Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma

Background: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. Objective: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. Design, setting, and participants: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). Outcome measurements and statistical analysis: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. Results and limitations: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. Conclusions: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. Patient summary: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications

MP14-07 PERFORMANCE OF A NEW RISK ASSESSMENT TOOL FOR PATIENTS WITH METASTATIC RENAL CELL CARCINOMA UNDERGOING CYTOREDUCTIVE NEPHRECTOMY IN THE TARGETED THERAPY ERA: REMARCC SCORE

NTRODUCTION AND OBJECTIVE: In metastatic renal cell carcinoma (mRCC), the use of upfront cytoreductive nephrectomy (CN) has become controversial due to the outcomes of two randomized controlled trials (CARMENA/SURTIME). The objective of the current study was to examine overall survival (OS) and identify risk factors associated with patients not benefiting from CN in the targeted therapy era. METHODS: A purpose built multi-institutional international database (REgistry of MetAstatic RCC- REMARCC project) was used for this retrospective analysis. Patients with diagnosis of mRCC undergoing CN between 2004 and 2019 at participating centers were included. The Kaplan Meier method and Cox proportional hazards regression analyses were used to assess overall survival (OS). Covariates statistically significant at univariable analyses were included after stepwise selection in multivariable Cox regression model. The obtained coefficients from the multivariable model were used to compute a risk score. The latter was used to predict overall mortality (OM) at 1 year. Concordance index (c-index) and decision curve analyses (DCA) were fitted to test the score as continuous variable and after stratification according to the first and second tertiles, and for comparison with standard Heng criteria. RESULTS: A total of 484 patients were included with a median follow-up of 48 mo (IQR:22.7-90.2). On multivariable analysis, clinical risk factors associated with decreased OS included in the final model were: presence of sarcomatoid features (HR: 1.38, 95%CI:1.03-1.84, p[0.029), pN1 stage vs. pN0 (HR: 1.58, 95%CI:1.17-2.13, p[0.003), LDH >210 U/l (HR:1.32, 95%CI:1.04-1.68, p[0.020), calcium level >10.2 mg/dl (HR:1.98, 95%CI: 1.12-3.48, p[0.018) and bone metastases (HR:1.51, 95%CI: 1.13-2.02, p[0.005). Cox regression model showed a statistically significant correlation of the score with OM (HR:2.08, 95%CI:1.67-2.58, p<0.001). The cohort was stratified into three groups according to the score tertiles, namely low risk (23.1%), intermediate risk (40.5%) and high risk (36.4%) patients. The 1-year OS rates were 82.2 3.9, 74.8 3.3 and 55.1 3.9% in the favorable, intermediate and low risk category, respectively. At prediction of 1-year OM, the estimated c-index for the continuous score, stratified score and Heng criteria were 61.7, 61.7 and 57.9%, respectively. DCA showed comparable performance for all the three predictors, however our score as continuous variable and after stratification showed a slightly better performance compared to the Heng's criteria when predicting 1-year OM. CONCLUSIONS: Our analysis identifies risk factors for 1-yr OM in patients treated with CN for primary mRCC. We developed a new score based on these risk factors, which may help in personalized counselling and tailored management. The REMARCC score could be easily implemented in clinical practic

Rates and Predictors of Perioperative Complications in Cytoreductive Nephrectomy: Analysis of the Registry for Metastatic Renal Cell Carcinoma

BACKGROUND: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. OBJECTIVE: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. DESIGN, SETTING, AND PARTICIPANTS: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. RESULTS AND LIMITATIONS: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. CONCLUSIONS: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. PATIENT SUMMARY: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications.status: publishe

Proposal for a Two-Tier Re-classification of Stage IV/M1 domain of Renal Cell Carcinoma into M1 (“Oligometastatic”) and M2 (“Polymetastatic”) subdomains: Analysis of the Registry for Metastatic Renal Cell Carcinoma (REMARCC)

PurposeWe hypothesized that two-tier re-classification of the “M” (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC).MethodsMulticenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, “Oligometastatic”) and M2 (&amp;gt;3, “Polymetastatic”). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current “M” staging.Results429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p&amp;lt;0.001). Comparing M1-oligometastatic vs. M2-polymetastatic groups, KMA revealed significantly higher 5-year OS (36% vs. 21%, p&amp;lt;0.001) and 5-year CSS (39% vs. 17%, p&amp;lt;0.001). ROC analyses comparing OS and CSS, for M1/M2 reclassification versus unitary M designation currently in use demonstrated improved c-index for OS (M1/M2 0.635 vs. unitary M 0.500) and CSS (M1/M2 0.627 vs. unitary M 0.500).ConclusionSubclassification of Stage “M” domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging.</jats:sec

Proposal for a Two-Tier Re-classification of Stage IV/M1 domain of Renal Cell Carcinoma into M1 ("Oligometastatic") and M2 ("Polymetastatic") subdomains: Analysis of the Registry for Metastatic Renal Cell Carcinoma (REMARCC)

PurposeWe hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC). MethodsMulticenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (&lt;= 3, "Oligometastatic") and M2 (&gt;3, "Polymetastatic"). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current "M" staging. Results429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p&lt;0.001). Comparing M1-oligometastatic vs. M2-polymetastatic groups, KMA revealed significantly higher 5-year OS (36% vs. 21%, p&lt;0.001) and 5-year CSS (39% vs. 17%, p&lt;0.001). ROC analyses comparing OS and CSS, for M1/M2 reclassification versus unitary M designation currently in use demonstrated improved c-index for OS (M1/M2 0.635 vs. unitary M 0.500) and CSS (M1/M2 0.627 vs. unitary M 0.500). ConclusionSubclassification of Stage "M" domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging