Renal Cell Carcinoma Patients Research Articles

Efficacy and Safety of Lenvatinib in Combination With Other Tyrosine Kinase Inhibitors for Metastatic Renal Cell Carcinoma: A Meta-analysis.

This meta-analysis evaluates the efficacy and safety of lenvatinib, both as monotherapy and in combination with other (tyrosine kinase inhibitors) TKIs, compared with other TKIs in metastatic renal cell carcinoma (RCC) treatment. We searched for relevant studies from inception to February 2024 using PubMed, Web of Science, Cochrane Library, and Scopus. Eligible studies reported on the efficacy and safety of lenvatinib alone or in combination with other TKIs versus other TKIs for metastatic RCC. Primary outcomes included progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR), adverse events (AEs), and health-related quality of life (HRQOL). Seventeen studies met the inclusion criteria. Lenvatinib, especially in combination therapies, significantly improved PFS (HR: 0.46, 95% CI: 0.38-0.54, P<0.001) and OS (HR: 0.80, 95% CI: 0.70-0.91, P<0.001) compared with other TKIs. Quality of life analyses showed mixed results, with EQ-5D demonstrating significant improvement (HR: 1.21, 95% CI: 0.90-1.53, P<0.001), while EORTC QLQ-C30 was not statistically significant. ORR analysis indicated a higher likelihood of achieving a complete or partial response with lenvatinib (OR: 2.04, 95% CI: 1.15-2.93, P=0.00). The analysis of total AEs above grade 3 showed no significant difference between lenvatinib and other TKIs (OR: -0.08, 95% CI: -0.21 to 0.06, P=0.26). Lenvatinib significantly enhances survival outcomes in metastatic RCC patients compared with other TKIs. While associated with various adverse events, its safety profile is comparable to other TKIs.

Predicting the prognosis of patients with renal cell carcinoma based on the systemic immune inflammation index and prognostic nutritional index

The aim of the study was to analyze and discuss the value of preoperative systemic immune inflammation index (SII) and prognostic nutritional index (PNI) in predicting the prognosis of patients with renal cell carcinoma (RCC) after operation, and to establish a nomogram prediction model for patients with RCC after operation based on SII and PNI. From January 2014 to December 2018, 210 patients with RCC who underwent surgical treatment at the Xuzhou Central Hospital were selected as the research object. The receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value for preoperative SII, PNI, LMR, PLR, NLR and the patients were divided into groups according to the optimal cutoff values. The survival rate of patients was evaluated. The risk factors that affect the prognosis of patients with RCC were determined by LASSO and Cox regression analysis, and a prognostic nomogram was constructed based on this result. The bootstrap method was used for internal verification of the nomogram model. The prediction efficiency and discrimination of the nomogram model were evaluated by the calibration curve and index of concordance (C-index), respectively. The average overall survival (OS) of all patients was 75.385 months, and the 1-, 2-and 3-year survival rates were 95.5%, 86.6% and 77.2%, respectively. The survival curve showed that the 5-year OS rate of low SII group was significantly higher than that of high SII group (89.0% vs. 64.5%; P < 0.05), and low PNI group was significantly lower than those in high PNI group (43.4% vs. 87.9%; p < 0.05). There were significant differences between preoperative SII and CRP, NLR, PLR, LMR, postoperative recurrence, pathological type and AJCC stage (P < 0.05). There were significant differences between preoperative PNI and BMI, platelet, NLR, PLR, LMR, postoperative recurrence, surgical mode and Fuhrman grade (P < 0.05). The ROC curve analysis showed that the AUC of PNI (AUC = 0.736) was higher than that of other inflammatory indicators, followed by the AUC of SII (0.718), and the difference in AUC area between groups was statistically significant (P < 0.05). The results from multivariate Cox regression analysis showed that SII, PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade were independent risk factors for postoperative death of patients with RCC. According to the results of Cox regression analysis, a prediction model for the prognosis of RCC patients was established, and the C-index (0.918) showed that the model had good calibration and discrimination. The subject’s operating characteristic curve indicates that the nomogram has good prediction efficiency (the AUC = 0.953). Preoperative SII and PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade are closely related to the postoperative prognosis of patients with renal cell carcinoma. The nomogram model based on SII, PNI, tumor size, tumor necrosis, surgical mode, pathological type, CRP, AJCC stage and Fuhrman grade has good accuracy, discrimination and clinical prediction efficiency.

