Incidence Rates Of Renal Cell Carcinoma Research Articles

Renal Findings in Patients with Thalassemia at Abdominal Ultrasound: Should We Still Talk about "Incidentalomas"? Results of a Long-Term Follow-Up.

We retrospectively collected all ultrasound imaging data of our thalassemia patients over a period of 10 years with the aim of assessing the prevalence and the risk factors of renal stones and cysts. Moreover, we assessed the incidence of renal-cell carcinoma (RCC) among thalassemia patients (133 with thalassemia major (TM) and 157 with thalassemia intermedia (TI)) and its association with demographic and clinical findings. Renal stones were detected in 15.2% of patients. In the multivariable Cox regression analysis, the independent predictors were blood consumption, splenectomy, and proteinuria. Renal cysts were detected in 18.4% of patients. In the multivariable analysis, age emerged as the only independent predictor. After the first detection, 35% of the patients showed changes in the number, size, or grading of renal cysts. During the study period, the crude incidence rate of RCC was 75.9 cases per 100,000 person-years. The most frequent histological subtype (80%) included clear-cell RCC. In total, 80% of patients with RCC had TM and all were positive for hepatitis C virus antibodies. Thalassemia patients are significantly affected by asymptomatic renal diseases such as stones, cysts, and cancer, suggesting the need for regular screening by imaging.

Association of Processed Meats and Alcohol Consumption with Renal Cell Carcinoma: A Worldwide Population-Based Study

The link between diet and renal cell carcinoma (RCC) is still unclear. The purpose of this study was to evaluate the association of diet with RCC’s incidence and mortality rates worldwide. We conducted an ecological study including 170 countries, whose data on age-standardized (AS) incidence and mortality rates of RCC, dietary factors, and potentially confounding factors such as obesity, insufficient physical activity, tobacco smoking, hypertension, diabetes, and human development index (HDI) were collected and available on May 2020 from the Global Cancer Observatory, the Global Dietary Database, the Global Health Observatory data repository, the Diabetes Atlas 9th edition and the Human Development Report 2019. Univariable and multivariable linear regression analyses were performed to determine the association of dietary factors with incidence and mortality rates of RCC adjusted for the effects of population age and potentially confounding factors. Intake of processed meats and consumption of alcohol were both positively associated with AS incidence rates of RCC (β = 0.11, P < 0.001 and β = 0.1, P = 0.044, respectively). We suggest that high consumption of processed meats and/or alcohol is a risk factor for RCC. However, they were not associated with mortality. Further research is needed at an individual level. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2020.1856388.

Le cancer du rein dans le département de L’Hérault : résultats de 30 ans d’enregistrement

The objective of the study was to determine the specificities of renal cell carcinoma (RCC) in the department of Herault using the Herault Tumor Registry over 30 years. Data of this study were obtained from the Herault cancer database. We analysed the evolution of RCC from 1987 to 2016, including the incidence, mortality, cancer pathology and staging at the moment of diagnosis. We compared our results with national and international data. We identified 3769 newly diagnosed RCC: 2628 in men (69,7%) and 1141 in women (30,3%). In 2016, RCC was the 8th most frequent cancer, both genders combined, the 7th most frequent cancer in men and the 11th in women. New cases of RCC increased by 4.2 in men and 3.3 in women over the study period. The number of localised forms increased by 9% over 20 years. In 2016, the probability of having a RCC before the age of 75 was of 2.11% for a man and of 0.62% for a woman. Over 30 years, the incidence rate of RCC increased in the department of Herault; however, mortality decreased over the same period. This analytical data should be improved by the development of the Registry of Herault Specialised in Onco-Urology (RHESOU). 3.

