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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. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiotherapy (SBRT) is a treatment technique that delivers higher doses of conformal radiation precisely to specific targets. SBRT is utilized for the treatment of the more common cancers such as lung, liver and prostate malignancies, both in the early stage and the oligometastatic setting. The aim of this review is to highlight the current role of SBRT for renal cell carcinoma (RCC), a disease which was previously thought to be radioresistant, particularly to conventionally fractionated radiotherapy. There is now an increasing body of literature encompassing published phase II trials, reviews and meta-analyses demonstrating the effectiveness of SBRT in both early-stage RCC (as an alternative to patients who are not surgical candidates) and within the context of metastasis-directed therapy (MDT) for patients with oligometastatic and oligoprogressive RCC. Ongoing randomized trials are also exploring the role of SBRT as a cytoreductive treatment in metastatic RCC. 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. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to determine the impact of positive surgical margins (PSM) after PN on very long-term recurrence in a contemporary cohort. Methods: Patients who underwent PN for a localized renal tumour were included. Patients were stratified according to the presence of PSM. Data on patients' characteristics, the tumour, the peri- and postoperative events were collected. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan–Meier method and compared by the log-rank test. Sensitivity analyses using weighted propensity score analysis was performed to account for potential selection biases arising from the nonrandom allocation of patients to different groups. Results: A total of 1115 patients were included in the study. The incidence of PSM was 5.4% (n = 61). The median follow-up time was 51 months for the PSM group and 61 months for the NSM group (p = 0.31). Recurrence rates were significantly higher in the PSM group (13%, n = 8) compared to the NSM group (7%, n = 73) (p = 0.05). This resulted in a significant reduction in DFS in the PSM group (p = 0.004), particularly pronounced in patients with clear cell renal cell carcinoma. Additionally, OS was significantly lower in the PSM group (p < 0.01). Propensity score analysis confirmed a decrease in DFS for the PSM group (p = 0.05), while there was no significant difference in OS between the two groups (p = 0.49). Conclusion: In this retrospective multicenter study, PSM impact on oncological outcomes, increasing recurrence, but no difference in OS was observed post-adjustment for biases. [ABSTRACT FROM AUTHOR]

Purpose: The management of renal cell carcinoma (RCC) relies on clinical and histopathological features for treatment decisions. Recently, radiomics, which involves the extraction and analysis of quantitative imaging features, has shown promise in improving RCC management. This review evaluates the current application and limitations of radiomics for predicting treatment and oncological outcomes in RCC. Methods: A systematic search was conducted in Medline, EMBASE, and Web of Science databases or studies that used radiomics to predict response to treatment and survival outcomes in patients with RCC. The study quality was assessed using the Radiomics Quality Score (RQS) tools. Results: The systematic review identified a total of 27 studies, examining 6,119 patients. The most used imaging modality was contrast-enhanced abdominal CT. The reviewed studies extracted between 19 and 3376 radiomics features, including Histogram, Texture, Filter, or transformation method. Radiomics-based risk stratification models provided valuable insights into treatment response and oncological outcomes. All developed signatures demonstrated at least modest accuracy (AUC range: 0.55–0.99). The studies included in this analysis reported heterogeneous results regarding radiomics methods. The range of Radiomics Quality Score (RQS) was from − 5 to 20, with a mean RQS total of 9.15 ± 7.95. Conclusion: Radiomics has emerged as a promising tool in the management of RCC. It offers the potential for improved risk stratification and response assessment. However, future trials must demonstrate the generalizability of findings to prospective cohorts before progressing towards clinical translation. [ABSTRACT FROM AUTHOR]

Renal Cell Carcinoma (RCC) is the most common malignant tumor (85%) of kidney cancer and has a complex histological pattern and nuclear structure. The manual diagnosis of kidney cancer or any other cancer from histopathology image depends on the knowledge and experience of pathologists, and the pathologist's experience influences the results. According to studies, the kind of histology in kidney cancer is related to the prognosis and course of treatment. Since the kind of histology, molecular profile, and stage of the disease all affect how the disease is treated, there is an essential need to develop an automated system that can precisely analyze the histopathological images of the disease. This work demonstrates how a deep learning framework can be used to predict and classify associated grades of RCC from provided haematoxylin and eosin (H &E) images. The proposed model focuses on two important tasks- First to capture and extract associated features from the H &E images of five different grades. Second, to classify the new set of unseen H &E images into five separate grades using the obtained features. The proposed architecture has been tested and experimented on two independent datasets containing H &E stained histopathology images. The proposed architecture has been examined using the following performance metrics namely precision, recall, F1 - score, accuracy, Floating-point operations (FLOPs), and the total number of parameters. The obtained results show that the proposed architecture attains better results over seven state-of-the-art deep learning architectures on two different H &E stained histopathology image datasets. [ABSTRACT FROM AUTHOR]

Background: The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. Methods: We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). Results: In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. Conclusions: The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

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 b-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. [ABSTRACT FROM AUTHOR]

Purpose: To compare the oncological outcomes of clear cell RCC (ccRCC), which is common in renal cell carcinomas (RCC), and chromophobic RCC (chRCC), which is less common, and to define the factors affecting survival in the Turkish patient population for both RCC subclassifications. Materials and Methods: Patients with a pathologically confirmed RCC diagnosis after radical or partial nephrectomy in the Turkish Urooncology Association (TUOA), Urological Cancers Database-Kidney (UroCaD-K), were retrospectively reviewed. Patients with ccRCC and chRCC were included in the study. The primary outcomes of this study are recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) for each histological subtype. Results: Data from 5300 patients in the TUOA UroCaD-K are reviewed and a total of 2560 patients (2225 in the ccRCC group and 335 in the chRCC group) are included in the final analysis. In the comparison of the groups, tumor size was greater both radiologically and pathologically in chRCC (p = 0.019 vs 0.002 respectively). Recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) rates are worse in ccRCC subgroup. In the evaluation of risk factors; pathological stage, local invasion and Fuhrmann grade were found to be significant for recurrence in ccRCC. Age, body mass index and pathological stage were the risk factors affecting overall mortality (OM). Pathological tumor size was an independent risk factor for recurrence in chRCC, while age was analyzed as the only parameter affecting OM. Conclusion: chRCC oncological data and OS, CSS and RFS rates were found to be better than ccRCC in the Turkish patient population. [ABSTRACT FROM AUTHOR]

