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Background: Partial nephrectomy (PN) has become the dominant treatment modality for cT1 renal tumor lesions. Tumors suspected of malignant potential are indicated for surgery, but some are histologically classified as benign lesions after surgery. This study aims to analyze the number of benign findings after PN according to definitive histology and to evaluate whether there is an association between malignant tumor findings and individual factors., Methods: The retrospective study included 555 patients who underwent open or robotic-assisted PN for a tumor in our clinic from January 2013 to December 2020. The cohort was divided into groups according to definitive tumor histology (malignant tumors vs. benign lesions). The association of factors (age, sex, tumor size, R.E.N.A.L.) with the malignant potential of the tumor was further evaluated., Results: In total, 462 tumors were malignant (83%) and 93 benign (17%). Of the malignant tumors, 66% were clear-cell RCC (renal cell carcinoma), 12% papillary RCC, and 6% chromophobe RCC. The most common benign tumor was oncocytoma in 10% of patients, angiomyolipoma in 2%, and papillary adenoma in 1%. In univariate analysis, there was a higher risk of malignant tumor in males (OR 2.13, 95% CI 1.36-3.36, p = 0.001), a higher risk of malignancy in tumors larger than 20 mm (OR 2.32, 95% CI 1.43-3.74, p < 0.001), and a higher risk of malignancy in tumors evaluated by R.E.N.A.L. as tumors of intermediate or high complexity (OR 2.8, 95% CI 1.76-4.47, p < 0.001). In contrast, there was no association between older age and the risk of malignant renal tumor (p = 0.878)., Conclusions: In this group, 17% of tumors had benign histology. Male sex, tumor size greater than 20 mm, and intermediate or high R.E.N.A.L. complexity were statistically significant predictors of malignant tumor findings., (© 2024. The Author(s).)

The landscape of the management of renal cell carcinoma has evolved substantially in the last decade, leading to improved survival in localised and advanced disease. We review the epidemiology, pathology, and diagnosis of renal cell carcinoma and discuss the evidence for current management strategies from localised to metastatic disease. Developments in adjuvant therapies are discussed, including use of pembrolizumab-the first therapy to achieve overall survival benefit in the adjuvant setting. The treatment of advanced disease, including landmark trials that have established immune checkpoint inhibition as a standard of care, are also reviewed. We also discuss the current controversies that exist surrounding the management of metastatic renal cell carcinoma, including the use of risk assessment models for disease stratification and treatment selection for frontline therapy. Management of non-clear cell renal cell carcinoma subtypes is also reviewed. Future directions of research, including a discussion of ongoing clinical trials and the need for reliable biomarkers to guide treatment in kidney cancer, are also highlighted., Competing Interests: Declaration of interests No funding or payment has been directed towards this review or the authors' decision to submit for publication. MY has received honoria from Eisai. BS has received reimbursement for travel expenses from Genentech, Merck Sharp & Dohme (MSD), Pfizer, and Bristol-Myers Squibb (BMS); has received research funding from Roche, Genentech, Merck Sharp & Dohme, Pfizer, and Bristol-Myers Squibb; and has received honoraria from Merck, Roche, Pfizer, Ellipses, Ipsen, and Janssen. TP declares grants from or contracts with AstraZeneca, BMS, Exelixis, Ipsen, MSD, Novartis, Pfizer, Seagen, Merck Serono, Astellas, Johnson & Johnson, Eisai, and Roche; TP reports payment or honoraria for lectures, presentations, or speakers' bureaus from AstraZeneca, BMS, Exelixis, Incyte, Ipsen, MSD, Novartis, Pfizer, Seagen, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, and Mash Up; and reports travel support from Roche, Pfizer, MSD, AstraZeneca, and Ipsen. CS declares research funding from AB Science, Aragon Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim España, BMS, Clovis Oncology, Exelixis, Genentech, GlaxoSmithKline, F Hoffmann-La Roche, Novartis, Pfizer, and Sanofi-Aventis; speakers' bureau fees from Astellas Pharma, BMS, F Hoffmann-La Roche, Ipsen, and Pfizer; participation on a data safety monitoring board or advisory board for Astellas Pharma, Bayer, BMS, Eusa Pharma, F Hoffmann-La Roche, Ipsen, MSD, Novartis, Pfizer, and Sanofi-Aventis. AB has received company speaker honoraria from Pfizer; and has participated in trials for Pfizer Europe; has participated in advisory boards for BMS, GlaxoSmithKline, and Novartis; is a consultant for Pfizer and Novartis; and has received grants and research support from Pfizer. All other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Renal cell carcinoma (RCC) is a leading urological malignancy with an age-standardised incidence rate of 2.5 per 100,000 per year in Oman. Experts are inclined towards the early detection and use of minimally invasive technology for the treatment of RCC. This study aimed report the shifting trend in the clinical presentation and management of RCC in Oman, comparing the outcomes of laparoscopic and open nephrectomy., Methods: This retrospective study included adult RCC patients from Sultan Qaboos University Hospital, Muscat, Oman, diagnosed from 2011-2022. Patient biodata, mode of presentation, diagnostic modality, final histopathology and details of treatment received including the perioperative outcomes were analysed., Results: A total of 56 patients that underwent surgical treatment for RCC, 34 underwent laparoscopic nephrectomy (LN) and 22 underwent open nephrectomy (ON). The mean ages in the LN and ON groups were 53.82 ± 13.44 years and 56.22 ± 15.00 years ( P = 0.53), respectively. There were 47 patients of Omani descent and 9 patients were expatiates. The patients' mean tumour size was 6.25 ± 3.16 cm and 9.23 ± 5.20 cm for the LN and ON groups, respectively; 55.35% of the RCC cases were incidentally diagnosed. A trend towards LN was observed., Conclusion: This study found a trend towards early diagnosis of RCC in Oman, with the majority of cancers being discovered incidentally in the studied period. LN is more commonly used in the surgical management of RCC with acceptable morbidity. These trends remain aligned with those found in the global literature on RCC., Competing Interests: CONFLICT OF INTEREST: The authors declare no conflict of interests., (© Copyright 2024, Sultan Qaboos University Medical Journal, All Rights Reserved.)

Introduction: Kidney transplantation is the optimal treatment modality for patients with end-stage chronic kidney disease. The long-term mortality of kidney recipients is 48-82% lower than that of patients on the waiting list. However, the risk of developing malignancies in these patients is twice as high as in the healthy population. Specifically, the incidence of renal cell carcinoma (RCC) in transplant recipients is 10-30 times higher than in non-transplanted patients. The reason for the increased risk is poorly understood, but is most likely related to continuous immunosuppressive therapy. The problem of kidney graft neoplasia has not been adequately addressed in the medical literature., Objective: To determine the incidence of renal cell carcinoma in transplanted kidneys, enhance the efficacy of its treatment, and study the etiology of RCC development., Materials and Methods: A retrospective analysis of RCC incidence in kidney grafts was conducted in 3,270 patients who underwent kidney transplantation between 2013 and 2023. We evaluated the effectiveness of surgical interventions for these complications. Patients with histologically confirmed RCC of the transplanted kidney underwent genetic study to determine the etiology of the neoplasm., Results: The incidence of RCC in transplanted kidneys was found to be 0.95% (n = 31), 28 patients underwent laparoscopic resection of the renal transplant tumor, 2 patients were treated with radiofrequency ablation of the tumor. Transplantectomy was performed in 1 patient., Conclusion: Laparoscopic resection is an effective and safe method for the treatment of RCC in kidney transplants. Transplanted kidney cancer originates from the donor tissue. The clear cell variant of transplanted kidney cancer is a genetically determined disease., (© 2024. The Author(s).)