Renal cell carcinoma incidence rates and trends in young adults aged 20-39 years

BackgroundThe burden of renal cell carcinoma (RCC) in young adults received marginal attention. We assessed contemporary gender, race and stage-specific incidence and trends of RCC among young adults (20–39 years-old) in the United States. MethodsWithin Surveillance, Epidemiology, and End Results database (2000–2016), patients aged 20–39 years with histologically confirmed RCC were included. Age-standardized incidence rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC). ResultsFrom 2000–2016, 7767 new RCC cases were recorded (ASR 0.6, AAPC + 5.0 %, p < 0.001). ASRs were higher in males than in females (0.7 and 0.5, respectively) and increased significantly in both genders (AAPC + 5.0 % and +4.7 % both p < 0.001, respectively). Non-Hispanic American Indian/Alaska Native had the highest incidence (ASR 1.0) vs. non-Hispanic Asian or Pacific Islander the lowest (ASR 0.3). ASRs significantly increased in all ethnic groups. T1aN0M0 and T1bN0M0 stages showed the highest incidence and increase (ASR 0.3, AAPC + 5.9 %, p < 0.001 and ASR 0.1, AAPC + 5.7 %, p < 0.001, respectively). Also regional and distant stages increased (AAPC + 3.7 %, p = 0.001 and AAPC + 1.5 %, p = 0.06). The most frequent tumor characteristics were G2 (44.4 %, ASR 0.3, AAPC + 6.3 %, p < 0.001) and G1 (13.1 %, ASR 0.1, AAPC + 1.1 %, p = 0.2), as well as clear cell histology (54.8 %, ASR 0.3, AAPC + 7.6 %, p < 0.001). ConclusionsRCC in young adults is rare, but increasing. This is mainly due to T1aN0M0 tumors. Nonetheless, also regional diseases are significantly increasing. Differences between ethnic groups exist and may warrant further research.

Abstract D121: Predicting African American and European American patient response to kidney cancer immunotherapy by stage using the tumor microenvironment

Abstract Background Kidney cancer ranks as a top ten leading site of new cancer cases (~64,000) in the US each year. Renal Cell Carcinoma (RCC) is the predominant type of kidney cancer (~90% cases). The most common RCC subtypes include clear cell RCC (ccRCC, 75%), papillary RCC types I and II (pRCC I and II, 5% and 10%), and chromophobe RCC (chRCC, 5%). RCC subtypes have distinct responses to immunotherapy. Combination checkpoint inhibitors are the first-line treatment for advanced stage ccRCC. Unfortunately, response varies in advanced stage patients, suggesting stage-specific differences in tumor biology. Tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME) have been shown to directly influence checkpoint inhibitor response. African Americans (AAs) have higher RCC incidence rates than European Americans (EAs) for reasons that are unclear. Biological determinants of this cancer health disparity have been largely understudied. To our knowledge, no study to date has profiled the TME by stage in AA and EA RCC patients and explored its usefulness as a predictor of checkpoint inhibitor response. Hypothesis TIL abundances and composition varies by stage between AAs and EAs with RCC. Methods Downloaded mRNA-sequencing and clinical data for 531 ccRCC patients, 52 Type I pRCC patients, 66 Type II pRCC patients, and 66 chRCC patients in the TCGA discovery cohort. Differential expression analyses for checkpoint inhibitor drug targets (PD-1, PD-L1, and CTLA-4) were carried out. CIBERSORT, a computation tool that quantifies abundances for 22 TILs based on gene expression, was used to characterize the TME. 1-way ANOVAs between Stages I-IV were performed with GraphPad Prism 8. Significant racial differences for relevant TILs were determined using two-tailed unpaired Welch t tests. Kidney cancer immunotherapy drug responses were inferred based on published clinical studies. Results PD-1 and CTLA-4 significantly increased in advanced stage ccRCC patients. 6/22 TILs showed stage-specific increases and decreases in ccRCC patients. Interestingly, three of these (follicular helper T cells, regulatory T cells, and CD8+ T cells) showed the same trend as the checkpoint inhibitor targets. In pRCC I and II, some TILs also demonstrated a linear increase by stage (Both: regulatory T cells, M1 macrophages; Type II only: naive B cells). M2 macrophage abundance increased significantly by stage in chRCC patients. When comparing AA (n=55) and EA (n=461) ccRCC patients, follicular helper T cells and regulatory T cells increased by stage in EA only. CD8+ T cells increased in abundance in both racial groups. Regulatory T cells and M2 macrophages have been reported to mediate clinical response to checkpoint inhibitor immunotherapy. Conclusions/Future Directions Our data suggests AA and EA RCC patients with advanced stage disease will respond differently to kidney cancer immunotherapy due to TME differences, namely TIL abundance and composition. Future studies include validating these findings in the expO cohort. Citation Format: Jacquelyn Cobb, Heinric Williams, Khadijah A. Mitchell. Predicting African American and European American patient response to kidney cancer immunotherapy by stage using the tumor microenvironment [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D121.