Genitourinary (GU) malignancies, including prostate, urothelial, kidney, testicular, penile, and adrenocortical cancers, comprise a significant burden of cancers worldwide. While many practice-changing advances have been made in the management of GU malignancies in the last decade, there is still significant room for improvement. MicroRNAs (miRNAs) are noncoding RNAs that regulate post-transcription gene expression and which have been implicated in multiple mechanisms of carcinogenesis. Therefore, they have the potential to revolutionize personalized cancer therapy, with several ongoing preclinical and clinical studies underway to investigate their efficacy. In this review, we describe the current landscape of miRNAs as diagnostics, therapeutics, and biomarkers of response for GU malignancies, reflecting a novel frontier in cancer treatment. [ABSTRACT FROM AUTHOR]

We performed a secondary analysis of an important subset of patients from the EVEREST trial. Among patients with completely resected clear cell renal cell carcinoma (RCC) who were at very high risk of recurrence, adjuvant everolimus was associated with significantly better recurrence-free survival in comparison to placebo. These results can help inform the design and development of future adjuvant trials in RCC. EVEREST is a phase 3 trial in patients with renal cell cancer (RCC) at intermediate-high or very high risk of recurrence after nephrectomy who were randomized to receive adjuvant everolimus or placebo. Longer recurrence-free survival (RFS) was observed with everolimus (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.72–1.00; p = 0.051), but the nominal significance level (p = 0.044) was not reached. To contextualize these results with positive phase 3 trials of adjuvant sunitinib and pembrolizumab, we conducted a secondary analysis in a similar population of EVEREST patients with very high-risk disease and clear cell histology. Postnephrectomy patients with any clear cell component and very high-risk disease, defined as pT3a (grade 3–4), pT3b–c (any grade), T4 (any grade), or node-positive status (N+), were identified. A Cox regression model stratified by performance status was used to compare RFS and overall survival (OS) between the treatment arms. Of 1499 patients, 717 had clear cell histology and very high-risk disease; 699 met the eligibility criteria, of whom 348 were randomized to everolimus arm, and 351 to the placebo arm. Patient characteristics were similar between the arms. Only 163/348 (47%) patients in the everolimus arm completed all treatment as planned, versus 225/351 (64%) in the placebo arm. Adjuvant everolimus resulted in a statistically significant improvement in RFS (HR 0.80; 95%CI 0.65–0.99, p = 0.041). Evidence of a survival benefit was not seen (HR 0.85; 95%CI 0.64–1.14, p = 0.3) In patients with clear cell RCC at very high-risk for recurrence, adjuvant everolimus resulted in significantly improved RFS compared to placebo but resulted in a high discontinuation rate due to adverse events. Although the treatment HR for OS was consistent with RFS findings, it did not reach statistical significance. With a focus on risk stratification tools and/or biomarkers to minimize toxicity risk in those not likely to benefit, this information can help inform the design of future adjuvant trials in high-risk RCC [ABSTRACT FROM AUTHOR]

Objectives: To comprehensively compare quality‐of‐life (QoL) outcomes between open partial nephrectomy (OPN) and robot‐assisted PN (RAPN) from the randomised ROBOtic‐assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non‐existent, especially not from randomised controlled trials (RCTs). Patients and Methods: The ROBOCOP II was a single‐centre, open‐label RCT between OPN and RAPN. The pre‐planned analyses of QoL outcomes are presented. Data were analysed descriptively in a modified intention‐to‐treat population. Results: A total of 50 patients underwent surgery. At postoperative Day 90 (POD90), there was no significant difference for the Kidney Disease Quality of Life‐Short Form questionnaire score (mean [sd] OPN 72 [20] vs RAPN 76 [15], P = 0.850), while there were advantages for RAPN in the subdomains of 'Pain' (P = 0.006) and 'Physical functioning' (P = 0.011) immediately after surgery. For the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30‐item core there were overall advantages directly after surgery (mean [sd] score OPN 63 [20] vs RAPN 75 [17], P = 0.031), as well as for the subdomains 'Fatigue' (P = 0.026), 'Pain' (P = 0.002) and 'Constipation' (P = 0.045) but no differences at POD90. There were no differences for the EuroQoL five Dimensions five Levels questionnaire at POD90 (mean [sd] score OPN 70 [22] vs RAPN 72 [17], P = 1.0) or at any other time point. Finally, no significant differences were found for the overall Convalescence and Recovery Evaluation questionnaire score at POD90 (mean [sd] OPN 84 [13] vs RAPN 86 [10], P = 0.818) but less pain in the RAPN group (P = 0.017) directly after surgery. Conclusions: Pain and physical functioning as subdomains of QoL are improved after RAPN compared to OPN in the early postoperative course, while there are no differences anymore after 3 months. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) comprises various histologically distinct subtypes, each characterized by specific genetic alterations, necessitating individualized management and treatment strategies for each subtype. An exhaustive search of the PubMed database was conducted without any filters or restrictions. Inclusion criteria encompassed original English articles focusing on molecular mechanisms of kidney cancer. On the other hand, all non-original articles and articles published in any language other than English were excluded. Hereditary kidney cancer represents 5–8% of all kidney cancer cases and is associated with syndromes such as von Hippel–Lindau syndrome, Birt–Hogg–Dubè syndrome, succinate dehydrogenase-deficient renal cell cancer syndrome, tuberous sclerosis complex, hereditary papillary renal cell carcinoma, fumarate hydratase deficiency syndrome, BAP1 tumor predisposition syndrome, and other uncommon hereditary cancer syndromes. These conditions are characterized by distinct genetic mutations and related extra-renal symptoms. The majority of renal cell carcinoma predispositions stem from loss-of-function mutations in tumor suppressor genes. These mutations promote malignant advancement through the somatic inactivation of the remaining allele. This review aims to elucidate the main molecular mechanisms underlying the pathophysiology of major syndromes associated with renal cell carcinoma. By providing a comprehensive overview, it aims to facilitate early diagnosis and to highlight the principal therapeutic options available. [ABSTRACT FROM AUTHOR]

Emerging Industry 5.0 designs promote artificial intelligence services and data-driven applications across multiple places with varying ownership that need special data protection and privacy considerations to prevent the disclosure of private information to outsiders. Due to this, federated learning offers a method for improving machine-learning models without accessing the train data at a single manufacturing facility. We provide a self-adaptive framework for federated machine learning of healthcare intelligent systems in this research. Our method takes into account the participating parties at various levels of healthcare ecosystem abstraction. Each hospital trains its local model internally in a self-adaptive style and transmits it to the centralized server for universal model optimization and communication cycle reduction. To represent a multi-task optimization issue, we split the dataset into as many subsets as devices. Each device selects the most advantageous subset for every local iteration of the model. On a training dataset, our initial study demonstrates the algorithm's ability to converge various hospital and device counts. By merging a federated machine-learning approach with advanced deep machine-learning models, we can simply and accurately predict multidisciplinary cancer diseases in the human body. Furthermore, in the smart healthcare industry 5.0, the results of federated machine learning approaches are used to validate multidisciplinary cancer disease prediction. The proposed adaptive federated machine learning methodology achieved 90.0%, while the conventional federated learning approach achieved 87.30%, both of which were higher than the previous state-of-the-art methodologies for cancer disease prediction in the smart healthcare industry 5.0. [ABSTRACT FROM AUTHOR]

