noted in postoperative complications or renal function after 6 months. CONCLUSIONS: The transition from off to on clamp robotic partial nephrectomy is associated with renal mass diameter and complexity. Under the specific conditions of the current trial no harm was related to this decision.

Elective Nephron Sparing Surgery Decreases Other Cause Mortality Relative to Radical Nephrectomy Only in Specific Subgroups of Patients with Renal Cell Carcinoma.

PURPOSE: There is no consensus regarding a protective effect on mortality due to a cause other than cancer in patients treated with elective nephron sparing surgery relative to their radical nephrectomy counterparts. We test whether the protective effect of nephron sparing surgery relative to radical nephrectomy is universal or present in specific subgroups of patients. MATERIALS AND METHODS: A collaborative database of 5 institutions was queried to evaluate 1,783 patients without chronic kidney disease diagnosed with a clinical T1 renal mass that was treated with nephron sparing surgery or radical nephrectomy. Multivariable Cox regression analysis was done to assess the impact of surgery type (nephron sparing surgery vs radical nephrectomy) on other cause mortality after adjustment for patient and cancer characteristics. Interaction terms were used to test the hypothesis that the impact of surgery type varies according to specific subcohorts of patients. RESULTS: Ten-year other cause mortality-free survival rates were 90% and 88% after nephron sparing surgery and radical nephrectomy, respectively. In the overall population radical nephrectomy was not associated with an increased risk of other cause mortality on multivariable analysis compared to nephron sparing surgery (HR 0.91, 95% CI 0.6-1.38, p = 0.6). However, radical nephrectomy increased the risk of other cause mortality according to the increasing baseline Charlson comorbidity index (interaction test p = 0.0008). For example, in a patient with a Charlson comorbidity index of 4 the probability of 10-year other cause mortality-free survival was 86% after nephron sparing surgery and 60% after radical nephrectomy. CONCLUSIONS: Elective nephron sparing surgery does not improve other cause survival relative to radical nephrectomy consistently in all patients with kidney cancer. Patients who are more ill with relevant comorbidities are those who benefit the most from nephron sparing surgery in terms of other cause mortality.

Features, risk factors and clinical outcome of "very late" recurrences after surgery for localized renal carcinoma: A retrospective evaluation of a cohort with a minimum of 10 years of follow up.

OBJECTIVE: To evaluate the features and the predictors of "very late" recurrences after surgery for localized renal cell carcinoma. METHODS: Since 1983, an institutional database with data of more than 2300 consecutive patients treated for renal cancer has been prospectively maintained. Patients N0 /Nx M0 followed for a minimum of 10 years without recurrences were retrieved. The site, time and treatment of recurrences observed afterwards were recorded, and the predictors were investigated by Cox regression analysis. RESULTS: A total of 554 patients (231 women, 323 men; age 59.3 ± 11.6 years) followed for a mean/median time of 15.1/13.6 years (range 10.0-34.1 years) were analyzed. A recurrence was observed in 26 patients (4.6%) after a mean/median interval of 13.3/12.3 years (range 10.5-30.2 years). The pathological stage 2/3 was the only independent predictor of recurrence (P = 0.003), and it was related also to the latency of recurrence (mean/median latency 15.4/14.0, 11.4/10.8 and 12.5/12.0 years, respectively, for stage 1, 2 and 3; P < 0.005 for stage 1 vs stage 2 or 3). The contralateral kidney was the most frequent site of relapse in patients with stage pT1, whereas multiple sites were more frequent for stage pT2 and pT3. CONCLUSIONS: The risk of a "very late" recurrence of renal cancer is approximately 5%, and it depends on the pathological stage. For stage pT1, the kidney/s should be surveilled for indefinite time, preferably by ultrasound to reduce the X-ray exposition; for stage pT2 and pT3, the abdomen and the lungs should be monitored, by computed tomography scan during the first years, and then by abdominal ultrasound and chest X-ray.

Venous tumor thrombus consistency is not predictive of survival in patients with renal cell carcinoma: A retrospective study of 147 patients.