Contemporary Age-adjusted Incidence and Mortality Rates of Renal Cell Carcinoma: Analysis According to Gender, Race, Stage, Grade, and Histology

BackgroundRecent data showed that North America has the highest incidence of renal cell carcinoma (RCC) worldwide. ObjectiveTo assess contemporary gender-, race-, and stage-specific incidence; survival rates; and trends of RCC patients in the USA. Design, setting, and participantsWithin the Surveillance, Epidemiology, and End Results database (2001–2016), all patients aged ≥18 yr with histologically confirmed renal parenchymal tumors were included. Outcome measurements and statistical analysisAge-adjusted incidence rates and 5-yr cancer-specific survival (CSS) rates were estimated. Temporal trends were calculated through Joinpoint regression analyses to describe the average annual percent change (AAPC). Results and limitationsThe age-adjusted incidence rate of RCC was 11.3/100 000 person years (AAPC+2.0%, p<0.001). Five-year CSS rates increased from 78.4% to 84.5% (AAPC +0.8%, p<0.001). Male incidence was double that of females (15.5 and 7.7, respectively). CSS marginally favored females (84.5% vs 82.0%), but improved equally in both genders (both AAPC +0.8%). The highest incidence (14.1/100 000 person years, AAPC +2.8%) and lowest survival (80.1%) were recorded in non-Hispanic American Indian/Alaska Native populations. T1aN0M0 had the highest incidence rates (4.6/100 000 person years), the highest increase over time (AAPC +3.6%), and the highest CSS (97.6%) of all stages. Limitations include retrospective nature and lack of information on risk factors. ConclusionsThe incidence of RCC increased significantly from 2001 to 2016, and 5-yr CSS after RCC improved. This was mainly due to T1aN0M0 tumors that showed the highest increase in the incidence and highest CSS. Unfavorable outcomes in specific ethnic groups warrant further research. Patient summaryWe examined contemporary incidence and cancer-specific survival rates of kidney cancer. Males had double the incidence rates of females, but lower survival. Natives showed the highest incidence rates and the lowest survival rates. Small renal masses showed the highest incidence and survival rates.

The long-term rapid increase in incidence of adenocarcinoma of the kidney in the USA, especially among younger ages.

We previously observed a rapid increase in the incidence of renal cell carcinoma (RCC) in men and women between 1935 and 1989 in the USA, using data from the Connecticut Tumor Registry. This increase appeared to be largely explained by a positive cohort effect, but no population-based study has been conducted to comprehensively examine age-period-cohort effects by histologic types for the past decade. We calculated age-adjusted and age-specific incidence rates of the two major kidney-cancer subtypes RCC and renal urothelial carcinoma, and conducted an age-period-cohort analysis of 114 138 incident cases of kidney cancer reported between 1992 and 2014 to the Surveillance, Epidemiology, and End Results programme. The age-adjusted incidence rates of RCC have been increasing consistently in the USA among both men and women (from 12.18/100 000 in 1992-1994 to 18.35/100 000 in 2010-2014 among men; from 5.77/100 000 in 1992-1994 to 8.63/100 000 in 2010-2014 among women). Incidence rates generally increased in successive birth cohorts, with a continuing increase in rates among the younger age groups (ages 0-54 years) in both men and women and among both Whites and Blacks. These observations were confirmed by age-period-cohort modelling, which suggested an increasing birth-cohort trend for RCC beginning with 1955 birth cohorts, regardless of the assumed value for the period effect for both men and women and for Whites and Blacks. Known risk factors for kidney cancer may not fully account for the observed increasing rates or the birth-cohort pattern for RCC, prompting the need for additional etiologic hypotheses (such as environmental exposures) to investigate these descriptive patterns.

Renal cell carcinoma trends in Latvia: incidence, mortality, and survival rates. Population-based study.

IntroductionBaltic States including Latvia are reported as having one of the highest renal cell carcinoma (RCC) incidence and mortality rates in the world. However, data are often presented without stage-specific stratification, making assessment of the overall RCC diagnosis and survival trends challenging.Material and methodsWe collected data on all newly diagnosed RCC patients from the national population-based cancer registry between 1997 and 2016. We analyzed RCC incidence, mortality and survival trends using Joinpoint analysis. Kaplan-Meier analysis was performed for 5- and 10-year cancer specific survival rate calculations.ResultsThere were a total of 7893 patients with newly diagnosed RCC. The age standardized (AS) incidence rate (per 100,000) increased slightly from 8.9 in 1997 to 9.8 in 2016. There were no specific changes in the incidence rate trend. Detection of early stage RCC increased by 5.4% annually. The AS mortality rates (per 100,000) decreased from 4.9 in 1997 to 3.9 in 2016, however, it did not reach a statistically significant change. The mortality rates decreased significantly in females and in the age group of 60-69 years. The 5-year cancer specific survival (CSS) rate increased from 55.1% in 1997-2001 to 66.6% in years 2007–2011. The 10-year CSS rate increased from 49.1% in 1997–2001 to 56.5% in years 2002–2006.ConclusionsDuring the study period, RCC incidence rates increased and overall mortality rates did not change. Similar to the rest of the world, the incidence of RCC diagnosed at an earlier stage increased and 5- and 10-year survival rates improved.