Prognostic significance of CD3+ and CD8+ T-cells immunoscore in renal cell carcinoma: A comparison between two simple models for assessment

The immunoscore (ISc) has been extensively investigated as a prognostic indicator for numerous solid tumors. In renal cell carcinoma (RCC), its prognostic significance has been evaluated in a small number of studies. This study was designed to ascertain the prognostic value of ISc based on CD3+ and CD8+ T cells in patients with RCC. This study included 115 non-metastatic RCC patients who underwent nephrectomy. The ISc was obtained by estimating the densities of CD3+ and CD8+ cells at the invasive margin and center of the tumor using two methods: cell count per square millimeter (cell count/mm2) and percentage of cells per square millimeter (% of cells/mm2). The patients were categorized into low and high groups according to the ISc. The associations between the ISc and clinicopathological characters, including survival, were analyzed statistically. Adverse clinicopathologic factors were significantly associated with high ISc. Patients with high ISc had significantly worse overall survival (OS) and disease-free survival (DFS) rates over three years (p < 0.001). High ISc was considered a predictor of shortened DFS in univariate analysis (p < 0.001). However, in multivariate analysis, it was a dependent predictor. High ISc could help identify individuals more likely to develop recurrence and may impact treatment strategy for more effective personalized care. Moreover, establishing a modified objective, automated, digital quantification method of immune cells (% of cells/mm2 instead of cell count/mm2) is expected to be simple to implement in routine, highly affordable, time efficient, clinically meaningful, and will improve assay performance.

Complications of Tumor Nephrectomy with and Without Tumor Thrombus in the Vena Cava, Recorded with the Clavien–Dindo Classification: A Matched-Pair Analysis

Background/Objectives: Radical nephrectomy (RN) with inferior vena cava thrombectomy (IVCT) is indicated for the curative management of renal cell carcinoma (RCC) with tumor thrombus (TT). In the literature, any direct comparison of complications between RNs with or without IVCT is lacking. The objective of this study was to analyze and compare complications after RNs with or without IVCT. Methods: A retrospective evaluation of the complications recorded in RCC patients who underwent RN with (TT group, n = 44) or without (non-TT group, n = 44) IVCT between 2009 and 2021 was conducted. The non-TT group was identified via propensity-score matched-pair analysis. Postoperative complications up until discharge or postoperative day 30, whichever came first, were classified using the Clavien–Dindo classification (CDC). Complications were categorized into cardiovascular, pulmonary, bleeding, gastrointestinal, neurological/psychiatric, wound, urinary tract, dysglycemia, and other groups. Statistical analyses using descriptive statistics included the chi2 and Mann–Whitney U tests. Results: All CDC-grade postoperative complications were more frequent in the TT than in the non-TT group regarding the number of patients affected (93% vs. 73%), as well as per patient (median: 3 vs. 1; p &lt; 0.001). Complications in CDC grade ≥ 3 were rare and comparable between groups. Cardiovascular, gastrointestinal, neurological/psychiatric, and bleeding complications occurred significantly more often in the TT group. However, its small study population and retrospective character limit this study. Conclusions: Significantly more patients undergoing an RN-IVCT experience more frequent postoperative complications than patients with an RN but without IVCT. Surgeons performing the procedures should be experienced, and hospital staff should be trained in the early recognition and treatment of complications.

Integrative analysis of single-cell and bulk multi-omics data to reveal subtype-specific characteristics and therapeutic strategies in clear cell renal cell carcinoma patients.

Background: Kidney renal clear cell carcinoma (KIRC) is the most prevalent subtype of malignant renal cell carcinoma and is well known as a common genitourinary cancer. Stratifying tumors based on heterogeneity is essential for better treatment options. Methods: In this study, consensus clusters were constructed based on gene expression, DNA methylation, and gene mutation data, which were combined with multiple clustering algorithms. After identifying two heterogeneous subtypes, we analyzed the molecular characteristics, immunotherapy response, and drug sensitivity differences of each subtype. And we further integrated bulk data and single-cell RNA sequencing (scRNA-Seq) data to infer the immune cell composition and malignant tumor cell proportion of subtype-related cell subpopulations. Results: Among the two identified consensus subtypes (CS1 and CS2), CS1 was enriched in more inflammation-related and oncogenic pathways than CS2. Simultaneously, CS1 showed a worse prognosis and we found more copy number variations and BAP1 mutations in CS1. Although CS1 had a high immune infiltration score, it exhibited high expression of suppressive immune features. Based on the prediction of immunotherapy and drug sensitivity, we inferred that CS1 may respond poorly to immunotherapy and be less sensitive to targeted drugs. The analysis of bulk data integrated with single-cell data further reflected the high expression of inhibitory immune features in CS1 and the high proportion of malignant tumor cells. And CS2 contained a large number of plasmacytoid B cells, presenting an activated immune microenvironment. Finally, the robustness of our subtypes was successfully validated in four external datasets. Conclusion: In summary, we conducted a comprehensive analysis of multi-omics data with 10 clustering algorithms to reveal the molecular characteristics of KIRC patients and validated the relevant conclusions by single-cell analysis and external data. Our findings discovered new KIRC subtypes and may further guide personalized and precision treatments.

