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.

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.

Socioeconomic determinants of racial disparities in survival outcomes among patients with renal cell carcinoma.

PURPOSE: Racially driven outcomes in cancer are challenging to study. Studies evaluating the impact of race in renal cell carcinoma (RCC) outcomes are inconsistent and unable to disentangle socioeconomic disparities from inherent biological differences. We therefore seek to investigate socioeconomic determinants of racial disparities with respect to overall survival (OS) when comparing Black and White patients with RCC. METHODS: We queried the National Cancer Database (NCDB) for patients diagnosed with RCC between 2004 and 2017 with complete clinicodemographic data. Patients were examined across various stages (all, cT1aN0M0, and cM1) and subtypes (all, clear cell, or papillary). We performed Cox proportional hazards regression with adjustment for socioeconomic and disease factors. RESULTS: There were 386,589 patients with RCC, of whom 46,507 (12.0%) were Black. Black patients were generally younger, had more comorbid conditions, less likely to be insured, in a lower income quartile, had lower rates of high school completion, were more likely to have papillary RCC histology, and more likely to be diagnosed at a lower stage of RCC than their white counterparts. By stage, Black patients demonstrated a 16% (any stage), 22.5% (small renal mass [SRM]), and 15% (metastatic) higher risk of mortality than White patients. Survival differences were also evident in histology-specific subanalyses. Socioeconomic factors played a larger role in predicting OS among patients with SRMs than in patients with metastasis. CONCLUSIONS: Black patients with RCC demonstrate worse survival outcomes compared to White patients across all stages. Socioeconomic disparities between races play a significant role in influencing survival in RCC.

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.

Race/Ethnicity Determines Life Expectancy in Surgically Treated T1aN0M0 Renal Cell Carcinoma Patients.

BACKGROUND: Life expectancy (LE) is an important consideration in the clinical decision-making for T1aN0M0 renal cell cancer (RCC) patients. OBJECTIVE: To test the effect of race/ethnicity (Caucasian, African American, Hispanic/Latino, and Asian) on LE predictions from Social Security Administration (SSA) life tables in male and female T1aN0M0 RCC patients. DESIGN, SETTING, AND PARTICIPANTS: We relied on the Surveillance, Epidemiology, and End Results database. INTERVENTION: Radical nephrectomy (RN) and partial nephrectomy (PN). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Five-year and 10-yr observed overall survival (OS) of pT1aN0M0 RCC patients treated between 2004 and 2006 were compared with the LE predicted from SSA life tables. We repeated the comparison in a more contemporary cohort (2009-2011), with 5-yr follow-up and higher PN rates. RESULTS AND LIMITATIONS: In the 2004-2006 cohort, PN rate was 40.7%. OS followed the predicted LE in Caucasians, Hispanics/Latinos, and Asians, but not in African Americans, in whom 5-yr OS rates were 5.0% (male) and 8.7% (female) and 10-yr rates were 4.2% (male) and 11.1% (female) lower than predicted. In the 2009-2011 cohort, PN rate was 59.4%. Same observations were made for OS versus predicted LE in Caucasians, Hispanics/Latinos, and Asians. In African Americans, 5-yr OS rates were 1.5% (male) and 4.9% (female) lower than predicted. CONCLUSIONS: In RN- or PN-treated pT1aN0M0 RCC patients, LE predictions closely approximated OS of Caucasians, Hispanics/Latinos, and Asians. In African-American patients, SSA life tables overestimated LE, more in females than in males. The limitations of our study are its retrospective nature, its validity for US patients only, and the under-representation of racial/ethnic minorities. PATIENT SUMMARY: Social Security Administration life tables can be used to estimate long-term life expectancy in patients who are surgically treated for renal cancer (≤4 cm). However, while for Caucasians, Hispanics/Latinos, and Asians, the prediction performs well, life expectancy of African Americans is generally overestimated by life table predictions. TAKE HOME MESSAGE: In the clinical decision-making process for T1aN0M0 renal cell cancer patients eligible for radical or partial nephrectomy, the important influence of patient sex and race/ethnicity on life expectancy should be taken into account, when using Social Security Administration life tables.

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).

Racial/ethnic disparities in renal cell carcinoma: Increased risk of early-onset and variation in histologic subtypes.

