Comparison of outcomes for Hispanic and non-Hispanic patients with advanced renal cell carcinoma in the International Metastatic Renal Cell Carcinoma Database.

BACKGROUND: Existing data on the impact of Hispanic ethnicity on outcomes for patients with renal cell carcinoma (RCC) is mixed. The authors investigated outcomes of Hispanic and non-Hispanic White (NHW) patients with advanced RCC receiving systemic therapy at large academic cancer centers using the International Metastatic Renal Cell Carcinoma Database (IMDC). METHODS: Eligible patients included non-Black Hispanic and NHW patients with locally advanced or metastatic RCC initiating systemic therapy. Overall survival (OS) and time to first-line treatment failure (TTF) were calculated using the Kaplan-Meier method. The effect of ethnicity on OS and TTF were estimated by Cox regression hazard ratios (HRs). RESULTS: A total of 1563 patients (181 Hispanic and 1382 NHW) (mostly males [73.8%] with clear cell RCC [81.5%] treated with tyrosine kinase inhibitor [TKI] monotherapy [69.9%]) were included. IMDC risk groups were similar between groups. Hispanic patients were younger at initial diagnosis (median 57 vs. 59 years, p = .015) and less likely to have greater than one metastatic site (60.8% vs. 76.8%, p < .001) or bone metastases (23.8% vs. 33.4%, p = .009). Median OS and TTF was 38.0 months (95% confidence interval [CI], 28.1-59.2) versus 35.7 months (95% CI, 31.9-39.2) and 7.8 months (95% CI, 6.2-9.0) versus 7.5 months (95% CI, 6.9-8.1), respectively, in Hispanic versus NHW patients. In multivariable Cox regression analysis, no statistically significant differences were observed in OS (adjusted hazard ratio [HR], 1.07; 95% CI, 0.86-1.31, p = .56) or TTF (adjusted HR, 1.06; 95% CI, 0.89-1.26, p = .50). CONCLUSIONS: The authors did not observe statistically significant differences in OS or TTF between Hispanic and NHW patients with advanced RCC. Receiving treatment at tertiary cancer centers may mitigate observed disparities in cancer outcomes.

Efficacy and safety of lenvatinib plus pembrolizumab vs sunitinib in the East Asian subset of patients with advanced renal cell carcinoma from the CLEAR trial.

In the CLEAR trial, lenvatinib plus pembrolizumab met study endpoints of superiority vs sunitinib in the first-line treatment of patients with advanced renal cell carcinoma. We report the efficacy and safety results of the East Asian subset (ie, patients in Japan and the Republic of Korea) from the CLEAR trial. Of 1069 patients randomly assigned to receive either lenvatinib plus pembrolizumab, lenvatinib plus everolimus or sunitinib, 213 (20.0%) were from East Asia. Baseline characteristics of patients in the East Asian subset were generally comparable with those of the global trial population. In the East Asian subset, progression-free survival was considerably longer with lenvatinib plus pembrolizumab vs sunitinib (median 22.1 vs 11.1 months; HR 0.38; 95% CI: 0.23-0.62). The HR for overall survival comparing lenvatinib plus pembrolizumab vs sunitinib was 0.71; 95% CI: 0.30-1.71. The objective response rate was higher with lenvatinib plus pembrolizumab vs sunitinib (65.3% vs 49.2%; odds ratio 2.14; 95% CI: 1.07-4.28). Dose reductions due to treatment-emergent adverse events (TEAEs) commonly associated with tyrosine kinase inhibitors occurred more frequently than in the global population. Hand-foot syndrome was the most frequent any-grade TEAE with lenvatinib plus pembrolizumab (66.7%) and sunitinib (57.8%), a higher incidence compared to the global population (28.7% and 37.4%, respectively). The most common grade 3 to 5 TEAEs were hypertension with lenvatinib plus pembrolizumab (20%) and decreased platelet count with sunitinib (21.9%). Efficacy and safety for patients in the East Asian subset were generally similar to those of the global population, except as noted.

Racial and ethnic disparities in surgery for kidney cancer: a SEER analysis, 2007-2014.