Comparison of the effects of transperitoneal and retroperitoneal robot-assisted partial nephrectomy

Objective: To compare the effects of transperitoneal and retroperitoneal approaches for robotic assisted partial nephrectomy (RAPN) in patients with renal cell carcinoma (RCC). Methods: We conducted a retrospective cohort study on RAPN at Affiliated Hospital of Jiangsu University. Between September 2020 and February 2024, the included patients underwent either transperitoneal approach or retroperitoneal approach. Perioperative status, stress response, quality of life, and incidence of complications were compared between the groups. Results: A total of 105 patients were included in this analysis, with 54 patients in the Retroperitoneal group, and 51 patients in the Transperitoneal group. The retroperitoneal approach was associated with significantly better perioperative indicators compared to the transperitoneal method (P&lt;0.05). After the surgery, serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), white blood cell count (WBC), and cortisol (Cor) in the Retroperitoneal group were lower than in the Transperitoneal group (P&lt;0.05). The quality-of-life scores of patients in the Retroperitoneal group were higher (P&lt;0.05), but no statistically significant difference in the incidence of complications between the groups (P&gt;0.05). Conclusions: Compared with the transperitoneal approach, the retroperitoneal method of RAPN is equally safe and is associated with improved perioperative status, lower stress response, and better quality of life for RCC patients. doi: https://doi.org/10.12669/pjms.40.10.10613 How to cite this: Tao M, Cheng K, Xu W, Qian Z, Pan P. Comparison of the effects of transperitoneal and retroperitoneal robot-assisted partial nephrectomy. Pak J Med Sci. 2024;40(10):2202-2207. doi: https://doi.org/10.12669/pjms.40.10.10613 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Unenhanced CT as an Alternative to Contrast-Enhanced CT in Evaluating Renal Cryoablation Zones.

Background Advances in imaging technology and the increased use of abdominal imaging have led to a rise in renal cell carcinoma (RCC) detection. While surgery remains the primary treatment for small RCCs, minimally invasive procedures like cryoablation are gaining popularity, particularly for patients with comorbidities or renal dysfunction. CT-guided cryoablation offers advantages, including high spatial resolution and real-time visualization during the procedure. Post-procedure imaging is essential for assessing treatment success, with contrast-enhanced CT (CE-CT) typically considered vital. However, many patients, especially older individuals, have renal dysfunction that limits the use of contrast agents. In such cases, unenhanced CT (UE-CT) presents a viable alternative for post-procedural evaluation. This study explored the effectiveness of UE-CT in assessing cryoablation zones as a substitute for CE-CT. Materials and Methods This retrospective study included 54 patients (58 tumors) who underwent cryoablation at a single institution between 2014 and 2024. Only patients with available early follow-up CT (within three days post-cryoablation) and subsequent follow-up were included. Tumors marked with lipiodol prior to cryoablation and cases requiring transcatheter arterial embolization due to extravasation immediately after cryoablation were excluded. Percutaneous renal cryoablation was performed under CT fluoroscopy, and the ablation zone was assessed using a 64-channel multi-slice CT scanner. UE-CT was conducted before the procedure, followed by both UE-CT and CE-CT within three days after cryoablation. CT attenuation values were measured for pre-procedure UE-CT (kidneys and tumor), post-procedure UE-CT (kidneys, cryoablation zone, and tumor), and post-procedure CE-CT (kidneys, cryoablation zone, and tumor). Tumor volumes in the post-procedure regions were evaluated on both UE-CT and CE-CT. Statistical analyses were performed using Wilcoxon's signed-rank test and Spearman's rank correlation coefficient, with interobserver agreement determined by the intraclass correlation coefficient. Results The median tumor diameter was 1.56 cm (IQR: 1.33-2.00 cm). On UE-CT, the cryoablation zone exhibited high attenuation, while it showed low attenuation on CE-CT. The median attenuation values of the kidneys on UE-CT before and after cryoablation were not significantly different (33.6 Hounsfield unit (HU) vs. 34.3 HU, P = 0.17). However, on CE-CT, the median attenuation values of normal kidneys and the cryoablation zone significantly differed (171.7 HU vs. 55.7 HU, P < 0.0001). Similarly, on UE-CT, there was a significant difference in the median attenuation values between normal kidneys and the cryoablation zone (34.3 HU vs. 47.4 HU, P < 0.0001). The median renal volumes of the unenhanced regions on CE-CT and those with attenuation changes on UE-CT were not significantly different (26.52 cm³ vs. 28.83 cm³, P = 0.86). These values showed a strong correlation (r = 0.95; 95% CI: 0.91-0.97). Conclusions This study showed that UE-CT can reliably estimate the ablation zone in RCC patients post-cryoablation. While the contrast between the ablation zone and normal renal parenchyma was lower on UE-CT compared to CE-CT, the ablation zone was still detectable and highly correlated with CE-CT results. Further research with larger sample sizes is needed to validate the clinical utility of UE-CT and assess the reproducibility of these findings.

