Avoidable Benign Kidney Tumor Resections-Data from a Tertiary Care Cancer Institute.

Enhancing renal masses are conventionally treated as malignant unless proven otherwise due to the difficulty distinguishing between malignant and benign tumors based on imaging. Data from the Western registries suggests overtreatment of renal tumors with a Benign Kidney Tumor Resection Rate (BKTRR) ranging from 10 to 33%, with an increasing trend. Since robust, population-based data from India was unavailable, we sought to determine BKTRR in an apex cancer institute, which would provide insight into the rates in the community. The institutional kidney tumor database was queried for all patients aged ≥18 years with renal neoplasms between January 2000 and December 2022. Patients who underwent surgery, either radical or partial nephrectomy, with intent to cure were analyzed and the BKTRR during the study period was evaluated. A total of 330 patients underwent surgery for renal tumors presumed to be malignant. A final pathologic diagnosis of the benign tumor was made in 16 (4.8%) patients, comprising 7.2, 7.2, and 3.7% of resections with LTD ≤4, 4-7, and >7 cm, respectively. Asymptomatic benign tumors ≤7 cm comprised 3.0% of all resections, and these were potentially unnecessary surgeries. A multivariable analysis suggested that no patient or imaging characteristic could predict a final benign extirpative pathology. Our study suggests a lower rate of BKTRR compared to the published international literature but is likely to be the lower limit of that in the community. Population-based studies are required to determine the true BKTRR and the quantum of potentially unnecessary surgeries for benign kidney tumors.

Exploring prognostic implications of miRNA signatures and telomere maintenance genes in kidney cancer.

Kidney cancer, particularly clear cell renal cell carcinoma (KIRC), presents significant challenges in disease-specific survival. This study investigates the prognostic potential of microRNAs (miRNAs) in kidney cancers, including KIRC and kidney papillary cell carcinoma (KIRP), focusing on their interplay with telomere maintenance genes. Utilizing data from The Cancer Genome Atlas, miRNA expression profiles of 166 KIRC and 168 KIRP patients were analyzed. An evolutionary learning-based kidney survival estimator identified robust miRNA signatures predictive of 5-year survival for both cancer types. For KIRC, a 37-miRNA signature showed a correlation coefficient (R) of 0.82 and mean absolute error (MAE) of 0.65 years. Similarly, for KIRP, a 23-miRNA signature exhibited an R of 0.82 and MAE of 0.64 years, demonstrating comparable predictive accuracy. These signatures also displayed diagnostic potential with receiver operating characteristic curve values between 0.70 and 0.94. Bioinformatics analysis revealed targeting of key telomere-associated genes such as TERT, DKC1, CTC1, and RTEL1 by these miRNAs, implicating crucial pathways such as cellular senescence and proteoglycans in cancer. This study highlights the significant link between miRNAs and telomere genes in kidney cancer survival, offering insights for therapeutic targets and improved prognostic markers.

Upgrading Isoquercitrin Concentration via Submerge Fermentation of Mulberry Fruit Extract with Edible Probiotics to Suppress Gene Targets for Controlling Kidney Cancer and Inflammation.

In recent years, kidney cancer has become one of the most serious medical issues. Kidney cancer is treated with a variety of active compounds that trigger genes that cause cancer. We identified in our earlier research that isoquercitrin (IQ) can activate PIK3CA, IGF1R, and PTGS2. However, it has a very low bioavailability because of its lower solubility in water. So, we utilized sub-merge fermentation technology with two well-known probiotics, Lactobacillus acidophilus and Bacillus subtilis, as a microbial source and mulberry fruit extract as a substrate, which has a high IQ level to improve IQ yield. Furthermore, we compared the total phenolic, flavonoid, and antioxidant contents of fermented and non-fermented samples, and we found that the fermented samples had greater levels than non-fermented sample. In addition, the high-performance liquid chromatography (HPLC) results showed that the fermented mulberry fruit extract from B. subtilis and L. acidophilus showed higher IQ values (190.73 ± 0.004 µg/ml and 220.54 ± 0.007 µg/ml, respectively), compared to the non-fermented samples, which had IQ values (80.12 ± 0.002 µg/ml). Additionally, at 62.5 µg/ml doses of each sample, a normal kidney cell line (HEK 293) showed higher cell viability for fermented and non-fermented samples. Conversely, at the same doses, the fermented samples of L. acidophilus and B. subtilis in a kidney cancer cell line (A498) showed an inhibition of cell growth around 36% and 31%, respectively. Finally, we performed RT and qRT PCR assay, and we found a significant reduction in the expression of the PTGS2, PIK3CA, and IGF1R genes. We therefore can conclude that the fermented samples have a higher concentration of isoquercitrin, and also can inhibit the expression of the genes PTGS2, PIK3CA, and IGF1R, which in turn regulates kidney cancer and inflammation.