BACKGROUND: Racial/ethnic minority groups have a higher burden of renal cell carcinoma (RCC), but RCC among Hispanic Americans (HAs) and American Indians and Alaska Natives (AIs/ANs) are clinically not well characterized. We explored variations in age at diagnosis and frequencies of RCC histologic subtypes across racial/ethnic groups and Hispanic subgroups using National Cancer Database (NCDB) and Arizona Cancer Registry Data. METHODS: Adult RCC cases with known race/ethnicity were included. Logistic regression analysis was performed to estimate odds and 95% confidence interval (CI) of early-onset (age at diagnosis <50 years) and diagnosis with clear cell RCC (ccRCC) or papillary RCC. RESULTS: A total of 405 073 RCC cases from NCDB and 9751 cases from ACR were identified and included. In both datasets, patients from racial/ethnic minority groups had a younger age at diagnosis than non-Hispanic White (NHW) patients. In the NCDB, AIs/ANs had twofold increased odds (OR, 2.21; 95% CI, 1.88-2.59) of early-onset RCC compared with NHWs. HAs also had twofold increased odds of early-onset RCC (OR, 2.14; 95% CI, 1.79-2.55) in the ACR. In NCDB, ccRCC was more prevalent in AIs (86.3%) and Mexican Americans (83.5%) than NHWs (72.5%). AIs/ANs had twofold increased odds of diagnosis with ccRCC (OR, 2.18; 95% CI, 1.85-2.58) in the NCDB, but the association was stronger in the ACR (OR, 2.83; 95% CI, 2.08-3.85). Similarly, Mexican Americans had significantly increased odds of diagnosis with ccRCC (OR, 2.00; 95% CI, 1.78-2.23) in the NCDB. CONCLUSIONS: This study reports younger age at diagnosis and higher frequencies of ccRCC histologic subtype in AIs/ANs and Hispanic subgroups. These variations across racial/ethnic groups and Hispanic subgroups may have potential clinical implications.

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.

Racial and Ethnic Disparities in Renal Cell Carcinoma: An Analysis of Clinical Characteristics.

BACKGROUND: Racial/ethnic minority groups, including Hispanic Americans (HAs) and Native Americans (NAs), have a heavier burden of kidney cancer than European Americans (EAs). We investigated variations in clinical characteristics of HA and NA patients with renal cell carcinoma (RCC) who were previously underrepresented. MATERIALS AND METHODS: Clinical records of 294 patients with RCC (151 EAs, 95 HAs, 22 NAs, and 26 others) without prior diagnosis of cancer were reviewed. Logistic regression analysis was performed to understand patients' clinical characteristics. RESULTS: HAs had about 5 years younger average age at diagnosis than EAs (55.8 vs. 60.5 years) and an almost 3-fold increased odds of diagnosis before age 50 years (odds ratio [OR], 2.77; 95% confidence interval [CI], 1.39-5.54). The mean age of diagnosis among NAs was 49.7 years, and NAs had an over 6-fold higher odds of diagnosis at a younger age (OR, 6.23; 95% CI, 2.00-19.46). Clear-cell RCC (ccRCC) was more common in HAs and NAs than EAs. Over 90% of HA patients had ccRCC, whereas only 78.8% of EA patients had ccRCC. HAs had increased odds of diagnosis with ccRCC compared with EAs (OR, 2.79; 95% CI, 1.15-6.80). Among HAs, older patients and patients who spoke Spanish as their primary language were more likely to have advanced stage RCC at diagnosis (OR, 10.48; 95% CI, 1.69-64.89 and OR, 4.61; 95% CI, 1.38-15.40). CONCLUSION: HA and NA patients with RCC had different clinical characteristics than EA patients. It is necessary to better understand the clinical characteristics of these underserved HA and NA populations with high kidney cancer burden.

Significance of Age in Japanese Patients Receiving Sunitinib as First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: Comparative Assessment of Efficacy and Safety between Patients Aged <75 and ≥75 Years.

BACKGROUND/AIM: To date, it has not been well characterized whether sunitinib is effective in elderly patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to investigate the impact of age on clinical outcomes of mRCC patients receiving sunitinib. PATIENTS AND METHODS: The efficacy and safety of first-line sunitinib in 154 consecutive mRCC patients were retrospectively compared between patients aged <75 (n=125) and ≥75 (n=29) years. RESULTS: There were no significant differences in the major clinicopathological characteristics between younger and older patients; however, the reduction of the initial dose of sunitinib was significantly more frequent in older than younger patients. No significant difference in response rate, clinical benefit rate or proportion of patients going on to receive second-line therapy was noted between these two groups. Furthermore, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two groups, and no significant impact of age on PFS or OS was documented by the Cox proportional hazards regression analyses. Of several adverse events, only anemia and fatigue were significantly more frequently observed in older than younger patients. Although there was no significant difference in the incidence of dose reduction or discontinuation of sunitinib between the two groups, the interruption of sunitinib was more frequently required in older than younger patients. CONCLUSION: These findings suggest that advanced age alone should not be regarded as a contraindication to the introduction of sunitinib as first-line systemic therapy for mRCC patients.

Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial.