BACKGROUND AND OBJECTIVES: Compared with White patients, Black and American Indian/Alaskan Native (AI/AN) patients experience higher rates of kidney cancer incidence, and Black, AI/AN, and Hispanic patients face later stages of disease at diagnosis, poorer survival rates, and greater risk of mortality. Despite the importance that appropriate treatment has in ensuring positive outcomes, little is known about the association between race and ethnicity and receipt of treatment for kidney cancer. Accordingly, the aim of this study was to explore differences in receipt of treatment and patterns of refusal of recommended treatment by race and ethnicity. DESIGN: 96,745 patients ages 45-84 with kidney cancer were identified in the Surveillance, Epidemiology, and End Results (SEER) program between 2007 and 2014. Logistic regression models were used to examine the association of race and ethnicity with treatment and with patient refusal of recommended treatment. Outcomes of interest were (1) receiving any surgical procedure, and (2) refusing recommended surgery. RESULTS: Relative to White patients, Black and AI/AN patients had lower odds of undergoing any surgical procedure (OR = 0.76; 95% CI: 0.72-0.81; p < 0.001, and OR = 0.92; 95% CI: 0.76-1.10; p = 0.36, respectively) after adjusting for gender, age, insurance status, stage at diagnosis, unemployment status, education status, and income as additive effects. Black and AI/AN patients also had higher odds of refusing recommended surgery (OR = 1.93; 95% CI: 1.56-2.39; p < 0.001, and OR = 1.99; 95% CI: 1.05-3.76; p = 0.035, respectively). Hispanic patients had slightly higher odds of undergoing any surgical procedure (OR = 1.10; 95% CI: 1.04-1.17; p = 0.001) and lower odds of refusal (OR = 0.67; 95% CI: 0.50-0.90; p = 0.007, respectively). CONCLUSIONS: Compared with White patients, Black patients were less likely to receive potentially life-saving surgery, and both Black and AI/AN patients were more likely to refuse recommended surgery.

Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study.

BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking. METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI). RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving < 85%. Of the 145 evaluable patients, 56 (39%) remained progression free at 12 months, and the median PFS was 10 months (95% CI: 8.48-11.83). 19% of patients (21/109) were long-term responders (on pazopanib for ≥18 months). The best response per RECIST 1.1 was CR/PR in 24%, stable disease in 44%, and PD in 31%. Most frequent (> 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%). CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.

Racial and ethnic differences in survival in contemporary metastatic renal cell carcinoma patients, according to alternative treatment modalities.

PURPOSE: To test the association between African-American race and overall mortality (OM) rates in patients with metastatic renal cell carcinoma (mRCC). METHODS: Within the Surveillance, Epidemiology, and End Results registry (2006-2015), we identified patients with clear cell (ccmRCC) and non-clear cell mRCC (non-ccmRCC). African-Americans, Caucasians, and Hispanics were identified. Stratification was made according to histology and treatments: (1) no treatment, (2) systemic therapy (ST), (3) cytoreductive nephrectomy (CNT), (4) CNT + ST. Kaplan-Meier plots and multivariable Cox regression analyses were used. RESULTS: Of ccmRCC patients, 410 (7%), 4353 (75%), and 1005 (17%) were African-American, Caucasian, and Hispanic, respectively. Of non-ccmRCC patients, 183 (25%), 479 (65%), and 77 (10%) were African-American, Caucasian, and Hispanic, respectively. In ccmRCC, African-Americans were associated with higher OM rates (HR 1.20; 95% CI 1.05-1.37). Conversely, in non-ccmRCC, African-Americans were associated with lower OM rates (HR 0.75; 95% CI 0.59-0.97). CONCLUSION: African-American race is associated with prolonged survival in non-ccmRCC, but it is also associated with lower survival rates in ccmRCC. The exception to these observations consisted of patients treated with combination of CNT + ST for either ccmRCC or non-ccmRCC.

Understanding racial disparities in renal cell carcinoma incidence: estimates of population attributable risk in two US populations.

