Leibovich, Bradley C.

Objectives To evaluate the peri‐operative and renal functional outcomes of patients undergoing synchronous bilateral partial nephrectomy (PN) or percutaneous cryoablation (PCA). Patients and Methods We retrospectively reviewed our institutional nephrectomy and renal mass ablation registries to identify all patients with synchronous bilateral renal masses who underwent simultaneous bilateral PN ( n = 76) or PCA ( n = 13) between 1974 and 2013. Changes in estimated glomerular filtration rate (eGFR) as well as peri‐operative complications are descriptively reported for each procedure. Results The number of treated renal masses in the 76 patients in the PN group and the 13 patients in the PCA group was 249 and 28, respectively. The median (interquartile range [IQR]) age at treatment was 62 (50, 71) years for the PN group and 67 (56, 72) for the PCA group. The median (IQR) maximum tumour sizes were 4.6 (3.4, 6.5) cm and 2.6 (2.4, 3.2) cm for the PN and PCA groups, respectively. The median (IQR) length of hospital stay was 7 (5, 8) days for the PN group and 1 (1, 10) days for the PCA group. The median (IQR) change in eGFR from baseline to discharge was −32 (−46, −15)% for the PN group and −17% (−33, −3) for the PCA group. By 3 months, median (IQR) renal function improved, with changes of −9 (−19, 0)% and −8 (−11, 15)%, respectively, compared with baseline. No patient in either group required renal replacement therapy in the peri‐operative period. Early postoperative complications (within 30 days) occurred in 16 patients (21.6%) in the PN and four patients in the PCA group. In particular, angioembolization for bleeding was required in the postoperative period in two patients (2.7%) in the PN and one patient in the PCA group. Conclusions Our experience suggests that synchronous bilateral PN or PCA are feasible treatment options for select patients presenting with bilateral renal masses. In select cases, both approaches appear to have reasonable rates of peri‐operative complications and effects on renal function.

704 Background: While the probability of benign versus malignant histology based on renal tumor size has been described, this alone does not sufficiently inform decision-making in the modern era since indolent malignant tumors can be surveilled. Thus, we sought to characterize the probability of indolent versus aggressive histology based on radiographic tumor size. Methods: We evaluated patients who underwent radical or partial nephrectomy at Mayo Clinic for a pT1-2, pNx/0, M0 solid renal tumor between 1990-2010. Pathology was reviewed by one genitourinary pathologist. Benign tumors, low grade (1-2) clear cell and papillary renal cell carcinoma (RCC), and any chromophobe, clear cell papillary, mucinous tubular and spindle cell, SDH-B deficient, and tubulocystic RCC were considered indolent. All other histologies were considered aggressive, as were any malignancies with necrosis or sarcomatoid differentiation. Cancer-specific survival (CSS) was estimated using the Kaplan Meier method. Logistic regression models were used to estimate the probability of malignant and aggressive histology based on tumor size. Sex-stratified analyses were also performed. Results: Of the 2650 patients included, there were 1773 patients with indolent tumors (303 benign; 1470 malignant) and 877 with aggressive tumors. Ten-year CSS was 96% for indolent malignant tumors and 82% for aggressive tumors. The predicted probabilities of any malignant histology and aggressive malignant histology increased with tumor size (Table; 1-7cm point estimates shown). For example, a 3 cm tumor had an 87% probability of malignancy and a 27% probability of being aggressive. For any given tumor size, men had a greater probability of aggressive histology than women. Conclusions: We present tumor size-based estimates of the probability of aggressive histology for renal masses. This information should be useful for patient counseling and treatment decision-making. [Table: see text]

703 Background: Clinical and pathologic factors alone have limited prognostic ability in patients with metastatic clear cell renal cell carcinoma (ccRCC). We sought to determine if tissue biomarkers, along with our previously reported clinical metastases score, can be used to predict cancer specific survival (CSS) in patients with metastatic ccRCC. Methods: Patients with metastatic ccRCC who underwent nephrectomy between 1990-2004 were identified using the Mayo Clinic Nephrectomy Registry. Sections from paraffin-embedded primary tumor tissue blocks were used for immunohistochemistry staining for PD-1, B7-H1 (PD-L1), B7-H3, Bim (downstream pro-apoptotic signaling molecule in PD-1 pathway), CA-IX, IMP3, Ki67, and survivin. CSS was the primary outcome. Biomarkers that were significantly associated with CSS after adjusting for the metastases score were used to develop a biomarker-specific multivariable model using a bootstrap resampling approach and forward selection. Predictive ability was summarized using a bootstrap-corrected c-index. Results: The cohort included 602 patients, 192 (32%) with metastases at diagnosis and 410 (68%) who developed metastases after nephrectomy. Median follow-up among survivors was 9.6 years (IQR 4.2,12.8) and 504 patients died of RCC. Bim, IMP3, Ki67, and survivin expression were significantly associated with CSS after adjusting for the metastases score and were used to develop a biomarker-specific model. High Bim (HR 1.44; 95%CI 1.16-1.78; p < 0.001), high survivin (HR 1.35; 95%CI 1.08-1.68; p = 0.008), and the metastases score (HR 1.13 per one point; 95%CI 1.10-1.16; p < 0.001) were retained as independent predictors in the final multivariable model (c-index 0.69). Conclusions: We created a prognostic model combining the clinical metastases score and two primary tissue expression biomarkers, Bim and survivin, for patients with metastatic RCC who underwent nephrectomy. External validation will be required prior to clinical use.

