Renal Malignancy Research Articles

Characterization of malignant kidney tumors in childhood by 18F-FDG PET/CT.

To evaluate the role of semiquantitative parameters derived from 18F-FDG PET/CT in characterizing pediatric malignant kidney tumors. 54 children with pathologically confirmed renal malignancies who underwent pretreatment 18F-FDG PET/CT were retrospectively reviewed. Association between PET-derived semiquantitative parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and tumor histology, disease stage, and loss of heterozygosity were analyzed. Of the 54 patients, 43 had Wilms tumor (WT), 4 had clear cell sarcoma of the kidney (CCSK), 3 had rhabdoid tumor of kidney, 2 had renal cell carcinoma, and 2 had congenital mesoblastic nephroma. 18F-FDG PET/CT detected all primary renal tumors, with SUVmax ranging from 1.2 to 14.5. PET-derived parameters showed no significant differences among different tumor types, except for CCSK, which exhibited lower FDG uptake compared to WT (SUVmax 3.60 ± 1.02 vs. 6.10 ± 2.25, p = 0.034). Higher MTV, TLG, and lactate dehydrogenase were associated with stage IV disease. ROC analysis showed that TLG had the highest AUC (0.931) for predicting stage IV disease in the whole cohort, while SUVmax had the highest AUC (0.867) for predicting stage IV and V in WT. Furthermore, Children with 1q gain exhibited higher MTV in WT (447 ± 354 vs. 207 ± 189, p = 0.041). PET-derived semiquantitative parameters highly associated with disease stage both in the overall cohort of renal malignancies and specifically in the WT group. Additionally, volumetric metabolic indices might provide further insights into loss of heterozygosity in children with WT.

Urothelial carcinoma of the renal pelvis with squamous and sarcomatoid differentiation complicated by hydronephrosis and pyelonephritis: a case report and literature review

BackgroundRenal pelvic urothelial carcinoma with multiple histological variants co-occurs with hydronephrosis and pyelonephritis extremely rarely. The diagnosis of renal pelvic urothelial carcinoma can be complicated by these conditions, leading to delayed or missed diagnosis or misdiagnosis.Case presentationWe report the evolutionary course of a rare case of renal pelvic urothelial carcinoma containing squamous and sarcomatoid differentiation associated with hydronephrosis and pyelonephritis in a low-functioning kidney. Preoperative clinical and imaging manifestations were highly suggestive of hydronephrosis and pyelonephritis; however, all corresponding therapeutic measures failed. Eventually, nephrectomy was performed, and postoperative pathological examination revealed renal pelvic urothelial carcinoma with squamous and sarcomatoid differentiation. Further residual ureter and bladder cuff resection was refused by the patient. Regular cisplatin-based postoperative chemotherapy and bladder perfusion were arranged, and cystoscopy and imaging examinations were performed regularly for follow-up.ConclusionHydronephrosis and pyelonephritis can mask the typical clinical and imaging manifestations of renal pelvic urothelial carcinoma. Renal pelvic malignancy should be considered in patients with intractable pyelonephritis and hydronephrosis. There is no standard treatment for renal pelvic carcinoma with multiple pathological types. Radical surgery is considered an appropriate option and should be performed as early as possible. Chemotherapy and immunotherapy may improve patient survival.

Comprehensive assessment of the association between tumor-infiltrating immune cells and the prognosis of renal cell carcinoma.

