Staging Of Renal Cell Carcinoma Research Articles

12 Concordance Analysis of Tissue and Circulating Tumor DNA (ctDNA) in Renal Cell Carcinoma (RCC): Insights from a Multimodal Real-World Database

Abstract Background Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) has emerged as a powerful complement to tissue NGS, offering a noninvasive and serially conductible test. Its application holds promise in enhancing the assessment of spatial and temporal molecular tumor heterogeneity, thus providing valuable insights into cancer progression and treatment response. In this study, we explore the mutational landscape of renal cell carcinoma (RCC) patients through comprehensive profiling of mutations in ctDNA and matched tissue samples, aiming to elucidate the concordance and clinical significance of molecular alterations detected in both circulating and tissue-derived DNA. Methods From the Tempus multimodal database, we retrospectively analyzed de-identified NGS data from patients with RCC that had dual tissue (Tempus xT, 648 genes) and ctDNA testing (Tempus xF, 105 genes). Patients with matched samples (collected +/- 90 days of one another) were included. We evaluated socio-demographic and clinical characteristics and select pathogenic somatic short variants (PSSV) and copy number variants [(amplifications and deletions, two copy number losses (CNL)]. Concordance analyses were restricted to the 105 genes tested on the ctDNA panel and further restricted to short variants, with the exception of amplifications and CNL detected by both xF and xT. Analysis was further stratified by metastatic status (n=260, metastatic, n=120 non-metastatic) prior to collection of both xT and xF. Results Among all patients (n=393), the median age was 61 years, and 71% were male. The patient cohort comprised a diverse population based on race, with 75% white, 12% African American, 4.8% Asian and 8% others. The median time from tissue to blood collection was 21 days (IQR, 7, 39). 67% (n=265) and 68% (n=266) had metastatic disease at the time of tissue and blood collection, respectively. The most common tissue sites were kidney (49%, n=189), bone (11%, n=43), lung (9%, n=34), lymph node (8%, n=29), liver (6%, n=23), and brain/CNS (4%, n=17). Genes harboring the most common PSSV in tissue included VHL (59% n=232), PBRM1 (31%, n=123), SETD2 (23%, n=91), TP53 (14%, n=54), BAP1 (12%, n=46) and TERT (11%, n=45). Genes with common PSSV in ctDNA included TP53 (23%, n=91), VHL (18%, n=69), BAP1 (6%, n=23), PBRM1 (5%, n=21), PTEN (4%, n=15), KRAS (4%, n=14) and NF2 (4%, n=14). The combination of tissue and ctDNA testing increased the detection of mutations (Table 1). There was higher concordance between somatic alterations in select genes among patients with metastases vs. non-metastases, including BAP1 (55.9% vs. 9.1%), TP53 (36.8% vs. 9.1%), VHL (32.3% vs. 12.5%), ARID1A (25% vs. 16.7%), and ATM (25% vs. 0%). Table 1: Detection of genetic mutations in tissue and ctDNA testing Conclusions The analysis conducted in this study highlights the complementary nature of ctDNA profiling alongside tissue-based NGS in RCC, demonstrating an increased detection of mutations. Particularly, we observed a higher concordance between ctDNA and tissue profiling in individuals with metastatic disease, suggesting the potential utility of ctDNA analysis in advanced stages of RCC. Further research is warranted to elucidate how longitudinal ctDNA analysis can delineate biomarkers of response and resistance at both the mutation and ctDNA fraction levels. Understanding these dynamics could offer valuable insights into disease progression and guide personalized treatment strategies for RCC patients. DOD CDMRP Funding: no

Interaction between microglial cells and CD1C+ B dendritic cells leads to CD8+ T cells depletion during the early stages of renal clear cell carcinoma.