Purpose: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC). Methods: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005–2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models. Results: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR. Conclusion: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this systematic review is to assess the clinical implications of employing various Extended Reality (XR) tools for image guidance in urological surgery. Methods: In June 2023, a systematic electronic literature search was conducted using the Medline database (via PubMed), Embase (via Ovid), Scopus, and Web of Science. The search strategy was designed based on the PICO (Patients, Intervention, Comparison, Outcome) criteria. Study protocol was registered on PROSPERO (registry number CRD42023449025). We incorporated retrospective and prospective comparative studies, along with single-arm studies, which provided information on the use of XR, Mixed Reality (MR), Augmented Reality (AR), and Virtual Reality (VR) in urological surgical procedures. Studies that were not written in English, non-original investigations, and those involving experimental research on animals or cadavers were excluded from our analysis. The quality assessment of comparative and cohort studies was conducted utilizing the Newcastle-Ottawa scale, whilst for randomized controlled trials (RCTs), the Jadad scale was adopted. The level of evidence for each study was determined based on the guidelines provided by the Oxford Centre for Evidence-Based Medicine. Results: The initial electronic search yielded 1,803 papers after removing duplicates. Among these, 58 publications underwent a comprehensive review, leading to the inclusion of 40 studies that met the specified criteria for analysis. 11, 20 and 9 studies tested XR on prostate cancer, kidney cancer and miscellaneous, including bladder cancer and lithiasis surgeries, respectively. Focusing on the different technologies 20, 15 and 5 explored the potential of VR, AR and MR. The majority of the included studies (i.e., 22) were prospective non-randomized, whilst 7 and 11 were RCT and retrospective studies respectively. The included studies that revealed how these new tools can be useful both in preoperative and intraoperative setting for a tailored surgical approach. Conclusions: AR, VR and MR techniques have emerged as highly effective new tools for image-guided surgery, especially for urologic oncology. Nevertheless, the complete clinical advantages of these innovations are still in the process of evaluation. [ABSTRACT FROM AUTHOR]

In patients with advanced or metastatic non–clear cell renal cell carcinoma, cabozantinib plus nivolumab demonstrated promising efficacy, with an objective response rate of 48%, and potential for sustained responses, with a median duration of response of 17 mo. The toxicity profile was as expected for the two agents. Treatment options are limited for patients with non–clear cell renal cell carcinoma (nccRCC). Patients with nccRCC experienced a favorable objective response rate (ORR) in a phase 2 trial of cabozantinib plus nivolumab. We now report updated efficacy and safety results at median follow-up of 34 mo for patients with papillary, unclassified, or translocation-associated RCC. Cabozantinib and nivolumab were administered at standard doses to patients with metastatic nccRCC that had progressed on zero or one line of systemic therapy. The primary endpoint was the ORR according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and adverse events. Forty patients were treated. At median follow-up of 34 mo for survivors, the ORR was 48% (95% confidence interval [CI] 31.5–63.9%). Median PFS was 13 mo (95% CI 7–16); the 12-mo and 24-mo PFS rates were 51% (95% CI 34–65%) and 23% (95% CI 11–37%), respectively. Median OS was 28 mo (95% CI 23–43); the 18-mo and 36-mo OS rates were 70% (95% CI 53–82%) and 44% (95% CI 28–60%), respectively. No new safety signals were seen with cabozantinib and nivolumab. This extended follow-up analysis demonstrates promising efficacy, and highlights the potential for sustained responses with cabozantinib plus nivolumab in patients with metastatic nccRCC. [ABSTRACT FROM AUTHOR]

The aim of the project was to evaluate the association between selenium (Se) and zinc (Zn) levels in blood and serum and kidney cancer mortality. In a prospective group of 284 consecutive, unselected patients with kidney cancer, we evaluated their 10-year survival rate in relation to the levels of Se and Zn in their blood and serum. Micronutrient levels were measured using an inductively coupled plasma mass spectrometer. Patients were divided into quartiles based on the distribution of Se and Zn levels arranged in increasing order. The following variables were taken into account in the multivariable models: age at diagnosis, gender, smoking, type of surgery and histopathological examination results. We observed a statistically significant association of all-cause mortality when subgroups with low blood selenium levels were compared to patients with high selenium levels (HR = 7.74; p < 0.001). We found, in addition, that this correlation was much stronger when only men were assessed (HR = 11.6; p < 0.001). We did not find a statistically significant association for zinc alone. When we combined selenium and zinc levels (SeQI-ZnQI vs. SeQIV-ZnQIV), we observed the hazard ratio for kidney cancer death to be 12.4; p = 0.016. For patients in the highest quartile of blood zinc/selenium ratio, compared to those in the lowest, the HR was 2.53; p = 0.008. Our study suggests that selenium levels, combined selenium and zinc levels (SeQI-ZnQI vs. SeQIV-ZnQIV) and zinc-to-selenium ratio (Zn/Se) are attractive targets for clinical trials aimed at improving the survival of kidney cancer patients. [ABSTRACT FROM AUTHOR]

Background and objective: Metabolic syndrome (MetS) is a clinical condition associated with higher rates of overall and cardiovascular mortality. There is scarce evidence regarding the impact of MetS on surgical and functional outcomes for patients undergoing partial nephrectomy (PN) for clinically localized small renal masses (SRMs). Methods: We analyzed data from a prospectively maintained institutional database for 690 patients with cT1a renal cancer undergoing PN between 2000 and 2023 at a tertiary referral center. MetS was defined according to international guidelines. Cumulative incidence curves were used to estimate the 5-yr risk of stage IIIB–V chronic kidney disease (CKD) stage and other-cause mortality (OCM). Multivariable regression models were used to analyze the impact of MetS on the risk of complications, acute kidney injury (AKI), stage IIIB–V CKD, and OCM. Key findings and limitations: Overall, 10% of the PN cohort had MetS. The MetS group was older (median age 70 yr, interquartile range [IQR] 65–74 vs 61 yr, IQR 50–69; p