According to current statistics, renal cancer accounts for 3% of all cancers worldwide. Renal cell carcinoma (RCC) is the most common solid lesion in the kidney and accounts for approximately 90% of all renal malignancies. Increasing evidence has shown an association between immune infiltration in RCC and clinical outcomes. To discover possible targets for the immune system, we investigated the link between tumor-infiltrating immune cells (TIICs) and the prognosis of RCC. To investigate the effects of 22 TIICs on the prognosis of RCC patients and identify potential therapeutic targets for RCC immunotherapy. The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions. Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC. A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes. Furthermore, multivariate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC. A value of P < 0.05 was regarded as statistically significant. Compared to normal tissues, RCC tissues exhibited a distinct infiltration of immune cells. An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC. High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve (P = 1E-05). The immunological risk score model was demonstrated to be a dependable predictor of survival risk (area under the curve = 0.747) via the receiver operating characteristic curve. According to multivariate Cox regression analysis, the immune risk score model independently predicted RCC patients' prognosis (hazard ratio = 1.550, 95%CI: 1.342-1.791; P < 0.001). Finally, we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC. TIICs play various roles in RCC prognosis. The immunological risk score is an independent predictor of poor survival in kidney cancer cases.

EFFICACY OF NEOADJUVANT TARGETED THERAPY IN TREATMENT OF PATIENTS WITH LOCALISED CLEAR-CELL RENAL CELL CARCINOMA

Clear-cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, accounting for approximately 75-80% of all renal malignancies. Objectives: The main objective of the study is to find the efficacy of neoadjuvant targeted therapy in the treatment of patients with localised clear-cell renal cell carcinoma. Methods: This prospective study was conducted at Mardan Medical Complex from June 2023 to January 2024. Data were collected from 85 patients. Patients aged&gt;18 years and have a histologically confirmed diagnosis of localized ccRCC were included in the study. Tumor size was required to be 4 cm or larger, but confined to the kidney, corresponding to Stage I to III disease. Results: Data were collected from 85 patients with an average baseline tumour size for the entire cohort was 7.5 cm, and after 12 weeks of treatment, tumours shrank to an average of 5.6 cm, resulting in a mean tumour reduction of 25%. In the sunitinib group, the tumour size decreased from 7.5 cm to 5.55 cm, reflecting a 26% reduction. Similarly, in the pazopanib group, the tumour size was reduced from 7.5 cm to 5.65 cm, with an average reduction of 24%. Conclusion: It is concluded that neoadjuvant targeted therapy, using agents such as sunitinib and pazopanib, effectively reduces tumour size and improves surgical outcomes in patients with localized clear-cell renal cell carcinoma.

Diagnosis and management of Canine Renal Cell Carcinoma with special reference to Shear Wave Elastography

This report focuses on the diagnosis and surgical management of unilateral renal cell carcinoma in a 7-year-old male intact German Shepherd dog. The dog was presented with fever, haematuria, inappetence, infrequent bouts of emesis, and progressive weight loss. Palpation revealed a hard, round mass in the right cranial abdomen. A presumptive diagnosis of unilateral renal neoplasm was made based on clinical signs, haematobiochemical analysis, and radiography. B-mode ultrasound examination demonstrated an enlarged right kidney extending up to the ventral midline. The kidney exhibited heterogenous echotexture, loss of renal architecture, and only a small healthy portion at the caudal pole. Point Shear Wave Elastography analysis revealed elevated values both in terms Shear Wave Velocity (m/sec) and Young’s Modulus Stiffness Value (kPa), indicating the presence of renal malignancy. To treat the condition, unilateral nephroureterectomy was performed under general anaesthesia. Histopathological examination confirmed the diagnosis of renal cell carcinoma. Consequently, it can be concluded that B-mode ultrasonography, Point Shear Wave Elastography, and nephroureterectomy played crucial roles in the successful diagnosis and surgical management of unilateral renal cell carcinoma.

Radiological evaluation of a calyceal diverticulum presenting with hematuria

Calyceal diverticulum, also known as pyelogenic cysts, is a relatively uncommon condition, usually asymptomatic and incidentally diagnosed during routine imaging. Sometimes it may lead to concerning symptoms such as hematuria and flank pain, mimicking the presence of a renal tumor. In this case report, the patient suffered from hematuria which was initially suspected to be indicative of a renal malignancy but that was ultimately attributed to a calyceal diverticulum. The reported case gives the opportunity to evaluate one of the rarest and underestimated causes of hematuria and to describe the main imaging features of the calyceal diverticulum. In particular, the following diagnostic imaging methods have been performed: Ultrasound, Computed Tomography Urography, Dual Energy Computed Tomography, and Magnetic Resonance Urography. Subsequently, this case report has also an educative purpose.