PURPOSE: Renal cell carcinoma (RCC) incidence is higher among black than white Americans. The reasons for this disparity remain unclear. METHODS: We calculated race- and sex-specific population attributable risk percentages (PAR%) and their 95% confidence intervals (CI) for hypertension and chronic kidney disease (CKD) among black and white subjects ≥ 50 years of age from the US Kidney Cancer Study (USKC; 965 cases, 953 controls), a case-control study in Chicago and Detroit, and a nested case-control study in the Kaiser Permanente Northern California health care network (KPNC; 2,162 cases, 21,484 controls). We also estimated PAR% for other modifiable RCC risk factors (cigarette smoking, obesity) in USKC. RESULTS: In USKC, the PAR% for hypertension was 50% (95% CI 24-77%) and 44% (95% CI 25-64%) among black women and men, respectively, and 29% (95% CI 13-44%) and 27% (95% CI 14-39%) for white women and men, respectively. In KPNC, the hypertension PAR% was 40% (95% CI 18-62%) and 23% (95% CI 2-44%) among black women and men, and 27% (95% CI 20-35%) and 19% (95% CI 14-24%) among white women and men, respectively. The PAR% for CKD in both studies ranged from 7 to 10% for black women and men but was negligible (<1%) for white subjects. In USKC, the PAR% for current smoking was 20% and 8% among black and white men, respectively, and negligible and 8.6% for black and white women, respectively. The obesity PAR% ranged from 12 to 24% across all race/sex strata. CONCLUSIONS: If the associations found are causal, interventions that prevent hypertension and CKD among black Americans could potentially eliminate the racial disparity in RCC incidence (hypothetical black:white RCC incidence ratio of 0.5).

Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup 3-year follow-up analysis from the Phase III CheckMate 025 study.

BACKGROUND: Nivolumab treatment resulted in superior efficacy and safety versus everolimus treatment in the 2-year follow-up of the CheckMate 025 Phase III study, with consistent results in the global population and the Japanese population. Here, we report the 3-year follow-up in both groups. METHODS: Patients were randomized 1:1 to nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10 mg orally once daily until progression/intolerable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included objective response rate, progression-free survival, safety and patient-reported quality of life. RESULTS: Of 410 and 411 patients randomized to nivolumab and everolimus, 37 and 26 were Japanese, respectively. The median OS for the global population was 25.8 months with nivolumab and 19.7 months with everolimus (hazard ratio 0.74; 95.5% confidence interval [CI]: 0.63-0.88; P = 0.0005); in the Japanese population, median OS was 45.9 months and not reached (hazard ratio 1.08; 95% CI: 0.50-2.34; P = 0.85), respectively. The investigator-assessed objective response rate was 26% versus 5% with nivolumab versus everolimus (odds ratio [OR] 6.19; 95% CI: 3.82-10.06) in the global population and 43% versus 8% in the Japanese population (OR 6.80; 95% CI: 1.60-28.91; P = 0.0035), respectively. The incidence of any-grade treatment-related adverse events was lower with nivolumab versus everolimus in both the global patient population (80% versus 89%) and the Japanese population (81% versus 100%). CONCLUSIONS: At the 3-year follow-up, the efficacy and safety results of CheckMate 025 are generally consistent in the global and the Japanese populations.

Adherent Perinephric Fat in Asian Patients: Predictors and Impact on Perioperative Outcomes of Partial Nephrectomy.

INTRODUCTION: This study is aimed at evaluating the incidence and predictors of adherent perinephric fat (APF) in Asians during partial nephrectomy (PN), and determining the impact of APF on perioperative outcomes. MATERIALS AND METHODS: A total of 231 Asian patients with renal tumors underwent PN, and their Mayo adhesive probability (MAP) score was calculated. APF was intraoperatively determined, and the perioperative data were compared according to the presence of APF. The predictors of APF were examined using logistic regression analyses. RESULTS: APF was observed in 40 (17%) patients. In multivariate analysis, male gender and higher MAP score were the independent predictors of APF. The estimated blood loss was higher in patients with APF, however, the complication rates did not differ between the 2 groups. CONCLUSIONS: The MAP score can predict APF in an Asian population. The presence of APF was associated with greater blood loss; however it did not increase the postoperative complications in PN.