Trends in Renal-Cell Carcinoma Incidence and Mortality in the United States in the Last 2 Decades: A SEER-Based Study.

Renal-cell carcinoma (RCC) is one of the common malignancies in the United States. RCC incidence and mortality have been changing for many reasons. We performed a thorough investigation of incidence and mortality trends of RCC in the United States using the cell Surveillance, Epidemiology, and End Results (SEER) database. The 13 SEER registries were accessed for RCC cases diagnosed between 1992 and 2015. Incidence and mortality were calculated by demographic and tumor characteristics. We calculated annual percentage changes of these rates. Rates were expressed as 100,000 person-years. A total of 104,584 RCC cases were reviewed, with 47,561 deaths. The overall incidence was 11.281 per 100,000 person-years. Incidence increased by 2.421% per year (95% confidence interval, 2.096, 2.747; P< .001) but later became stable since 2008. However, the incidence of clear-cell subtype continued to increase (1.449%; 95% confidence interval, 0.216, 2.697; P= .024). RCC overall mortality rates have been declining since 2001. However, mortality associated with distant RCC only started to decrease in 2012, with an annual percentage change of 18.270% (95% confidence interval,-28.775,-6.215; P= .006). Despite an overall increase in the incidence of RCC, there has been a recent plateau in RCC incidence rates with a significant decrease in mortality.

Renal cell carcinoma: links and risks.

This review provides an overview of the incidence of renal cell carcinoma (RCC) and a summary of the most commonly associated risk factors. A literature review was performed with a focus on recent studies with a high level of evidence (large prospective cohort studies and meta-analyses). The incidence rate of RCC varies globally, with the rate rising rapidly in more developed regions, demonstrating the effects of increased use of diagnostic imaging and prevalence of modifiable risk factors. Based on the current evidence, cigarette smoking, obesity, and hypertension are the most well-established risk factors for sporadic RCC worldwide. Acquired cystic kidney disease is also a significant risk factor, specifically in dialysis patients. There is increasing evidence for an inverse association between RCC risk and moderate alcohol consumption. Certain analgesics and occupational exposure have been linked to an increased risk of RCC, although data are limited. Diets rich in fruits and vegetables may provide a protective effect.

Within-state Geographical Variations in Renal Cell Carcinoma Incidence: Rural Disparities in the State of Illinois

Objectives: Rural-urban disparities in renal cell carcinoma (RCC) mortality have been observed, and we sought to determine if increased male RCC incidence rates in six contiguous counties (S6Co) in rural southern Illinois (IL) could be explained by known risk factors or require consideration of other etiological influences. Methods: We analyzed incidence and behavioral risk factor data for the S6Co, similarly rural IL and US counties (rural-urban classification codes 7 through 9; ILRUCC 7-9 and USRUCC 7-9), the remaining IL counties (ILr), and total IL and US. Results: ILRCC rates are higher than the US at both the total population (22.2/100,000 (95% CI=21.8-22.6) vs. 19.9 (19.8-20.1)) and rural (RUCC7-9; 23.7 (21.7-25.8) vs. 20.7 (19.9-21.5)) levels, with S6Co the highest (30.8 (24.8-37.5)). Within IL, the S6Co RCC rate remained significantly increased compared to both IL r and IL RUCC 7-9 after adjustment for smoking, obesity and hypertension. Conclusion: Rural IL males experience increased RCC risk which may be attributed to a locally-specific combination of genetic, environmental and cultural factors. State-level chronic disease control programs should examine how such factors may significantly vary across relatively small geographical scales.

Contemporary incidence and mortality rates of kidney cancer in the United States.