Predicting post-surgical complications using renal scoring systems.

Current surgical approaches for renal malignancies primarily rely on qualitative factors such as patient preferences, surgeon experience, and hospital capabilities. Applying a quantitative method for consistent and reliable assessment of renal lesions would significantly enhance surgical decision-making and facilitate data comparison. Nephrometry scoring (NS) systems systematically evaluate and describe renal tumors based on their anatomical features. These scoring systems, including R.E.N.A.L., PADUA, MAP scores, C-index, CSA, and T-index, aim to predict surgical complications by evaluating anatomical and patient-specific factors. In this review paper, we explore the components and methodologies of these scoring systems, compare their effectiveness and limitations, and discuss their application in advancing patient care and optimizing surgical outcomes.

Spectrum of Renal Tumors Other Than Renal Cell Carcinoma with Emphasis on Cytomorphological, Immunohistochemical, and Cytogenetic Study

Abstract Background: The role of fine needle aspiration cytology (FNAC) in the diagnosis of renal malignancies is established and has been getting more precise and important over a period of time. Knowledge of the pathology of uncommon renal neoplasms along with radiological and clinical correlations often aids in correct diagnosis. Aims: The present study aims to describe the cytomorphological and immunohistochemical findings in the varied spectrum of renal tumors, other than renal cell carcinomas (RCC). Materials and Methods: Data of 238 cases of ultrasound-guided renal FNAC performed in our tertiary cancer institute over 4 years were collected from the department registry. All nondiagnostic cases and cases diagnosed as RCC were excluded from the study, so 57 cases of renal tumors were reviewed along with the cell blocks and ancillary studies. Results: Out of the 57 cases, 35 cases were primary renal neoplasms, which included renal oncocytoma (3.5%), angiomyolipoma (3.5%), rhabdoid tumor (1.8%), Wilms tumor (28.0%), Ewing sarcoma (3.5%), urothelial carcinoma (8.8%), and small round cell tumor unclassified (12.3%). Twenty two cases were metastatic tumors, which included hematolymphoid neoplasm (14%) and metastatic carcinomas (24.6%) from various other primary carcinomas. Conclusion: Our study shows that renal FNAC is safe and fairly accurate in diagnosing a wide spectrum of renal tumors and has high diagnostic accuracy, when performed along with cell block and immunohistochemistry. Awareness of the pathology of uncommon renal tumors along with relevant clinical history and radiological findings may aid in identifying the type of tumor for further appropriate management.

Stratification of Wilms tumor patients using physicochemical properties of the adaptive immune receptor polypeptides, IGL and TRG

Wilms tumor (WT) is the most common pediatric renal malignancy. Current guidelines that stratify WT risk and determine treatment courses are inadequate, as over 60% of WT survivors develop treatment-related complications. Recently, numerous advances in establishing patient sub-groups with different clinical features have been realized by evaluating the adaptive immune receptor (IR) complementarity determining region-3 (CDR3) amino acid (AA) sequences, a reasonable series of successes, given the prominent role of the CDR3 in antigen binding, including tumor antigen binding. However, the possibility that adaptive IR chemical variability correlates with distinct survival outcomes for WT has not yet been explored. The goal of this study was to isolate the T-cell receptor and B-cell receptor recombination, sequencing reads from WT RNAseq files, representing the actual tumor tissue, translate the sequences to AAs, identify the adaptive IR CDR3 domains, and determine whether the physicochemical properties of those CDR3 AA sequences correlated with survival probability distinctions. WT RNA-seq files were mined to obtain the CDR3 AAs for various adaptive IRs. The physicochemical properties of these CDR3s were examined for trends in how those properties correlated with survival probabilities for WT patients, using a Kaplan-Meier analyses, verified via several approaches. The above processes indicated the association of the (a) IGL CDR3s' instability index and the (b) TRG CDR3s' fraction disorder promoting features with better outcomes. Additionally, the IGL CDR3 data were assessed using the Predictor of Natural Disordered Regions web tool, which strengthened the evidence for the association with the IGL CDR3 instability index with a better outcome. The approaches described here indicate that greater adaptive IR CDR3 instability and flexibility may serve as prognostic indicators; and may indicate the flexibility of CDR3 domains provides for greater opportunity to bind tumor antigens. Further exploration and development of these approaches and findings may lead to new guidelines for more precise treatment regimens, or even watchful waiting periods, that could thereby decrease the lifetime occurrence of adverse events.