Background: Bladder cancer (BC) and Renal cell carcinoma (RCC) are the most common urogenital cancers among both sexes, with a yearly global incidence of around 500 000 each. Both BC and RCC have been linked to diabetes. Poor glycemic control (malglycemia) is a serious consequence of diabetes and a possible consequence of systemic treatments used in BC and RCC. The objective of this study was to investigate the prevalence of diabetes and use of hospital-based care for malglycemia in people with BC or RCC., Methods: This Swedish retrospective population-based register study used national health-data registers for longitudinal data on cancer incidence covering 15 years, use of hospital-based health care, and filled prescriptions of outpatient medications. Study endpoints included co-prevalence of diabetes in individuals with BC/RCC, healthcare resource utilization due to malglycemia, use of systemic corticosteroids, and changes in diabetes management for people with concomitant type 2 diabetes., Results: We identified 36,620 and 15,581 individuals diagnosed with BC and RCC, respectively, between 2006 and 2019. The proportion of individuals registered with diabetes was 24% in BC and 23% in RCC. An association between BC/RCC and poor glycemic control was found, although the number of malglycemic events in hospital-based care were few (65/59 per 1000 individuals with diabetes and BC/RCC respectively with at least one event). An earlier switch to insulin-based diabetes management was observed in BC/RCC compared to matched individuals with type 2 diabetes but no cancer. The results also indicated an association between steroid treatment and poor glycemic control, and that systemic corticosteroids were more common among people with BC/RCC compared to diabetes controls., Conclusion: The high prevalence of diabetes and increased use of systemic corticosteroid treatment observed in this large national study highlights the need for specific clinical management, risk-assessment, and monitoring of individuals with BC/RCC and diabetes., (© 2024. The Author(s).)

Background: The current available evidence on the management of metastatic renal cell cancer (mRCC) in real life is scarce in our environment. We present a summary of the existing real-world data and the results of an analysis describing the clinical characteristics, treatments, and health outcomes of patients with mRCC in northern Spain., Methods: Retrospective observational study. Adult patients diagnosed with mRCC between Jan 2007 and Dec 2019 were included. Epidemiological, efficacy and toxicity data were collected. Median overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier method., Results: A total of 829 patients were included (median age at diagnosis:63 years;73% men). Median follow-up was 180 months. The preponderant histology was clear cell (85%). In 50% the initial diagnosis was advanced disease. The distribution according to IMDC prognosis was good (24%), intermediate (50%) and poor (26%). The most frequent metastatic locations were lung (68.3%) and lymph node (41.0%). Most patients (95%) received a first line (1L) systemic treatment, 60% were treated with a second line (2L) of therapy and 37% received third line (3L). A VEGFR-TKIs was the most common treatment (1L: 90%, n = 507; 2L: 49%, n = 233; 3L: 54%, n = 156) followed by mTOR inhibitors (1L: 2%, n = 4; 2L: 27%, n = 126; 3L: 23%, n = 68) and immunotherapy (1L: 3.7%, n = 25; 2L: 27%, n = 126). Median OS was 24.5 months in the general population. According to IMDC prognostic groups, OS was 52.5, 25.7 and 9 months respectively. From the start of the 1L, 2L, and 3L treatment, median PFS was: 1L: 7.8 (6.8-9.0); 2L: 4.9 (4.3-5.5); 3L: 4.3 (3.8-4.8) months. No unexpected toxicity was reported., Conclusions: The Real-World Data on the management of mRCC in Northern Spain are comparable in epidemiology, efficacy, and safety to studies conducted in other areas of the world. The significant reduction in the number of patients receiving second and subsequent lines of therapy hampers the access to new therapies developed in this context., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC)., Methods: We identified all patients diagnosed with incident RCC during 1995-2019, using population-based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population., Results: The absolute 1- and 20-year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person-years (PY) (SIR, 2.3; 95% CI: 2.1-2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow-up (SIR, 1.3; 95% CI: 1.2-1.4), and 6 per 1000 PY beyond 5 years of follow-up (SIR, 1.4; 95% CI: 1.3-1.5). The sustained elevated cancer risk beyond 1 year of follow-up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006-2019 than in 1995-2005, but only during the first year of follow-up., Conclusion: Patients with incident RCC have a sustained 40% elevated long-term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Patients with type 2 diabetes (T2D) are at a higher risk of developing renal cell carcinoma (RCC) than the general population. In vitro and in vivo investigations of the effects of sodium glucose cotransporter-2 inhibitors (SGLT2I) have shown a significantly reduced risk of RCC. However, the impact of these drugs on the incidence of RCC in the human population is unclear. This study aimed to examine the association between SGLT2I use and RCC risk in patients with T2D. We undertook a nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016-2020). The primary outcome was the risk of incident RCC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression modeling was applied to analyze the association between SGLT2I use and RCC risk in patients with T2D. In a cohort of 241,772 patients with T2D who were using SGLT2Is and 483,544 participants who were not, 220 and 609 RCC cases, respectively, were recorded. The mean follow-up period of the study subjects was 2 years. There was a decreased risk of RCC for SGLT2I users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.68; 95% CI, 0.58-0.81). The sensitivity test for the propensity score 1:1-matched analyses showed similar results (adjusted HR 0.67; 95% CI, 0.55-0.81). The subgroup analysis revealed consistent results for sex, age (<70 years), and comorbidity with chronic kidney disease. The present study indicates that SGLT2I therapy significantly decreases RCC risk in patients with T2D. This finding was also consistent among the sensitivity test and subgroup analysis for those with or without chronic kidney disease/hypertension., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Many patients diagnosed with cancer adopt dietary changes and supplement use, and a growing body of evidence suggests that such modifications can affect outcomes to cancer therapy. We sought to assess the prevalence of these practices and the surrounding physician-patient dialogue among patients with metastatic renal cell carcinoma. An online survey was administered by Kidney Cancer Research Alliance (KCCure), interrogating dietary modification patterns, supplement usage, out-of-pocket expenditure related to supplements, and patients' views toward alternative medicine practices. Patients with metastatic renal cell carcinoma receiving combination therapy were actively solicited. In total, 289 unique responses were collected. The most common first-line treatments were nivolumab/ipilimumab (32.4%) and axitinib/pembrolizumab (13.1%). Within the cohort, 147 (50.9%) started using supplements following diagnosis of renal cell carcinoma; the most utilized supplements were probiotics, cannabidiol (CBD) oil/marijuana, and Vitamin C, reported by 70 (47.6%), 61 (41.4%), and 54 (36.7%), respectively. Dietary modifications following cancer diagnosis were reported by 101 (34.9%) respondents, of which 19.8% followed the Mediterranean diet and 18.8% adopted a ketogenic diet. Most respondents (71.3%) noted that they consistently report supplement usage to their physicians. A substantial proportion of patients with metastatic renal cell carcinoma utilize dietary modification and supplements as an adjunct to antineoplastic therapy. Considering the widespread adoption of these practices and the reported effects on cancer treatment, it is crucial for healthcare providers to engage in discussions with patients regarding supplement use.

Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers by age, sex, race/ethnicity, and histology in the United States (US) from 2000 to 2020. The data was obtained from the Surveillance, Epidemiology, and End Results (SEER) 22 database. The identification of patients with kidney and renal pelvis cancers with morphologies of renal cell carcinoma, nephroblastoma, sarcoma, and neuroendocrine tumor was conducted utilizing the International Classification of Diseases for Oncology version 3. The average annual percent change (AAPC) were presented. All estimates were given in the form of counts and delayed age-standardized incidence rates (ASIRs) per 100,000 people. From 2000 to 2019, a total of 490,481 cases of kidney and renal pelvic cancer were recorded across all age groups in the US. The majority of them were among Non-Hispanic Whites (NHWs) (69.75%) and those aged 55-69 years (39.96%). The ASIRs per 100,000 for kidney and pelvis cancers were 22.03 for men and 11.14 for women. Non-Hispanic Black men had the highest ASIR (24.53 [24.24, 24.81]), and increase in ASIR over the 2000-2019 period (AAPC: 2.19% [1.84, 2.84]). There was a noticeable increase in incidence of kidney and renal pelvis cancers. Individuals aged 70-84 years had the highest ASIR for kidney and renal pelvis cancers. The COVID-19 era has resulted in a significant reduction in incidence rates across all demographics., (© 2024. The Author(s).)