BACKGROUND: The international, phase 3 COMPARZ study demonstrated that pazopanib and sunitinib have comparable efficacy as first-line therapy in patients with advanced renal cell carcinoma, but that safety and quality-of-life profiles favor pazopanib. Our report analyzed pazopanib and sunitinib safety in Asian and non-Asian subpopulations. METHODS: Patients were randomized 1:1 to receive pazopanib 800 mg once daily (continuous dosing) or sunitinib 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off). RESULTS: Safety population was composed of 363 Asian patients and 703 non-Asian patients. Asian patients had similar duration of exposure to either drug compared with non-Asian patients, although Asian patients had a higher frequency of dose modifications. Overall, hematologic toxicities, cytopenias, increased AST/ALT, and palmar-plantar erythrodysesthesia (PPE) were more prevalent in Asian patients, whereas gastrointestinal toxicities were more prevalent in non-Asian patients. Among Asian patients, hematologic adverse events and most non-hematologic AEs were more common in sunitinib-treated versus pazopanib-treated patients. Among Asian patients, the most common grade 3/4 AEs with pazopanib were hypertension (grade 3, 22%) and alanine aminotransferase increased (grade 3, 12%; grade 4, 1%); the most common grade 3/4 AEs with sunitinib were thrombocytopenia/platelet count decreased (grade 3, 36%; grade 4, 10%), neutropenia/neutrophil count decreased (grade 3, 24%; grade 4, 3%) hypertension (grade 3, 20%), and PPE (grade 3, 15%). CONCLUSIONS: A distinct pattern and severity of adverse events was observed in Asians when compared with non-Asians with both pazopanib and sunitinib. However, the two drugs were well tolerated in both subpopulations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00720941 , Registered July 22, 2008 ClinicalTrials.gov, NCT01147822 , Registered June 22, 2010.

Racial Disparities and Preventive Measures to Renal Cell Carcinoma.

Kidney cancer ranks among the top 10 cancers in the United States. Although it affects both male and female populations, it is more common in males. The prevalence rate of renal cell carcinoma (RCC), which represents about 85% of kidney cancers, has been increasing gradually in many developed countries. Family history has been considered as one of the most relevant risk factors for kidney cancer, although most forms of an inherited predisposition for RCC only account for less than four percent. Lifestyle and other factors such as occupational exposure, high blood pressure, poor diet, and heavy cigarette smoking are highly associated with its incidence and mortality rates. In the United States, White populations have the lowest prevalence of RCC compared to other ethnic groups, while Black Americans suffer disproportionally from the adverse effects of RCC. Hence, this review article aims at identifying the major risk factors associated with RCC and highlighting the new therapeutic approaches for its control/prevention. To achieve this specific aim, articles in peer-reviewed journals with a primary focus on risk factors related to kidney cancer and on strategies to reduce RCC were identified. The review was systematically conducted by searching the databases of MEDLINE, PUBMED Central, and Google Scholar libraries for original articles. From the search, we found that the incidence and mortality rates of RCC are strongly associated with four main risk factors, including family history (genetics), lifestyle (poor diet, cigarette smoking, excess alcohol drinking), environment (community where people live), and occupation (place where people work). In addition, unequal access to improvement in RCC cancer treatment, limited access to screening and diagnosis, and limited access to kidney transplant significantly contribute to the difference observed in survival rate between African Americans and Caucasians. There is also scientific evidence suggesting that some physicians contribute to racial disparities when performing kidney transplant among minority populations. New therapeutic measures should be taken to prevent or reduce RCC, especially among African Americans, the most vulnerable population group.

Effect of African-American race on cancer specific mortality differs according to clear cell vs. non-clear cell histologic subtype in metastatic renal cell carcinoma.

AIM: To test the effect of African-American race on cancer specific mortality (CSM) in clear cell metastatic renal cell carcinoma (ccmRCC) and non-ccmRCC. PATIENTS AND METHODS: Within Surveillance, Epidemiology and End Results registry (2001-2014), we identified patients with ccmRCC and non-ccmRCC. We relied on propensity score (PS) matching to reduce the effect of inherent differences between African-American vs. Caucasian patients. After PS matching that included access to cytoreductive nephrectomy (CNT), cumulative incidence, competing-risks regression (CRR) models and landmark analyses tested the effect of race on CSM. RESULTS: Before PS matching, African-American patients accounted for 7.0 and 24.5% of respectively ccmRCC (N = 6742) and non-ccmRCC patients (N = 766). After PS matching, African-American patients accounted for 22.3 and 33.5% of respectively ccmRCC (N = 2050) and non-ccmRCC (N = 391) matched cohorts. In multivariable CRR models focusing on ccmRCC, higher CSM was recorded in African-Americans (HR:1.27, p < 0.001). Conversely, in non-ccmRCC, lower CSM was recorded in African-Americans (HR:0.54, p < 0.001). Landmark analyses rejected the hypothesis of immortal time bias. CONCLUSION: African-Americans experienced higher CSM in ccmRCC. Conversely, African-Americans experienced lower CSM, when diagnosed with non-ccmRCC. These differences are independent of access to CNT and warrant further study since they may have an impact on efficacy or access to systemic therapies.