This is a timely update of incidence and mortality for renal cell carcinoma (RCC) in the United States. Relying on the Surveillance, Epidemiology, and End Results (SEER) database, we computed age-adjusted incidence, mortality rates and 5-year cancer-specific survival (CSS) for patients with histologically confirmed kidney cancer between 1975 and 2009. Long-term (1975-2009) and short-term (2000-2009) trends were examined by joinpoint analysis, and quantified using the annual percent change (APC). The reported findings were stratified according to disease stage. Age-adjusted incidence rates of RCC increased by +2.76%/year between 1975 and 2009 (from 6.5 to 17.1/100 000 person-years, p < 0.001), and by +2.85%/year between 2000 and 2009 (p < 0.001). For the same time points, the corresponding APC for the incidence of localized stage were +4.55%/year (from 3.0 to 12.2/100 000 person years, p < 0.001), and +4.42%/year (p < 0.001), respectively. The incidence rates of regional stage increased by +0.88%/year between 1975 and 2009 (p < 0.001), but stabilized in recent years (2000-2009: +0.56%/year, p = 0.4). Incidence rates of distant stage remained unchanged in long- and short-term trends. Overall mortality rates increased by +1.72%/year between 1975 and 2009 (from 1.2 to 5.0/100 000 person-years, P<0.001), but stabilized between 1994 and 2004 (p = 0.1). Short-term mortality rates increased in a significant fashion by +3.14%/year only for localized stage (p < 0.001). In contemporary years, there is a persisting upward trend in incidence and mortality of localized RCC.

Characteristics of patients diagnosed with both melanoma and renal cell cancer

Patients with renal cell carcinoma (RCC) and malignant melanoma (MM) have an increased risk of additional malignancies. We identified characteristics of MM and RCC associated with a patient developing both cancers. A total of 147,656 cases of RCC and 225,548 of MM submitted to the Surveillance, Epidemiology, and End Results database between 1973 and 2008 were analyzed. Standardized incidence ratios (SIR) with 95 % confidence intervals (CI) were calculated for MM after RCC and vice versa. Clinical and pathological characteristics were compared between patients with RCC or MM only and with both cancers using multivariable proportional hazards and competing risks regression models. Overall 1,241 patients developed both cancers. The crude incidence rates of RCC in patients with a prior MM diagnosis and vice versa were 5.2 and 9.4 per 10,000 person-years, respectively. There was an excess of MM in RCC patients (SIR 1.45, CI 1.34-1.57) and of RCC in MM patients (SIR 1.34, CI 1.25-1.43). Median years from RCC to MM diagnosis was 4.3 (2.0-7.8) and from MM to RCC 4.7(2.3-9.9). Patients with a history of MM had more papillary RCC (10.2 vs. 4.8 %, p = 0.01) and were more likely to be female (25.9 vs. 20.5 %, p < 0.001). On multivariable analyses, ocular MM was independently associated with subsequent RCC (HR 1.76 CI 1.24-2.49), as were increasing age, and male sex. We confirmed a bidirectional association between RCC and MM. A history of MM was found to be associated with papillary RCC and advanced RCC. Ocular MM predicted an increased risk of RCC diagnosis. Further research is warranted into the mechanisms responsible for the association between RCC and MM.

Reply

We appreciate the kind and thoughtful editorial remarks. As previously stated, the incidence of renal cell carcinoma (RCC) has been rising steadily in the United States for several decades, and many have attributed this in part to the increased detection of small, incidental renal masses found on cross-sectional imaging. 1 Chow W.H. Devesa S.S. Warren J.L. et al. Rising incidence of renal cell carcinoma in the United States. JAMA. 1999; 281: 1628-1631 Crossref PubMed Scopus (1333) Google Scholar , 2 Homma Y. Kawabe K. Kitamura T. et al. Increased incidental detection and reduced mortality in renal cancer – recent retrospective analysis at eight institutions. Int J Urol. 1995; 2: 77-80 Crossref PubMed Scopus (142) Google Scholar , 3 Hollingsworth J.M. Miller D.C. Daignault S. et al. Rising incidence of small renal masses: a need to reassess treatment effect. J Natl Cancer Inst. 2006; 98: 1331-1334 Crossref PubMed Scopus (907) Google Scholar , 4 Simard EP, Ward EM, Siegel R, et al. Cancers with increasing incidence trends in the United States: 1999 through 2008 [e-pub ahead of print]. CA Cancer J Clin. doi:10.3322/caac.20141. Accessed May 15, 2012. Google Scholar However, several observations have challenged the assertion that these incidence trends are solely due to the incidental detection of localized renal tumors by routine imaging. For example, Chow et al demonstrated not only an increased incidence of advanced stage tumors but also a steady parallel rise in the RCC mortality rate (a trend that was upheld even after adjusting for stage). 1 Chow W.H. Devesa S.S. Warren J.L. et al. Rising incidence of renal cell carcinoma in the United States. JAMA. 1999; 281: 1628-1631 Crossref PubMed Scopus (1333) Google Scholar , 5 Sun M. Thuret R. Abdollah F. et al. Age-adjusted incidence, mortality, and survival rates of stage-specific renal cell carcinoma in North America: a trend analysis. Eur Urol. 2011; 59: 135-141 Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar Therefore, the question of whether these adverse temporal trends in RCC incidence rates are mostly driven by factors related to the year of diagnosis (period-related factors such as increased abdominal imaging) or to factors related to the year of birth (cohort-related factors such as rates of obesity, hypertension, new genetic mutations, etc), or a combination thereof, has become increasingly germane. Indeed, a more thorough understanding of the factors that mediate RCC risk would help guide investigators and public health officials to design and implement thoughtful screening and detection programs in high-risk populations. Editorial CommentUrologyVol. 82Issue 1PreviewRenal cell carcinoma (RCC) has a steadily increasing incidence in the United States.1 The change in incidence and natural history of RCC is often attributed to the widespread use of abdominal imaging and the incidental detection of small renal masses. However, the etiology of sporadic RCC remains poorly understood. Full-Text PDF