Introduction: Papillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10-15% of cases. Traditionally, pRCC is divided into type 1 and type 2, although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period., Materials and Methods: A Population based retrospective study including consecutive cases of RCC in Iceland from 1971-2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan-Meier method and Cox regression were used for outcome analysis., Results: A total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p < 0.001). Age standardized cancer specific mortality (ASCSM) of pRCC was 0.6/100.000 and 0.19/100.000 for males and females, respectively. The annual average increase in ASI was 3.6% for type 1 pRCC, but the ASI for type 2 pRCC and ASCSM for both subtypes did not change significantly. Male to female ratio was 4.4 for type 1 pRCC and 2.3 for type 2. The average tumor size for type 1 and 2 was 58.8 and 73.7 mm, respectively. Metastasis at diagnosis was found in 8.7% in the type 1 pRCC, compared to 30.0% of patients with type 2 pRCC (p < 0.001). Estimated 5-year cancer-specific survival (CSS) were 94.4%, 80.7%, and 69.3% for chRCC, pRCC and ccRCC, respectively (p < 0.001). For the pRCC subtypes, type 1 was associated with better 5-year CSS than type 2 (86.3% vs. 66.0%, p < 0.001), although this difference was not significant after adjusting for cancer stage and grading., Conclusions: pRCC histology was slightly less common in Iceland than in other countries. Males are more than three times more likely to be diagnosed with pRCC, compared to other RCC histologies. The subtype of pRCC was not found to be an independent risk factor for worse survival, and as suggested by the most recent WHO Classification of Urinary Tumors, grade and TNM-stage seem to be the most important factors for estimation of survival for pRCC patients., (© 2024. The Author(s).)

Adult polycystic kidney disease (APKD) is a genetic disorder leading to premature renal dysfunction and failure. The prevalence of malignant renal tumors occurring in the APKD setting has been rarely reported., Objective: To better characterize malignant renal tumors in nephrectomy specimens of APKD and apply modern pathologic evaluation., Methods: We reviewed our database of APKD specimens over the past 11 years (from 2012 to 2023) for primary malignant tumors within the kidneys of APKD., Results: Of 48 nephrectomy specimens with APKD evaluated, 10 malignant renal tumors were identified, indicating a prevalence of 20.8 % (10/48). These included three clear cell (cc) renal cell carcinomas (RCC) (ranging from 1 mm to 6.7 cm), three papillary RCCs (2.5, 3.5, and 14 cm with lymph node metastasis), two cases of clear cell papillary (CCP) RCC, one acquired cystic disease (ACD) with associated RCC (4 mm), and one urothelial adenocarcinoma. The urothelial adenocarcinoma was found near a tubulovillous adenoma in a collecting duct and stained positively for GATA3 and Uroplakin-2 but was negative for PAX8 & CDX2. The tumor showed extensive invasion into perirenal fatty tissue and the rectum. Next generating sequencing (NGS) analysis of the tumor showed mutations in TERT, RB1, TP53, ERBB2, and TET1 genes, further supporting its urothelial origin., Conclusions: We found a prevalence of 20.8%, which was higher than in previous reports of malignant renal tumors in patients who underwent resections for APKD. Renal tumors were mostly from damaged proximal tubular origins (clear cell or papillary RCC), but less commonly were from distal tubular or urothelial cells as well (clear cell papillary RCC and urothelial adenocarcinoma)., (© 2024 by the Association of Clinical Scientists, Inc.)

Background/aim: Renal cell carcinoma (RCC) presents a formidable clinical challenge due to its aggressive behavior and limited therapeutic options. Matrix metalloproteinase-8 (MMP-8) has recently emerged as a potential biomarker and therapeutic target for various cancers. However, the genetic involvement of MMP-8 in RCC has remained largely obscure. This study aimed to elucidate the role of MMP-8 genotypes in RCC susceptibility., Materials and Methods: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to scrutinize the genotypes of MMP-8 C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072) among 118 RCC patients and 590 controls. Furthermore, potential associations between MMP-8 genotypes and age, sex, smoking, alcohol consumption, hypertension, diabetes, and family history status in relation to RCC risk were assessed., Results: No significant disparities in the distribution of MMP-8 rs11225395, rs34009635, and rs35866072 genotypes were observed between the RCC case and control cohorts (p>0.05). Individuals with CT and TT genotypes at MMP-8 rs11225395 exhibited 0.86- and 0.80-fold RCC risks, respectively (OR=0.57-1.31 and 0.42-1.55, p=0.5585 and 0.6228, respectively). Intriguingly, hypertensive individuals carrying the MMP-8 rs11225395 CT or TT genotype demonstrated an elevated risk for RCC compared to those with wild-type CC genotype (p=0.0440). No interactions of MMP-8 genotypes with age, sex, smoking, alcohol consumption, or diabetes status were evident (all p>0.05). No significant association was discerned for MMP-8 rs34009635 or rs35866072 genotypes., Conclusion: MMP-8 genotypes appear to have a modest influence on individual susceptibility to RCC. Hypertensive patients with the CT or TT MMP-8 rs11225395 genotype may have an elevated risk of RCC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden 1 . In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence 2 . Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics., (© 2024. The Author(s).)

Purpose: To evaluate the impact of the COVID-19 pandemic on renal cell carcinoma (RCC) care in the Netherlands., Methods: Newly diagnosed RCCs between 2018 and 2021 were selected from the Netherlands Cancer Registry; 2020-2021 was defined as COVID period and 2018-2019 as reference period. Numbers of RCCs were evaluated using 3-week-moving averages, overall and by disease stage and age. Changes in treatment were evaluated with logistic regression analyses. To evaluate possible delays in care, time to start of treatment was assessed. The cumulative number of metastatic RCC (mRCC) over time was assessed to evaluate stage shift., Results: During the 1st COVID wave (weeks 9-22, 2020), the number of new RCC diagnoses decreased with 15%. Numbers restored partially in 2020, but remained 10% lower compared to 2018/2019. The decline was mostly due to a drop in T1a/T1b RCCs and in age > 70 years. 2021 showed similar numbers of new RCC diagnoses compared to 2018/2019 without an increase due to previously missed RCCs. Treatment-related changes during the 1st COVID wave were limited and temporarily; less surgery in T1a RCCs in favor of more active surveillance, and in mRCC targeted therapy was preferred over immunotherapy. Time to start of firstline treatment was not prolonged during the 1st COVID wave. No increase in mRCC was found until the end of 2021., Conclusions: The COVID-19 pandemic resulted in fewer RCC diagnoses, especially T1a/T1b tumors. Treatment-related changes appeared to be limited, temporarily and in accordance with the adapted guidelines. The diagnostic delay could lead to more advanced RCCs in later years but there are no indications for this yet., (© 2024. The Author(s).)

Background: Urogenital tumors are among the most common solid malignancies after kidney transplantation (TX)., Objective: We analyzed the incidence and mortality of urogenital tumors after kidney TX in our own patient population as well as answered the question of recommended follow-up necessity and frequency in this cohort., Materials and Methods: Retrospective monocentric data collection of tumor diseases and the most common urogenital tumors after kidney TX at the Transplant Center Dresden between 2010 and 2020 was done. From this, we derived recommendations for a useful follow-up concept., Results: A total of 13% (93/710) of kidney TX patients developed a neoplasm. Older patients (60.1 ± 10.6 vs. 53.8 ± 12.5; p < 0.001), with higher Charlson scores (≥ 4: 68% vs. 46%; p < 0.001) and a previous tumor history (18% vs. 8%; p < 0.001) were more likely to develop a neoplasm after transplantation. In the multivariate analysis, previous tumor history was found to be an independent predictor of tumor development after renal transplantation (OR 2.2; 95%-KI [1.2-4.1]; p = 0.01). Urogenital tumors accounted for 30% (28/93) of all malignancies. Renal cell carcinoma of the native kidney was the most common (n = 12) neoplasm, followed by prostate cancer (n = 9)., Conclusion: Most solid malignancies after kidney TX arise from the urinary tract. Due to their frequency, there is an urgent need for specialized urological therapy and long-term follow-up care. Even before listing for TX, risk factors can be recognized and individual concepts for follow-up care can be developed., (© 2024. The Author(s).)