Abstract 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

Background: Cardiovascular disease (CVD) is a major concern of morbidity and mortality among cancer survivors. However, few evidence exists on the shortand long-term risk of CVD in kidney cancer (KCa) survivors. Methods: In this nationwide, large population-based retrospective cohort study, we used the Korean national health insurance and medical checkup survey linkage database (2007-2021), drawn from the entire Korean population. We included adults diagnosed with KCa as the first primary cancer and matched them to an individual without KCa at a 1:5 ratio. The primary outcome was CVD incidence, including myocardial infarction, stroke, atrial fibrillation, heart failure, peripheral arterial occlusion, and venous thromboembolism (VTE). We evaluated CVD risk at 6 months, 1 year, and 5 years following cancer diagnosis, using Fine-Gray competing risk models that accounted for death as a competing factor. Results: A total of 149,232 participants were included (KCa survivors: N=20,093 and matched non-KCa individuals: N=129,139). After 6-month follow-up, KCa survivors showed an increased risk of CVD compared to the general population (subdistribution hazard ratio (HR) 2.70, 95% confidence interval (CI) 2.31-3.15). After 1 year, KCa survivors had a higher risk of CVD (HR=1.77, 95% CI: 1.56-2.00). After 5 years, this elevated CVD risk remained (HR=1.10, 95% CI: 1.03-1.18), with VTE identified as the primary contributing disease (HR=3.05, 95% CI:2.59-3.59). Conclusion: KCa survivors had an increased risk of CVD up to 5 years after cancer diagnosis compared to the general population. Our findings emphasize the importance of comprehensive healthcare management for both CVD and KCa throughout cancer survivorship. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Tumor structure is heterogeneous and complex, and it is difficult to obtain complete characteristics by two‐dimensional analysis. The aim of this study was to visualize and characterize volumetric vascular information of clear cell renal cell carcinoma (ccRCC) tumors using whole tissue phenotyping and three‐dimensional light‐sheet microscopy. Here, we used the diagnosing immunolabeled paraffin‐embedded cleared organs pipeline for tissue clearing, immunolabeling, and three‐dimensional imaging. The spatial distributions of CD34, which targets blood vessels, and LYVE‐1, which targets lymphatic vessels, were examined by calculating three‐dimensional density, vessel length, vessel radius, and density curves, such as skewness, kurtosis, and variance of the expression. We then examined those associations with ccRCC outcomes and genetic alteration state. Formalin‐fixed paraffin‐embedded tumor samples from 46 ccRCC patients were included in the study. Receiver operating characteristic curve analyses revealed the associations between blood vessel and lymphatic vessel distributions and pathological factors such as a high nuclear grade, large tumor size, and the presence of venous invasion. Furthermore, three‐dimensional imaging parameters stratified ccRCC patients regarding survival outcomes. An analysis of genomic alterations based on volumetric vascular information parameters revealed that PI3K‐mTOR pathway mutations related to the blood vessel radius were significantly different. Collectively, we have shown that the spatial elucidation of volumetric vasculature information could be prognostic and may serve as a new biomarker for genomic alterations. High‐end tissue clearing techniques and volumetric immunohistochemistry enable three‐dimensional analysis of tumors, leading to a better understanding of the microvascular structure in the tumor space. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) play a regulatory role in various human cancers. The roles of hsa-miR-15a-5p, hsa-miR-99b-5p, and hsa-miR-181a-5p have not been fully explored in the angiogenesis of renal cell carcinoma (RCC). Aims: The present study aimed to evaluate the expression of these miRNAs in tumorous and adjacent healthy tissues of RCC. Methods: Paired tumorous and adjacent normal kidney tissues from 20 patients were studied. The expression levels of hsa-miR-15b-5p, hsa-miR-99b-5p, and hsa-miR-181a-5p were quantified by TaqMan miRNA Assays. Putative targets were analyzed by qRT-PCR. Results: Significant downregulation of all three miRNAs investigated was observed in tumorous samples compared to adjacent normal kidney tissues. Spearman analysis showed a negative correlation between the expression levels of miRNAs and the pathological grades of the patients. Increased expression of vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α), a tissue inhibitor of metalloproteinases-1 (TIMP-1), was observed in tumorous samples compared to adjacent normal tissues. Depletion of tissue inhibitors of metalloproteinase-2 (TIMP-2) and metalloproteinase-2 (MMP-2) was detected compared to normal adjacent tissues. The examined miRNAs might function as contributing factors to renal carcinogenesis. However, more prospective studies are warranted to evaluate the potential role of miRNAs in RCC angiogenesis. [ABSTRACT FROM AUTHOR]

The identification of the VHL gene and its role in regulating the hypoxia-inducible factor signaling pathway has helped to revolutionize the treatment of renal cell carcinoma (RCC). Belzutifan is a novel small-molecule inhibitor of hypoxia-inducible factor 2α which has demonstrated efficacy in treating von Hippel–Lindau (VHL) disease, earning regulatory approvals for this indication. There is also early evidence for efficacy in sporadic RCC. Belzutifan has a favorable safety profile. Several clinical trials are currently ongoing, which should help in identifying this promising drug's role in RCC and beyond. This review summarizes the history, pharmacology and clinical evidence for belzutifan use to date, and also explores unanswered questions as they relate to this novel therapeutic agent. The novel drug belzutifan was developed after years of research in identifying the VHL gene and how genetic abnormalities in VHL may result in tumor growth. Belzutifan has been approved for use in patients with VHL disease – a rare familial disorder first described in the 19th century that presents with a variety of cancerous and noncancerous tumors, including kidney cancer. Growing evidence supports belzutifan's use in non-familial kidney cancer as well. This is important because most patients eventually develop resistance to the currently available cancer treatments, highlighting the need for drugs with a different mechanism of action. Belzutifan works by blocking a protein called HIF-2a, which causes tumor growth in patients with VHL disease. Belzutifan is well tolerated, with the most common side effects being low energy, hemoglobin and blood oxygen. This review summarizes the history, mechanism of action and research evidence to date supporting the use of belzutifan in VHL disease and cancer treatment. We also discuss future directions, including remaining clinical questions and areas of ongoing research. Executive summary Introduction Although the last decade has ushered in a new era of systemic therapy options for the management of metastatic renal cell carcinoma (RCC), including molecular targeted therapies and immune checkpoint inhibitors, most patients will eventually develop disease progression. This emphasizes the need for therapeutics with alternative mechanisms of action in the management of metastatic RCC. The VHL gene & its role in the cellular oxygen sensing pathway The VHL gene was identified in 1993, nearly a century after the first historical descriptions of von Hippel–Lindau (VHL) disease. VHL disease is caused by a germline variant in VHL, with an additional somatic inactivation/deletion of VHL in tumor cells. Variants in VHL may manifest in the absence of functional VHL protein, creating a cellular pseudohypoxic state whereby hypoxia-inducible factor (HIF) transcription factors are not degraded as they normally are in the presence of oxygen, ultimately leading to proangiogenic and tumorigenic gene expression. Belzutifan clinical pharmacology Belzutifan (MK-6482) is a first-in-class, second-generation HIF-2α inhibitor that selectively disrupts the heterodimerization of the HIF transcription complex, preventing downstream target gene transcription and resultant oncogenesis. Evidence to date suggests that belzutifan has a well-tolerated toxicity profile. The most commonly experienced side effects include fatigue, anemia and hypoxia. Clinical efficacy of belzutifan LITESPARK-001 was the first-in-human, phase I study of belzutifan that investigated its pharmacodynamics, pharmacokinetics and toxicity in 95 patients with locally advanced or metastatic solid tumors. In this study, belzutifan was well tolerated without dose-limiting toxicities, establishing 120 mg once daily as the recommended phase II dose. Belzutifan for VHL disease was first evaluated in the nonrandomized, phase II LITESPARK-004 study, in which 61 patients with VHL-associated, localized RCC were treated with belzutifan 120 mg orally daily. The demonstrated efficacy for RCC and non-RCC lesions led to the US FDA's approval of belzutifan in 2021 for the treatment of adult patients with VHL disease, with Health Canada and other regulatory bodies following suit. The interim analysis of the phase III study LITESPARK-005 was presented at the European Society for Medical Oncology Congress in 2023, showing superior objective response rate and progression-free survival for belzutifan compared with everolimus in previously treated patients with advanced RCC. Discussion To date, belzutifan has not been approved in any jurisdiction for treatment beyond VHL disease, for which the evidence is most robust. Growing evidence suggests belzutifan's efficacy in sporadic RCC; however, its place in the treatment algorithm has not yet been clearly established due the paucity of phase III trial evidence. There are numerous phase III trials evaluating the safety and efficacy of belzutifan in combination with other treatments in the second- and first-line and adjuvant settings for RCC. If belzutifan finds its way into the armamentarium of systemic therapy for metastatic RCC, this agent could be practice-changing beyond the VHL population. [ABSTRACT FROM AUTHOR]