1300 ESTIMATING THE BURDEN OF PREOPERATIVELY MISCLASSIFIED, SURGICALLY REMOVED BENIGN RENAL MASSES IN THE UNITED STATES: IMPLICATIONS FOR THE CURRENT STANDARD OF CARE

You have accessJournal of UrologyKidney Cancer: Localized (II)1 Apr 20131300 ESTIMATING THE BURDEN OF PREOPERATIVELY MISCLASSIFIED, SURGICALLY REMOVED BENIGN RENAL MASSES IN THE UNITED STATES: IMPLICATIONS FOR THE CURRENT STANDARD OF CARE David Johnson, Angela Smith, Josip Vukina, Jed Ferguson, Will Kirby, Mathew Raynor, Michael Woods, Eric Wallen, Raj Pruthi, and Matthew Nielsen David JohnsonDavid Johnson Chapel Hill, NC More articles by this author , Angela SmithAngela Smith Chapel Hill, NC More articles by this author , Josip VukinaJosip Vukina Chapel Hill, NC More articles by this author , Jed FergusonJed Ferguson Chapel Hill, NC More articles by this author , Will KirbyWill Kirby Chapel Hill, NC More articles by this author , Mathew RaynorMathew Raynor Chapel Hill, NC More articles by this author , Michael WoodsMichael Woods Chapel Hill, NC More articles by this author , Eric WallenEric Wallen Chapel Hill, NC More articles by this author , Raj PruthiRaj Pruthi Chapel Hill, NC More articles by this author , and Matthew NielsenMatthew Nielsen Chapel Hill, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2654AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The incidence of renal cell carcinoma (RCC) is increasing and the average size at diagnosis is decreasing. Surgical resection without tissue confirmation is within the standard of care for renal masses suspicious for RCC, which results in a currently unknown number of preoperatively misclassified benign renal masses (BRM) undergoing nephrectomy. Against this backdrop, we estimate the population-level burden of surgically removed benign renal masses in the US. METHODS A literature review for studies providing estimates of the likelihood of BRM for resected renal masses was conducted. Studies reporting the likelihood of BRM based on tumor size (<1.0 cm, 1-2 cm, 2-3 cm, 3-4 cm, 4-7 cm, >7 cm) were included. The results were pooled for a single estimate of likelihood of BRM for each size category. Combining these results with size-specific incidence rates of RCC from SEER and population estimates from census data, we estimated the burden of surgically resected BRM for 2000 and 2009. RESULTS The size-specific likelihood of BRM was compiled from 4 studies of tumors <4 cm and 5 studies of tumors > 4 cm. The pooled estimates of the likelihood of benign histology are 41.2%, 21.5%, 20.3%, 17.7%, 9.3%, and 6.4% for <1 cm, 1-2 cm, 2-3 cm, 3-4 cm, 4-7 cm, and > 7 cm tumors, respectively. The estimated number of surgically resected benign renal masses in the United States in 2000 and 2009 for these respective size strata are 198 and 428, 386 and 1087, 790 and 1866, 788 and 1379, 925 and 1283, and 675 and 751. Overall, the estimates for preoperatively misclassified BRM undergoing surgical resection are 3762 in 2000 and 6794 in 2009, representing an 80% increase. CONCLUSIONS Given the evolving epidemiology of RCC, the burden of preoperatively misclassified BRM is an important and previously unstudied phenomenon, as no specific data are available to directly quantify this. These indirect estimates suggest the burden may be quite substantial and potentially increasing at a dramatic rate. These data underscore an important dimension of overtreatment due to unnecessary morbidity, mortality and health care costs. Furthermore, long-term effects on renal and cardiovascular health must also be considered, particularly given the still substantial proportion of the population who undergo radical nephrectomy, even for small masses. These data support further consideration of the role of renal mass biopsy and other strategies to optimize management. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e531 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Johnson Chapel Hill, NC More articles by this author Angela Smith Chapel Hill, NC More articles by this author Josip Vukina Chapel Hill, NC More articles by this author Jed Ferguson Chapel Hill, NC More articles by this author Will Kirby Chapel Hill, NC More articles by this author Mathew Raynor Chapel Hill, NC More articles by this author Michael Woods Chapel Hill, NC More articles by this author Eric Wallen Chapel Hill, NC More articles by this author Raj Pruthi Chapel Hill, NC More articles by this author Matthew Nielsen Chapel Hill, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Estrogen Inhibits Renal Cell Carcinoma Cell Progression through Estrogen Receptor-β Activation