Adult Uterine Wilm’s Tumor Miss-interpreted as Carcinosarcoma: A Case Report

Introduction: Wilm’s tumor (WT) is a common renal malignancy in children. Adult extrarenal WT involving the uterus is extremely rare. Herein, we reported a case of uterine WT in an old woman who was primarily diagnosed with carcinosarcoma. Case Presentation: A 63-year-old woman presented with abdominal pain and radiologic evidence of pelvic mass originating from the uterus, which was suggestive of sarcoma. Her Serum levels of Cancer Antigen 125 (CA125), Human Epididymis protein 4 (HE4), Cancer Antigen 19-9 (CA19-9), and Alpha Fetoprotein (AFP) were found to be elevated. She underwent total hysterectomy, bilateral salpingo-oophrectomy, and omentectomy. Pathologic examination of the specimens revealed a large uterine mass with serosal surface and omental invasion. The initial diagnosis was carcinosarcoma based on the mixed epithelial and mesenchymal components observed on microscopic examination. Triphasic components of papillary, primitive tubules, and glomeruloid structures, along with mesenchymal and blastemal elements were identified upon second opinion. An immunohistochemistry (IHC) study revealed positive reactions for WT1, CKAE1 /AE3, EMA, Glypican-3, and CD56 in all components of the tumor cells. P53 expression was normal. GATA3, ER, PR, and CD10 were negative. The final diagnosis was changed to WT. Conclusions: Uterine WT is an extremely rare malignancy, which could be associated with elevated serum AFP. Diagnosis and treatment of these rare tumors pose challenges for both pathologists and clinicians.

Inter-Ethnic Variations in the Clinical, Pathological, and Molecular Characteristics of Wilms Tumor.

Wilms tumor is the commonest primary renal malignancy in children and demonstrates substantial inter-ethnic variation in clinical, pathological, and molecular characteristics. Wilms tumor occurs at a lower incidence and at a younger age in Asians compared to Caucasians and Africans. Asians also present at an earlier stage of disease, with a higher incidence of favorable histology tumors and a lower incidence of perilobar nephrogenic rests compared to Caucasians, while African children present with more advanced disease. Studies have implicated population differences in the incidence of WT1 mutations, loss of imprinting of the IGF2 locus, and loss of heterozygosity of 1p/16q, or 1q gain as possible bases for epidemiological differences in the disease profile of Wilms tumors in various ethnic groups. Yet, evidence to support these associations is confounded by differences in treatment protocols and inequalities in the availability of treatment resources and remains limited by the quality of population-based data, especially in resource-limited settings.

Horseshoe kidney with teratoid type of Wilms tumor: a rare case report

BackgroundHorseshoe kidney is the most common renal fusion anomaly, and Wilms tumor is the most frequent renal malignancy in children. The occurrence of Wilms tumor in association with horseshoe kidney is a scarce anomaly. However, the arising of a teratoid type, which is a rare variant of Wilms tumor in a horseshoe kidney, is exceptionally unique.Case presentationThis report presents a 5-year-old male admitted with horseshoe kidney involved by a large heterogeneous calcified mass that was diagnose on biopsy as Wilms tumor blastemal dominant. According to the local and regional extension and metastatic tumor in the lungs, the patient underwent neoadjuvant chemotherapy and then surgery. Post-operative pathologic findings confirmed the diagnosis of teratoid Wilms tumor.ConclusionsThe occurrence of renal anomalies associated with a malignancy might be more frequent in the clinical environment. There are numerous differential diagnoses for renal tumors and masses, but the possibility of exceptional anomalies should not be denied, and clinicians should be prepared for these occasions. Although studies propose that chemotherapy has a trivial effect on teratoid Wilms tumors, it is essential to evaluate the tumor for any possibility of regression in non-teratoid regions before proceeding to upfront tumoral resection.

