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Objectives: Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC., Methods: From 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CN + IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes., Results: Of 391 patients, 221 (56.5%) received CN + IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN + IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN., Conclusion: Using a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Radical nephrectomy with inferior vena cava thrombectomy (RN-IVCT) is a complicated procedure for which the impact of hospital case volume on overall survival (OS) is unknown., Objective: To assess the degree to which renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVC-TT) care is centralized and to evaluate the impact of hospital case volume on outcomes following RN-IVCT., Design, Setting, and Participants: The National Cancer Data Base was queried for patients with pT3b-c RCC treated with RN-IVCT. Hospitals were classified by case volume percentile as low (<75th percentile, <0.67 cases annually), intermediate (75th-95th percentile, 0.67-2.99 cases annually), or high (>95th percentile, >3 cases annually)., Outcome Measurements and Statistical Analysis: The primary outcome was OS. Secondary outcomes were short-term (30- and 90-d) mortality rates according to hospital case volume. Kaplan-Meier curves and Cox regression model were used to evaluate OS and the effect of covariables., Results and Limitations: There were 2664 cases of RN-IVCT for pT3b-c tumors reported by 573 institutions, of which 435, 108, and 30 were classified as low, intermediate, and high volume, accounting for 28.5%, 34.5%, and 37% of cases, respectively. Treatment at high-volume institutions was associated with better OS: the median OS was 42, 53, and 60 months for low, intermediate and high-volume centers, respectively (p=0.009). After multivariable adjustment, treatment at a high-volume institution was associated with a 24% relative risk reduction for all-cause mortality compared to treatment at a low-volume institution (hazard ratio 0.76, 95% confidence interval 0.65-0.89; p=0.001). There was no significant difference in short-term mortality following RN-IVCT when stratified by hospital case volume., Conclusions: Higher hospital case volume was associated with longer OS for patients undergoing RN-IVCT. These findings support efforts to centralize care for cases of advanced RCC., Patient Summary: In this study we looked at the impact of hospital case volume on survival following surgery for renal cell carcinoma and inferior vena cava thrombectomy. Survival was significantly better in high-volume hospitals performing three or more procedures per year., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The optimal timing of targeted therapy (TT) initiation for metastatic renal-cell carcinoma (mRCC) is not clear. We used a nationwide cancer registry to determine clinical and social factors associated with delayed TT and to evaluate the association of a delayed approach with overall survival (OS)., Patients and Methods: We performed a retrospective observational study utilizing the National Cancer Data Base from 2006 to 2012 for patients diagnosed with mRCC (clear-cell histology) treated with cytoreductive nephrectomy and TT. Time to initiation of TT was defined as early (within 2 months), moderately delayed (2-4 months), delayed (4-6 months), and late (> 6 months)., Results: Of the 2716 patients included in the analysis, the median (interquartile range) time from diagnosis to initiation of TT was 2.1 (1.3-3.23) months. A total of 1255 patients (46.2%) had early TT, 1072 patients (39.5%) had moderately delayed TT, 284 patients (10.5%) had delayed TT, and 105 patients (3.9%) had late TT. Delay in TT initiation was not independently associated with OS in multivariable analysis. The time interval from diagnosis to TT initiation was not correlated with time from initiation of TT to death (r = 0.04, P = .08)., Conclusion: We found that delayed initiation of TT was not an independent predictor of worse OS. Although this study is subject to limitations of observation study design and selection bias, the results are consistent with the notion that in carefully selected patients, outcomes might not be compromised with initial observation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To characterize the presence of bland (nontumor) thrombus in advanced renal cell carcinoma and assess the impact of this finding on cancer-specific survival., Methods: A multi-institutional database of patients treated with nephrectomy with caval thrombectomy for locally-advanced renal tumors was assembled from 5 tertiary care medical centers. Using clinicopathologic variables including patient age, body mass index, Eastern Cooperative Oncology Group performance status, tumor stage, grade, nodal status and histology, and nearest-neighbor and multiple-matching propensity score matched cohorts of bland thrombus vs nonbland thrombus patients were assessed. Multivariable analysis for predictors of cancer-specific survival was performed., Results: From an initial cohort of 579 patients, 446 met inclusion