Observational studies on the association between citrus fruit intake and risk of renal cell carcinoma (RCC) have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis. PubMed and Embase databases search was conducted including relevant studies published up to January, 2020. We included epidemiological studies that reported relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) for the association between citrus fruit intake and RCC risk. A total of eight epidemiological studies consisting of five cohort and three case-control studies were included. The overall analysis showed a significantly reduced risk of RCC for high intake of citrus fruit (OR = 0.84, 95% CI 0.73-0.95). No heterogeneity was detected among the included studies (p = 0.497 for heterogeneity; I 2  = 0). There was no significant publication bias by Begg's test (p = 0.266) or Egger's test (P = 0.578). A statistically significant association between citrus fruit intake and RCC was observed in case-control studies (OR = 0.84, 95% CI 0.71-0.98), while no association was observed in cohort studies (OR = 0.84, 95% CI 0.64-1.05). In addition, the dose-response analysis indicated that the RCC risk reduced by 13% (95%CI 1.0%-27%, p = 0.04 for heterogeneity) for each 100 grams per day increment of citrus fruit intake. In summary, our findings suggest an inverse association between citrus fruit intake and RCC incidence., (© 2023 John Wiley & Sons Australia, Ltd.)

Observational studies have suggested that there may be a connection between systemic lupus erythematosus (SLE) and a higher likelihood of developing urological cancers, although the exact cause-effect relationship is still unclear. This study therefore investigated the causal relationship between SLE and urological cancers using the Mendelian randomization (MR) approach. Our primary MR analysis involved using the inverse variance weighted method, which employed an inverse-variance-weighted approach, to examine the causal relationship between SLE and urological conditions. In addition, we performed various sensitivity analyses, such as MR-Egger regression, tests for heterogeneity, and leave-one-out sensitivity tests, to assess the reliability of our results. The findings from our analysis using Two-Sample MR showed that genetically predicted SLE was linked to a reduced likelihood of developing renal cell carcinoma (RCC) (odds ratio = 0.9996, 95% confidence interval = 0.9993-0.9999, P value = .0159). These results suggest a possible protective impact of SLE against RCC. Nevertheless, no substantial correlation was detected between SLE and the likelihood of developing bladder cancer or prostate cancer. Collectively, these findings offer significant fresh perspectives on the possible correlation between SLE and genitourinary malignancies, specifically RCC, which will provide ideas and basis for the treatment of RCC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose To investigate the prevalence of FLCN, BAP1, SDH , and MET mutations in an oncologic cohort and determine the prevalence, clinical features, and imaging features of renal cell carcinoma (RCC) associated with these mutations. Secondarily, to determine the prevalence of encountered benign renal lesions. Materials and Methods From 25 220 patients with cancer who prospectively underwent germline analysis with a panel of more than 70 cancer-predisposing genes from 2015 to 2021, patients with FLCN, BAP1, SDH , or MET mutations were retrospectively identified. Clinical records were reviewed for patient age, sex, race/ethnicity, and renal cancer diagnosis. If RCC was present, baseline CT and MRI examinations were independently assessed by two radiologists. Summary statistics were used to summarize continuous and categorical variables by mutation. Results A total of 79 of 25 220 (0.31%) patients had a germline mutation: FLCN , 17 of 25 220 (0.07%); BAP1 , 22 of 25 220 (0.09%); SDH , 39 of 25 220 (0.15%); and MET , one of 25 220 (0.004%). Of these 79 patients, 18 (23%) were diagnosed with RCC ( FLCN , four of 17 [24%]; BAP1 , four of 22 [18%]; SDH , nine of 39 [23%]; MET , one of one [100%]). Most hereditary RCCs demonstrated ill-defined margins, central nonenhancing area (cystic or necrotic), heterogeneous enhancement, and various other CT and MR radiologic features, overlapping with the radiologic appearance of nonhereditary RCCs. The prevalence of other benign solid renal lesions (other than complex cysts) in patients was up to 11%. Conclusion FLCN, BAP1, SDH , and MET mutations were present in less than 1% of this oncologic cohort. Within the study sample size limits, imaging findings for hereditary RCC overlapped with those of nonhereditary RCC, and the prevalence of other associated benign solid renal lesions (other than complex cysts) was up to 11%. Keywords: Familial Renal Cell Carcinoma, Birt-Hogg-Dubé Syndrome, Carcinoma, Renal Cell, Paragangliomas, Urinary, Kidney © RSNA, 2024.

Background: In the United States, the rate of benign histology among resected renal tumors suspected to be malignant is increasing. We evaluated the rates in the Republic of Korea and assessed the racial effect using recent multi-institutional Korean-United States data., Methods: We conducted a multi-institutional retrospective study of 11,529 patients (8,812 from The Republic of Korea and 2,717 from the United States) and compared the rates of benign histology between the two countries. To evaluate the racial effect, we divided the patients into Korean, Asian in the US, and Non-Asian in the US., Results: The rates of benign histology and small renal masses in Korean patients were significantly lower than that in United States patients (6.3% vs. 14.3%, p < 0.001) and (≤ 4 cm, 7.6% vs. 19.5%, p < 0.001), respectively. Women, incidentaloma, partial nephrectomy, minimally invasive surgery, and recent surgery were associated with a higher rate of benign histology than others., Conclusions: In Korea, the rate of benign histology among resected renal tumors was significantly lower than that in the United States. This disparity could be caused by environmental or cultural differences rather than racial differences. Our findings suggest that re-evaluating current context-specific standards of care is necessary to avoid overtreatment., (© 2024. The Author(s).)

Background: Sarcomatoid renal cell carcinoma (RCC) is defined by the presence of any amount of sarcomatoid components admixed with other RCC histologic subtypes. Our investigation utilizes a large, diverse set of sarcomatoid RCC patients to summarize clinical, demographic, and pathological factors along with demographic disparities that may affect the prognosis and survival of sarcomatoid RCC patients., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was employed to compile data from 2000 to 2018 from 2695 patients diagnosed with sarcomatoid RCC., Results: The mean age for sarcomatoid RCC diagnosis is 62.8 years. Males (68.2%) and White patients (82.6%) were more likely to be diagnosed with sarcomatoid RCC. Among the 64.4% of tumors with known size, 35.4% were less than 7 cm, 27.6% were 7.1 to 10 cm, and 36.4% were larger than 10 cm. Among the 95.8% of patients with known stage, 15.3% were localized, 28.9% were regionalized, and 55.8% were found in distant sites. Among the 44.2% of cases with known metastases site, lung was found to be the most common metastatic site.. Surgery was the most common treatment (70.9%). While the overall 5-year survival was 18.1%, it was 27.1% among patients who underwent surgery. Independent risk factors for mortality include age > 60 years, distant stage, and tumor size > 10 cm, per our multivariate analysis., Conclusion: Sarcomatoid RCC most commonly affects White males in their seventh decade. Increased age, distant stage, and size > 10 cm tumor size have associations with unfavorable prognosis. Surgery is associated with better survival outcomes in localized disease and multimodal therapy (surgery with adjuvant chemoradiation was associated with better survival.)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To determine recurrence incidence after partial nephrectomy (PN) for renal cell carcinoma and identify predictors for local recurrence (LR) and metastasis., Material and Methods: We retrospectively evaluated a cohort of 524 patients from the Cancer Registry of Norway, who underwent PN between January 2014 and December 2015 and were followed-up for >6 years. Patient demographics and pathological characteristics were correlated with recurrence and progression-free survival using Kaplan-Meier and Cox regression analyses., Results: Median patient age was 64 years, and the median tumour size was 2.6 cm. A positive surgical margin (PSM) was observed in 11% of the cases, while the LR and metastasis rates were 3.4% and 3.2%, respectively. PSM (hazard ratio [HR], 55.4; 95% confidence interval [CI], 12.55-244.6), tumour number (HR, 45.4; 95% CI, 6.5-316.1) and stage (HR, 33.5; 95% CI, 5.4-205.3) were independent predictors for LR. Undetermined margin status was also a risk factor for LR. Tumour stage (HR, 41.05; 95% CI, 8.52-197.76), tumour necrosis (HR, 1.3; 95% CI, 0.4-4.31) and age (HR, 1.07; 95% CI, 1.01-1.14) were predictors for metastasis., Conclusions: Both local and distant recurrences after PN were rare, and the pT stage was a common predictor. PSM or indeterminate surgical margin and tumour number were LR predictors, while age at surgery and the presence of tumour necrosis predicted metastasis.