OBJECTIVES: To evaluate the prognostic role of venous tumor thrombus consistency in patients with renal cell carcinoma. METHODS: A retrospective evaluation of the data of patients with renal cell carcinoma and a tumor thrombosis submitted to surgery from 2000 to 2013 was carried out. Histological slides were revised by two uropathologists, blinded of the clinical outcome, to assess venous tumor thrombus consistency classified as solid venous tumor thrombus consistency or friable venous tumor thrombus consistency. The statistical correlation between venous tumor thrombus consistency and other adverse features was assessed. Then the predictive ability of an integrated prognostic model, generated by Cox regression and random survival forest, was evaluated, with and without the inclusion of venous tumor thrombus consistency, by integrated Brier score, dynamic receiver operating characteristic curves, integrated discrimination improvement index and category-less net reclassification index. RESULTS: The data of 147 patients were analyzed, 79 with a solid venous tumor thrombus consistency and 68 with a friable venous tumor thrombus consistency, followed for a median period of 40.5 months. Venous tumor thrombus consistency was assessed with a high interobserver agreement (145/147 cases). The presence of a friable venous tumor thrombus consistency was associated with some adverse prognostic factors (symptoms, lymphnodal and distant metastasis, larger tumor diameter, higher cephalad thrombosis level, necrosis, microvascular invasion) and to a worse cancer-specific and overall survival at univariate analysis. However, venous tumor thrombus consistency was not predictive of survival, and did not improve the performance of a multivariable model that included a set of informative predictors. CONCLUSION: Venous tumor thrombus consistency does not seem to have an independent prognostic role in patients with renal cell carcinoma.

The IRON Study: Investigation of Robot-assisted Versus Open Nephron-sparing Surgery.

Background: Current literature does not provide large-scale data regarding clinical outcomes of robot-assisted (RAPN) versus open (OPN) partial nephrectomy. Moreover, data assessing predictors of long-term oncologic outcomes after RAPN are scarce. Objective: To compare perioperative, functional, and oncologic outcomes of RAPN versus OPN, and to investigate the predictors of oncologic outcomes after RAPN. Design setting and participants: This study included 3467 patients treated with OPN (n = 1063) or RAPN (n = 2404) for a single cT1-2N0M0 renal mass from 2004 to 2018 at nine high-volume European, North American, and Asian institutions. Outcome measurements and statistical analysis: The study outcomes were short-term postoperative, functional, and oncologic outcomes. Regression models investigated the effect of surgical approach (open vs Robot assisted) on study outcomes, and interaction tests were used for subgroup analyses. Propensity score matching for demographic and tumor characteristics was used in sensitivity analyses. Multivariable Cox-regression analyses identified predictors of oncologic outcomes after RAPN. Results and limitations: Baseline characteristics were similar between patients receiving RAPN and OPN, with only few differences. After adjusting for confounding, RAPN was associated with lower odds of intraoperative (odds ratio [OR]: 0.39, 95% confidence interval [CI]: 0.22, 0.68) and Clavien-Dindo ≥2 postoperative (OR: 0.29, 95% CI: 0.16, 0.50) complications (both p < 0.05). This association was not affected by comorbidities, tumor dimension, PADUA score, or preoperative renal function (all p > 0.05 on interaction tests). On multivariable analyses, we found no differences between the two techniques with respect to functional and oncologic outcomes (all p > 0.05). Overall, there were 63 and 92 local recurrences and systemic progressions, respectively, with a median follow-up after surgery of 32 mo (interquartile range: 18, 60). Among patients receiving RAPN, we assessed predictors of local recurrence and systemic progression with discrimination accuracy (ie, C-index) that ranged from 0.73 to 0.81. Conclusions: While cancer control and long-term renal function did not differ between RAPN and OPN, we found that the intra- and postoperative morbidity-especially in terms of complications-was lower after RAPN than after OPN. Our predictive models allow surgeons to estimate the risk of adverse oncologic outcomes after RAPN, with relevant implications for preoperative counseling and follow-up after surgery. Patient summary: In this comparative study on robotic versus open partial nephrectomy, functional and oncologic outcomes were similar between the two techniques, with lower morbidity-especially in terms of complications-for robot-assisted surgery. The assessment of prognosticators for patients receiving robot-assisted partial nephrectomy may help in preoperative counseling and provides relevant data to tailor postoperative follow-up.

