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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.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.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.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.

We sought to determine whether loss of renal function increases risk of recurrence and metastases in renal cell carcinoma (RCC), and whether this impact was age-related.We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry. Patients were separated into younger (65 years old) and elder (≥65 years old) age groups, and rates of de novo estimated glomerular filtration rate (eGFR45 mL/min/1.73m2 [eGFR45]) were calculated. Multivariable analysis (MVA) was conducted for predictors of progression-free survival (PFS) and all-cause mortality (ACM). Kaplan-Meier Analysis (KMA) was conducted for PFS and overall survival (OS) in younger and elder age groups stratified by functional status.We analyzed 1805 patients (1113 age65, 692 age≥65). On MVA in patients65, de novo eGFR45 was independently associated with greater risk for worsened progression (HR=1.61, P=.038) and ACM (HR=1.82, P=.018). For patients ≥65, de novo eGFR45 was not independently associated with progression (P=.736), or ACM (P=.286). Comparing patients with de novo eGFR45 vs. eGFR ≥45, KMA demonstrated worsened 5-year PFS and OS in patients65 (PFS: 68% vs. 86%, P.001; OS: 73% vs. 90%, P.001), while in patients ≥65, only 5-year OS was worsened (77% vs. 81%, P.021).Development of de novo eGFR45 was associated with more profound impact on patients65 compared to patients ≥65, being an independent risk factor for PFS and ACM. The mechanisms of this phenomenon are unclear but underscore desirability for nephron preservation when safe and feasible in younger patients.

To evaluate effects of worsening surgically induced chronic kidney disease (CKD-S) on oncological and non-oncological survival outcomes in renal cell carcinoma (RCC).We performed a retrospective analysis of patients who underwent partial (PN) or radical nephrectomy (RN) and were free of preoperative CKD (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 mWe analysed 3239 patients. The mean preoperative and last-follow-up eGFRs were 87.4 and 69.5 mL/min/1.73 mDevelopment of CKD-S Stage 3b and 4, but not 3a, was associated with worsened ACM and NCM. The decision to proceed with nephron preservation via PN should be individualised based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3a.

418 Background: Chemotherapy for testicular cancer (TC) is highly effective yet associated with significant consequences on long-term health-related quality of life. We evaluate the impact of chemotherapy on anxiety, depression, and suicidality amongst TC survivors. Methods: We conducted a retrospective cohort study of US veterans diagnosed with TC in the Veterans Health Affairs database from 1990-2016. Patients with non-primary germ cell tumor histologies were excluded. Baseline disease characteristics and treatment received were ascertained from the VA Central Cancer Registry. Anxiety or depression was a composite endpoint comprised of diagnosis codes for anxiety, depression, or administration of medications used to treat these diagnoses. Incident suicidality was defined as a diagnosis code for suicidal ideation. Time to event was defined as time from diagnosis to event or censor at the time of last follow-up. Rates of outcomes were reported through cumulative incidences. Associations with outcomes and receipt of chemotherapy were assessed through multivariable Cox regression models. Results: In total, 1684 patients (1174 seminoma, 510 nonseminoma) were included in the cohort. Median age at diagnosis in the cohort was 40 years old. Median follow up time was 7.67 years for surviving patients. 1506 (89.4%) patients were white, 114 (6.8%) were African American, and 64 (3.8%) were another or unknown race. There were 1066 (63.3%) stage I patients, 191 (11.3%) stage II, 198 (11.8%) stage III, and 229 (13.6%) unknown stage patients. 579 (34.4%) patients received chemotherapy. At the time of diagnosis, 104 (6.2%) patients already experienced anxiety or depression. At 10 years, cumulative incidence of the diagnosis of anxiety or depression as 44.1% in the entire cohort. At 10 years, cumulative incidence of the diagnosis of suicidality was 5.5%. On multivariable Cox regression, factors associated with a higher risk of anxiety or depression were older age at diagnosis (Hazard Ratio (HR): 1.11 per standard deviation increase, p=0.01), being unemployed (HR: 1.25, p=0.01), and receipt of chemotherapy (HR: 1.43, p