NODESAFE Nomogram: A Novel Score System to Predict Lymph Node Involvement at the Time of Nephrectomy or Nodal Recurrence in Nonmetastatic Renal Cell Carcinoma

ObjectiveWe sought to develop a preoperative nomogram called NODESAFE (NODE SAFEty) to predict nodal involvement (NI) at time of surgery or subsequent follow up in localized renal cell carcinoma (RCC), as the role of lymphadenectomy in localized RCC remains controversial. MethodsWe conducted a multicenter retrospective analysis of RCC patients who underwent primary surgical resection. Patients with clinical metastasis at presentation were excluded. NI was defined as presence of histological RCC with lymphadenectomy at time of surgery, or subsequent development histologically proven NI. The dataset was divided into training (70%) and testing subsets to facilitate model evaluation which was constructed through a stepwise multivariable logistic regression (MLR) model. Accuracy was tested with receiver operator characteristic estimated area under the curve (AUC). ResultsTotal 3308 patients (2221 [67.1%] male) met inclusion criteria. During follow-up 25 patients (0.76 %) experienced nodal recurrence, and 22/25 were preoperatively classified as cN0. In our cohort, 112 (3.4%) patients had clinical lymphadenopathy preoperatively (cN1), and 34/112 were pN1. The following covariates were found to be statically significant on a MLR model: hypertension (Odds ratio [OR] 3.35, < 0.001), Charlson Comorbidity Index ≥ 5 (OR 1.93 P = .025), tumor size ≥ 6 cm (OR 2.63, P = .001), tumor necrosis at CT scan (OR 1.83, P = .036), cN1 (OR 5.59, P < .001) and CRP ≥ 8.5 mg/L (1.96, P = .018). Testing the prediction performance of the model in the validation set AUC of the model was 0.89. NODESAFE demonstrated a sensitivity of 83.9%, specificity of 86.1% and 99.1% negative predictive values using a 4% threshold probability. ConclusionCombining clinical features, serum biomarkers and radiographic findings, we developed a model capable of predicting NI with high degree of accuracy. NODESAFE may refine clinical decision making with respect to the performance of lymphadenectomy at the time of surgery, postsurgical surveillance, and spur consideration for adjuvant therapy.

Low Serum Alanine Aminotransferase Blood Activity Is Associated with Shortened Survival of Renal Cell Cancer Patients and Survivors: Retrospective Analysis of 1830 Patients

Background: Sarcopenia is characterized by a loss of muscle mass and function and is often associated with frailty, a syndrome linked to physical disability and shortened survival in various patient populations, including cancer patients. Low serum alanine aminotransferase (ALT) values, serving as a biomarker for sarcopenia, were previously associated with frailty and shortened survival in several cancers. In the current study, we aimed to test the association between low ALT and shorter survival in renal cell carcinoma (RCC) patients and survivors. Methods: This was a retrospective analysis of RCC patients and survivors, both in- and outpatients. We defined patients with sarcopenia as those presenting with ALT &lt; 17 IU/L. Results: We identified records of 3012 RCC patients. The cohort included 1830 patients (mean age 65.6 ± 13.3 years, 68% were men) of whom only 179 underwent surgical treatment. Out of the eligible cohort, 811 patients (44.3%) had ALT &lt; 17 IU/L, with a mean ALT value of patients within the low-ALT group of 11.79 IU/L, while the mean value in the higher ALT level group was 24.44 IU/L (p &lt; 0.001). Patients in the low-ALT group were older (67.9 vs. 63.7 years; p &lt; 0.001) and had lower BMIs (26.6 vs. 28; p &lt; 0.001). In addition, patients with low ALT had lower hemoglobin values (12.14 vs. 12.91 g/dL; p &lt; 0.001), higher serum creatinine (1.49 vs. 1.14; p &lt; 0.001) and higher platelet to lymphocyte ratios (178 vs. 156; p &lt; 0.001). In a univariate analysis, low ALT levels were associated with a 72% increase in mortality (95% CI 1.46–2.02, p &lt; 0.001). In a multivariate model controlled for age, gender, hemoglobin, platelets, LDH, neutrophil to lymphocyte ratios and platelet to lymphocyte ratios, low ALT levels were still associated with a 27% increase in mortality (HR = 1.27, 95% CI 1.08–1.51; p = 0.005). Conclusion. Low ALT values, associated with sarcopenia and frailty, are also associated with shortened survival in RCC patients, and survivors and could potentially be applied for optimizing individual treatment decisions.

Renal Cell Carcinoma With Tumor Thrombus Extending Into the Inferior Vena Cava and the Right Atrium Demonstrated by 68 Ga-DOTATATE PET/CT.