Perirenal Adipose Tissue: Clinical Implication and Therapeutic Interventions

Perirenal adipose tissue (PRAT) has been identified as an important factor in local and general homeostasis of the human body and is especially important in regulating renal and cardiovascular functions. It has also been identified as a crucial risk factor to consider in cardiovascular and renal disorders, malignancies, and various other diseases. Having a concrete idea of the effects of therapeutic interventions on the size and metabolism of the PRAT could prove highly beneficial. This review summarizes what is known about the PRAT and provides a collection of studies on the effects of therapeutic interventions on PRAT and its related diseases. We used papers written on a variety of subjects, mainly concerning adipose tissue and the effects of therapeutic procedures on it. Our main challenge was to excerpt the information specifically related to the PRAT in these papers. These effects vary greatly, from an increase or decrease in mass or size of the PRAT to changes in metabolism and drug residue accumulation. The current studies often fail to consider PRAT as an individual subject of research and only examine the adipose tissue of the entire body as a whole. This leads us to believe this field could benefit greatly from further research.

Double Trouble: A Case of Synchronous Breast and Renal Malignancies Associated with ATM Gene Mutation in a 41-Year-Old Filipino Female

Double Trouble: A Case of Synchronous Breast and Renal Malignancies Associated with ATM Gene Mutation in a 41-Year-Old Filipino Female

A rare presentation of antenatally diagnosed Wilms tumor: A case report

Background: Wilms’ tumor is the most common renal malignancy in children, with a peak incidence between 1 and 4 years of age. The prevalence of antenatal renal tumors is scarce, around 7 in 100,000 live births. We report a case of an antenatally diagnosed Wilms tumor. Case Presentation: A 2-month-old infant presented with a right renal lump since birth. The antenatal USG done at 35 weeks of gestation, showed an ill-defined heteroechoic area of size 57.3X29.9 mm at the upper pole of the right kidney, with few cystic areas with increased echogenicity. A right nephroureterectomy was done. It was WT1 and Vimentin positive and focally positive for Cyclin D1, whereas negative for Desmin, SMA, and PAX8, thus confirming the histopathological diagnosis of Wilms’ tumor. Conclusion: Antenatal Wilms’ tumor is rarely detected. A high degree of suspicion and active investigations should be conducted in antenatal and immediate neonatal periods for prompt decision-making and better outcomes.

60 Dissecting the Cellular and Epigenetic Landscape of Clear Cell Renal Cell Carcinoma Through Paired snRNA/ATAC-Seq Analysis