723 Background: C-reactive protein (CRP) has been demonstrated to be an independent predictor of survival outcomes in renal cell carcinoma (RCC). The use of biomarkers to predict post-surgical complications is not well studied. We sought to investigate predictive factors for major complications following surgery for RCC and delineate their impact on mortality outcomes. Methods: We performed a two-center retrospective analysis of patients who underwent partial (PN) and radical nephrectomy (RN) for RCC. Patients who had complications within 30 days after surgery were identified and the complications were scored using the Clavien-Dindo classification system. Patients were grouped based on whether they experienced 30-day major (Clavien ≥3) complications and whether they had elevated preoperative CRP defined as >5mg/L. Primary outcome was non-cancer mortality (NCM), with secondary outcomes being all-cause (ACM) and cancer-specific (CSM) mortality. Multivariable analyses (MVA) were conducted to evaluate predictors for Clavien ≥3 complications, NCM, CSM, and ACM. Kaplan-Meier analyses (KMA) were performed to compare overall survival (OS), noncancer-specific survival (NCS), and cancer-specific survival (CSS) between patients with non-elevated and elevated preoperative CRP and between patients without and with 30-day Clavien ≥3 complications. Results: A total of 2,234 patients were analyzed [116 (5.2%) experienced Clavien ≥3 complications; median follow up 44 months]. MVA revealed that coronary artery disease (OR 2.37, p=0.005), elevated CRP (OR 2.25, p=0.004), PN (OR 2.79, p

734 Background: T1a renal cell carcinoma (RCC) is associated with excellent cure rates. However, a small fraction present with metastasis. We sought to determine the clinical characteristics, variables associated with synchronous metastasis, and survival outcomes in patients with pT1a and cT1a RCC using the National Cancer Database (NCDB). We secondarily evaluated whether surgery impacted risk of all cause mortality in cT1a RCC with synchronous lung and bone metastasis. Methods: From 2004 to 2019, all cases of RCC in patients age ≥18 were extracted from NCDB. pT1a and cT1a RCC were characterized as those 1) with no metastasis at diagnosis, 2) with synchronous metastasis [pT1aNxM1 at diagnosis]. Impact of surgery on all cause mortality was not evaluated for cT1a with synchronous metastasis to liver and brain due to low sample sizes. Results: The table describes selected characteristics of the cohorts. On multivariable logistic regression, diagnosis of pT1a with synchronous metastasis was associated with age (OR 1.02), male sex (OR 1.64), tumor size (OR 1.84), cN1 (OR 1.08), sarcomatoid (OR 5.50), tumor grade (OR 2.84) (p1 site (HR 2.48, p=0.032), and inversely with radical (HR 0.42, p

728 Background: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnoses at earlier clinical tumor stage and has rendered the phenomenon of the ‘small renal mass’ as a dominant presenting clinical paradigm. While thought of as being low risk, emerging knowledge about heterogeneity of RCC histologies and consequent impact on prognosis, in addition to awareness of impact of functional decline and demographic drivers on outcomes led us to further explore outcomes and predictive factors in T1a RCC patients treated with surgical resection. Methods: The INMARC database was queried for patients with small renal masses (≤ 4 cm) who underwent surgery via partial or radical nephrectomy and who presented without nodal or distant metastases. Patients were stratified into two groups based on having recurrence (distant or loco-regional) or not. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed to analyze clinicopathological variables associated with recurrence and identify predictors of recurrence, cancer-specific mortality (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) were performed to compare recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) between histology types clear cell, chromophobe, papillary, and “other.” Results: We analyzed 1,878 cT1aN0M0 RCC patients; 101 (5.4%) developed recurrence (median follow up 53.6 months; median time to recurrence 19.3 months); 51.1% developed distant recurrence, 35.6% had loco-regional recurrence, and 13.9% experienced distant and loco-regional recurrence. MVA demonstrated age (HR=1.02, p=0.02), sex (HR=1.71, p=0.045), diabetes (HR=1.94, p=0.006), high/unclassified grade (HR=2.82-4.40, p

644 Background: Pathological upstaging to pT3a disease can occur after the surgical treatment of clinical T1 and T2 Renal Cell Carcinomas (RCCs), and this upstaging has been previously shown to be associated with poorer outcomes. With an intent to delve deeper into the disparateness in outcomes of pT3a disease, we investigated the survival of patients with an initial clinical stage of cT1, cT2 and cT3a. Methods: Using the National Cancer Database (NCDB), patients with RCC were categorized by pathological and clinical staging of RCC according to the American Joint Committee on Cancer Guidelines (AJCC). The primary outcome was measured as overall survival (OS) at the end of follow up. Five-year survival rates and Kaplan-Meier Analysis assessed the differences between cT1 → pT3a, cT2 → pT2, cT2 → pT3a, and cT3a → pT3a. Multivariable cox regression (MVA) assessed predictors OS with age, sex, ethnicity, Charlson Score, socioeconomic status, geography, tumor size histology and grade, lymph node metastasis, surgical margins, and surgery type (partial versus radical nephrectomy) as covariates. Results: 53908 patients were analyzed (10789 cT1 → pT3a, 22183 cT2 → pT2, 9676 cT2 → pT3a, 11260 cT3a → pT3a, mean follow up 62.3 months). Of all pT3a patients, 64.5% were upstaged from cT1-2. MVA for OS demonstrated Hispanic ethnicity to be protective (hazard ratio [HR]=0.88, P