Quantifying preserved renal volume and function in patients undergoing standard partial nephrectomy vs. tumor enucleation for localized renal tumors.

INTRODUCTION: Renal parenchymal volume loss from standard partial nephrectomy (SPN) is a significant prognosticator for postoperative renal function. Tumor enucleation (TE) minimizes parenchymal loss compared to SPN. Little is known regarding discrete changes in renal function associated with volume loss. We sought to quantify the differences between SPN and TE in preserving parenchymal volume and estimated glomerular filtration rate (eGFR). METHODS: We identified 420 patients who underwent robotic partial nephrectomy (SPN or TE) at our tertiary care center from 2009 to 2022. Parenchymal volumes were calculated using TeraRecon 3D reconstruction software from axial imaging performed preoperatively and within 6 months postoperatively. Renal volume preserved and renal function were evaluated with multivariable linear and logistic regression models. RESULTS: At 1 year, eGFR was 7% lower in patients undergoing SPN compared to TE (P < 0.01). Across both SPN and TE, only volume of preserved parenchyma was predictive of eGFR and chronic kidney disease (CKD) progression (both P < 0.01). TE preserved more healthy parenchymal volume compared to SPN (median percentage 97.6% vs 89.2%; P < 0.001). Each 1% of volumetric loss corresponded to a 0.35% decrease in eGFR at 1 year postoperatively (P < 0.01). CONCLUSIONS: Volume of preserved renal parenchyma was the strongest factor associated with preserved eGFR and reduced odds of CKD progression. TE preserved more parenchyma than SPN, which translated to higher eGFR preservation at 1 year postoperatively.

Empowering patients: how accurate and readable are large language models in renal cancer education.

Background: The incorporation of Artificial Intelligence (AI) into healthcare sector has fundamentally transformed patient care paradigms, particularly through the creation of patient education materials (PEMs) tailored to individual needs. This Study aims to assess the precision and readability AI-generated information on kidney cancer using ChatGPT 4.0, Gemini AI, and Perplexity AI., comparing these outputs to PEMs provided by the American Urological Association (AUA) and the European Association of Urology (EAU). The objective is to guide physicians in directing patients to accurate and understandable resources. Methods: PEMs published by AUA and EAU were collected and categorized. kidney cancer-related queries, identified via Google Trends (GT), were input into CahtGPT-4.0, Gemini AI, and Perplexity AI. Four independent reviewers assessed the AI outputs for accuracy grounded on five distinct categories, employing a 5-point Likert scale. A readability evaluation was conducted utilizing established formulas, including Gunning Fog Index (GFI), Simple Measure of Gobbledygook (SMOG), and Flesch-Kincaid Grade Formula (FKGL). AI chatbots were then tasked with simplifying their outputs to achieve a sixth-grade reading level. Results: The PEM published by the AUA was the most readable with a mean readability score of 9.84 ± 1.2, in contrast to EAU (11.88 ± 1.11), ChatGPT-4.0 (11.03 ± 1.76), Perplexity AI (12.66 ± 1.83), and Gemini AI (10.83 ± 2.31). The Chatbots demonstrated the capability to simplify text lower grade levels upon request, with ChatGPT-4.0 achieving a readability grade level ranging from 5.76 to 9.19, Perplexity AI from 7.33 to 8.45, Gemini AI from 6.43 to 8.43. While official PEMS were considered accurate, the LLMs generated outputs exhibited an overall high level of accuracy with minor detail omission and some information inaccuracies. Information related to kidney cancer treatment was found to be the least accurate among the evaluated categories. Conclusion: Although the PEM published by AUA being the most readable, both authoritative PEMs and Large Language Models (LLMs) generated outputs exceeded the recommended readability threshold for general population. AI Chatbots can simplify their outputs when explicitly instructed. However, notwithstanding their accuracy, LLMs-generated outputs are susceptible to detail omission and inaccuracies. The variability in AI performance necessitates cautious use as an adjunctive tool in patient education.