Kidney cancer is the 14th most common cancer globally. The 5-year relative survival rate of kidney cancer at a localized stage is 92.9% and it declines to 17.4% in metastatic stage. Currently, the most accurate method of its diagnosis is tissue biopsy. However, the invasive and costly nature of biopsies makes it undesirable in many patients. Therefore, novel biomarkers for diagnosis and prognosis should be explored. Urinary extracellular vesicles (uEVs) are small vesicles (50-200 nm) in urine carrying nucleic acids, proteins and lipids as their cargos. These uEVs' cargos can provide non-invasive alternative to monitor kidney health. In this review, we have summarized recent studies investigating potential use of uEVs' cargos as biomarkers in kidney cancer for diagnosis, prognosis and therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Kidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk. Methods: We performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses. Results: During a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results. Conclusion: Our findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals. [ABSTRACT FROM AUTHOR]

In this review, we aim to provide a comprehensive assessment of the evolving landscape of the perioperative management in renal cell carcinoma (RCC), emphasizing its dynamic and intricate nature. We explore academic and clinical insights into the perioperative treatment paradigm of RCC. Up-to-date treatment options are discussed and the evolving role of neoadjuvant and adjuvant therapy in RCC is highlighted. [ABSTRACT FROM AUTHOR]

This study presents a high-accuracy deep learning-based decision support system for kidney cancer detection. The research utilizes a relatively large dataset of 10,000 CT images, including both healthy and tumour-detected kidney scans. After data preprocessing and optimization, various deep learning models were evaluated, with DenseNet-201 emerging as the top performer, achieving an accuracy of 99.75 %. The study compares multiple deep learning architectures, including AlexNet, EfficientNet, Darknet-53, Xception, and DenseNet-201, across different learning rates. Performance metrics such as accuracy, precision, sensitivity, F1-score, and specificity are analysed using confusion matrices. The proposed system outperforms different deep learning networks, demonstrating superior accuracy in kidney cancer detection. The improvement is attributed to effective data engineering and hyperparameter optimization of the deep learning networks. This research contributes to the field of medical image analysis by providing a robust decision support tool for early and rapid diagnosis of kidney cancer. The high accuracy and efficiency of the proposed system make it a promising aid for healthcare professionals in clinical settings. [ABSTRACT FROM AUTHOR]

Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea's National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age–sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116–2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252–3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP. [ABSTRACT FROM AUTHOR]

Purpose: To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC). Methods: cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM +. Multivariable analyses (MVA) were fitted to predict factors that could influence time between detection and histological diagnosis of the pulmonary mass, and how this interval could impact on survivals. Results: 87% had RCCM + and 13% had LC. LC were more likely to have smoking history (75% vs. 29%, p < 0.001) and less aggressive RCC features (cT1-2: 94% vs. 65%, p = 0.01; pT1-2: 88% vs. 41%, p = 0.02; G1-2: 88% vs. 37%, p < 0.001). The median interval between RCC surgery and lung mass detection was longer between LC (55 months [32.8–107.2] vs. 20 months [9.0–45.0], p = 0.01). RCCM + had a higher likelihood of multiple (3[1–4] vs. 1[1–1], p < 0.001) and bilateral (51% vs. 6%, p = 0.002) pulmonary nodules, whereas LC usually presented with a solitary pulmonary nodule, less than 20 mm. Univariate analyses revealed that smoking history (OR:0.79; 95% CI 0.70–0.89; p < 0.001) and interval between RCC surgery and lung mass detection (OR:0.99; 95% CI 0.97–1.00; p = 0.002) predicted a higher risk of LC. Conversely, size (OR:1.02; 95% CI 1.01–1.04; p = 0.003), clinical stage (OR:1.14; 95% CI 1.06–1.23; p < 0.001), pathological stage (OR:1.14; 95% CI 1.07–1.22; p < 0.001), grade (OR:1.15; 95% CI 1.07–1.23; p < 0.001), presence of necrosis (OR:1.17; 95% CI 1.04–1.32; p = 0.01), and lymphovascular invasion (OR:1.18; 95% CI 1.01–1.37; p = 0.03) of primary RCC predicted a higher risk of RCCM +. Furthermore, number (OR:1.08; 95% CI 1.04–1.12; p < 0.001) and bilaterality (OR:1.23; 95% CI 1.09–1.38; p < 0.001) of pulmonary lesions predicted a higher risk of RCCM +. Survival analysis showed a median second PFS of 10.9 years (95% CI 3.3-not reached) for LC and a 3.8 years (95% CI 3.2–8.4) for RCCM +. The median OS time was 6.5 years (95% CI 4.4-not reached) for LC and 6 years (95% CI 4.3–11.6) for RCCM +. Conclusions: Smoking history, primary grade and stage of RCC, interval between RCC surgery and lung mass detection, and number of pulmonary lesions appear to be the most valuable predictors for differentiating new primary lung cancer from RCC progression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non‐contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. Subjects and Methods: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non‐contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one‐third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short‐form of the Spielberger State–Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ‐5D‐5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ‐5D‐5L), and ethnicity. Results: A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01–0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. Conclusion: Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings. [ABSTRACT FROM AUTHOR]