Prevalence and Characteristics of Patients with Suspected Inherited Renal Cell Cancer: Application of the ACMG/NSGC Genetic Referral Guidelines to Patient Cohorts.

Patients with suspected hereditary renal cell cancer (RCC) are under-referred for genetic evaluation. Characterizing the prevalence and characteristics of suspected inherited RCC is a crucial step toward advancing personalized, genetically-based cancer risk management for patients and their families. To evaluate the prevalence and characteristics of suspected inherited RCC syndromes based on consensus criteria, we performed a cross-sectional analysis of patients with a diagnosis of RCC in SEER (2001-2011, n = 105,754) and in our institutional cancer registry (2004-2013, n = 998). Consensus criteria for referral of patients with RCC for genetic evaluation from the American College of Medical Genetics and Genomics and National Society of Genetic Counselors (ACMG/NSGC) were applied to the two cohorts. The associations between meeting referral criteria with demographic characteristics were assessed with chi-square tests. Overall, 24.0 % of the SEER cohort and 33.7 % of our institutional cohort met ACMG/NSGC referral criteria for genetic counseling. While white patients more commonly met early onset clear cell RCC criteria, black patients met papillary RCC criteria at twice the rate of whites in both cohorts (p < 0.0001). As many as 1 in 5 individuals with RCC meet referral criteria for genetic evaluation based on newly emerging guidelines, with differences in pathology noted by race. Prospective genetic testing studies utilizing emerging referral guidelines should help to refine the genetic spectrum of inherited kidney cancer. This study supports efforts to increase awareness of referral of patients with RCC for genetic counseling particularly among urologic providers.

Ethnic disparities in renal cell carcinoma: An analysis of Hispanic patients in a single-payer healthcare system.

OBJECTIVE: To investigate differences between Hispanics and non-Hispanic whites diagnosed with and treated for renal cell carcinoma in an equal access healthcare system. METHODS: We carried out a retrospective cohort study within the Kaiser Permanente healthcare system using records from renal cell carcinoma cases. Ethnicity was identified as Hispanic or non-Hispanic whites. Patient characteristics, comorbidities, tumor characteristics and treatment were compared. Overall and disease-specific survival was calculated, and a Cox proportion hazard model estimated the association of ethnicity and survival. RESULTS: A total of 2577 patients (2152 non-Hispanic whites, 425 Hispanic) were evaluated. Hispanics were diagnosed at a younger age (59.6 years vs 65.3 years). Clear cell renal cell carcinoma was more prevalent, whereas papillary renal cell carcinoma was less common among Hispanics. Hispanics had a lower American Joint Committee on Cancer stage (I/II vs III/IV) than non-Hispanic whites (67.4% vs 62.2%). Hispanics were found to have a greater frequency of comorbidities, such as chronic kidney disease and diabetes, but were more likely to receive surgery. The presence of metastases, nodal involvement, increased tumor size, non-surgical management, increasing age and Hispanic ethnicity were independent predictors of worse cancer-specific outcome. CONCLUSIONS: Within an equal access healthcare system, Hispanics seem to be diagnosed at younger ages, to have greater comorbidities and to present more frequently with clear cell renal cell carcinoma compared with non-Hispanic white patients. Despite lower stage and greater receipt of surgery, Hispanic ethnicity seems to be an independent predictor of mortality. Further work is necessary to confirm these findings.

Chronic kidney disease and risk of renal cell carcinoma: differences by race.