Stereotactic Body Radiotherapy (SBRT) for the Treatment of Primary Localized Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

CONTEXT: Surgery is the gold standard for the local treatment of primary renal cell carcinoma (RCC), but alternatives are emerging. We conducted a systematic review and meta-analysis to assess the results of prospective studies using definitive stereotactic body radiotherapy (SBRT) to treat primary localised RCC. EVIDENCE ACQUISITION: This review was prospectively registered in PROSPERO (CRD42023447274). We searched PubMed, Embase, Scopus, and Google Scholar for reports of prospective studies published since 2003, describing the outcomes of SBRT for localised RCC. Meta-analyses were performed for local control (LC), overall survival (OS), and rates of adverse events (AEs) using generalised linear mixed models (GLMMs). Outcomes were presented as rates with corresponding 95% confidence intervals (95% CIs). Risk-of-bias was assessed using the ROBINS-I tool. EVIDENCE SYNTHESIS: Of the 2983 records, 13 prospective studies (n = 308) were included in the meta-analysis. The median diameter of the irradiated tumours ranged between 1.9 and 5.5 cm in individual studies. Grade ≥ 3 AEs were reported in 15 patients, and their estimated rate was 0.03 (95%CI: 0.01-0.11; n = 291). One- and two-year LC rates were 0.98 (95%CI: 0.95-0.99; n = 293) and 0.97 (95%CI: 0.93-0.99; n = 253), while one- and two-year OS rates were 0.95 (95%CI: 0.88-0.98; n = 294) and 0.86 (95%CI: 0.77-0.91; n = 224). There was no statistically significant heterogeneity, and the estimations were consistent after excluding studies at a high risk of bias in a sensitivity analysis. Major limitations include a relatively short follow-up, inhomogeneous reporting of renal function deterioration, and a lack of prospective comparative evidence. CONCLUSIONS: The short-term results suggest that SBRT is a valuable treatment method for selected inoperable patients (or those who refuse surgery) with localised RCC associated with low rates of high-grade AEs and excellent LC. However, until the long-term data from randomised controlled trials are available, surgical management remains a standard of care in operable patients.

Stereotactic Body Radiotherapy for Renal Cell Carcinoma-A Review of Use in the Primary, Cytoreductive and Oligometastatic Settings.

Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published.

An Exogenous Ketone Ester Slows Tumor Progression in Murine Breast and Renal Cancer Models.

BACKGROUND/OBJECTIVES: Ketone esters (KEs) exhibit promise as anti-cancer agents but their impact on spontaneous metastases remains poorly understood. Although consumption of a ketogenic diet (KD) that is low in carbohydrates and high in fats can lead to KE production in vivo, the restrictive composition of KDs may diminish adherence in cancer patients. METHODS: We investigated the effects of an exogenous ketone ester-supplemented (eKET), carbohydrate-replete diet on tumor growth, metastasis, and underlying mechanisms in orthotopic models of metastatic breast (4T1-Luc) and renal (Renca-Luc) carcinomas. Mice were randomized to diet after tumor challenge. RESULTS: Administration of KEs did not alter tumor cell growth in vitro. However, in mice, our eKET diet increased circulating ß-hydroxybutyrate and inhibited primary tumor growth and lung metastasis in both models. Body composition analysis illustrated the overall safety of eKET diet use, although it was associated with a loss of fat mass in mice with renal tumors. Immunogenetic profiling revealed divergent intratumoral eKET-related changes by tumor type. In mammary tumors, Wnt and TGFß pathways were downregulated, whereas in renal tumors, genes related to hypoxia and DNA damage repair were downregulated. CONCLUSIONS: Thus, our eKET diet exerts potent antitumor and antimetastatic effects in both breast and renal cancer models, albeit with different modes of action and physiologic effects. Its potential as an adjuvant dietary approach for patients with diverse cancer types should be explored further.