Renal clear cell carcinoma (RCC) is a type of malignant tumor, which, in addition to surgical resection, radiotherapy, and chemotherapy, has been widely treated through immunotherapy recently. However, the influence of the tumor microenvironment and the infiltrating immune cells within it on immunotherapy remains unclear. It is imperative to study the interactions between various immune cells of RCC. The scRNA-seq dataset from GEO's database was used to analyze the immune cells present in tumor tissue and peripheral blood samples. Through quality control, clustering, and identification, the types and proportions of infiltrating immune cells were determined. The cellular differences were determined, and gene expression levels of the differentially present cells were investigated. A protein-protein interaction network analysis was performed using string. KEGG and GO analyses were performed to investigate abnormal activities. The microglia marker CD68 and CD1C+ B dendritic cells marker CD11C were detected using multiplex immunofluorescence staining. Many depleted CD8+ T cells (exhausted CD8+ T cells) appeared in tumor tissues as well as microglia. CD1C+ B dendritic cells did not infiltrate tumor tissues. HSPA1A was correlated with DNAJB1 in microglia. Compared with Paracancer tissues, microglia increased while CD1C+ B dendritic cells decreased in pathological stages I and I-II in cancerous tissues. An altered tumor microenvironment caused by increases in microglia in RCC in the early stage resulted in an inability of CD1C+ B dendritic cells to infiltrate, resulting in CD8+ T cells being unable to receive the antigens presented by them, and in turn being depleted in large quantities.

Retroperitoneal laparoscopic radical nephrectomy in the treatment of renal cancer: a 5-year single-center experience in resource-scare setting

Based on a retrospective hospital-based analysis, this study examines the results of retroperitoneal laparoscopic radical nephrectomy for patients with T1-T2 renal cell carcinoma (RCC) from January 2019 to December 2023. Of the 73 patients, 4.1% had TNM stage II tumors and 95.8% had TNM stage I tumors (53.4% T1a and 42.4% T1b). In terms of frequency, clear cell RCC accounted for 84.9%, with papillary RCC coming in at 9.6% and chromophobe RCC at 4.1%. Following surgery, four patients experienced fevers, one needed a blood transfusion, two had infections, and one had emergency surgery. Lumbar masses and hematuria were absent in all patients. Subsequent metastatic lesions and abnormalities of the renal fossa were not observed on follow-up ultrasounds. 4.1% of the deaths after 25.9 months were due to the disease, and 1.4% were caused by accidents. At one, two, three, and four years, the cumulative survival rates were 100%, 97.2%, and 92.8%, respectively. 48.1 months was the mean postoperative survival period. For RCC stages T1-2, retroperitoneal laparoscopic radical nephrectomy offers significant benefits and comparable results to open surgery.

Cytotoxic T lymphocyte associated antigen-4 (CTLA4) expression with renal cell carcinoma subtype and staging

In Indonesia, approximately 45% of renal cell carcinoma (RCC) patients are at an advanced stage that requires checkpoint inhibition combination immunotherapy. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is associated with poor prognosis of RCC and it is the first checkpoint developed in cancer immunotherapy. This study aimed to investigate CTLA-4 expression among RCC subtypes and staging. Formalin fixed paraffin embedded (FFPE) tissue of RCC patients from 2018-2020 were obtained from the Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta. Expression of CTLA-4 among RCC subtypes and stage was measured using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and compared. Among the 40 patients involved in this study, the CTLA-4 expression was higher in papillary RCC/pRCC (95.88 + 31.58) compared to clear cell RCC/ccRCC (90.94 + 43.05). However, no significantly different in CTL-4 expression based on histologic subtypes and tumor stage (p>0.05). In conclusion, neither the histologic subtype nor the tumor stage of RCC can be predicted by CTLA-4 expression.

Pulmonary lesion after surgery for renal cancer: progression or new primary?

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). 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. 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 (55months [32.8-107.2] vs. 20months [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 20mm. 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 10.9years (95% CI 3.3-not reached) for LC and a 3.8years (95% CI 3.2-8.4) for RCCM + . The median OS time was 6.5years (95% CI 4.4-not reached) for LC and 6years (95% CI 4.3-11.6) for RCCM + . 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.

Update on Renal Cell Carcinoma Diagnosis with Novel Imaging Approaches.