Background: The incidence rate of malignant tumors after solid organ transplantation is higher than the normal population. The aim of our study is to identify the risk of renal cell carcinoma (RCC) after liver, kidney, heart and lung transplantation, respectively, and suggest that transplant patients can be screened early for tumors to avoid risk., Methods: PubMed, Embase and the Cochrane Library from their inception until August 16,2023. Retrospective and cohort studies which focus on the statistical data of standardized incidence ratios (SIRs) of RCC after solid organ transplantation (SOT) more than one year have been included and extracted. The study was registered with PROSPERO, CRD4202022343633., Results: Sixteen original studies have been included for meta-analysis. Liver transplantation could increase the risk of RCC (SIR = 0.73, 95%CI: 0.53 to 0.93) with no heterogeneity(P = 0.594, I 2  = 0.0%). And kidney transplantation could increase the risk of RCC(8.54, 6.68 to 10.40; 0.000,90.0%). Besides, heart and lung transplantation also could increase the risk of RCC(SIR = 0.73, 95%CI: 0.53 to 0.93; SIR = 1.61, 95%CI:0.50 to 2.71). Moreover, significance could also be found in most subgroups, especially the European group and retrospective study group. What's more, after removing studies which have a greater impact on the overall outcome in RCC rate after kidney transplantation, heterogeneity did not solve and significant different was also observed in the European group (7.15, 5.49 to 8.81; 0.000, 78.6%)., Conclusion: Liver, kidney, heart and lung transplantation patients have an increased risk of processing RCC compared to the general population and most subgroups, especially in geographic location of European subgroup, which suggested that patients should be screened frequently after transplantation., (© 2023. The Author(s).)

Purpose: Our purpose was to investigate the association between family history of renal cell carcinoma (RCC) and RCC risk., Materials and Methods: RCC cases diagnosed in Sweden between 2005 and 2014 and 10 matched controls were identified using the Renal Cell Cancer Database Sweden, with linkage to the Multigeneration Register and the Swedish Cancer Registry. The association between a family history of RCC and RCC was investigated, overall and by sex and age groups., Results: Among 9416 RCC cases, 294 (3.1%) had 1 or more parent or sibling (first-degree relative [FDR]) with RCC. Median age at diagnosis for cases with an affected FDR was 65 years (IQR 59-71) and 68 years (IQR 60-75) for all cases. The proportion of women was significantly higher among familial RCC compared to sporadic RCC (44.6% vs 38.5% , P = .035). RCC was twice as likely with 1 or more FDR with RCC (OR 1.9; CI 1.65-2.16). Stratified analysis showed an OR of 2.4 for women (CI 1.93-2.92) and 1.6 for men (CI 1.35-1.93). Two or more FDRs was associated with a sixfold increased risk (95% CI 2.37-15.5). Familial RCC was strongly associated with bilateral and multifocal tumors (OR 5.5; CI 2.36-13.0, OR 3.5; CI 1.89-6.49)., Conclusions: In this Swedish data set, 3.1% of RCC patients have 1 or more FDR diagnosed with RCC. There was no statistical difference in median age between sporadic RCC and familial RCC. Having 1 or more FDR with RCC approximately doubles the risk of RCC with a higher risk increase for women than for men. People with 2 FDRs with RCC constitute a small high-risk group that may benefit from screening.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition; however, its relationship with renal cell carcinoma (RCC) remains unclear. This paper aims to establish the prevalence of RCC and its subtypes amongst ADPKD patients., Methods: A database search was conducted to retrieve studies reporting RCC occurrence within ADPKD patients until July 2023. Key outcomes included number and subtype of RCC cases, and number of RCCs presenting incidentally. A random-effects meta-analysis was performed., Results: Our search yielded 569 articles, 16 met the inclusion criteria. Nephrectomy specimens from 1,147 ADPKD patients were identified. Of studies reporting per-kidney results (n = 13), 73 RCCs were detected amongst 1,493 kidneys, equating to a per-kidney prevalence of 4.3% (95% CI, 3.1-5.7, I2 = 15.7%). 75 ADPKD patients were found to have RCC (75/1,147), resulting in a per-person prevalence of 5.7% (95% CI, 3.7-7.9, I2 = 40.3%) (n = 16). As 7 patients had bilateral disease, 82 RCCs were detected in total. Of these, 39 were clear cell RCC, 35 were papillary and 8 were other. As such, papillary RCCs made up 41.1% (95% CI, 25.9-56.9, I2 = 18.1%) of detected cancers. The majority of RCCs were detected incidentally (72.5% [95% CI, 43.7-95.1, I2 = 66.9%])., Conclusion: ADPKD appears to be associated with the papillary RCC subtype. The clinical implications of these findings are unclear, however, may become apparent as outcomes and life expectancy amongst APDKD patients improve., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: We examine the heterogeneity and distribution of the cohort populations in two publicly used radiological image cohorts, the Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCIA TCGA KIRC) collection and 2019 MICCAI Kidney Tumor Segmentation Challenge (KiTS19), and deviations in real-world population renal cancer data from the National Cancer Database (NCDB) Participant User Data File (PUF) and tertiary center data. PUF data are used as an anchor for prevalence rate bias assessment. Specific gene expression and, therefore, biology of RCC differ by self-reported race, especially between the African American and Caucasian populations. AI algorithms learn from datasets, but if the dataset misrepresents the population, reinforcing bias may occur. Ignoring these demographic features may lead to inaccurate downstream effects, thereby limiting the translation of these analyses to clinical practice. Consciousness of model training biases is vital to patient care decisions when using models in clinical settings., Methods: Data elements evaluated included gender, demographics, reported pathologic grading, and cancer staging. American Urological Association risk levels were used. Poisson regression was performed to estimate the population-based and sample-specific estimation for prevalence rate and corresponding 95% confidence interval. SAS 9.4 was used for data analysis., Results: Compared to PUF, KiTS19 and TCGA KIRC oversampled Caucasian by 9.5% (95% CI, -3.7 to 22.7%) and 15.1% (95% CI, 1.5 to 28.8%), undersampled African American by -6.7% (95% CI, -10% to -3.3%), and -5.5% (95% CI, -9.3% to -1.8%). Tertiary also undersampled African American by -6.6% (95% CI, -8.7% to -4.6%). The tertiary cohort largely undersampled aggressive cancers by -14.7% (95% CI, -20.9% to -8.4%). No statistically significant difference was found among PUF, TCGA, and KiTS19 in aggressive rate; however, heterogeneities in risk are notable., Conclusion: Heterogeneities between cohorts need to be considered in future AI training and cross-validation for renal masses., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Renal medullary carcinoma (RMC) is an aggressive and rare renal malignancy that predominantly affects Black patients but is also found in individuals of other ethnicities. To date, only a few hundred cases have been reported in the urologic literature. Due to this extreme rarity, the exact pathophysiology and optimal treatment have yet to be well described. This study aims to determine the predictors of mortality and overall survival outcomes in patients with RMC., Methods: We utilized the Surveillance, Epidemiology, and End Results Program (SEER) database 18 registries to retrieve demographic and clinical information on patients with RMC between 1996 and 2018. A multivariate analysis was performed to determine predictors of mortality in the study population. Kaplan-Meier survival curves were then created to display the differences in overall survival of Black versus non-Black patients diagnosed with renal medullary carcinoma during the study period., Results: We identified 100 patients diagnosed with renal medullary carcinoma using the SEER Database in the study period. The mean age was 28.0 ± 12.0 (95% confidence interval [CI] 25.7-30.4). Among the patients, 76% were male and 24% were female. Most RMC patients were Black (83%) with only 17% identifying as White. The mean survival in months was 13.8 ± 3.0 (95% CI 7.9-19.7). The majority (70%) of patients in this study presented with distant, metastatic disease at the time of diagnosis. Black patients with RMC were less likely to receive surgery and five times more likely to die in comparison to their White counterparts OR = 5.4 (95% CI 1.09-26.9, P = 0.04). Not only did Black patients have a lower survival rate at 12 mo compared to White patients, but they also continued to experience a sharp decline in survival to 10.2% at 24 mo (P < 0.05) and 7.6% at 48 mo (P < 0.05) following diagnosis of renal medullary carcinoma., Conclusions: These data confirm that RMC is a rare disease that disproportionately affects Black patients. The prognosis appears to be substantially worse for Black subjects diagnosed with this cancer than non-Black patients. The worse outcomes seen in Black subjects are of an unclear etiology and are yet to be investigated., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to conduct a population-based study to determine the prognosis of renal cell carcinoma (RCC) in children and adolescents., Methods: Patients with RCC who were registered in the Surveillance, Epidemiology, and End Results (SEER) program between 2000 and 2018 had their demographic and clinical characteristics evaluated retrospectively. The log-rank test was used to compare survival curves. Kaplan-Meier estimates were used to generate survival curves based on various factors. To identify factors associated with overall survival, Cox proportional-hazards regression was used., Results: A total of 251 patients were enrolled in the study. For all patients, the overall survival (OS) rates at 3- and 5- year were 93.5% and 92.0%, respectively. A multivariable study revealed that the following factors were independently associated with overall survival: sex, race, histologic type, SEER stage, AJCC stage, and type of surgery. Cox analysis showed that white patients had the lowest risk of mortality (hazard ratio (HR) 2.58, 95% confidence interval (CI), 1.33-4.99; P = 0.005), compared with black patients. Patients having metastatic disease had significantly higher mortality risk (HR 43, 95% CI, 14.8-125; P < 0.001) than the patients with localized tumour., Conclusions: Our study emphasizes the importance of race, SEER stage, and surgery in the prognosis of paediatric RCC, providing valuable epidemiological evidence for clinical practice. Economic studies assessing a race/ethnic group specific strategy are also required., (© 2023 Royal Australasian College of Surgeons.)