Tissue-specific distribution and fatty acid content of PFAS in the northern Bohai Sea fish: Risk-benefit assessment of legacy PFAS and emerging alternatives.

This study aimed to examine the distribution of poly- and perfluoroalkyl substances (PFAS) in 15 marine fish species from the northern Bohai Sea, investigate their sources of contamination, and evaluate the benefits-risks associated with the concurrent consumption of fish fatty acids and PFAS. The ∑PFAS concentrations in fish ranged from 9.38 to 262.92 ng·g-1 (dry weight). The highest PFAS levels were found in the viscera and gills, while the lowest levels were found in the muscles. Industrial effluents and sewage treatment plant discharges were the primary sources of PFAS contamination. The individual PFAS concentrations in fish were insignificantly correlated with their trophic levels (p > 0.05). However, the concentrations of hexafluoropropylene oxide dimer acid (HFPO-DA) or long-chain PFAS (C > 8) significantly increased with fish size (e.g., total length, weight) and lipid content (p < 0.001). The benefit-risk analysis suggests that HPFO-DA poses a higher health risk than perfluorooctanoic acid (PFOA) in fish (p < 0.05). Long-term consumption of contaminated fish may significantly increase human serum PFOA concentration and kidney cancer risk (p < 0.05). Daily consumption of 5 g (wet weight) muscle from Ditrema temmincki and Konosirus punctatus is recommended to meet the requirements for fatty acid supplementation without posing health risks.

Differences in the treatment patterns of small renal masses: A disaggregated analyses by race/ethnicity.

OBJECTIVE: To characterize differences in the management of small renal masses among disaggregated race/ethnic subgroups. MATERIAL AND METHODS: We used the National Cancer Database to identify patients diagnosed with clinically localized kidney cancer and tumor size ≤4cm. We studied 16 predefined racial/ethnic subgroups and compared 1) the use of surveillance for tumors <2cm and 2) the use of radical nephrectomy for tumors ≤4cm. We used multivariable logistic regression to evaluate the independent association of race/ethnicity with management, adjusting for baseline characteristics. We also compared our disaggregated analyses to the 6 National Institute of Health aggregate race categories. RESULTS: We identified 286,063 patients that met inclusion criteria. For tumors <2cm, Black Non-Hispanic (aOR 1.43) and Mexican patients (aOR 1.29) were significantly more likely to undergo surveillance compared to White patients. For tumors ≤4cm, Black Non-Hispanic (aOR 1.43), Filipino (aOR 1.28), Japanese (aOR 1.28), Mexican (aOR 1.32), and Native Indian patients (aOR 1.15) were significantly more likely to undergo radical nephrectomy compared to White patients. When comparing our disaggregated analyses to the NIH categories, we found that many disaggregated race/ethnic subgroups had associations with management strategies that were not represented by their aggregated group. CONCLUSIONS: In this study, we found that the use of surveillance for tumors <2cm and radical nephrectomy for tumors ≤4cm varied significantly among certain race/ethnic subgroups. Our disaggregated approach provides information on differences in treatment patterns in particular subgroups that warrant further study to optimize kidney cancer care for all patients.

Relationship between low-level arsenic exposure in drinking water and kidney cancer risk in Texas.

Kidney cancer rates are increasing in the US and worldwide. Arsenic, a known human carcinogen, is a suspected contributor to this rise, particularly in areas with arsenic-rich groundwater. However, research on the connection between low-level arsenic in drinking water and kidney cancer is limited. In our ecological study, we assessed the association between county-level drinking water arsenic levels and kidney cancer incidences using data from 240 counties in Texas. The analysis included 28,896 cancer cases among adults aged ≥20 years and 101,776,294 person-years during the period 2016-2020. Spatial Poisson regression models estimated the risk ratio (RR) for incident kidney cancer based on drinking water arsenic levels, adjusting for demographic, socioeconomic, and other risk factors, as well as spatial factors. Population-weighted drinking water arsenic levels were calculated using data from water testing for both public water systems and private wells, adjusted for populations served from each source. After adjusting for spatial factors and covariates, we observed 6% and 22% higher incidence of cancer in the medium (1-5 ppb) (RR 1.06, 95% CI 1.01, 1.11) and high arsenic (>5 ppb) group counties (RR 1.22, 95% CI 1.12, 1.34) compared to the low arsenic level ones (<1 ppb), showing a dose-response relationship (p-trend <0.001). Additionally, when arsenic was treated as a continuous variable, the incidence increased by 4% for each doubling of drinking water arsenic level (RR 1.04, 95% CI 1.02, 1.07) when considering drinking water arsenic level as a continuous variable. Our study suggests that exposure to low-level drinking water arsenic may be associated with an increased risk of kidney cancer. Further prospective studies are required to confirm our findings.

Impact of tumor dissecting technique on trifecta achievement in patients requiring extended warm ischemia during robot-assisted partial nephrectomy.

PURPOSE: To clarify specific factors associated with surgical outcomes in robot-assisted partial nephrectomy (RAPN) that require extended warm ischemia time (WIT), which may have a negative impact, but cannot always be avoided. METHODS: We included 1,182 patients who had RAPN performed between January 2016 and December 2022 from a prospectively generated multi-institutional RAPN database, divided into normal WIT (nWIT) (≤ 20 min; 843 patients) and extended WIT (eWIT) (> 20 min; 339 patients) groups. Primary outcome measures were WIT and the Surface-Intermediate-Base (SIB) margin score, which contribute to postoperative trifecta achievement. Results were compared between the two groups using logistic regression. RESULTS: Patients in the eWIT group had larger tumors, higher RENAL nephrometry scores, and lower SIB scores than those of the nWIT group. The trifecta achievement rate was significantly different between the two groups (nWIT: 70.1 vs. 49.0%, p < 0.001). In the nWIT group, WIT (coefficient: -0.105 [standard error 0.020], p < 0.001) and SIB score (coefficient: -0.107 [0.053], p = 0.045) were significant predictors of trifecta achievement. In the eWIT group, the SIB score (coefficient - 0.216 [0.082], p = 0.008) was significantly associated with trifecta attainment, whereas WIT only showed a trend toward significance. Limitations included a lack of long-term survival, renal function, and chronic complications data. CONCLUSIONS: For patients with eWIT during RAPN, the tumor dissection technique may be more important than WIT in predicting postoperative outcomes. Further prospective studies are required to confirm our results.

Cost-effectiveness of pembrolizumab as an adjuvant treatment of renal cell carcinoma post-nephrectomy in Switzerland.

AIMS: Pembrolizumab has demonstrated significantly prolonged disease-free survival and overall survival (OS) among adult patients post-nephrectomy who have an intermediate-high risk, high-risk, or M1 stage with no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component. The aim of this study was to evaluate the cost-effectiveness of pembrolizumab for patients with RCC post-nephrectomy versus observation in Switzerland. MATERIALS AND METHODS: A previously published Markov model was adapted for the Swiss setting to estimate the cost-effectiveness of adjuvant pembrolizumab versus observation from the Swiss statutory health insurance perspective. Transition probabilities between model states were estimated using survival curves from KEYNOTE-564 (data cut-off: June 14, 2021). Outcomes included costs (2022 Swiss francs [CHF]), quality-adjusted life-years (QALYs), and life-years (LYs), measured over a lifetime horizon. Costs included drug acquisition and administration for adjuvant and subsequent therapy. Both costs and effectiveness were discounted at 3.0% annually. Cost-effectiveness was evaluated at a hypothetical willingness-to-pay (WTP) threshold of CHF 100,000 Sensitivity was assessed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. RESULTS: Over a lifetime horizon, the total incremental cost for pembrolizumab versus observation was CHF 59,089, providing incremental gains of 0.90 QALYs (1.07 LYs); the incremental cost-effectiveness ratio was CHF 65,299/QALY. Pembrolizumab was deemed cost-effective versus observation, with a 69.9% probability of cost-effectiveness. LIMITATIONS: A more recent interim analysis data cut from KEYNOTE-564 with median follow up of 57.2 months has since been published; however, these were not available at the time of analysis. It would likely have minimal impact on transition probabilities from disease-free, and the current approach remains conservative for predicting OS for pembrolizumab. CONCLUSIONS: As an adjuvant treatment of RCC post-nephrectomy, pembrolizumab was found to be cost-effective versus observation in Switzerland at a WTP threshold of CHF 100,000/QALY. Policy makers should consider pembrolizumab as an adjuvant treatment for patients with RCC post-nephrectomy when making decisions regarding resource allocation.