672 Background: The optimal sequence of cytoreductive nephrectomy (CN) and targeted therapy (TT) for patients with metastatic renal cell carcinoma (mRCC) remains to be established. Herein, we compared overall survival (OS) between patients with mRCC receiving initial CN with or without subsequent TT versus initial TT with or without subsequent CN. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed between 2006-2013 with RCC that was metastatic at diagnosis who received CN, TT, or both. Those with other prior cancer history were excluded. The cumulative incidence of receiving TT after CN and CN after TT were evaluated, with death prior to second treatment as a competing risk. To account for treatment selection bias, inverse probability of treatment weighting (IPTW) was performed based on the propensity to receive initial CN or TT. OS from diagnosis was compared using Cox regression. Sensitivity analyses were performed. Results: The cohort included 15,068 patients, of whom 6,731 underwent initial CN and 8,337 underwent initial TT. At 6 months from diagnosis, the probability of receiving TT after CN was 46.2%, with 13.6% of patients having died after initial CN prior to receiving TT. Meanwhile, the probability at 6 months of undergoing CN after initial TT was 4.4%, with 38.3% of this group having died prior to undergoing CN. In the IPTW analysis, baseline characteristics were balanced (standardized difference < 0.1). Initial CN was associated with improved OS compared to initial TT (median 16.5 vs 9.2 months; HR 0.62; 95%CI 0.61-0.64; p < 0.001). Findings were similar in all sensitivity analyses (propensity score matching and adjustment; regression adjustment; 6-month landmark analysis; clear cell mRCC subset; exclusion of patients who had metastasectomy). Conclusions: Although initial CN was associated improved OS versus initial TT in this national dataset, initial CN was associated with delays in, and even death prior to, receipt of TT. As such, while the survival data here support initial CN in appropriate surgical candidates, continued efforts to develop the optimal multimodal approach to these patients are warranted.

Our objective was to evaluate the role of retroperitoneal lymph node dissection ( LND ) in non‐metastatic (M0) and metastatic (M1) renal cell carcinoma ( RCC ). We searched Medline, EMBASE , Web of Science and Scopus from database inception to 29 August 2017 for studies of patients who underwent partial or radical nephrectomy for M0 or M1 RCC . Two investigators independently selected studies for inclusion. Risk of bias was assessed using the Newcastle–Ottawa scale, Cochrane Collaboration tool and National Heart, Lung and Blood Institute Quality Assessment Tool. Random effects meta‐analysis was performed for all‐cause‐mortality. The GRADE approach was used to characterize quality of evidence. A total of 51 unique studies were included in the qualitative systematic review. Risk of bias was low in 41/51 (80%) studies. LND was not associated with all‐cause mortality in either M0 (hazard ratio [ HR ] 1.02, 95% confidence interval [ CI ] 0.92–1.12; I 2 = 0%; four studies), M1 ( HR 1.04, 95% CI 0.83–1.29; I 2 = 0%; two studies), or pooled M0 and M1 settings ( HR 1.00, 95% CI 0.92–1.09; I 2 = 0%; seven studies), with no statistically significant differences according to M stage subgroups ( P = 0.50). In the three studies that examined M0 subgroups with a high risk of nodal metastasis, LND was not associated with improved oncological outcomes. Studies on the association of extent of LND with survival reported inconsistent results. Meanwhile, a small proportion of patients with pN 1M0 disease demonstrate durable long‐term oncological control after surgery, with 10‐year cancer‐specific survival of 21–31%. Nodal involvement is independently associated with adverse prognosis in both M0 and M1 settings. GRADE quality of evidence was moderate or low for the outcomes examined. Although LND yields independent prognostic information, the existing literature does not support a therapeutic benefit to LND in either M0 or M1 RCC . High‐risk M0 patient groups warrant further study, as a subset of patients with isolated nodal metastases experience long‐term survival after surgical resection.