BACKGROUND: The incidence of renal cell carcinoma in the United States differs by race/ethnicity. To better understand these disparities, we conducted a nested case-control study investigating renal cell carcinoma risk factors across racial/ethnic groups within the Kaiser Permanente Northern California health care network. METHODS: Our study included 3136 renal cell carcinoma cases (2152 whites, 293 blacks, 425 Hispanics, and 255 Asians) diagnosed between 1998 and 2008 and 31031 individually matched controls (21478 whites, 2836 blacks, 4147 Hispanics, and 2484 Asians). Risk of renal cell carcinoma was assessed in relation to smoking status, body mass index (BMI), hypertension, and chronic kidney disease. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, and population attributable risk (PAR) to estimate by race the proportion of cases attributable to hypertension and chronic kidney disease. RESULTS: The association between chronic kidney disease and renal cell carcinoma differed markedly by race (Pinteraction < 0.001), with associations observed among blacks (OR = 10.4 [95% CI = 6.0-17.9]), Asians (5.1 [2.2-11.7]), and Hispanics (2.3 [1.1-4.6]) but not whites (1.1 [0.6-1.9]). Hypertension, high BMI, and smoking were associated with renal cell carcinoma, but findings generally did not differ by race. Relative to other racial/ethnic groups, blacks had the highest proportion of renal cell carcinoma incidence attributable to hypertension and chronic kidney disease (combined, PAR = 37%; hypertension only, PAR = 27%; chronic kidney disease, PAR = 10%). CONCLUSIONS: Our findings suggest that hypertension and chronic kidney disease likely have contributed to the observed excess in renal cell carcinoma incidence among blacks compared with whites.

Anti-VEGF therapy in mRCC: differences between Asian and non-Asian patients.

BACKGROUND: Several reports suggest that vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma (mRCC) may be more toxic in Asian vs non-Asian populations. Comparative efficacy of these agents with respect to ethnicity is not well characterised. METHODS: A multicentre, retrospective, cohort study using Asian and non-Asian centres which collected data on ethnicity, dose reductions and outcomes using the International mRCC Database Consortium. RESULTS: This study included 1024 (464 Asian, 560 non-Asian) patients with a 29.4 months median follow-up. The percentage of dose modifications/reductions between non-Asians and Asians was similar (55% vs 61% P=0.1197). When adjusted for risk groups, there was no difference in overall or progression-free survival between non-Asians and Asians. Patients with dose reductions due to toxicity had longer treatment durations and overall survival than those who did not in both non-Asian (10.6 vs 5.0 months, P<0.0001; 22.6 vs 16.1 months, P=0.0016, respectively) and Asian populations (8.9 vs 5.4 months, P=0.0028; 28.0 vs 18.7 months, P=0.0069, respectively). CONCLUSIONS: Adjusting for risk groups, there appears to be no difference in outcome between Asian vs non-Asian patients with mRCC treated with VEGF-targeted therapy. Judicious dose reductions may allow for better outcomes in both populations due to longer treatment durations, but direct comparisons are needed.

Kidney cancer incidence and mortality among American Indians and Alaska Natives in the United States, 1990-2009.

OBJECTIVES: We describe rates and trends in kidney cancer incidence and mortality and identify disparities between American Indian/Alaska Native (AI/AN) and White populations. METHODS: To improve identification of AI/AN race, incidence and mortality data were linked with Indian Health Service (IHS) patient records. Analysis focused on residents of IHS Contract Health Service Delivery Area counties; Hispanics were excluded. We calculated age-adjusted kidney cancer incidence (2001-2009) and death rates (1990-2009) by sex, age, and IHS region. RESULTS: AI/AN persons have a 1.6 times higher kidney cancer incidence and a 1.9 times higher kidney cancer death rate than Whites. Despite a significant decline in kidney cancer death rates for Whites (annual percentage change [APC] = -0.3; 95% confidence interval [CI] = -0.5, 0.0), death rates for AI/AN persons remained stable (APC = 0.4; 95% CI = -0.7, 1.5). Kidney cancer incidence rates rose more rapidly for AI/AN persons (APC = 3.5; 95% CI = 1.2, 5.8) than for Whites (APC = 2.1; 95% CI = 1.4, 2.8). CONCLUSIONS: AI/AN individuals have greater risk of developing and dying of kidney cancers. Incidence rates have increased faster in AI/AN populations than in Whites. Death rates have decreased slightly in Whites but remained stable in AI/AN populations. Racial disparities in kidney cancer are widening.

Impact of Socioeconomic Status on Patient Adherence in Managing Renal Masses.