A Nomogram for the Prediction of Intermediate Significant Renal Function Loss After Robot-assisted Partial Nephrectomy for Localized Renal Tumors: A Prospective Multicenter Observational Study (RECORd2 Project).

BACKGROUND: Robot-assisted partial nephrectomy (RAPN) is increasingly adopted for the treatment of localized renal tumors; however, rates and predictors of significant renal function (RF) loss after RAPN are still poorly investigated, especially at a long-term evaluation. OBJECTIVE: To analyze the predictive factors and develop a clinical nomogram for predicting the likelihood of ultimate RF loss after RAPN. DESIGN, SETTING, AND PARTICIPANTS: We prospectively evaluated all patients treated with RAPN in a multicenter series (RECORd2 project). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Significant RF loss was defined as >25% reduction in estimated glomerular filtration rate (eGFR) from preoperative assessment at 48th month follow-up after surgery. Uni- and multivariable logistic regression analyses for RF loss were performed. The area under the receiving operator characteristic curve (AUC) was used to quantify predictive discrimination. A nomogram was created from the multivariable model. RESULTS AND LIMITATIONS: A total of 981 patients were included. The median age at surgery was 64.2 (interquartile range [IQR] 54.3-71.4) yr, and 62.4% of patients were male. The median Charlson Comorbidity Index (CCI) was 1 (IQR 0-2), 12.9% of patients suffered from diabetes mellitus, and 18.6% of patients showed peripheral vascular disease (PVD). The median Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score was 7 (IQR 7-9). Imperative indications to partial nephrectomy were present in 3.6% of patients. Significant RF loss at 48th month postoperative evaluation was registered in 108 (11%) patients. At multivariable analysis, age (p = 0.04), female gender (p < 0.0001), CCI (p < 0.0001), CCI (p < 0.0001), diabetes (p < 0.0001), PVD (p < 0.0001), eGFR (p = 0.02), imperative (p = 0.001) surgical indication, and PADUA score (p < 0.0001) were found to be predictors of RF loss. The developed nomogram including these variables showed an AUC of 0.816. CONCLUSIONS: We developed a clinical nomogram for the prediction of late RF loss after RAPN using preoperative and surgical variables from a large multicenter dataset. PATIENT SUMMARY: We developed a nomogram that could represent a clinical tool for early detection of patients at the highest risk of significant renal function impairment after robotic conservative surgery for renal tumors.

Impact of Metastasectomy on Cancer Specific and Overall Survival in Metastatic Renal Cell Carcinoma: Analysis of the REMARCC Registry.

BACKGROUND: Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group. METHODS: Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group. RESULTS: Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P < .001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups. CONCLUSIONS: Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.

Predictors of Positive Surgical Margins after Robot-Assisted Partial Nephrectomy for Localized Renal Tumors: Insights from a Large Multicenter International Prospective Observational Project (The Surface-Intermediate-Base Margin Score Consortium).

Background: To explore predictors of positive surgical margins (PSM) after robotic partial nephrectomy (PN) in a large multicenter international observational project, harnessing the Surface-Intermediate-Base (SIB) margin score to report the resection technique after PN in a standardized way. Methods: Data from consecutive patients with cT1-2N0M0 renal masses treated with PN from September 2014 to March 2015 at 16 tertiary referral centers and included in the SIB margin score International Consortium were prospectively collected. For the present study, only patients treated with robotic PN were included. Uni- and multivariable analysis were fitted to explore clinical and surgical predictors of PSMs after PN. Results: Overall, 289 patients were enrolled. Median (IQR) preoperative tumor size was 3.0 (2.3−4.2) cm and median (IQR) PADUA score was 8 (7−9). SIB scores of 0−2 (enucleation), 3−4 (enucleoresection) and 5 (resection) were reported in 53.3%, 27.3% and 19.4% of cases, respectively. A PSM was recorded in 18 (6.2%) patients. PSM rate was 4.5%, 11.4% and 3.6% in case of enucleation, enucleoresection and resection, respectively. Patients with PSMs had tumors with a higher rate of contact with the urinary collecting system (55.6% vs. 27.3%; p < 0.001) and a longer median warm ischemia time (22 vs. 16 min; p = 0.02) compared with patients with negative surgical margins, while no differences emerged between the two groups in terms of other tumor features (i.e., pathological diameter, PADUA score). In multivariable analysis, only enucleoresection (SIB score 3−4) versus enucleation (SIB score 0−2) was found to be an independent predictor of PSM at final pathology (HR: 2.68; 95% CI: 1.25−7.63; p = 0.04), while resection (SIB score 5) was not. Conclusions: In our experience, enucleoresection led to a higher risk of PSMs as compared to enucleation. Further studies are needed to assess the differential impacts of resection technique and surgeon's experience on margin status after robotic PN.