615 Background: A significant portion of patients presenting with clinically localized stage 1-2 renal cell carcinoma are pathologically upstaged to Stage 3 following surgical intervention. This is due to previously undetected extension into the renal venous system, perirenal or renal sinus fat, or collecting system. Improved detection of potential T3 upstaging may prompt changes in disease management, which may impact patient survival. We sought to compare pathologically upstaged and non-upstaged T3a RCC cases to identify characteristics of upstaged masses, predictors of T3a disease, and impact on oncological outcomes. Methods: We conducted a single center retrospective analysis of patients with pathologic T3a RCC who underwent surgical intervention. The cohort was divided into a group of patients with masses not preoperatively identified as cT3a (upstaged, cT1-cT2/pT3a) and a group of patients with masses preoperatively identified as cT3a (non-upstaged, cT3a/pT3a) for descriptive and outcomes analyses. We sought to delineate proportion of under-diagnosed pT3a RCC, location of upstaged disease, and predictors of upstaging. Primary outcome was overall survival (OS) and secondary outcome was recurrence-free survival (RFS). Multivariate analyses (MVA) were performed to identify predictors of T3a invasion site and outcomes. Kaplan Meier survival analyses (KMA) were performed to compare survival outcomes. Results: We analyzed 185 patients, of which 120 (64.9%) were upstaged and 65 (35.1%) were non-upstaged. When compared to non-upstaged masses, upstaged masses were significant for smaller size (6.8 vs 8.2 cm, p=0.008), lower RENAL score (8.7 vs 9.9, p

To investigate association of African-American race and survival in Renal Cell Carcinoma (RCC).We queried the International Marker Consortium for Renal Cancer database for patients who underwent partial or radical (RN) nephrectomy. The cohort was divided into African American (AA) and non-African American (NAA) patients. Primary outcome was all-cause mortality. Secondary outcome was cancer-specific mortality. Multivariable Analysis and Kaplan-Meier Analysis were used to elucidate predictive factors and survival outcomes.Three thousand eight hundred and ninety-three patients were analyzed (AA, n = 564/NAA, n = 3329). AA had greater Stage I (73.8% vs 63.9%, P.001) and papillary RCC (29.8% vs 8.5%, P.001). Multivariable Analysis revealed increasing age (HR = 1.03, P.001), AA (HR = 1.24, P = .027), higher stage (HR = 1.30-3.19, P.001), RN (HR = 2.45, P.001), clear cell (HR = 1.23, P.001), positive margin (HR = 1.34, P .004), and high-grade (HR = 1.58, P.001) to be associated with worsened all-cause mortality. Increasing age (HR = 1.02, P.001), AA (HR = 1.48, P = .025), RN (HR = 2.98, P.001), high-grade (HR = 3.11, P.001), and higher stage (HR = 3.03-13.2, P.001) were predictive for cancer-specific mortality. Kaplan-Meier Analysis revealed worsened 5-year overall survival for AA in stage I (80% vs 88%, P = .001), stage III (26% vs 70%, P = .001), and stage IV (23% vs 44%, P = .009). Five-year cancer-specific survival was worse for AA in stage III (36% vs 81%, P.001) and stage IV (30% vs 49%, P = .007).Despite presenting with more indolent histology and lower stage, African-Americans were at greater risk for diminished survival, faring worse in overall survival for all stages and cancer-specific survival in for stage III/IV RCC. Further investigation into factors associated with these disparities is warranted.