INTRODUCTION: Previous literature suggests socioeconomic status and racial disparities impact management decisions for patients with small renal masses. We aim to build upon these findings and examine how these modalities impact patient adherence to their management plan. METHODS: This retrospective study analyzed our Kidney Tumor Program database (n = 1476) containing patients from 2000 to 2020. Socioeconomic status was estimated using 2 modalities: Area Deprivation Index and household income. Patients were then evaluated for differences in adherence, nonadherence, and loss to follow-up. Adherent patients completed all recommended appointments within 6 months of their initial follow-up. Nonadherent patients did not complete all recommended appointments within 6 months of their originally scheduled follow-up but eventually did. Patients lost to follow-up were recommended to follow up but never did. RESULTS: Patient adherence was not significantly different across sex or primary treatment method but differed with respect to race/ethnicity. Black patients were significantly more likely to be nonadherent (P = .021) and lost to follow-up (P = .008). After adjusting for race/ethnicity, Area Deprivation Index and income bracket were significantly associated with adherence and loss to follow-up. Patients with a high socioeconomic status had significantly higher rates of adherence (ADI, quartile [Q] 1 vs Q4, P = .038; income, >$120,000 vs $30,000-$59,999, P < .003) and decreased loss to follow-up (ADI, Q1 vs Q4, P = .03; income, >$120,000 vs $30,000-$59,999, P = .002). CONCLUSIONS: Our results demonstrate that Black race and low socioeconomic status are associated with decreased adherence and increased loss to follow-up. Possible strategies to target these disparities include financial assistance programming, social determinants of health screening, and nurse navigator programs.

Kidney Cancer Incidence among Non-Hispanic American Indian and Alaska Native Populations in the United States, 1999 to 2020.

BACKGROUND: Non-Hispanic American Indian and Alaska Native (NH-AI/AN) people exhibit a disproportionate incidence of kidney cancer. Nationally aggregated data do not allow for a comprehensive description of regional disparities in kidney cancer incidence among NH-AI/AN communities. This study examined kidney cancer incidence rates and trends among NH-AI/AN compared with non-Hispanic White (NHW) populations by geographic region. METHODS: Using the United States Cancer Statistics American Indian and Alaska Native (AI/AN) Incidence Analytic Database, age-adjusted incidence rates (per 100,000) of kidney cancers for NH-AI/AN and NHW people for the years 2011 to 2020 combined using surveillance, epidemiology, and end Results (SEER)∗stat software. Analyses were restricted to non-Hispanic individuals living in purchased/referred care delivery area (PRCDA) counties. Average annual percent changes (AAPCs) and trends (1999-2019) were estimated using Joinpoint regression analyses. RESULTS: Rates of kidney cancer incidence were higher among NH-AI/AN compared with NHW persons in the United States overall and in five of six regions. Kidney cancer incidence rates also varied by region, sex, age, and stage of diagnosis. Between 1999 and 2019, trends in kidney cancer rates significantly increased among NH-AI/AN males (AAPC = 2.7%) and females (AAPC = 2.4%). The largest increases were observed for NH-AI/AN males and females aged less than 50 years and those diagnosed with localized-stage disease. CONCLUSIONS: Study findings highlight growing disparities in kidney cancer incidence rates between NH-AI/AN and NHW populations. IMPACT: Differences in geographic region, sex, and stage highlight the opportunities to decrease the prevalence of kidney cancer risk factors and improve access to preventive care.

Area Vulnerability and Disparities in Therapy for Patients With Metastatic Renal Cell Carcinoma.