criteria (174 with bland thrombus, 272 without). At baseline, patients with bland thrombus had significantly worse performance status, higher tumor stage, higher prevalence of regional nodal metastases and higher nuclear grade (P < .01 for all). In both nearest-neighbor and multiple-matching propensity score matched cohorts, the presence of bland thrombus presence was associated with inferior median cancer-specific survival (28.1 months vs 156.8 months, and 28.1 months vs 76.7 months, P < .001 for both). The presence of bland thrombus remained independently associated with an increased risk of cancer-specific mortality on multivariable analysis (hazard ratio 4.33, 95% confidence interval 2.79-6.73, P < .001)., Conclusion: Presence of bland thrombus is associated with adverse survival outcomes in patients treated surgically for renal tumors with venous tumor thrombus. These findings may have important implications in patient counseling, selection for surgery and inclusion in clinical trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: A prospective study of partial vs. radical nephrectomy demonstrated worse overall survival in patients undergoing partial nephrectomy which appeared to be driven by cardiovascular outcomes. We sought to determine if the blood pressures or use of antihypertensive medications differed between patients who underwent partial or radical nephrectomy., Materials and Methods: A tertiary-referral institutional renal mass database was queried for patients between 2006 and 2012 undergoing partial or radical nephrectomy. Serial blood pressure follow-up, clinicopathologic variables, and changes in medications were collected. Patients were excluded for inadequate data, noncurative-intent surgery, noncancer surgical indication, and absence of medication information. Time-dependent hemodynamic changes were compared by split-plot analysis of variance and addition to antihypertensive regimen was studied as time-to-event survival analyses with Kaplan-Meier curves and a Cox proportional hazards model., Results: A final cohort of 264 partial nephrectomy and 130 radical nephrectomy cases were identified. Patients undergoing partial nephrectomy were younger, more likely to have T1 tumors, and had lower preoperative creatinine (P<0.001 for all). No differences were noted on postoperative hemodynamics (P>0.05). Significantly more patients who underwent partial nephrectomy added antihypertensive medications postoperatively (P≤0.001) and surgical treatment remained as a significant independent predictor on Cox regression (hazard ratio = 2.51, P = 0.002). Limitations include the retrospective nature of the study and potential for unidentified confounders., Conclusion: Hemodynamic parameters after radical or partial nephrectomy may be different. The etiology of this observation, is currently unexplored. Additional prospective mechanistic investigations are warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus., Materials and Methods: Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models., Results: A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02)., Conclusions: We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To compare changes in renal function after radical nephrectomy for renal cell carcinoma (RCC) and radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), and assess their effects on non-cancer-specific mortality (CSM)., Methods: Clinicopathologic data from 1114 patients with RCC or UTUC treated surgically from 1997 to 2013 were compiled. Patients who underwent nephron-sparing surgeries, had bilateral disease, received chemotherapy, or had <1 month of follow-up were excluded. Renal function (estimated glomerular filtration rate [eGFR]) was calculated preoperatively, 3 months postoperatively, and at last follow-up. Events were defined as ≥25% decline in eGFR from baseline. Event-free survival and non-CSM were assessed using Kaplan-Meier analysis. Multivariable Cox regression was performed to identify predictors of events., Results: Four hundred thirty-five patients were included (317 radical nephrectomy, 118 radical nephroureterectomy). Median follow-up was 38.2 months. UTUC patients were older (P < .001), had worse Charlson score (P < .001), and more frequently used tobacco (P = .006). Median baseline eGFR was lower in UTUC patients (58.4 vs 74.9, P < .001). RCC patients experienced a larger event rate following surgery at first (56.8% vs 31.4%, P < .001) and last (51.7% vs 35.6%, P = .003) follow-up than UTUC patients. On Kaplan-Meier analysis, UTUC patients exhibited worse non-CSM (P < .001). Postsurgical decline in renal function was a significant predictor of non-CSM in RCC patients at first (hazard ratio = 4.71, P = .041) and last (hazard ratio = 4.56, P = .018) follow-up, whereas this was not the case for UTUC patients., Conclusion: UTUC patients had worse baseline eGFR and overall health status than RCC patients. RCC patients experienced greater postsurgical declines in renal function. These results shed light on differences in patient characteristics between these forms of kidney cancer and guide expectations for postoperative renal function., (Copyright © 2016 Elsevier Inc. All rights reserved.)