Post-Metastasectomy Adjuvant Therapy in Patients with Renal Cell Carcinoma: A Systematic Review.

BACKGROUND: Pembrolizumab is established as adjuvant therapy for patients with high-risk clear cell renal cell carcinoma (ccRCC) after resection. Patients with completely resected metastatic disease (M1 NED) seem to have greater benefit from adjuvant pembrolizumab in both disease-free survival (DFS) and overall survival (OS); yet, with other agents, adjuvant therapy has not been shown to improve survival. As newer therapies evolve, it is important to understand the efficacy of systemic agents in this patient population. OBJECTIVE: We aimed to systematically review available trials investigating adjuvant therapy after metastasectomy in RCC. METHODS: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through January 2024. For inclusion, studies were required to include completely resected patients with known metastatic RCC. Patients with only locally advanced and/or regional nodal involvement (N1) alone were excluded. Titles and abstracts were screened to identify articles for full-text, and then a descriptive review was performed. RESULTS: A total of 149 articles were initially identified. Ultimately 9 articles published before the end of January 2024 met our inclusion criteria and were included in the analysis. Data were extracted and organized to reflect the role of adjuvant treatment - both targeted therapies as well as immunotherapy in patients who had undergone metastasectomy and rendered M1 NED. With the exception of pembrolizumab, adjuvant therapy in M1 NED was not found to be associated with improved survival. CONCLUSIONS: Pembrolizumab appears to benefit M1 NED ccRCC patients after resection even more than other high-risk ccRCC patients. Yet, this same benefit has not been seen with other agents. Future research should focus on trying to establish which M1 NED patients benefit from adjuvant treatment.

Exploring the gut microbiome and immunological landscape in kidney cancer: a Mendelian randomization analysis.

Introduction: Kidney cancer (KC) is a significant health burden globally, with over 400,000 new cases estimated in 2020. The prognosis of KC is influenced by various factors, including tumor spread, pathological characteristics, and molecular genetic changes. Recent studies have emphasized the involvement of gut microbiota and the immune system's contribution in the onset of KC. This extensive research endeavor sought to investigate the potential associations between diverse immune cell phenotypes, specific gut microbiota species, and their impact on the risk of developing KC, alongside the examination of circulating inflammatory proteins. Methods: Adhering to the STROBE-MR guidelines, our investigation involved a two-stage Mendelian randomization (2SMR) analysis grounded on three fundamental assumptions: relevance, independence, and exclusion restriction. The exposure data utilized in this study originated from genome-wide association studies (GWAS) specifically designed to explore immune traits, inflammatory proteins, and gut microbiota compositions. Results: Our analysis identified 25 immune phenotypes, 4 circulating inflammatory proteins, and 12 gut microbiota features that exhibited significant causal associations with KC (P < 0.05). 10 immune phenotypes were protective against KC, while 15 were risk factors. Among the inflammatory proteins, CCL28 and IL-2 were protective, whereas FGF-23 and ß-NGF were risk factors. Gut microbiota features associated with reduced KC risk included biosynthetic pathways involving amino acids and specific bacterial genera, whereas others, like Butyrivibrio crossotus and Odoribacter splanchnicus, were risk factors. Conclusion: Immune, inflammatory, and gut microbiota factors impact KC development. Identified factors hint at biomarkers and therapeutic targets. It is very important to understand the relationship between these factors and KC.