Background/Aim: Numerous new treatment options have been approved for metastatic renal cell carcinoma (mRCC) in the last decade. Nevertheless, not all patients receive systemic therapy. Certain patients present with very advanced disease, poor Eastern Cooperative Oncology Group performance status (ECOG PS), or severe comorbidity, i.e. factors that lead oncologists to prefer best supportive care (BSC) instead of systemic therapy. The aim of this quality-of-care study was to identify baseline factors (disparities) associated with receipt of systemic therapy rather than BSC. Patients and Methods: This retrospective analysis included 140 consecutive patients managed in a rural region of Norway (2007-2022). Two differently managed groups were compared in univariate tests followed by multi-nominal regression. Results: The majority of patients (n=95, 68%) had received systemic therapy. Typical patients were males in their 60s or 70s, with clear cell histology, prior nephrectomy, and intermediate prognostic features. Patients who received systemic therapy lived significantly longer than those who did not (median 30.4 versus 5.0 months, p<0.001). Survival benefit of systemic treatment was observed even in patients with ECOG PS3 or age =80 years. In addition to younger age (p<0.001) and better ECOG PS (p<0.001), metachronous presentation was associated with higher rates of systemic therapy utilization (p=0.03). Conclusion: Assignment to systemic therapy for mRCC was individualized in the present patient population. In all age and ECOG PS subgroups, systemic therapy was associated with better survival (doubling at least). Optimum utilization rates are difficult to determine. However, in light of the survival outcomes, a rate of 12% in patients aged 80 years or older appears rather low. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively compare long-term oncologic outcomes of percutaneous computed tomography-guided microwave ablation (MWA) and robot-assisted partial nephrectomy (RAPN) for the treatment of stage 1 (T1a and T1b) renal cell carcinoma (RCC) patients. Materials and Methods: Institutional database research identified all T1 RCC patients who underwent either MWA or RAPN. Models were adjusted with propensity score matching. Kaplan–Meier log-rank test analyses and Cox proportional hazard regression models were used to compare the oncologic outcomes. Patient and tumor characteristics, technical success as well as oncologic outcomes were evaluated and compared between the 2 groups. Results: After propensity score matching, a total of 71 patients underwent percutaneous MWA (mean age 70 ± 10 years) and 71 underwent RAPN (mean age 60 ± 9 years). At 8-year follow-up, the estimated survival rates for MWA cohort were 98% (95% confidence interval [CI] 95–100%) for overall survival, 97% (95% CI 93–100%) for recurrence-free survival, and 97% (95% CI 93–100%) for metastasis-free survival. The matched cohort that underwent RAPN exhibited survival rates of 100% (95% CI 100–100%) for overall survival, 98% (95% CI 94–100%) for recurrence-free survival, and 98% (95% CI 94–100%) for metastasis-free survival. After performing log-rank testing, these rates were not significantly different (p values of 0.44, 0.67, and 0.67, respectively). Conclusion: The results of the present study suggest that both MWA and RAPN are equally effective in terms of oncologic outcome for the treatment of T1 RCC. [ABSTRACT FROM AUTHOR]

A survey conducted by Kidney Cancer UK over the past decade reveals important insights into patient perspectives on kidney cancer care. The survey found that patients feel the pathway to diagnosis could be improved, with a sharp rise in the proportion of respondents waiting more than three months for a specialist diagnosis in 2020. Timely diagnosis remains a key area for improvement. The survey also highlighted the need for better communication and support for patients, as well as more equitable access to treatment options and clinical trials. Overall, the survey data emphasize the need for improvements in early detection, patient communication, and access to care for kidney cancer patients. [Extracted from the article]

Cellular therapies against solid tumors face three major barriers: low persistence, insufficient specificity, and high costs. In a recent study, Pal et al. tackle these challenges in kidney cancer by using novel, 'persistence-tuned' allogeneic chimeric antigen receptor (CAR) T cells directed against a stable antigen. [ABSTRACT FROM AUTHOR]

Background: Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. Methods: The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater. Results: During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. Conclusions: For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data. [ABSTRACT FROM AUTHOR]

Background: Our aimed to conduct a meta-analysis of cohort studies on risk of genitourinary (GU) cancers in workers exposed to welding fumes (WF). Methods: We performed a systematic review of studies published on Pubmed, Scopus and Embase following PRISMA criteria. Two researchers selected cohort studies on WF exposure. From 2582 articles, 7 non-overlapping studies were included. Quality of studies was scored according to CASP. We run a random effects meta-analysis to calculate the relative risk (RR) and 95% confidence intervals (CI) of GU cancer, overall and stratified by cancer, country, and quality score. Results: We included seven studies reporting results on GU cancers, including prostate, bladder and kidney cancer (PC, BC, and KC). The RR was 1.19 (95% CI = 1.07–1.32, 16 risk estimates) for GU cancer; 1.13 (95% CI = 0.90–1.42, 4 risk estimates) for PC; 1.26 (95% CI = 0.98–1.60, 7 risk estimates) for BC and 1.28 (95% CI = 1.12–1.47, 5 risk estimates) for KC. Heterogeneity was present in all meta-analyses (p < 0.001). The increased risk was more pronounced in North American than in European studies (respectively, OR = 1.35, 95% CI = 1.18–1.55; OR = 1.13, 95% CI = 1.01–1.27 p heterogeneity = 0.03). There was no heterogeneity according to quality score (p = 0.4). Data were insufficient to investigate associations by industry or welding type. Publication bias for each cancer was excluded. Conclusion: This meta-analysis suggests increased risk of KC and BC, but not of PC, in workers exposed to WF. Confounding by other occupational and non-occupational risk factors could not be excluded. Data were not adequate to address the risk of specific exposure circumstances. [ABSTRACT FROM AUTHOR]