The impact of positive surgical margins (PSM) on outcomes in partial nephrectomy (PN) is controversial. We investigated impact of PSM for patients undergoing PN on overall survival (OS) in different stages of renal cell carcinoma (RCC).Retrospective analysis of patients from the US National Cancer Database who underwent PN for cT1a-cT2b N0M0 RCC between 2004-13. Patients were stratified by pathological stage (pT1a, pT1b, pT2a, pT2b, and pT3a [upstaged]) and analyzed by margin status. Cox Regression multivariable analysis (MVA) was performed to investigate associations of PSM and covariates on all-cause mortality (ACM). Kaplan-Meier analysis (KMA) of OS was performed for PSM versus negative margin (NSM) by pathological stage. Sub-analysis of Charlson Comorbidity Index 0 (CCI=0) subgroup was conducted to reduce bias from comorbidities.We analyzed 42,113 PN (pT1a: 33,341 [79.2%]; pT1a, pT1b: 6689 [15.9%]; pT2a: 757 [1.8%]; pT2b: 165 [0.4%]; and pT3a: upstaged 1161 [2.8%]). PSM occurred in 6.7% (2823) (pT1a: 6.5%, pT1b: 6.3%, pT2a: 5.9%, pT2b: 6.1%, pT3a: 14.1%, P0.001). On MVA, PSM was associated with 31% increase in ACM (HR 1.31, P0.001), which persisted in CCI=0 sub-analysis (HR: 1.25, P0.001). KMA revealed negative impact of PSM vs. NSM on 5-year OS: pT1 (87.3% vs. 90.9%, P0.001), pT2 (86.7% vs. 82.5%, P=0.48), and upstaged pT3a (69% vs. 84.2%, P0.001).PSM after PN was independently associated with across-the-board decrement in OS, which worsened in pT3a disease and persisted in sub-analysis of patients with CCI=0. PSM should prompt more aggressive surveillance or definitive resection strategies.

395 Background: Radical nephrectomy (RN) is a mainstay of management of localized renal cancer larger than 4 cm in size. RN is associated with renal functional decline, however impact of age on functional decline is unclear. We investigated impact of age on post RN function, focusing on decline to moderate and severe chronic kidney disease (CKD). Methods: This was a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry of patients who underwent RN. Primary outcome was development of de novo CKD stage IIIB [estimated glomerular filtration rate (eGFR)30). Patients clinical characteristics were stratified by age groups (70 years old). Multivariable logistic regression analysis (MVA) was utilized to identify risk factors with renal functional decline to different CKD stages. Kaplan-Meier analysis (KMA) was utilized to evaluate functional outcomes with respect to the different age groups. Results: Overall, 2,436 patients were analyzed (≤50 years, n=513; 50-70 years, n=1,344; >70, n=579; median follow up 31.9 months). On MVA, increasing age was independently associated with increased risk of development of CKD Stage IIIb [compared to ≤50 years (referent), 50-70 years, OR 3.35, p70 years OR 7.7, p70 years OR 9.4, p70 years was independently associated with increased risk of development of CKD Stage IV [OR 1.96, p=0.027]. In addition, male (OR 1.49, p= 0.036), increasing BMI (OR 1.03, p=0.003), diabetes mellitus (OR 2.69, p 70 years 37.06%, p70 years 55.5%, p70 years 81.2%, p< 0.001). Conclusions: Increasing age is an independent risk factor for progressive and clinically significant renal functional decline after radical nephrectomy. Prioritization for nephron sparing management should be considered whenever safe and feasible in elderly patients to reduce potential risk of sequelae of functional decline.

394 Background: Studies have discussed the prognostic use of C-reactive protein (CRP) and De Ritis ratio (AST/ALT or AAR) in the evaluation of renal malignant masses. Elevated pre-treatment CRP has been shown to be associated with non-cancer mortality. Additionally increased preoperative AAR has been found to be a prognostic factor for overall survival. With studies showing the ethnic disparities in mortality rate in certain underserved ethnic groups, there is a need for investigation into possible ethnic differences. Our aim is to evaluate the association between these elevated preoperative markers and all-cause mortality (ACM) and cancer specific mortality (CSM) among ethnic groups. Methods: Retrospective review of the International Marker Consortium for Renal Cancer (INMARC) was performed. Patients with renal malignancies who underwent partial or radical nephrectomy (PN, RN) were included. Patients were grouped according to ethnicity and African American (AA), White, Asian, and Hispanic ethnic groups were selected for descriptive, survival and multivariable analysis of outcomes. A Cox-regression multivariable analysis (MVA) was performed for each group. The primary outcome was overall survival and cancer specific survival from time of surgery to last follow-up, which was evaluated using Kaplan-Meyer Analysis (KMA). Results: A total of 4,810 patients were analyzed (627 AA, 2,344 White, 462 Hispanic, 1,094 Asian). Preoperative CRP and AAR were considered elevated if above 5 mg/L and 1.26, respectively. Descriptive analysis showed significant differences in age, diabetes mellitus status, hypertension status, tumor size, surgery type (PN vs. RN), preoperative CRP, preoperative AAR, ACM and CSM between ethnicities (p-value

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