Abdominal Noncontrast Computed Tomography Scanning to Screen for Kidney Cancer and Other Abdominal Pathology Within Community-based Computed Tomography Screening for Lung Cancer: Results of the Yorkshire Kidney Screening Trial.

BACKGROUND AND OBJECTIVE: The Yorkshire Kidney Screening Trial (YKST) assessed the feasibility of adding abdominal noncontrast computed tomography (NCCT) to lung cancer screening to screen for kidney cancer and other abdominal pathology. METHODS: A prospective diagnostic study offered abdominal NCCT to 55-80-yr-old ever-smokers attending a UK randomised lung cancer screening trial (May 2021 to October 2022). The exclusion criteria were dementia, frailty, previous kidney/lung cancer, and computed tomography (CT) of the abdomen and thorax within previous 6 and 12 mo, respectively. Six-month follow-up was undertaken. KEY FINDINGS AND LIMITATIONS: A total of 4438 people attended lung screening, of whom 4309 (97%) were eligible for and 4019 (93%) accepted abdominal NCCT. Only 3.9% respondents regretted participating. The additional time to conduct the YKST processes was 13.3 min. Of the participants, 2586 (64%) had a normal abdominal NCCT, whilst 787 (20%) required an abdominal NCCT imaging review but no further action and 611 (15%) required further evaluation (investigations and/or clinic). Of the participants, 211 (5.3%) had a new serious finding, including 25 (0.62%) with a renal mass/complex cyst, of whom ten (0.25%) had histologically proven kidney cancer; ten (0.25%) with other cancers; and 60 (1.5%) with abdominal aortic aneurysms (AAAs). Twenty-five (0.62%) participants had treatment with curative intent. Of the participants, 1017 (25%) had nonserious findings, most commonly benign renal cysts (727 [18%]), whereas only 259 (6.4%) had nonserious findings requiring further tests. The number needed to screen to detect one serious abdominal finding was 18; it was 93 to detect one suspicious renal lesion and 402 to detect one histologically confirmed renal cancer. Limitations of the cohort were fixed age range and being prior lung cancer screening attendees. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this first prospective risk-stratified screening study of abdominal NCCT offered alongside CT thorax, uptake and participant satisfaction were high. The prevalence of serious findings, cancers, and AAAs, is in the range of established screening programmes such as bowel cancer. Longer-term outcomes and cost effectiveness should now be evaluated.

Clinical Outcomes for Metastatic Renal Cell Carcinoma (mRCC) Patients Ineligible for Front-line Clinical Trials.

Clinical trials for immunotherapy-based regimens in metastatic renal cell carcinoma (mRCC) have extensive inclusion and exclusion criteria. We investigated the clinical outcomes in a real-world cohort of patients who would not have met the criteria for inclusion in front-line mRCC trials. Patients treated with ipilimumab/nivolumab and axitinib/pembrolizumab for front-line mRCC were identified and divided into clinical trial eligible (CTE) and clinical trial ineligible (CTI) cohorts based on key inclusion or exclusion criteria from their respective Phase-3 registration trials. Clinical outcomes were compared in CTE and CTI cohorts. A total of 62 patients treated with axitinib/pembrolizumab and 103 treated with ipilimumab/nivolumab were identified. The International Metastatic RCC Database Consortium (IMDC) criteria were similar across CTE and CTI patients in axitinib/pembrolizumab and ipilimumab/nivolumab cohorts. In the axitinib/pembrolizumab cohort (n = 62), 24 (39%) patients were CTI. The major reasons for the ineligibility were lab abnormalities (n = 11), histology (n = 9), and brain metastases (n = 3). There was no significant difference in response rates (P = 0.08). The median progression-free survival (PFS) was numerically longer in CTE patients (28 vs 12 months; P = 0.09). The overall survival (OS) was higher in the CTE patients (P = 0.02). In the ipilimumab/nivolumab cohort (n = 103), 59 (57%) were CTI. The most common reasons for ineligibility were brain metastases (n = 18), lab abnormalities (n = 16), and histology (n = 16). There was no significant difference in response rates (P = 0.22). However, PFS (P = 0.003) and OS (P < 0.0001) were higher in the CTE patients. In conclusion, many real-world patients are ineligible for RCC clinical trials and had worse outcomes when compared to trial-eligible patients. Additional treatment options are needed for these patients, as well as strategies to include them in prospective trials.