Renal cell carcinoma (RCC) originates in the lining of the proximal convoluted tubule and accounts for approximately 3% of adult malignancies. The RCC incidence rate increases annually and is twofold higher in males than in females. Female hormones such as estrogen may play important roles during RCC carcinogenesis and result in significantly different incidence rates between males and females. In this study, we found that estrogen receptor β (ERβ) was more highly expressed in RCC cell lines (A498, RCC-1, 786-O, ACHN, and Caki-1) than in breast cancer cell lines (MCF-7 and HBL-100); however, no androgen receptor (AR) or estrogen receptor α (ERα) could be detected by western blot. In addition, proliferation of RCC cell lines was significantly decreased after estrogen (17-β-estradiol, E2) treatment. Since ERβ had been documented to be a potential tumor suppressor gene, we hypothesized that estrogen activates ERβ tumor suppressive function, which leads to different RCC incidence rates between males and females. We found that estrogen treatment inhibited cell proliferation, migration, invasion, and increased apoptosis of 786-O (high endogenous ERβ), and ERβ siRNA-induced silencing attenuated the estrogen-induced effects. Otherwise, ectopic ERβ expression in A498 (low endogenous ERβ) increased estrogen sensitivity and thus inhibited cell proliferation, migration, invasion, and increased apoptosis. Analysis of the molecular mechanisms revealed that estrogen-activated ERβ not only remarkably reduced growth hormone downstream signaling activation of the AKT, ERK, and JAK signaling pathways but also increased apoptotic cascade activation. In conclusion, this study found that estrogen-activated ERβ acts as a tumor suppressor. It may explain the different RCC incidence rates between males and females. Furthermore, it implies that ERβ may be a useful prognostic marker for RCC progression and a novel developmental direction for RCC treatment improvement.

The Authors Reply: Renal Cell Carcinoma in Kidney Transplant Recipients and Dialysis Patients