This review highlights recent advances in renal cell carcinoma (RCC) imaging. It begins with dual-energy computed tomography (DECT), which has demonstrated a high diagnostic accuracy in the evaluation of renal masses. Several studies have suggested the potential benefits of iodine quantification, particularly for distinguishing low-attenuation, true enhancing solid masses from hyperdense cysts. By determining whether or not a renal mass is present, DECT could avoid the need for additional imaging studies, thereby reducing healthcare costs. DECT can also provide virtual unenhanced images, helping to reduce radiation exposure. The review then provides an update focusing on the advantages of multiparametric magnetic resonance (MR) imaging performance in the histological subtyping of RCC and in the differentiation of benign from malignant renal masses. A proposed standardized stepwise reading of images helps to identify clear cell RCC and papillary RCC with a high accuracy. Contrast-enhanced ultrasound may represent a promising diagnostic tool for the characterization of solid and cystic renal masses. Several combined pharmaceutical imaging strategies using both sestamibi and PSMA offer new opportunities in the diagnosis and staging of RCC, but their role in risk stratification needs to be evaluated. Although radiomics and tumor texture analysis are hampered by poor reproducibility and need standardization, they show promise in identifying new biomarkers for predicting tumor histology, clinical outcomes, overall survival, and the response to therapy. They have a wide range of potential applications but are still in the research phase. Artificial intelligence (AI) has shown encouraging results in tumor classification, grade, and prognosis. It is expected to play an important role in assessing the treatment response and advancing personalized medicine. The review then focuses on recently updated algorithms and guidelines. The Bosniak classification version 2019 incorporates MRI, precisely defines previously vague imaging terms, and allows a greater proportion of masses to be placed in lower-risk classes. Recent studies have reported an improved specificity of the higher-risk categories and better inter-reader agreement. The clear cell likelihood score, which adds standardization to the characterization of solid renal masses on MRI, has been validated in recent studies with high interobserver agreement. Finally, the review discusses the key imaging implications of the 2017 AUA guidelines for renal masses and localized renal cancer.

Label-Free SERS of Urine Components: A Powerful Tool for Discriminating Renal Cell Carcinoma through Multivariate Analysis and Machine Learning Techniques.

The advent of Surface-Enhanced Raman Scattering (SERS) has enabled the exploration and detection of small molecules, particularly in biological fluids such as serum, blood plasma, urine, saliva, and tears. SERS has been proposed as a simple diagnostic technique for various diseases, including cancer. Renal cell carcinoma (RCC) ranks as the sixth most commonly diagnosed cancer in men and is often asymptomatic, with detection occurring incidentally. The onset of symptoms typically aligns with advanced disease, aggressive histology, and unfavorable prognosis, and therefore new methods for an early diagnosis are needed. In this study, we investigated the utility of label-free SERS in urine, coupled with two multivariate analysis approaches: Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) and Support Vector Machine (SVM), to discriminate between 50 RCC patients and 44 healthy donors. Employing LDA-PCA, we achieved a discrimination accuracy of 100% using 13 principal components, and an 88% accuracy in discriminating between different RCC stages. The SVM approach yielded a training accuracy of 100%, a validation accuracy of 99% for discriminating between RCC and controls, and an 80% accuracy for discriminating between stages. The comparative analysis of raw and normalized SERS spectral data shows that while raw data disclose relative concentration variations in urine metabolites between the two classes, the normalization of spectral data significantly improves the accuracy of discrimination. Moreover, the selection of principal components with markedly distinct scores between the two classes serves to alleviate overfitting risks and reduces the number of components employed for discrimination. We obtained the accuracy of the discrimination between the RCC patients cases and healthy donors of 90% for three PCs and a linear discrimination function, and a 88% accuracy of discrimination between stages using six PCs, mitigating practically the risk of overfitting and increasing the robustness of our analysis. Our findings underscore the potential of label-free SERS of urine in conjunction with chemometrics for non-invasive and early RCC detection.