Renal cell carcinoma (RCC) incidence has doubled over the past few decades. However, death rates have remained stable as the number of incidental renal mass diagnoses peaked. RCC has been recognized as a European health care issue, but to date, no screening programmes have been introduced. Well-known modifiable risk factors for RCC are smoking, obesity and hypertension. A direct association between cigarette consumption and increased RCC incidence and RCC-related death has been reported, but the underlying mechanistic pathways for this association are still unclear. Obesity is associated with an increased risk of RCC, but interestingly, improved survival outcomes have been reported in obese patients, a phenomenon known as the obesity paradox. Data on the association between other modifiable risk factors such as diet, dyslipidaemia and physical activity with RCC incidence are conflicting, and potential mechanisms underlying these associations remain to be elucidated., (© 2023. Springer Nature Limited.)

Purpose: To test for regional differences in clear cell metastatic renal cell carcinoma (ccmRCC) patients across the USA., Methods: The Surveillance, Epidemiology, and End Results (SEER) database (2000-2018) was used to tabulate patient (age at diagnosis, sex, race/ethnicity), tumor (N stage, sites of metastasis) and treatment characteristics (proportions of nephrectomy and systemic therapy), according to 12 SEER registries. Multinomial regression models, as well as multivariable Cox regression models, tested the overall mortality (OM) adjusting for those patient, tumor and treatment characteristics., Results: In 9882 ccmRCC patients, registry-specific patient counts ranged from 4025 (41%) to 189 (2%). Differences across registries existed for sex (24-36% female), race/ethnicity (1-75% non-Caucasian), N stage (N1 25-35%, NX 3-13%), proportions of nephrectomy (44-63%) and systemic therapy (41-56%). Significant inter-registry differences remained after adjustment for proportions of nephrectomy (46-63%) and systemic therapy (35-56%). Unadjusted 5-year OM ranged from 73 to 85%. In multivariable analyses, three registries exhibited significantly higher OM (SEER registry 5: hazard ratio (HR) 1.20, p = 0.0001; SEER registry 7:HR 1.15, p = 0.008M SEER registry 10: HR 1.15, p = 0.04), relative to the largest reference registry (n = 4025)., Conclusion: Important regional differences including patient, tumor and treatment characteristics exist, when ccmRCC patients included in the SEER database are studied. Even after adjustment for these characteristics, important OM differences persisted, which may require more detailed analyses to further investigate these unexpected differences., (© 2023. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We evaluated the temporal association between kidney function, assessed by estimated glomerular filtration rate (eGFR), and the risk of incident renal cell carcinoma (RCC). We also evaluated whether eGFR could improve RCC risk discrimination beyond established risk factors., Methods: We analyzed the UK Biobank cohort, including 463,178 participants of whom 1,447 were diagnosed with RCC during 5,696,963 person-years of follow-up. We evaluated the temporal association between eGFR and RCC risk using flexible parametric survival models, adjusted for C-reactive protein and RCC risk factors. eGFR was calculated from creatinine and cystatin C levels., Results: Lower eGFR, an indication of poor kidney function, was associated with higher RCC risk when measured up to 5 years prior to diagnosis. The RCC HR per SD decrease in eGFR when measured 1 year before diagnosis was 1.26 [95% confidence interval (95% CI), 1.16-1.37], and 1.11 (95% CI, 1.05-1.17) when measured 5 years before diagnosis. Adding eGFR to the RCC risk model provided a small improvement in risk discrimination 1 year before diagnosis with an AUC of 0.73 (95% CI, 0.67-0.84) compared with the published model (0.69; 95% CI, 0.63-0.79)., Conclusions: This study demonstrated that kidney function markers are associated with RCC risk, but the nature of these associations are consistent with reversed causality. Markers of kidney function provided limited improvements in RCC risk discrimination beyond established risk factors., Impact: eGFR may be of potential use to identify individuals in the extremes of the risk distribution., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Body mass index (BMI) is a known risk factor for renal cell cancer (RCC), but data are limited as to the effect of lifetime exposure to excess body weight., Methods: Using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 138,614, 527 incident RCCs), we identified several anthropometric measures to capture the lifetime BMI patterns: (i) BMI at specific ages; (ii) adulthood BMI trajectories; (iii) cumulative exposure to overweight/obesity denoted as weighted years of living overweight/obese (WYO); and (iv) weight change during each age span. We conducted multivariable Cox model to quantify the association between each anthropometric metric and incident RCC., Results: A higher BMI at ages 20 and 50 and at baseline was associated with a greater hazard of RCC. Compared with individuals who retained normal BMI throughout adulthood, we observed an increased hazard of RCC for BMI trajectory of progressing from normal BMI to overweight [HR, 1.49; 95% confidence interval (CI), 1.19-1.87], from normal BMI to obesity (HR, 2.22; 95% CI, 1.70-2.90), and from overweight to obesity (HR, 2.78; 95% CI, 1.81-4.27). Compared with individuals who were never overweight (WYO = 0), elevated HRs were observed among individuals who experienced low (HR, 1.31; 95% CI, 0.99-1.74), medium (HR, 1.57; 95% CI, 1.20-2.05), and high (HR, 2.10; 95% CI, 1.62-2.72) WYO tertile. Weight gain of ≥10 kg was associated with increased RCC incidence for each age span., Conclusions: Across the lifespan, being overweight/obese, weight gain, and higher cumulative exposure to excess weight were all associated with increased RCC risk., Impact: It is important to avoid weight gain and assess BMI from a life-course perspective to reduce RCC risk., (©2023 American Association for Cancer Research.)