Approximately 10% of all renal cell carcinoma (RCC) patients develop a venous tumor thrombus, a major negative prognostic factor. Surgical excision is commonly required for RCC patients with tumor thrombus. Accurate preoperative diagnosis and assessment of tumor thrombus level is vital because the level of thrombus may influence treatment decisions. MRI, contrast-enhanced CT, 18 F-FDG PET/CT, and 68 Ga-PSMA PET/CT have been used to diagnose and evaluate the extent of tumor thrombus in RCC. However, no case of RCC with inferior vena cava tumor thrombus showing 68 Ga-DOTATATE uptake has been reported yet. Herein, we report a case of metastatic RCC with tumor thrombus in the inferior vena cava on 68 Ga-DOTATATE PET/CT.

Potential of quantitative T1 mapping to serve as a novel prognostic predictor of clear cell renal cell carcinoma after nephrectomy.

Accurate preoperative risk stratification methods are important for clear cell renal cell carcinoma (ccRCC) patients to enable personalized treatment. However, there are still no accurate and quantitative prognostic factors. This study aimed to investigate the effectiveness of T1 mapping in predicting the progression-free survival (PFS) of ccRCC after nephrectomy. A retrospective cohort study was performed in a China tertiary care hospital. This study reviewed the clinical and magnetic resonance imaging (MRI) data of consecutive inpatients with pathologically confirmed ccRCCs between September 2014 and September 2021. PFS was evaluated by following patients until the first adverse event. Radiological features including T1 relaxation time of tumors were assessed by 2 radiologists. Cox regression and visual nomogram, Kaplan-Meier survival, and log-rank test were utilized for survival analysis. A total of 195 patients with pathologically confirmed ccRCCs (mean age ± standard deviation, 56.0±12.0 years; 133 men) with eligible data were included in the study. The median follow-up was 27.6 months (range, 1-88 months), and 22 (11.3%) patients experienced metastasis or recurrence. Univariate and multivariate survival analysis showed the higher post-contrasted T1 relaxation time [P=0.001; hazard ratio (HR), 2.077; 95% confidence interval (CI): 1.350-3.196] and the incomplete tumor capsule (P<0.001; HR, 7.849; CI: 2.614-23.570) were independently associated with a shorter PFS of patients. Patients with ≥222.73 ms post-contrasted T1 relaxation time ccRCCs had worse PFS than the lower post-contrasted T1 relaxation time group. The T1 mapping quantitative parameters may be a new potential biomarker for predicting PFS in patients with ccRCCs.

Age Does Not Impact Cancer Specific Mortality: From Sub-Distributional and Cause-Specific Hazard Analysis in RCC Patients Undergoing Radical Nephrectomy and Thrombectomy

ObjectiveTo evaluate the impact of age on cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients undergoing radical nephrectomy with thrombectomy (RNTx) for renal cell carcinoma (RCC) with venous thrombus. Patients and MethodsWe retrospectively analyzed data from 196 patients who underwent RNTx for RCC with venous thrombus between 1990 and 2018 at a single tertiary referral center. Patients were grouped into three age groups: <60 years, 60-69 years, and ≥70 years. Clinical and pathological characteristics were compared. The cumulative incidence function (CIF) for CSM and OCM was calculated using the Aalen-Johansen estimator. We employed both sub-distributional hazard (SDH) and cause-specific hazard (CSH) models to evaluate the impact of age on mortality, using hazard ratios (HR) and 95% confidence intervals (CI) quantified associations. ResultsThe median follow-up was 40.5 months. During this time, 105 patients experienced disease progression, 125 had cancer-related deaths, and 155 deceased from any cause. Perioperative outcomes, including ICU admission, 90-day readmission, and 90-day mortality, showed no significant differences among age groups. The CIF for CSM revealed significant differences at 5-year (p = 0.032) but not at 10-years (p = 0.246). OCM increased with age, notably in the oldest group at 10 years (p = 0.045). Multivariable adjusted CSH and SDH models showed no significant differences in CSM among age groups. ConclusionAlthough the CIF for 5-year CSM and 10-year OCM were associated with increasing age, aging does not increase the hazard of CSM in both SDH and CSH models. Perioperative outcome does not differ between all age groups. For RCC with venous thrombus patients, older age alone is not absolute contraindication for surgical intervention. Micro-AbstractThis study assessed the impact of age on cancer-specific and other-cause mortality in patients undergoing radical nephrectomy with thrombectomy for renal cell carcinoma with venous thrombus. Although older age was associated with higher other-cause mortality at 10 years, age did not significantly affect cancer-specific mortality, suggesting that age should not be a contraindication for surgery in these patients. Perioperative outcomes were similar across all age groups.