Hospital-Level Variability in the Adoption of Image-Guided Focal Therapy for Localized Prostate and Kidney Cancer.

BACKGROUND: Focal therapy, a minimally invasive procedure, offers targeted treatment for kidney and prostate cancer using image guidance. However, the current institutional landscape of its adoption in localized prostate and kidney cancer remains less understood. This analysis compares its usage between the 2 cancers to discern health system determinants affecting the adoption of these treatments. METHODS: The study used data from adult patients with localized prostate and kidney cancer from the National Cancer Database. We calculated adjusted probabilities of focal therapy usage per facility via multivariable mixed-effects logistic regression model with hospital-level random effects. We analyzed interhospital variability through ranked caterpillar plots and Spearman correlation coefficient. RESULTS: Among 1,559,334 prostate and 425,753 kidney cancer patients, 1.6% and 6.3% received focal therapy, respectively. The interhospital variation ranged from 0.13% to 32.17% for prostate cancer and 1.16% to 30.48% for kidney cancer. The hospital-level odds of focal therapy for prostate and kidney cancer were weakly correlated (Spearman's ρ = 0.21; P < .001). CONCLUSIONS: Our analysis revealed a substantial hospital-level discrepancy in the utilization of focal therapy. Despite this, there was a limited correlation between the use of focal therapy for these two types of cancer within the same hospital. Our findings emphasize the presence of multifaceted factors influencing the adoption of focal therapy, both at facility and healthcare system levels.

Regression of renal cell carcinoma by T cell receptor-engineered T cells targeting a human endogenous retrovirus.

BACKGROUND: We discovered a novel human endogenous retrovirus (CT-RCC HERV-E) that was selectively expressed in most clear cell renal cell carcinomas (ccRCC) and served as a source of antigens for T cell-mediated killing. Here, we described the cloning of a novel T cell receptor (TCR) targeting a CT-RCC HERV-E-derived antigen specific to ccRCC and characterized antitumor activity of HERV-E TCR-transduced T cells (HERV-E T cells). METHODS: We isolated a CD8+ T cell clone from a patient with immune-mediated regression of ccRCC post-allogeneic stem cell transplant that recognized the CT-RCC-1 HERV-E-derived peptide in an HLA-A11-restricted manner. We used 5'Rapid Amplification of cDNA Ends (RACE) to clone the full length HERV-E TCR and generated retrovirus encoding this TCR for transduction of T cells. We characterized HERV-E T cells for phenotype and function in vitro and in a murine xenograft model. Lastly, we implemented a good manufacturing practice-compliant method for scalable production of HERV-E T cells. RESULTS: The HLA-A11-restricted HERV-E-reactive TCR exhibited a CD8-dependent phenotype and demonstrated specific recognition of the CT-RCC-1 peptide. CD8+ T cells modified to express HERV-E TCR displayed potent antitumor activity against HLA-A11+ ccRCC cells expressing CT-RCC HERV-E compared with unmodified T cells. Killing by HERV-E T cells was lost when cocultured against HERV-E knockout ccRCC cells. HERV-E T cells induced regression of established ccRCC tumors in a murine model and improved survival of tumor-bearing mice. Large-scale production of HERV-E T cells under good manufacturing practice conditions generated from healthy donors retained specific antigen recognition and cytotoxicity against ccRCC. CONCLUSIONS: This is the first report showing that human ccRCC cells can be selectively recognized and killed by TCR-engineered T cells targeting a HERV-derived antigen. These preclinical findings provided the foundation for evaluating HERV-E TCR-transduced T cell infusions in patients with metastatic ccRCC in a clinical trial (NCT03354390).