Background: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied., Methods: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation., Results: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant "on-treatment" hypertension was not associated with MACE., Conclusions: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI-related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993-2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, OR continuous  = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), P trend  = 0.04; OR continuous  = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [OR continuous  = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objectives: Recent studies suggest that the radiological infiltrative feature (r-IF) of renal tumors is strongly correlated with poor oncologic outcomes in locally advanced renal cell carcinoma (RCC). This study investigated the prognostic impact of r-IF of primary renal tumors in metastatic RCC (mRCC) in comparison with International Metastatic RCC Database Consortium (IMDC) risk model., Methods: We retrospectively analyzed 91 patients with previously untreated mRCC. Dynamic computed tomography of the primary renal tumor was reviewed to assess r-IF, defined as a focally/extensively ill-defined tumor interface with normal renal parenchyma., Results: The median age was 67 years, and 69 patients (76%) were men. Prior nephrectomy was performed in 47 patients (52%). The median size of the primary renal tumor was 6.7 cm, and 50 patients (55%) presented with cT3-4 stage. Overall, 25 (28%)/52 (57%)/14 (15%) patients were classified into IMDC favorable/intermediate/poor-risk groups, respectively. An image review identified r-IFs in the primary renal tumor in 40 patients (44%). The incidences of r-IFs were 28%/46%/64% in IMDC favorable/intermediate/poor-risk groups, respectively. During a median follow-up of 2.6 years, 31 patients (34%) died of RCC. On multivariable analysis, r-IF and IMDC intermediate-poor risks were independently associated with poor cancer-specific survival (CSS). Two-year CSS were 64%/87% in patients with/without r-IF, respectively. C-index was improved from 0.73 to 0.81 by adding r-IF to the IMDC risk factors., Conclusions: R-IF of the primary renal tumor was an independent risk factor for poor CSS in patients with mRCC, which may improve the prognostic accuracy when combined with the IMDC risk model., (© 2023 The Japanese Urological Association.)

Adenosine N1 methylation (m1A) of RNA, a type of post-transcriptional modification, has been shown to play a significant role in the progression of cancer. The objective of the current research was to analyze the genetic alteration and prognostic significance of m1A regulators in kidney renal clear cell carcinoma (KIRC). Genomic and clinicopathological characteristics were obtained from 558 KIRC patients in the Cancer Genome Atlas (TCGA) and Gene Omnibus Expression (GEO) databases. Alterations in the gene expression of ten m1A-regulators were analyzed and survival analysis was performed using the Cox regression method. We also identified three clusters of patients based on their distinct m1A alteration patterns, using integrated analysis of the ten m1A-related regulators, which were significantly related to overall survival (OS), disease-free survival (DFS) and tumor microenvironment (TME) immune cell infiltration cells in KIRC. Our findings showed that m1A alteration patterns have critical roles in determining TME complexity and its immune cell composition. Furthermore, different m1A expression patterns were significantly associated with DFS and OS rates in KIRC patients. In conclusion, the identified m1A RNA modification patterns offer a potentially effective way to classify KIRC patients based on their TME immune cell infiltration, enabling the development of more personalized and successful treatment strategies for these patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The association between statin use and risk of renal cell carcinoma (RCC) has been debated. We aimed to evaluate whether statin use is associated with RCC risk. Material and methods: We studied 100,195 women in the Nurses' Health Study (NHS) from 1994 to 2016; 91,427 women in the Nurses' Health Study II (NHS II) from 1999 to 2015; and 45,433 men in the Health Professionals Follow-up Study (HPFS) from 1990 to 2016. Statins and covariate data were collected at baseline and then biennially. Outcome was measured as incidence of total RCC and clinically relevant disease subgroups. Cox proportional hazards models estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During follow-up, 661 participants developed RCC. There was no significant association between the use of statins and the risk of overall RCC, fatal RCC, or advanced or localized disease. Across cohorts, the adjusted HR for ever vs. never users was 0.97 (95% CI 0.81-1.16). Female ever users of statins were at increased risk of high-grade disease in the NHS only (HR 1.75, 95% CI 1.07-2.85). Among men only, ≥4 years of statin use was associated with an increased risk of clear cell RCC (HR 1.65, 95% CI 1.10-2.47). Conclusions: Statin use was not associated with the overall risk of RCC. However, it was associated with an increased risk of high-grade disease among women in the NHS cohort and an increased risk of clear cell RCC among men. The reasons for these inconsistent results by sex are unclear.

Purpose: This study is to compare risks of developing renal cell carcinoma or urothelial cancer between hemodialysis (HD) and peritoneal dialysis (PD) patients., Methods: The age-, sex-, and index year-matched patients with newly diagnosed end-stage kidney disease (ESKD) undergoing dialysis [HD (N = 22,587) or PD (N = 11,547)] from 2000 to 2015 in Taiwan were identified. Patients were followed until the development of renal cell carcinoma or urothelial cancer, renal transplantation, death, or the end of follow-up (December 31, 2017). The hazard ratio (HR), and sub-hazards ratio (SHR), in which death was considered as a competing risk, of developing renal cell carcinoma or urothelial cancer were compared between the HD and PD patients., Results: The incidence rate of renal cell carcinoma was higher in the PD group than in age-, sex-, and index year-matched HD group (11.5 versus 5.52 per 10,000 person-years), with an adjusted HR of 2.15 (95% confidence interval (CI) = 1.59, 2.92), and an adjusted SHR of 1.97 (95% CI = 1.46, 2.67). The incidence rate of urothelial cancer was also higher in the PD group than in corresponding HD group (40.3 and 34.0 per 10,000 person-years), with an adjusted HR of 1.15 (95% CI = 1.00, 1.33) and an adjusted SHR of 1.08 (95% CI = 0.94, 1.25). These findings were further validated in propensity score-matched dialysis cohorts., Conclusions: ESKD patients undergoing PD are at a higher risk of developing renal cell carcinoma than those on HD, but risks of developing urothelial cancer are similar among the two groups., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To describe the incidence, characteristics, clinical management, and outcomes of renal cell carcinoma (RCC) among a large, single-centre cohort of kidney transplant recipients (KTR)., Methods: We conducted an observational cohort study looking at KTR transplanted between January 2000-December 2017 (n = 2443) with ≥ 1 year of follow-up. Simultaneous kidney/pancreas transplants were excluded. The Kaplan-Meier product-limit method was used to determine the incidence of RCC. Characteristics and management of RCC were examined using descriptive statistics. Risk factors and clinical outcomes were analyzed using Cox regression models., Results: The incidence of RCC among our cohort was 0.32 per 100 person-years, 2.1% of all KTRs. Almost half (47.1%) of cases occurred within 4 years post-transplant. The majority of cases were T1a (86.3%), clear-cell (45.1%), and in the native kidney (80.4%). KTR diagnosed with RCC had a twofold higher incidence of other malignancies versus KTR without RCC. Overall mortality, but not cancer-specific mortality, at 2- and 5-years post-transplant was threefold higher among KTR with RCC than those without., Conclusions: Incidence of RCC among our KTR was slightly higher than the general population; majority of cases occur in the native kidneys and are low stage, low grade. Indolent histologic variants were more common than the general population. KTR with RCC had a higher incidence of other malignancies. Overall, but not cancer-specific, mortality was higher among KTRs diagnosed with RCC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ongoing research in the field of both localized, locally advanced and metastatic renal cell carcinoma has resulted in the availability of multiple treatment options. Hence, many questions are still unanswered and await further research. A nationwide collaborative registry allows to collect corresponding data. For this purpose, the Dutch PROspective Renal Cell Carcinoma cohort (PRO-RCC) has been founded, for the prospective collection of long-term clinical data, patient reported outcome measures (PROMs) and patient reported experience measures (PREMs)., Methods: PRO-RCC is designed as a multicenter cohort for all Dutch patients with renal cell carcinoma (RCC). Recruitment will start in the Netherlands in 2023. Importantly, participants may also consent to participation in a 'Trial within cohorts' studies (TwiCs). The TwiCs design provides a method to perform (randomized) interventional studies within the registry. The clinical data collection is embedded in the Netherlands Cancer Registry (NCR). Next to the standardly available data on RCC, additional clinical data will be collected. PROMS entail Health-Related Quality of Life (HRQoL), symptom monitoring with optional ecological momentary assessment (EMA) of pain and fatigue, and optional return to work- and/or nutrition questionnaires. PREMS entail satisfaction with care. Both PROMS and PREMS are collected through the PROFILES registry and are accessible for the patient and the treating physician., Trial Registration: Ethical board approval has been obtained (2021&#95;218) and the study has been registered at ClinicalTrials.gov (NCT05326620)., Discussion: PRO-RCC is a nationwide long-term cohort for the collection of real-world clinical data, PROMS and PREMS. By facilitating an infrastructure for the collection of prospective data on RCC, PRO-RCC will contribute to observational research in a real-world study population and prove effectiveness in daily clinical practice. The infrastructure of this cohort also enables that interventional studies can be conducted with the TwiCs design, without the disadvantages of classic RCTs such as slow patient accrual and risk of dropping out after randomization., (© 2023. The Author(s).)