Abstract Background Clear cell renal cell carcinoma (ccRCC) stands as one of the most prevalent and aggressive forms of renal malignancies, accounting for a substantial portion of kidney cancer-related mortality worldwide. The heterogeneity within ccRCC poses a significant challenge to understanding its molecular mechanisms and devising effective therapeutic strategies. [1] Previous studies utilizing single nucleus RNA sequencing (snRNA-seq) have revealed transcriptional contributions to cell-type specificity in both mature human and mouse kidneys. Moreover, recent advancements have expanded this approach to single-cell profiling of chromatin accessibility. Single-nuclei assay for transposase-accessible chromatin using sequencing (snATAC-seq) has enabled the measurement of chromatin accessibility in thousands of individual cells, providing insights into the dynamic process that drives nephron development and differentiation. Integration and analysis of multimodal single-cell datasets, such as snRNA-seq and snATAC-seq, allows for the prediction of cell-type-specific cis-regulatory DNA interactions and transcription factor activity, complementing the transcriptional information obtained by snRNA-seq.[2] [3] [1] Yang, Wang, and Yang, “Treatment Strategies for Clear Cell Renal Cell Carcinoma.” [2] Muto et al., “Single Cell Transcriptional and Chromatin Accessibility Profiling Redefine Cellular Heterogeneity in the Adult Human Kidney.” [3] Monteagudo-Sánchez, Noordermeer, and Greenberg, “The Impact of DNA Methylation on CTCF-Mediated 3D Genome Organization.” Methods This study leveraged paired snRNA/ATAC-seq in tumor and normal-adjacent samples from the Renal Tumor Biobank at Dartmouth (n= 63) to explore the ccRCC landscape at single-cell resolution using 10x multiome technology. The snRNA-seq dataset was processed with Seurat v5.0 to remove low-quality nuclei. Doublets were removed with DoubletFinder v2.02, and ambient DNA was removed using decontX from celda. Normalization was conducted via SCTransform, and missing data was imputed with ALRA. Clustering was performed by constructing a KNN graph and running the Louvain algorithm. Cell type assignments were predicted using Azimuth with the human kidney reference dataset. The snATAC-seq data was processed with ArchR v1.0.1, which performed dimensionality reduction and clustering. Cluster identities defined in the Seurat workflow were cross-annotated to the ATAT-seq data, and open peaks were identified within these cell-type clusters using MACS3 v3.0.1. Identification of marker peaks, motif enrichment, and motif enrichment deviations were inferred utilizing ArchR’s getmarkerFeatures, peakAnnoEnrichment, and addMotifAnnotations functions, respectively. Results Motif enrichment analysis revealed canonical cancer-associated transcription factor (TF) dysregulation in tumor cells (nephron loop-like), including enrichment of HNF1B, SMARCC1, FOSL1, and JUND. Interestingly, HNF and SMARCC were also enriched in the lymphoid compartment, indicating possible crosstalk between these two cell types. Previous work has investigated the involvement of the HNF1 in ccRCC and in chromophobe RCC for prognosis,and we plan on investigating the relationship of these enrichments to tumor grade, stage and outcome.[1] Additional TF enrichments included BCL families and ELF within the myeloid compartment, and vascularization related TF families in endothelial cell types including enrichment of various ETS TFs. Investigation of cell-cell interactions between immune and endothelial cell populations as well as between tumor and normal adjacent tissues will be performed to further disentangle the role differentially accessable chromatin plays in ccRCC. [1] Buchner et al., “Downregulation of HNF-1B in Renal Cell Carcinoma Is Associated With Tumor Progression and Poor Prognosis.” Conclusions Our multi-omic approach has several advantages. First, it enables the characterization of cellular heterogeneity within the tumor microenvironment, identifying cell populations and their contributions to disease progression. Secondly, by integrating transcriptomic and epigenomic data, we gain insights into the dynamic interplay between gene expression and chromatin accessibility, uncovering potential therapeutic vulnerabilities and biomarkers for personalized treatment strategies. DOD CDMRP Funding: yes

Comparative Review of Standardized Incidence Ratio of Nonlymphoid, De Novo Malignancies After Liver Transplant Versus After Kidney Transplant.