The Effect of Patient and Surgical Characteristics on Renal Function After Partial Nephrectomy.

BACKGROUND: The purpose of the study was to identify patient and disease characteristics that have an adverse effect on renal function after partial nephrectomy. PATIENTS AND METHODS: We conducted a retrospective review of 387 patients who underwent partial nephrectomy for renal tumors between 2006 and 2014. A line plot with a locally weighted scatterplot smoothing was generated to visually assess renal function over time. Univariable and multivariable longitudinal regression analyses incorporated a random intercept and slope to evaluate the association between patient and disease characteristics with renal function after surgery. RESULTS: Median age was 60 years and most patients were male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia time, history of smoking, and hypertension were significantly associated with lower preoperative estimated glomerular filtration rate (eGFR). In multivariable analysis, independent predictors of reduced renal function after surgery included advanced age, lower preoperative eGFR, and longer ischemia time. Length of time from surgery was strongly associated with improvement in renal function among all patients. CONCLUSION: Independent predictors of postoperative decline in renal function include advanced age, lower preoperative eGFR, and longer ischemia time. A substantial number of subjects had recovery in renal function over time after surgery, which continued past the 12-month mark. These findings suggest that patients who undergo partial nephrectomy can experience long-term improvement in renal function. This improvement is most pronounced among younger patients with higher preoperative eGFR.

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.

Association of race and margin status among patients undergoing robotic partial nephrectomy for T1 renal cell carcinoma: Results from a population-based cohort.

OBJECTIVE: To assess the relationship of race and margin status among patients undergoing robotic partial nephrectomy (RPN) for T1 renal tumors from a contemporary population-based cohort. METHODS: Using the National Cancer Database, we identified patients with localized renal cell carcinoma (RCC) (clinical T1N0M0) who underwent RPN from 2010 to 2013. The primary outcome was positive surgical margins (PSM). Multivariable logistic regression analyses were used to assess the association between race and PSM adjusting for patient clinicopathologic and hospital factors. RESULTS: Among 12,515 patients undergoing RPN in our cohort, 8.3% had PSM (n = 1,045). When compared to white patients undergoing RPN for T1 RCC with PSM (7.9%), we observed a higher proportion of PSM among African American (AA) (10.8%; P = 0.005) and Hispanic/Latino patients (8.8%; P = 0.005), respectively. On multivariable analysis, AA patients had higher odds of PSM compared to white patients (odds ratio = 1.40; P = 0.008). Other factors associated with higher odds of PSM were treatment at nonacademic centers relative to academic centers (10.4% vs. 6.9%; odds ratio = 1.57; P<0.001). CONCLUSIONS: In this contemporary population-based cohort, AA patients undergoing RPN for localized RCC tumors are at higher risk for PSM. These results suggest potential differences in quality of care and patient selection of RPN by race.

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.

Clear Cell Papillary Renal Cell Carcinoma: New Clinical and Imaging Characteristics.

OBJECTIVE: To investigate clear cell papillary (CCP) renal cell carcinoma (RCC), an uncommon tumor of low malignant potential characterized by low-grade, clear cells, showing papillary and tubular architecture. This relatively newly described entity is still being characterized. We present our series of CCP RCC with new clinical and imaging findings. MATERIALS AND METHODS: We reviewed the clinical, pathologic, and imaging findings of 28 CCP RCCs in 21 patients identified from our institution between 2010 and 2016. RESULTS: Sixteen of 21 (76%) patients were African American with an equal male-to-female ratio. Mean follow-up was 26.1 ± 16.9 months. Mean age at diagnosis was 58.3 ± 10.7 years, and mean preoperative creatinine was 2.7 ± 2.9 mg/dL. End-stage renal disease or chronic kidney disease was present in 10 of 21 (47.6%) patients. Mean tumor size was 2.2 ± 1.5 cm. All cases were stage pT1, and 25 of 28 (89%) tumors were grade 2. No necrosis or sarcomatoid features were identified. Two patients had synchronous clear cell RCC and 1 patient had synchronous papillary RCC. No recurrence or metastases were identified. On imaging, the majority of the lesions were solid, with relatively low-level enhancement, similar to papillary RCC, with regions of heterogeneous hyper-enhancement, similar to clear cell RCC. The rate of growth on serial imaging was comparable with that observed for other low-staged RCCs. CONCLUSION: In our series, CCP RCC was seen more commonly in African American patients and associated with end-stage renal disease or chronic kidney disease. Imaging characteristics are similar in both clear cell RCC and papillary RCC. A nephron-sparing approach is recommended when surgically feasible.