Purpose: The disparity in renal cell carcinoma (RCC) risk and treatment outcome between males and females is well documented, but the underlying molecular mechanisms remain poorly elucidated., Methods: We performed a narrative review synthesizing contemporary evidence on sex-specific molecular differences in healthy kidney tissue and RCC., Results: In healthy kidney tissue, gene expression differs significantly between males and females, including autosomal and sex-chromosome-linked genes. The differences are most prominent for sex-chromosome-linked genes and attributable to Escape from X chromosome-linked inactivation and Y chromosome loss. The frequency distribution of RCC histologies varies between the sexes, particularly for papillary, chromophobe, and translocation RCC. In clear-cell and papillary RCC, sex-specific gene expressions are pronounced, and some of these genes are amenable to pharmacotherapy. However, for many, the impact on tumorigenesis remains poorly understood. In clear-cell RCC, molecular subtypes and gene expression pathways have distinct sex-specific trends, which also apply to the expression of genes implicated in tumor progression., Conclusion: Current evidence suggests meaningful genomic differences between male and female RCC, highlighting the need for sex-specific RCC research and personalized sex-specific treatment approaches., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology., Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Results: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use., Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). Emerging data suggest that these agents can result in clinically significant cardiotoxicity, compromising the care., Methods: We conducted a prospective longitudinal study to evaluate the incidence of de novo cardiac dysfunction as assessed by echocardiography and blood biomarkers in mRCC patients receiving TKI with or without ICI followed at baseline, 3-month and 6-month. We recruited consecutive newly diagnosed mRCC patients treated at our institution between 2015 and 2018 as well as patients with localized RCC not treated with systemic therapies and healthy control (HC) subjects for comparison., Results: Twenty-eight patients were enrolled in the mRCC group (a mean age of 65.2 ± 7.5 years), 29 patients in the localized RCC group (63.6 ± 8.9 years), and 20 volunteers in the HC group (52.9 ± 9.6 years). At baseline, patients from all three groups had normal cardiac function as measured by left ventricular ejection fraction (LVEF), although patients with mRCC or localized RCC had significantly lower mean LVEF compared to HC (61.9%, 62.4%, and 68.1% respectively). Otherwise, there were no statistically significant changes in echocardiographic parameters or incidence of clinical heart failure from baseline to 6-months in patients with mRCC. Cardiac blood biomarkers including troponin I, brain natriuretic peptide, and galectin-3 remained stable over time., Conclusion: Our findings suggest that contemporary treatment strategies of mRCC at this single institution are well tolerated without clinically meaningful overt declines in cardiac function over time. Further studies are warranted to include a larger number of patients to better assess the overall cardiovascular safety associated with contemporary treatments of mRCC., Competing Interests: Declaration of Competing Interest Al authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Over the past decade and a half, advances in diagnostic imaging as well as an increased utilization of active surveillance (AS) and renal mass biopsy (RMB) have led to an improved ability to identify benign lesions prior to partial nephrectomy (PN). We seek to examine the incidence of benign pathology at the time of PN in a contemporary cohort of patients undergoing PN for presumed renal cell carcinoma (RCC)., Patients and Methods: We performed a chart review on a prospectively maintained database on a series of patients who underwent PN between January 1, 2006 and December 31, 2021 for solid renal masses concerning for RCC., Results: One thousand two hundred twenty-nine patients were included in the analysis, with 240 patients (19.2%) identified to have benign disease on final pathology. Of patients with benign disease, (23%) of patients had angiomyolipoma (AML) and 64% had oncocytoma. Between 2006 and 2021, there was a significant increase in the incidence of benign pathology after PN. When examining 3-year rolling averages over this same time period, the incidence of oncocytoma appeared to increase while the incidence of AML decreased., Conclusion: Despite improvements in diagnostic tools and increased utilization of active surveillance, the overall incidence of benign pathology, particularly oncocytoma, did not decrease over time in this contemporary cohort of patients undergoing PN., Competing Interests: Declaration of Competing Interest Dr. William Huang receives funding from Intuitive for research. The other authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Renal cell carcinoma (RCC) survival has improved due to recent developments in RCC treatment. Therefore, other co-morbid conditions may have a more critical role. This study aims to explore the common causes of death in patients with RCC to improve the management and survival of RCC., Method: We used the Surveillance, Epidemiology, and End Results (SEER) (1992-2018) database to get patients with RCC. We calculated the percentage of total deaths of six kinds of the cause of death (COD) and the cumulative incidence of death for each selected cause over survival time. The joinpoint regression was utilized to present the trend of mortality rate by COD., Results: We enrolled 107,683 cases with RCC. RCC was the leading cause of death in patients with RCC [25376(48.3%)], followed by cardiovascular diseases [9023(17.2%)], other cancers [8003 (15.2%)], other non-cancer diseases [4195 (8%)], non-disease cause [4023 (7.7%)], and respiratory diseases [1934 (3.6%)]. The proportion of patients who died of RCC decreased gradually over survival time, and this value decreased from 69.71% in 1992-1996 to 38.96% in 2012-2018. The non-RCC cause mortality rate showed an increasing trend, whereas a slight decrease was observed in RCC specific mortality rate. The distribution of such conditions varied across different patient populations., Conclusion: RCC was still the primary COD of patients with RCC. However, non-RCC cause death was increasingly important among RCC patients in recent two decades. Cardiovascular disease and other cancers were crucial co-morbidities that required significant attention in the management of RCC patients., (© 2023. The Author(s).)

Objective: To analyze the global epidemiology of renal cell carcinoma (RCC) in 2020. Methods: The incidence and mortality data of RCC in the cooperative database GLOBOCAN 2020 of International Agency for Research on Cancer of WHO and the human development index (HDI) published by the United Nations Development Programme in 2020 were collated. The crude incidence rate (CIR), age-standardized incidence rate (ASIR), crude mortality rate (CMR), age-standardized mortality rate (ASMR) and mortality/incidence ratio (M/I) of RCC were calculated. Kruskale-Wallis test was used to analyze the differences in ASIR or ASMR among HDI countries. Results: In 2020, the global ASIR of RCC was 4.6/100 000, of which 6.1/100 000 for males and 3.2/100 000 for females and ASIR was higher in very high and high HDI countries than that in medium and low HDI countries. With the rapid increase of age after the age of 20, the growth rate of ASIR in males was faster than that in females, and slowed down at the age of 70 to 75. The truncation incidence rate of 35-64 years old was 7.5/100 000 and the cumulative incidence risk of 0-74 years old was 0.52%. The global ASMR of RCC was 1.8/100 000, 2.5/100 000 for males and 1.2/100 000 for females. The ASMR of males in very high and high HDI countries (2.4/100 000-3.7/100 000) was about twice that of males (1.1/100 000-1.4/100 000) in medium and low HDI countries, while the ASMR of female (0.6/100 000-1.5/100 000) did not show significant difference. ASMR continued to increase rapidly with age after the age of 40, and the growth rate of males was faster than that of females. The truncation mortality rate of 35-64 years old was 2.1/100 000, and the cumulative mortality risk of 0-74 years old was 0.20%. M/I decreases with the increase of HDI, with M/I as 0.58 in China, which was higher than the global average of 0.39 and the United States' 0.17. Conclusion: The ASIR and ASMR of RCC presented significant regional and gender disparities globally, and the heaviest burden was in very high HDI countries.