Introduction: Genetic ancestry (GA) refers to population hereditary patterns that contribute to phenotypic differences seen among race/ethnicity groups, and differences among GA groups may highlight unique biological determinants that add to our understanding of health care disparities. Methods: A retrospective review of patients with renal cell carcinoma (RCC) was performed and correlated GA with clinicopathologic, somatic, and germline molecular data. All patients underwent next‐generation sequencing of normal and tumor DNA using Memorial Sloan Kettering‐Integrated Mutation Profiling of Actionable Cancer Targets, and contribution of African (AFR), East Asian (EAS), European (EUR), Native American, and South Asian (SAS) ancestry was inferred through supervised ADMIXTURE. Molecular data was compared across GA groups by Fisher exact test and Kruskal–Wallis test. Results: In 953 patients with RCC, the GA distribution was: EUR (78%), AFR (4.9%), EAS (2.5%), SAS (2%), Native American (0.2%), and Admixed (12.2%). GA distribution varied by tumor histology and international metastatic RCC database consortium disease risk status (intermediate‐poor: EUR 58%, AFR 88%, EAS 74%, and SAS 73%). Pathogenic/likely pathogenic germline variants in cancer‐predisposition genes varied (16% EUR, 23% AFR, 8% EAS, and 0% SAS), and most occurred in CHEK2 in EUR (3.1%) and FH in AFR (15.4%). In patients with clear cell RCC, somatic alteration incidence varied with significant enrichment in BAP1 alterations (EUR 17%, AFR 50%, SAS 29%; p =.01). Comparing AFR and EUR groups within The Cancer Genome Atlas, significant differences were identified in angiogenesis and inflammatory pathways. Conclusion: Differences in clinical and molecular data by GA highlight population‐specific variations in patients with RCC. Exploration of both genetic and nongenetic variables remains critical to optimize efforts to overcome health‐related disparities. This study identifies differences in clinical and molecular data by genetic ancestry and uncovers population‐specific variations that may impact specific patient populations with renal cell carcinoma. Exploration of genetic and nongenetic variables that contribute to these differences are critical to reduce health‐related disparities. [ABSTRACT FROM AUTHOR]

Tumor-to-tumor metastasis (TTM) is a rare phenomenon documented in patients with multiple primary cancers. This condition is defined as a metastasis between two true primary tumors. The most frequently reported recipient tumor is renal cell carcinoma (RCC), and the lung carcinomas are the most common metastatic tumor donors. Therefore, this paper attempts to address the current gap in knowledge about this rare phenomenon. The first part of this review outlines the recently proposed models and mechanisms involved in the TTM process. The second part then summarizes and analyzes previous case reports in the literature. We also present our experience with the case of lung cancer that metastasized into RCC. Given the sporadic incidence of TTM, no specific management guidelines exist. Therefore, considering TTM in patients with multiple primary tumors is important as it could potentially modify the oncological management offered. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic cancer (PC) is among the deadliest malignancies. Kidney cancer (KC) is a common malignancy globally. Chemo- or radio-therapies are not very effective to control PC or KC, and overdoses often cause severe site reactions to the patients. As a result, novel treatment strategies with high efficacy but without toxic side effects are urgently desired. Secoisolariciresinol diglucoside (SDG) belongs to plant lignans with potential anticancer activities, but clinical evidence is not available in PC or KC treatment. Patient Concerns: We report a rare case of an 83-year-old female patient with pancreatic and kidney occupying lesions that lacked the conditions to receive surgery or chemo- or radiotherapy. Diagnosis: Pancreatic and kidney cancers. Interventions: We gave dietary SDG to the patient as the only therapeutics. Outcomes: SDG effectively halted progression of both PC and KC. All clinical manifestations, including bad insomnia, loss of appetite, stomach symptoms, and skin itching over the whole body, all disappeared. The initial massive macroscopic hematuria became microscopic and infrequent, and other laboratory results also gradually returned to normal. Most of the cancer biomarkers, initially high such as CEA, CA199, CA724, CA125, came down rapidly, among which CA199 changed most radically. This patient has had progression-free survival of one year so far. Conclusion: These results demonstrate the potent inhibitory effects of SDG on PC and KC of this patient and provide promising novel therapeutics for refractory malignant tumors. [ABSTRACT FROM AUTHOR]

Objective: To identify the causal role of sodium‐glucose cotransporter 2 (SGLT2) inhibition on three urological cancers. Methods: Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results. Results: In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97–0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21–0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99–1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk. Conclusions: We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers. [ABSTRACT FROM AUTHOR]

Background: Understanding pre-diagnostic prescribing activity could reveal windows during which more timely cancer investigation and detection may occur. Aim: To examine prescription patterns for common urological clinical features prior to renal and bladder cancer diagnoses. Design and setting: A retrospective cohort study was performed using electronic primary care and cancer registry data on patients with bladder and renal cancer, who received their diagnosis between April 2012 and December 2015 in England. Method: Primary care prescriptions up to 2 years pre- diagnosis were analysed for five groups of clinical features (irritative urological symptoms, obstructive symptoms, urinary tract infections [UTIs], genital infections, and atrophic vaginitis). Poisson regressions estimating the inflection point from which the rate of prescriptions increased from baseline were used to identify the start of diagnostic windows during which cancer could be detected. Results: A total of 48 094 prescriptions for 5322 patients were analysed. Inflection points for an increase in UTI prescriptions were identified 9 months pre- diagnosis for renal (95% confidence interval [CI] = 5.3 to 12.7) and bladder (95% CI = 7.4 to 10.6) cancers. For bladder cancer, the change in UTI antibiotic prescription rates occurred 4 months earlier in females (11 months pre- diagnosis, 95% CI = 9.7 to 12.3) than in males (7 months pre-diagnosis, 95% CI = 5.4 to 8.6). For other clinical features, no inflection points were identified and, as such, no diagnostic windows could be defined. Conclusion: Prescription rates for UTIs increased 9 months before bladder and renal cancer diagnoses, indicating that there is potential to expedite diagnosis of these cancers in patients presenting with features of UTI. The greatest opportunity for more timely diagnosis may be in females with bladder cancer, who experienced the earliest increase in UTI prescription rate. [ABSTRACT FROM AUTHOR]