Importance: Area-level measures of sociodemographic disadvantage may be associated with racial and ethnic disparities with respect to receipt of treatment for metastatic renal cell carcinoma (mRCC) but have not been investigated previously, to our knowledge. Objective: To assess the association between area-level measures of social vulnerability and racial and ethnic disparities in the treatment of US Medicare beneficiaries with mRCC from 2015 through 2019. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries older than 65 years who were diagnosed with mRCC from January 2015 through December 2019 and were enrolled in fee-for-service Medicare Parts A, B, and D from 1 year before through 1 year after presumed diagnosis or until death. Data were analyzed from November 22, 2022, through January 26, 2024. Exposures: Five different county-level measures of disadvantage and 4 zip code-level measures of vulnerability or deprivation and segregation were used to dichotomize whether an individual resided in the most vulnerable quartile according to each metric. Patient-level factors included age, race and ethnicity, sex, diagnosis year, comorbidities, frailty, Medicare and Medicaid dual enrollment eligibility, and Medicare Part D low-income subsidy (LIS). Main Outcomes and Measures: The main outcomes were receipt and type of systemic therapy (oral anticancer agent or immunotherapy from 2 months before to 1 year after diagnosis of mRCC) as a function of patient and area-level characteristics. Multivariable regression analyses were used to adjust for patient factors, and odds ratios (ORs) from logistic regression and relative risk ratios (RRRs) from multinomial logistic regression are reported. Results: The sample included 15 407 patients (mean [SD] age, 75.6 [6.8] years), of whom 9360 (60.8%) were men; 6931 (45.0%), older than 75 years; 93 (0.6%), American Indian or Alaska Native; 257 (1.7%), Asian or Pacific Islander; 757 (4.9%), Hispanic; 1017 (6.6%), non-Hispanic Black; 12 966 (84.2%), non-Hispanic White; 121 (0.8%), other; and 196 (1.3%), unknown. Overall, 8317 patients (54.0%) received some type of systemic therapy. After adjusting for individual factors, no county or zip code-level measures of social vulnerability, deprivation, or segregation were associated with disparities in treatment. In contrast, patient-level factors, including female sex (OR, 0.78; 95% CI, 0.73-0.84) and LIS (OR, 0.48; 95% CI, 0.36-0.65), were associated with lack of treatment, with particularly limited access to immunotherapy for patients with LIS (RRR, 0.25; 95% CI, 0.14-0.43). Associations between individual-level factors and treatment in multivariable analysis were not mediated by the addition of area-level metrics. Disparities by race and ethnicity were consistently and only observed within the most vulnerable areas, as indicated by the top quartile of each vulnerability deprivation index. Conclusions and Relevance: In this cohort study of older Medicare patients diagnosed with mRCC, individual-level demographics, including race and ethnicity, sex, and income, were associated with receipt of systemic therapy, whereas area-level measures were not. However, individual-level racial and ethnic disparities were largely limited to socially vulnerable areas, suggesting that efforts to improve racial and ethnic disparities may be most effective when targeted to socially vulnerable areas.

Racial disparity in renal cell carcinoma patient survival according to demographic and clinical characteristics.

BACKGROUND: Patients with renal cell carcinoma (RCC) who are black tend to have poorer prognosis than similar patients who are white. This study examined whether the racial disparity in RCC patient survival varies by demographic and clinical characteristics. METHODS: Nearly 40,000 patients (4359 black and 34,991 white) diagnosed with invasive RCC from 1992 to 2007 were identified from 12 registries in the National Cancer Institute Surveillance, Epidemiology, and End Results program, covering approximately 14% of the US population. Relative survival rates through 2008 were computed using the actuarial method. RESULTS: Proportionally more blacks than whites were diagnosed with RCC under age 50 and with localized cancer. Overall, the 5-year relative survival rates were 72.6% (95% confidence interval 72.0%-73.2%) for white and 68.0% (66.2%-69.8%) for black patients. Survival was higher among women than men and among younger than older patients. Survival decreased with advancing tumor stage and, within each stage, decreased with increasing tumor size. Patients with clear cell RCC, a more common form among whites, had poorer prognosis than patients with papillary or chromophobe subtypes, which are more common among blacks. Survival for patients who received no surgical treatment (10.5% of white patients and 14.5% of black patients) was substantially lower than for patients treated with nephrectomy, with similar survival among whites and blacks. In all other demographic and clinical subgroups of patients, whites consistently had a survival advantage over blacks. CONCLUSIONS: Patients with RCC who are white consistently have a survival advantage over those RCC patients who are black, regardless of age, sex, tumor stage or size, histological subtype, or surgical treatment.

The association between chronic renal failure and renal cell carcinoma may differ between black and white Americans.