Survival rate comparisons of angioembolization and neoadjuvant targeted therapy on unresectable renal cell carcinoma patients: A systematic review

Objective: Renal cell cancer (RCC) is the most typical form of kidney cancer in adults, which accounts for 80% to 85% of all primary renal neoplasms. RCC develops inside the renal cortex. This study aimed to systematically review the survival rate of patients treated with targeted therapy and/or RC. Surgery is the standard therapy for RCC, even though after surgery, 20%–40% of patients with localized RCC would experience distant metastases. Metastases or large RCC are not amenable to surgery. Unresectable RCC can be treated palliatively with angioembolization or neoadjuvant therapy. This study aims to review the survival rate comparisons of angioembolization and neoadjuvant targeted therapy on unresectable renal cell carcinoma. Methods: A thorough search across databases such as PubMed, Cochrane Library, and ProQuest was conducted for articles published from 2018 to 2023. To uphold research integrity, duplicates, reviews, and incomplete articles were excluded, ensuring only pertinent and original research findings for subsequent analysis. Results: Database search yielded 247 articles, which were systematically eliminated, leaving 6 relevant articles. Analyzed articles showed the overall survival of patients treated with angioembolization and neoadjuvant agents. Conclusion: Unresectable RCC can be treated palliatively with angioembolization. Angioembolization may improve clinical effectiveness and lessen side effects by boosting local concentrations of drugs. Drug-eluting bead transarterial chemoembolization is a novel embolization option that can embolize the arteries that feed the tumor and cutoff the blood supply to the tumor. Sunitinib, the most studied medicinal agent, was found to have higher effectiveness when combined with angioembolization.

N6-methyladenosine-modified TRIM37 augments sunitinib resistance by promoting the ubiquitin-degradation of SmARCC2 and activating the Wnt signaling pathway in renal cell carcinoma

Tripartite motif-containing 37 (TRIM37) is reportedly a key member of the superfamily of TRIM proteins. Emerging evidence underscores the close association between dysregulated TRIM37 expression and the progression of various human malignancies. However, the precise biological functions and regulatory mechanisms of TRIM37 remain elusive. This study aimed to elucidate the impact of TRIM37 on the chemotherapy sensitivity of renal cell carcinoma (RCC) and uncover its specific molecular regulatory role. Using RT-qPCR and western blot assays, we assessed TRIM37 expression in both RCC patients and RCC cells. Through in vitro and in vivo experiments, we investigated the effects of TRIM37 silencing and overexpression on RCC cell proliferation, stemness capacity, and chemotherapy sensitivity using colony formation and sphere formation assays. Additionally, a co-immunoprecipitation (Co-IP) experiment was conducted to explore putative interacting proteins. Our results revealed elevated TRIM37 expression in both RCC patient tumor tissues and RCC cells. Functional experiments consistently demonstrated that TRIM37 silencing reduced proliferation and stemness capacity while enhancing chemotherapy sensitivity in RCC cells. Furthermore, we discovered that TRIM37 mediates the degradation of SMARCC2 via ubiquitin-proteasome pathways, thereby further activating the Wnt signaling pathway. In conclusion, this study not only sheds light on the biological role of TRIM37 in RCC progression but also identifies a potential molecular target for therapeutic intervention in RCC patients.

Accumulation of 3-Monochloro-Propanediol Esters in Kidney Tissues of Patients with Human Renal Cell Carcinoma

Background: 3-Monochloro-propanediol esters (3-MCPDEs), commonly found in refined edible oils and related products, have generated concerns due to their nephrotoxicity and carcinogenicity, yet clinical evidence remains limited. Objectives: In this study, we aimed to assess, for the first time, the accumulation of 3-MCPDEs in human kidney tissues, focusing on 68 participants, some with and others without renal cell carcinoma (RCC). Methods: An analytical method for 3-MCPDE determination in kidney tissues underwent partial validation to ensure its suitability for sample analysis. The analyst was blind to the sample groups. Results: Results revealed significantly higher 3-MCPDE levels in RCC patients compared to non-RCC counterparts (0.22 vs. 0.01 µg/g) (p &lt; 0.01). Moreover, no significant correlation was found between 3-MCPDE levels and tumor stage or size in the RCC group. Conclusions: Accumulation of 3-MCPDEs in humans, with significantly higher levels was observed in kidney tumor specimens compared to non-patients. These findings suggest minimizing the intake of 3-MCPD and its esters in diets in order to reduce potential negative health impacts.