Earlier detection and screening for kidney cancer has been identified as a key research priority, however the low prevalence of the disease in unselected populations limits the cost-effectiveness of screening. Risk-stratified screening for kidney cancer may improve early detection by targeting high-risk individuals whilst limiting harms in low-risk individuals, potentially increasing the cost-effectiveness of screening. A number of models have been identified which estimate kidney cancer risk based on both phenotypic and genetic data, and while several of the former have been shown to identify individuals at high-risk of developing kidney cancer with reasonable accuracy, current evidence does not support including a genetic component. Combined screening for lung cancer and kidney cancer has been proposed, as the two malignancies share some common risk factors. A modelling study estimated that using lung cancer risk models (currently used for risk-stratified lung cancer screening) could capture 25% of patients with kidney cancer, which is only slightly lower than using the best performing kidney cancer-specific risk models based on phenotypic data (27%–33%). Additionally, risk-stratified screening for kidney cancer has been shown to be acceptable to the public. The following review summarises existing evidence regarding risk-stratified screening for kidney cancer, highlighting the risks and benefits, as well as exploring the management of potential harms and further research needs. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the treatment safety of thermal ablation compared to surgical treatment of T1a tumors (small renal masses) at a high-volume center. We conducted an observational single-center study based on data collected form the National Swedish Kidney Cancer Register (NSKCR) between 2015 and 2021. In total, 444 treatments of T1a tumors were included. Patients underwent surgery (partial or total nephrectomy) or ablative treatment—radiofrequency ablation (RFA) or microwave ablation (MWA). Patient characteristics were retrieved from patient records, and tumor complexity was estimated from pre-interventional CT scans. The odds ratio (OR) of suffering from a severe surgical complication following ablative treatment was estimated using a logistic regression model adjusted for age, BMI, ASA physical status classification, smoking status and RENAL nephrometry score. The frequency of severe surgical complications was 6.3% (16/256 treatments) after surgical intervention and 2.1% (4/188 treatments) following ablative treatment. Our primary hypothesis that ablative treatment is associated with a lower risk of severe surgical complications is supported by the results (OR 0.39; 0.19–0.79; p = 0.013). When adjusting for age, smoking status, ASA score, BMI score and RENAL nephrometry score, we see an even greater difference between the two groups (OR 0.34; 0.17–0.68; p = 0.002). Our study was limited by the differences in patient and tumor characteristics between the two compared groups and the study design. If oncological outcomes are found to be comparable, ablative treatment should be considered as a first-line treatment for all small renal masses. [ABSTRACT FROM AUTHOR]

We report a case of a 57 years old woman with a solitary mass located in the pelvis diagnosed as an extrarenal papillary renal cell carcinoma, in the absence of a primary renal cancer. The diagnosis was based on cytomorphological features and further confirmed by immunochemistry findings following surgical excision. The hypothesis of a tumor developing in a supernumerary or ectopic kidney was excluded, since no normal renal tissue could be identified in the specimen and in the preoperative computed tomography and MRI images. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine the characteristics and utilization patterns of palliative care among the kidney cancer patients using a large-scale representative population-based sample. We retrospectively analyzed National Inpatient Sample hospitalization data from January 2020 to December 2020 to explore disparities in delivering palliative care to deceased kidney cancer patients and assess its impact on healthcare usage, focusing on hospital costs and length of stay (LoS). We used ICD-10 CM codes (International Classification of Diseases-classifying diagnoses and reasons for visits in all healthcare settings) to categorize the study population. We conducted univariable and multivariable linear and logistic regression analyses to calculate coefficients and odds ratios, considering relevant variables and addressing potential confounding factors. We studied 1437 deceased kidney cancer patients, with 53.9% receiving palliative care. Those receiving palliative care had lower total costs ($99,804 vs. $1,34,731) and a shorter LoS (7.19 days vs. 7.66 days), compared to those who didn't. No significant difference was discovered in LoS. Private insurance, higher income, and female patients were more likely to receive palliative care. Race, hospital teaching status, and hospital size showed no significant differences. This study revealed insights into palliative care use among deceased kidney cancer patients, with cost-saving benefits evident. Disparities showed that individuals with private insurance and higher income more likely accessed palliative care, and females received it more often than males. Physicians and policymakers must consider these findings for equitable resource allocation and improved access. [ABSTRACT FROM AUTHOR]

(1) Background: In the last decade, the number of detected renal cancer cases has increased, with the highest incidence in Western countries. Although renal biopsy is reported as a safe procedure, it is not adopted in all centres. As it is not possible to accurately distinguish benign tumours using imaging, this may lead to overtreatment. Most of the cancer detected on imaging is treated by surgery, radiofrequency ablation (RFA), or cryotherapy. (2) Methods: This was a single-centre retrospective study of 225 patients studied preoperatively with ultrasound (US)/CT-guided renal biopsy, with the aim of supporting clinical management. Decisions regarding the biopsy were based on either MDT indication or physician preference. US-guided renal biopsy was the first option for all patients; CT-guided biopsy was used when US-guided biopsy was not feasible. The efficacy of renal biopsy in terms of diagnostic performance and the concordance between biopsy results and definitive pathology were investigated. Additionally, adverse events related to the biopsy were recorded and analysed. Data collected throughout the study were analysed using binary logistic regression, Fisher's exact test, and Pearson's chi-square test to investigate possible correlations between post-procedural complications and the size of the lesion. (3) Results: Renal biopsy was not diagnostic in 23/225 (10.2%) patients. A CT-guided approach was necessary in 20/225 patients after failure of US-guided biopsy. The complication rate of renal biopsy was 4.8% overall—all Clavien grade I and without any serious sequelae. Interestingly, complications occurred in patients with very different sizes of renal cell carcinoma. No correlation between complications and anticoagulant/antiplatelet drugs was found. No seeding was reported among the patients who underwent partial/radical nephrectomy. (4) Conclusions: Renal biopsy was shown to be safe and effective, with a high concordance between biopsy results and definitive pathology and a low rate of complications. The use of a CT-guided approach whenever the US-guided approach failed improved the diagnostic performance of renal biopsy. [ABSTRACT FROM AUTHOR]

Background: Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort. Methods: Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM). Results: Patients with TT showed lower BMI (24 vs. 26 kg/m2) and preoperative Hb (11 vs. 14 g/mL; all—p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5 cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49–3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10–1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49–2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04–2.49, p < 0.03). Conclusions: The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time. [ABSTRACT FROM AUTHOR]

Carbon nanomaterials (CNMs), including carbon nanotubes (CNTs), graphene, and nanodiamonds (NDs), have shown great promise in detecting and treating numerous cancers, including kidney cancer. CNMs can increase the sensitivity of diagnostic techniques for better kidney cancer identification and surveillance. They enable targeted medicine delivery specifically to tumour locations, with little effect on healthy tissue. Because of their unique chemical and physical characteristics, they can avoid the body's defence mechanisms, making it easier to accumulate where tumours exist. Consequently, CNMs provide more effective drug delivery to kidney cancer cells. It also helps in improving the efficacy of treatment. This review explores the potential of several CNMs in improving therapeutic strategies for kidney cancer. We briefly covered the physicochemical properties and therapeutic applications of CNMs. Additionally, we discussed how structural modifications in CNMs enhance their precision in treating renal cancer. A thorough overview of CNM-based gene, peptide, and drug delivery strategies for the treatment of renal cancer is presented in this review. It covers information on other CNM-based therapeutic approaches, such as hyperthermia, photodynamic therapy, and photoacoustic therapy. Also, the interactions of CNMs with the tumour microenvironment (TME) are explored, including modulation of the immune response, regulation of tumour hypoxia, interactions between CNMs and TME cells, effects of TME pH on CNMs, and more. Finally, potential side effects of CNMs, such as toxicity, bio corona formation, enzymatic degradation, and biocompatibility, are also discussed. [ABSTRACT FROM AUTHOR]