To the editor: A limitation of our article is the absence of a control group and that this was not a prospective study. Our study was an insufficient randomized controlled cohort trial for acquired cystic kidney disease (ACKD). Our study would be better accepted if it was designed in a prospective manner, which would contain follow-up data for about 7,000 patients with end-stage renal disease (ESRD) for 14 years, with separate comparisons of the transplant group, dialysis-only group, and renal cancer patient group who underwent nephrectomy for ACKD. Because the study was performed in a retrospective manner, there was no strict protocol for imaging study. Furthermore, the diagnosis of ACKD in the native kidney was usually made by associated symptoms. This study made comparisons between the dialysis group and the transplanted group, who had undergone nephrectomy, retrospectively. Kojima et al. [1] observed that the incidence of renal cell carcinoma (RCC) in the native kidney was high in transplant recipients and reported that the incidence rate was high in dialysis patients. It was shown that 44 (1.68%) of 2,624 ESRD patients followed up during dialysis had developed RCC an average of 11.2 years after dialysis, and 36 of these cases (81.8%) were associated with ACKD. A positive correlation with the incidence rate of RCC was also found among transplant recipients. In 2007, Ianhez et al. [2] reported that 10 of 1375 patients developed RCC of the native kidney an average of 8.4 years after the renal replacement therapy, and all the RCC cases were associated with ACKD. In 1990, Matson and Cohen [3] investigated ACKD development and its correlation with RCC among ESRD patients. They demonstrated that ACKD was closely correlated with the duration of renal replacement therapy but not with the type of dialysis that was performed. Many studies on transplantation and ACKD have also reported that ACKD is observed more frequently, and the incidence rate of RCC is higher, in a kidney transplantation group than in a control group. Heinz-Peer et al. [4] analyzed 96 patients with ACKD detected by ultrasonography out of 385 renal transplant recipients in 1995 and found that the incidence of ACKD was higher with longer duration times of dialysis before kidney transplantation in older subjects and in males. The presence of ACKD was related to the occurrence of renal cancer, and the longer the duration of dialysis, the more likely the patient was to acquire ACKD. Only a few studies have been published regarding how renal transplantation itself affects ACKD, and yet, there is no definite answer as to the effects of renal transplantation on RCC. Our reports show that the frequency of ACKD was lower in the transplanted patient group than in the dialysis group, which still requires further explanation concerning the pathogenesis. Our institution follows the protocol for ESRD patients to undergo an annual ultrasonogram. This protocol is based on the results of this study and its main intent is to detect ACKD patients earlier. Therefore, we perform annual ultrasonograms for both dialysis patients and kidney transplantation patients. In the future, we hope that these approaches will contribute to the research and treatment in this field. REFERENCES

Age-Adjusted Incidence, Mortality, and Survival Rates of Stage-Specific Renal Cell Carcinoma in North America: A Trend Analysis

BackgroundThe rising incidence of renal cell carcinoma (RCC) has been largely attributed to the increasing use of imaging procedures. ObjectiveOur aim was to examine stage-specific incidence, mortality, and survival trends of RCC in North America. Design, setting, and participantsWe computed age-adjusted incidence, survival, and mortality rates using the Surveillance Epidemiology and End Results database. Between 1988 and 2006, 43 807 patients with histologically confirmed RCC were included. MeasurementsWe calculated incidence, mortality, and 5-yr survival rates by year. Reported findings were stratified according to disease stage. Results and limitationsAge-adjusted incidence rate of RCC rose from 7.6 per 100 000 person-years in 1988 to 11.7 in 2006 (estimated annual percentage change [EAPC]: +2.39%; p<0.001). Stage-specific age-adjusted incidence rates increased for localized stage: 3.8 in 1988 to 8.2 in 2006 (EAPC: +4.29%; p<0.001) and decreased during the same period for distant stage: 2.1 to 1.6 (EAPC: −0.57%; p=0.01). Stage-specific survival rates improved over time for localized stage but remained stable for regional and distant stages. Mortality rates varied significantly over the study period among localized stage, 1.3 in 1988 to 2.4 in 2006 (EAPC: +3.16%; p<0.001), and distant stage, 1.8 in 1988 to 1.6 in 2006 (EAPC: −0.53%; p=0.045). Better detailed staging information represents a main limitation of the study. ConclusionsThe incidence rates of localized RCC increased rapidly, whereas those of distant RCC declined. Mortality rates significantly increased for localized stage and decreased for distant stage. Innovation in diagnosis and management of RCC remains necessary.

Incidental renal tumours

To analyze the current literature regarding incidental finding of renal cell carcinoma (RCC). RCC incidence rates continue to rise among all racial, age, tumour size categories, with the most rapid increase for localized disease and small tumours. In parallel, it seems that mortality from RCC decreases in all these groups. Computed tomography guided tumour biopsies are gaining more accuracy and acceptance, whereas minimal invasive treatments such as cryoablation or radiofrequency ablation are competing with nephron-sparing surgery in certain patient categories. Finally, active surveillance is emerging as a new management modality for elderly patients with small renal masses. The emergence of incidental diagnosis of renal tumours which is related to the widespread use of imaging has played a pivotal role in the increased incidence of RCC and therefore potentially in improving survival in localized disease. However, a significant proportion of treated tumours are benign or undetermined and active surveillance has proven safe in selected patients. There is the risk in widening the treatment armamentarium that a certain number of patients are overtreated. In conclusion, accurate tools are needed for a proper selection of patients with incidentally detected tumours, so that they can benefit from nephron-sparing surgery, ablative therapies or observation.