De novo malignancies are the most common cause of death after solid-organ transplant. Here, we aimed to summarize standard incidence ratios of de novo malignancies after liver and kidney transplant within the same geographical locations, compare these ratios among differenttypes of de novo malignancies after liver and kidney transplant, and elucidate differences in de novo malignancies between liver and kidney transplant recipients. We performed a systematic review to identify studies on standard incidence ratios of de novo malignancies after liver and kidney transplant in the United Kingdom, Sweden, South Korea, and Taiwan. Four articles reported standard incidence ratios of de novo malignancies in 14 016 liver transplant recipients (mean follow-up 4.3 ± 0.7 y) and 48179 kidney transplant recipients (mean follow-up 6.1 ± 2.1 y). Mean ratios of oropharyngeal, pulmonary, colorectal, renal, and breast malignancies were 5.3, 1.6, 1.9, 1.8, and 1.1,respectively, after liver transplant and 3.2, 1.7, 1.5, 17.0, and 1.3, respectively, after kidney transplant. Mean ratios of bladder, cervixuterus, and stomach de novo malignancies were 1.8, 2.0, and 2.9, respectively, after liver transplant and 13.0, 1.9, and 1.9,respectively, after kidney transplant. Mean ratios of prostatic and esophageal malignancies were 1.6 and 1.8 after liver transplant and 1.2 and 1.1 after kidney transplant. Mean ratio of ovarian cancer was 1.2 and 2.9, respectively, after liver and kidney transplant. Low-frequency and lower standard incidence ratios were observed for testicular, ovarian and central nervous system malignancies after kidney and liver transplant. Standard incidence ratios of oropharyngeal and hepatic malignancies were higher after liver transplant compared with kidney transplant. After kidney transplant, standardized ration for renal malignancy were 9.4 times and bladder malignancies were 7.2 times higher compared with liver transplant recipients.

Lenvatinib plus pembrolizumab for untreated advanced renal cell carcinoma: a systematic review and cost-effectiveness analysis.

Renal cell carcinoma is the most common type of kidney cancer, comprising approximately 85% of all renal malignancies. Patients with advanced renal cell carcinoma are the focus of this National Institute for Health and Care Excellence multiple technology appraisal. A patient's risk of disease progression depends on a number of prognostic risk factors; patients are categorised as having intermediate/poor risk or favourable risk of disease progression. The objectives of this multiple technology appraisal were to appraise the clinical effectiveness and cost-effectiveness of lenvatinib plus pembrolizumab versus relevant comparators listed in the final scope issued by the National Institute for Health and Care Excellence: sunitinib, pazopanib, tivozanib, cabozantinib and nivolumab plus ipilimumab. The assessment group carried out clinical and economic systematic reviews and assessed the clinical and cost-effectiveness evidence submitted by Eisai, Hatfield, Hertfordshire, UK (the manufacturer of lenvatinib) and Merck Sharp & Dohme, Whitehouse Station, NJ, USA (the manufacturer of pembrolizumab). The assessment group carried out fixed-effects network meta-analyses using a Bayesian framework to generate evidence for clinical effectiveness. As convergence issues occurred due to sparse data, random-effects network meta-analysis results were unusable. The assessment group did not develop a de novo economic model, but instead modified the partitioned survival model provided by Merck Sharp & Dohme. The assessment group clinical systematic review identified one relevant randomised controlled trial (CLEAR trial). The CLEAR trial is a good-quality, phase III, multicentre, open-label trial that provided evidence for the efficacy and safety of lenvatinib plus pembrolizumab compared with sunitinib. The assessment group progression-free survival network meta-analysis results for all three risk groups should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons owing to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. The assessment group overall survival network meta-analysis results for the intermediate-/poor-risk subgroup suggested that there was a numerical, but not statistically significant, improvement in the overall survival for patients treated with lenvatinib plus pembrolizumab compared with patients treated with cabozantinib or nivolumab plus ipilimumab. Because of within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption, the assessment group overall survival network meta-analysis results for the favourable-risk subgroup and the all-risk population should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons. Only one cost-effectiveness study was included in the assessment group review of cost-effectiveness evidence. The study was limited to the all-risk population, undertaken from the perspective of the US healthcare system and included comparators that are not recommended by the National Institute for Health and Care Excellence for patients with untreated advanced renal cell carcinoma. Therefore, the extent to which resource use and results are generalisable to the NHS is unclear. The assessment group cost-effectiveness results from the modified partitioned survival model focused on the intermediate-/poor-risk and favourable-risk subgroups. The assessment group cost-effectiveness results, generated using list prices for all drugs, showed that, for all comparisons in the favourable-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated fewer benefits than all other treatments available to NHS patients. For the intermediate-/poor-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated more benefits than treatment with cabozantinib and nivolumab plus ipilimumab. Good-quality clinical effectiveness evidence for the comparison of lenvatinib plus pembrolizumab with sunitinib is available from the CLEAR trial. For most of the assessment group Bayesian hazard ratio network meta-analysis comparisons, it is difficult to reach conclusions due to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. However, the data (clinical effectiveness and cost-effectiveness) used to populate the economic model are relevant to NHS clinical practice and can be used to inform National Institute for Health and Care Excellence decision-making. The assessment group cost-effectiveness results, generated using list prices for all drugs, show that lenvatinib plus pembrolizumab is less cost-effective than all other treatment options. This study is registered as PROSPERO CRD4202128587. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis Programme (NIHR award ref: NIHR134985) and is published in full in Health Technology Assessment; Vol. 28, No. 49. See the NIHR Funding and Awards website for further award information.