Impact of Trifecta definition on rates and predictors of "successful" robotic partial nephrectomy for localized renal masses: results from the Surface-Intermediate-Base Margin Score International Consortium.

BACKGROUND: Over the years, five different Trifecta score definitions have been proposed to optimize the framing of "success" in partial nephrectomy (PN) field. However, such classifications rely on different metrics. The aim of the present study was to explore how the success rate of robotic PN, as well as its drivers, vary according to the currently available definitions of Trifecta. METHODS: Data from consecutive patients with cT1-2N0M0 renal masses treated with robotic PN at 16 referral centers from September 2014 to March 2015 were prospectively collected. Trifecta rate was defined for each of the currently available definitions. Multivariable logistic regression analysis was used to evaluate possible predictors of "Trifecta failure" according to the different adopted formulation. RESULTS: Overall, 289 patients met the inclusion criteria. Among the definitions, Trifecta rates ranged between 66.4% and 85.9%. Multivariable analysis showed that predictors for "Trifecta failure" were mainly tumor-related (i.e. tumor's nephrometry) for those Trifecta scores relying on WIT as a surrogate metric for postoperative renal function deterioration (definitions 1,2), while mainly surgery-related (i.e. ischemia time and excision strategy) for those including the percentage change in postoperative eGFR as the functional cornerstone of Trifecta (definitions 3-5). CONCLUSIONS: There was large variability in rates and predictors of "unsuccessful PN" when using different Trifecta scores. Further research is needed to improve the value of the Trifecta metrics, integrating them into routine patient counseling and standardized assessment of surgical quality across institutions.

Impact of surgical approach and resection technique on the risk of Trifecta Failure after partial nephrectomy for highly complex renal masses.

INTRODUCTION: We aimed to compare the outcomes of open vs robotic partial nephrectomy (PN), focusing on predictors of Trifecta failure in patients with highly complex renal masses. PATIENTS AND METHODS: We queried the prospectively collected database from the SIB International Consortium, including 507 consecutive patients with cT1-2N0M0 renal masses treated at 16 high-volume referral centres, to select those with highly complex (PADUA score ≥10) tumors undergoing PN. RT was classified as enucleation, enucleoresection or resection according to the SIB score. Trifecta was defined as achievement of negative surgical margins, no acute kidney injury and no Clavien-Dindo grade ≥2 postoperative surgical complications. Multivariable logistic regression analysis was used to assess independent predictors of Trifecta failure. RESULTS: 113 patients were included. Patients undergoing open PN (n = 47, 41.6%) and robotic PN (n = 66, 58.4%) were comparable in baseline characteristics. RT was classified as enucleation, enucleoresection and resection in 46.9%, 34.0% and 19.1% of open PN, and in 50.0%, 40.9% and 9.1% of robotic PN (p = 0.28). Trifecta was achieved in significantly more patients after robotic PN (69.7% vs. 42.6%, p = 0.004). On multivariable analysis, surgical approach (open vs robotic, OR: 2.62; 95%CI: 1.11-6.15, p = 0.027) and tumor complexity (OR for each additional unit of the PADUA score: 2.27; 95%CI: 1.27-4.06, p = 0.006) were significant predictors of Trifecta failure, while RT was not. The study is limited by lack of randomization; as such, selection bias and confounding cannot be entirely ruled out. CONCLUSIONS: Tumor complexity and surgical approach were independent predictors of Trifecta failure after PN for highly complex renal masses.