PURPOSE: In the United States, renal cell carcinoma (RCC) incidence is higher among blacks than among whites. Risk of RCC is elevated among end-stage renal disease patients, although no studies have looked at differences by race in the relationship between chronic renal failure and RCC. METHODS: We investigated RCC risk in relation to chronic renal failure in a population-based case-control study of blacks and whites in Chicago and Detroit. Data, including information on kidney disease, were collected from interviews with 1,217 RCC cases (361 blacks, 856 whites) and 1,235 controls (523 blacks, 712 whites). Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression. RESULTS: Risk of RCC was increased in relation to chronic renal failure (OR 4.7, 95 % CI 2.2-10.1) and dialysis (OR 18.0, 95 % CI 3.6-91). The association remained after defining exposure as those who had chronic renal failure ≥10 years prior to RCC diagnosis. Chronic renal failure was more strongly associated with RCC among blacks than among whites (OR 8.7, 95 % CI 3.3-22.9 and 2.0, 0.7-5.6, respectively; p (interaction) = 0.03) and among those without a history of diabetes relative to diabetic subjects (OR 8.3, 95 % CI 3.1-22.7 and 1.9, 0.6-5.9, respectively; p (interaction) = 0.03). CONCLUSIONS: These results suggest that chronic renal failure is a strong risk factor for RCC, particularly among black and non-diabetic subjects. Our findings of differences in risk estimates by race, to our knowledge the first such report, require replication.

Association of CXCL12 and CXCR4 gene polymorphisms with the susceptibility and prognosis of renal cell carcinoma.

CXCL12 and its unique receptor CXCR4, play important roles in inflammation and cancer metastasis. This study was undertaken to investigate the association of CXCL12 and CXCR4 polymorphisms with risk and prognosis of renal cell carcinoma (RCC) in the Chinese population. Blood was collected from 322 RCC patients and 402 healthy controls. The CXCL12 rs1801157G/A polymorphism and CXCR4 rs2228014C/T polymorphism were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Results showed that prevalence of CXCL12 rs1801157AA genotype was significantly increased in RCC cases than in controls [odds ratio (OR) = 3.07, 95% confidence interval (CI), 1.98-5.46, P = 6.1 × 10(-6) ; data were adjusted for age and sex]. Similarly, subjects carrying CXCR4 rs2228014CT or TT genotypes showed significantly high risk of RCC (OR = 1.77, 95% CI, 1.28-2.71, P = 0.0003; OR = 4.01, 95% CI, 1.87-9.12, P = 7.8 × 10(-4) , respectively; data were adjusted for age and sex). When analyzing the survival time of RCC, patients with CXCL12 rs1801157AA genotype revealed significantly shorter survival time compared to cases with CXCL12 rs1801157GG and GA genotypes (P = 0.001), whereas RCC patients carrying CXCR4 rs2228014CT and TT genotypes showed shorter survival time than the wild type (P = 0.002). These data indicated that CXCL12 and CXCR4 may be new risk factors for RCC and could be used as prognostic markers for this malignancy.

Adolescent obesity and paternal country of origin predict renal cell carcinoma: a cohort study of 1.1 million 16 to 19-year-old males.

PURPOSE: The incidence of renal cell carcinoma has increased in recent decades, particularly among middle-aged adults. Early precursors of renal cancer remain unclear. We evaluated the association of body mass index and height determined in late adolescence, and paternal or grandpaternal country of origin with the risk of renal cell carcinoma. MATERIALS AND METHODS: Health related data on 1,110,835 males at ages 16 to 19 years who were examined for fitness for military service between 1967 and 2005 were linked to the Israel National Cancer Registry in this nationwide, population based cohort study. We used Cox proportional hazards modeling to estimate the HR of renal cell carcinoma associated with birth year, body mass index, height, father country of origin and socioeconomic indicators. RESULTS: During 19,576,635 person-years of followup renal cancer developed in 274 examinees. Substantial excess risk was conferred by a body mass index of greater than 27.5 kg/m(2) compared to less than 22.5 kg/m(2) (HR 2.43, 95% CI 1.54-3.83, p <0.0001). Asian or African origin was protective compared to European origin (African origin HR 0.67, 95% CI 0.49-0.92). CONCLUSIONS: Overweight in late adolescence is a substantial risk factor for renal cell carcinoma. European origin is independently associated with excess risk and it persists among Israeli born males. Preventing childhood obesity may be a promising target for decreasing the burden of renal cancer.