Insights into Personalized Care Strategies for Wilms Tumor: A Narrative Literature Review.

Wilms tumor (WT), or nephroblastoma, is the predominant renal malignancy in the pediatric population. This narrative review explores the evolution of personalized care strategies for WT, synthesizing critical developments in molecular diagnostics and treatment approaches to enhance patient-specific outcomes. We surveyed recent literature from the last five years, focusing on high-impact research across major databases such as PubMed, Scopus, and Web of Science. Diagnostic advancements, including liquid biopsies and diffusion-weighted MRI, have improved early detection precision. The prognostic significance of genetic markers, particularly WT1 mutations and miRNA profiles, is discussed. Novel predictive tools integrating genetic and clinical data to anticipate disease trajectory and therapy response are explored. Progressive treatment strategies, particularly immunotherapy and targeted agents such as HIF-2α inhibitors and GD2-targeted immunotherapy, are highlighted for their role in personalized treatment protocols, especially for refractory or recurrent WT. This review underscores the necessity for personalized management supported by genetic insights, with improved survival rates for localized disease exceeding 90%. However, knowledge gaps persist in therapies for high-risk patients and strategies to reduce long-term treatment-related morbidity. In conclusion, this narrative review highlights the need for ongoing research, particularly on the long-term outcomes of emerging therapies and integrating multi-omic data to inform clinical decision-making, paving the way for more individualized treatment pathways.

Failure of the PD-1 Blocking Agent Pembrolizumab to Benefit a Patient with Renal Squamous Cell Cancer.

Renal squamous cell carcinoma (SCC) is a neoplasm with an extremely rare occurrence compared to other renal malignancies. The classic presentation includes a palpable mass and flank pain; however, the presentation is seldom non-specific. Our study describes the significance of programmed death ligand-1 (PD-L1) expression in renal cancer and its association with clinical outcomes, alongside available treatment options. An 80-year-old female with a history of hypertension and cerebral aneurysm presented with right flank pain and blood in urine and was diagnosed with pyelonephritis and left renal mass/phlegmon. A biopsy revealed SCC of the kidney with metastasis to the lung and aortocaval lymph node. Positron emission tomography (PET) scan confirmed malignancy in the kidney and lung. Treatment with pemrolizumab and carboplatin plus paclitaxel was initiated but poorly tolerated as the haemoglobin dropped rapidly. SCC poses a diagnostic challenge due to its rarity and non-specific symptoms, often leading to advanced stage diagnosis. PD-L1 expression is pivotal in assessing tumour aggressiveness and prognosis. PD-L1 inhibitors offer promise, but their efficacy in renal SCC warrants further investigation. Radical nephrectomy and systemic chemotherapy show potential in advanced cases, necessitating vigilant management of treatment-related side effects. This case emphasises the need for ongoing research to refine therapeutic approaches and enhance outcomes in renal SCC patients. PD-L1 expression is pivotal in assessing tumour aggressiveness and prognosis of renal cell carcinoma.PD-L1 inhibitors hold promise as a therapeutic intervention in renal squamous cancer.Radical nephrectomy and systemic chemotherapy show potential in managing advanced renal cancer.