The immunotherapy-based combination associated score as a robust predictor for outcome and response to combination of immunotherapy and VEGF inhibitors in renal cell carcinoma

BackgroundOver the past decade, the realm of immunotherapy-based combination therapy has witnessed rapid growth for renal cell carcinoma (RCC), however, success has been constrained thus far. This limitation primarily stems from the absence of biomarkers essential for identifying patients likely to derive benefits from such treatments. MethodsIn this study, the immunotherapy-based combination associated score (IBCS) was established using single-sample gene set enrichment analysis (ssGSEA) based on the genes identified in the key modules extracted by weighted correlation network analysis (WGCNA) in the IMmotion151 dataset, a randomized, global phase III trial. ResultsHigh IBCS patients showed better responses to immunotherapy-based combinations and had longer progression-free survival (PFS). Further transcriptomic analysis revealed that IBCS was negatively correlated to TIDE score, identifying a subset of RCC patients characterized by enrichment of T-effector and moderate cell-cycle/angiogenesis gene expression. Our analysis of hub genes unveiled a novel molecule that could potentially serve as a target antigen in RCC. Validation through multiplex immunofluorescence assays on tissue microarrays (TMAs) containing 180 samples confirmed the pivotal role of this hub gene in immunoregulation. Furthermore, we developed an independent risk score model, which is significant for prognostic evaluation and patient stratification. Notably, we devised a forecasting nomogram using this risk score model, surpassing the IMDC score (a widely accepted risk score for predicting survival in patients undergoing VEGF-targeted therapy) in prognostic accuracy for patients treated with immunotherapy-based combinations. ConclusionThis study has collectively developed an immunotherapy-based combination associated score, pinpointed effective biomarkers for prognostic and responsiveness of kidney cancer patients to immunotherapy-based combinations, and delved into their potential biological mechanisms, offering promising targets for further exploration.

New players in the landscape of renal cell carcinoma bone metastasis and therapeutic opportunities

AbstractApproximately one‐third of advanced renal cell carcinoma (RCC) patients develop osteolytic bone metastases, leading to skeletal complications. In this review, we first provide a comprehensive perspective of seminal studies on bone metastasis of RCC describing the main molecular modulators and growth factor signaling pathways most important for the RCC‐stimulated osteoclast‐mediated bone destruction. We next focus on newer developments revealing with in‐depth details, the bidirectional interplay between renal cancer cells and the immune and stromal microenvironment that can through epigenetic reprogramming, profoundly affect the behaviors of transformed cells. Understanding their mechanistic interactions is of paramount importance for advancing both fundamental and translational research. These new investigations into the landscape of RCC‐bone metastasis offer novel insights and identify potential avenues for future therapeutic interventions.

Radiomics predicts the prognosis of patients with clear cell renal cell carcinoma by reflecting the tumor heterogeneity and microenvironment

PurposeWe aimed to develop and externally validate a CT-based deep learning radiomics model for predicting overall survival (OS) in clear cell renal cell carcinoma (ccRCC) patients, and investigate the association of radiomics with tumor heterogeneity and microenvironment.MethodsThe clinicopathological data and contrast-enhanced CT images of 512 ccRCC patients from three institutions were collected. A total of 3566 deep learning radiomics features were extracted from 3D regions of interest. We generated the deep learning radiomics score (DLRS), and validated this score using an external cohort from TCIA. Patients were divided into high and low-score groups by the DLRS. Sequencing data from the corresponding TCGA cohort were used to reveal the differences of tumor heterogeneity and microenvironment between different radiomics score groups. What’s more, univariate and multivariate Cox regression were used to identify independent risk factors of poor OS after operation. A combined model was developed by incorporating the DLRS and clinicopathological features. The SHapley Additive exPlanation method was used for interpretation of predictive results.ResultsAt multivariate Cox regression analysis, the DLRS was identified as an independent risk factor of poor OS. The genomic landscape of different radiomics score groups was investigated. The heterogeneity of tumor cell and tumor microenvironment significantly varied between both groups. In the test cohort, the combined model had a great predictive performance, with AUCs (95%CI) for 1, 3 and 5-year OS of 0.879(0.868–0.931), 0.854(0.819–0.899) and 0.831(0.813–0.868), respectively. There was a significant difference in survival time between different groups stratified by the combined model. This model showed great discrimination and calibration, outperforming the existing prognostic models (all p values < 0.05).ConclusionThe combined model allowed for the prognostic prediction of ccRCC patients by incorporating the DLRS and significant clinicopathologic features. The radiomics features could reflect the tumor heterogeneity and microenvironment.

[89Zr]Zr-girentuximab for PET–CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial

With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect clear-cell renal cell carcinoma in patients with renal masses remain an unmet need. 89Zr-labelled monoclonal antibody ([89Zr]Zr-girentuximab) has high affinity for carbonic anhydrase 9, a tumour antigen highly expressed in clear-cell renal cell carcinoma. We aimed to evaluate [89Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma. ZIRCON was a prospective, open-label, multicentre, phase 3 trial conducted at 36 research hospitals and practices across nine countries (the USA, Australia, Canada, the UK, Türkiye, Belgium, the Netherlands, Spain, and France). Patients aged 18 years or older with an indeterminate renal mass 7 cm or smaller (cT1) suspicious for clear-cell renal cell carcinoma and scheduled for nephrectomy received a single dose of [89Zr]Zr-girentuximab (37 MBq ±10%; 10 mg girentuximab) intravenously followed by abdominal PET-CT imaging 5 days (±2 days) later. Surgery was performed no later than 90 days after administration of [89Zr]Zr-girentuximab. Blinded central review, conducted by three independent readers, determined the histology from surgical samples. The coprimary endpoints, determined for each individual reader, were the sensitivity and specificity of [89Zr]Zr-girentuximab PET-CT imaging to detect clear-cell renal cell carcinoma, with histopathological confirmation as standard of truth. Analyses were on the full analysis set of patients, defined as patients who had evaluable PET-CT imaging and a confirmed histopathological diagnosis. The trial is registered with ClinicalTrials.gov, NCT03849118, and EUDRA Clinical Trials Register, 2018-002773-21, and is closed to enrolment. Between Aug 14, 2019, and July 8, 2022, 371 patients were screened for eligibility, 332 of whom were enrolled. 300 patients received [89Zr]Zr-girentuximab (214 [71%] male and 86 [29%] female). 284 (95%) evaluable patients were included in the primary analysis. The mean sensitivity was 85·5% (95% CI 81·5-89·6) and mean specificity was 87·0% (81·0-93·1). No safety signals were observed. Most adverse events were not or were unlikely to be related to [89Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery. The most common grade 3 or worse adverse events were post-procedural haemorrhage (in six [2%] of 261 patients), urinary retention (three [1%]), and hypertension (three [1%]). In 25 (8%) of 300 patients, 52 serious adverse events were reported, of which 51 (98%) occurred after surgery. There were no treatment-related deaths. Our results suggest that [89Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing. Telix Pharmaceuticals.

The content of soluble forms of galectins -1, -3, -4, -7, -9 in patients with renal cell cancer of various morphological types

Background: Galectins are a family of β-galactoside binding proteins that regulate the vast majority of cellular functions, including proliferation, migration, adhesion, and phagocytosis in both health and disease. More and more experimental and clinical evidence indicates that galectins are involved in many stages of carcinogenesis, including patients with renal cell carcinoma (RCC). Aim: To analyze the clinical significance of soluble forms of galectins -1, -3, -4, -7, -9 in patients with various histological RCC types. Materials and methods: We performed a retrospective analysis of the clinical significance of galectins -1, -3, -4, -7, -9 in the serum of 140 RCC patients (84 with clear cell RCC (ccRCC), 38 with papillary (papRCC), 18 with chromophobe (chrRCC)) and in 73 healthy donors (control group), who were examined and treated from 2019 to 2023 in the N. N. Blokhin National Medical Research Center of Oncology. Galectin levels were measured in serum (obtained according to standard methods before the initiation of specific treatment) with an enzyme-linked immunosorbent assay. Results: There was a significant increase in serum galectin -1, -3, -9 levels in the whole RCC patient group, compared to the healthy donor control group; no increase was found for galectins -4 and -7. Serum galectin-1 levels in the ccRCC and papRCC patients were significantly higher than those in the controls (p = 0.0003 and p = 0.0135, respectively). No association between the serum galectins -1 and -7 and the clinical and morphological characteristics of RCC was found; however, serum galectin-7 levels in the papRCC patients correlated with the grade of tumor differentiation (r = -0.592; p = 0.001). The area under the ROC curve (AUC) for galectin-1 in ccRCC was 0.721 (p 0.0001), in papRCC 0.673 (p = 0.0086), and in chrRCC 0.576 (p = 0.355). For galectin-7, the ROC AUC values were 0.527 (p = 0.634) in ccRCC, 0.513 (p = 0.845) in papRCC, and 0.566 (p = 0.425) in chrRCC. In all histological types of RCC, there was a significant increase in serum galectin-3 compared to the controls (ccRCC, p = 0.0208; papRCC, p = 0.0014; chrRCC, p = 0.0041). The ROC analysis for galectin-3 in patients with RCC of various histological types showed AUC = 0.721 (p 0.0001) for ccRCC, 0.673 (p = 0.0086) for papRCC, and 0.576 (p = 0.355) for chrRCC. Galectin-9 levels was directly and significantly associated with the tumor size, as well as with regional metastases (r = 0.251, p = 0.021; r = 0.239, p = 0.028, respectively). The AUC values for galectin-4 were 0.619 (p = 0.021) in ccRCC, 0.577 (p = 0.214) in papRCC, and 0.534 (p = 0.666) for chrRCC. For galectin-9, they were 0.649 (p = 0.0075), 0.613 (p = 0.087), and 0.539 (p = 0.637), respectively. Conclusion: The study has demonstrated a certain association between serum galectin -1, -3, -4, -7, and -9 in the patients with RCC of various histological types. Although the results of the ROC analysis indicated average quality of the model, which does not allow for the use of the obtained data for diagnostic purposes, it is necessary to continue the research for better understanding of the mechanisms of galectin functioning, before galectin-based therapeutic agents would be introduced into clinical practice for the treatment of RCC.