Abstract 2509: Abundant glucocorticoid receptor (GR) expression in human tumors: A tissue microarray study on more more than 18,000 tumors

Abstract The glucocorticoid receptor (GR, or GCR) is a nuclear receptor protein for cortisol and other glucocorticoids and regulates the transcription of thousands of genes involved in metabolism, development, stress, and inflammatory response. In cancer, both an oncogenic and a tumor suppressive function of GR has been proposed. To comprehensively evaluate GR expression in normal and tumorous tissues, a tissue microarray containing 18,570 samples from 147 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). GR positivity was found in 76.3% of 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity of at least a fraction of tumors was found in all 147 analyzed tumor types and at least one strongly GR positive tumor was found in 136 tumor types. 77 of our 147 tumor entities showed GR positivity of variable intensity in all analyzed cases. 43 further tumor entities showed GR positivity in 80-99.9% of cases. 21 tumor entities had a GR positivity rate between 50 and 80%, including urothelial carcinoma as well as gastric and esophageal adenocarcinoma. Only 6 tumor types had less than 50% GR positive. These included adenomas (21.7-32.5%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum. Reduced GR staining was significantly associated with adverse histopathological and clinical features in several tumor types. Low GR expression was linked to grade progression in pTa (p&amp;lt;0.0001) and to nodal metastasis in pT2-4 urothelial carcinoma of the urinary bladder (p=0.0051), advanced pT stage (p=0.0006) and estrogen receptor positivity (p=0.0126) in breast carcinomas of no special type (NST), as well as to high grade (p≤0.0076), advanced pT stage (p&amp;lt;0.0001), distant metastasis (p=0.0081), and poor overall survival (p=0.002) in clear cell renal cell carcinoma. GR expression was unrelated to clinic-pathological parameters in gastric, pancreatic, and colorectal adenocarcinoma as well as in serous high-grade carcinoma of the ovary. In summary, our data demonstrate frequent GR expression across all cancer types. Significant associations between reduced GR expression and unfavorable tumor features in some but not all tumor types suggest that the functional importance of GR regulated genes for cancer progression depends on the cell of tumor origin. Citation Format: Christina Tsourlakis, Frederike Wegener, Katharina Möller, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Till Krech, Christoph Fraune, Natalia Gorbokon, Maximilian Lennartz, Sarah Minner, Florian Viehweger. Abundant glucocorticoid receptor (GR) expression in human tumors: A tissue microarray study on more more than 18,000 tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2509.

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1–4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1–2) or a high-grade group (WHO/ISUP grade 3–4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5–18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6–17.4) in the high-grade group and 28.0 months (21.1–34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0–10.0) for the high-grade group and 10.0 months (6.8–13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135–2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Tumor characteristics associated with detectable circulating tumor DNA preoperatively in patients with renal masses suspicious for RCC.

461 Background: Understanding the specific tumor characteristics associated with detectable ctDNA in the blood of patients with renal cell carcinoma (RCC) is critical to informing future studies seeking to establish the clinical utility of such testing. We characterized pathological and clinical characteristics associated with ctDNA detected preoperatively in patients with renal masses suspicious of RCC. Methods: Using our single institution prospectively maintained database, we identified consecutive patients who underwent partial or radical nephrectomy for non-metastatic suspected RCC (stages cT1b-cT3) during 2022-2023. Included were patients who had undergone tumor-informed ctDNA testing using the commercial Signatera assay (Natera). Baseline characteristics, pathology results, imaging study results, and oncological treatment and follow-up data were collected from the electronic medical records. ctDNA results were collected through the Natera portal. Study findings were reported using descriptive statistics. A p-value of &lt;0.05 was considered statistically significant. R programming language version 4.3 was used for all statistical analyses. Results: A total of 54 patients with a median age of 63 years (IQR 51-71) were included in the study. Twenty-one (39%) were women. The median follow-up time was 4 months (range: 1-21 months). Among the 54 patients, 27 (50%) had detectable ctDNA pre-operatively Post-operative results were available for 33 patients, and 3 (9%) had detectable tDNA (of those 2 had Inferior vena cava involvement). The first patient developed metastatic disease. The two other patients are receiving adjuvant immunotherapy. Analysis of 50 patients with solely malignant RCC revealed that patients with detectable versus undetectable ctDNA were older 67 vs. 54 years (p=0.03), had a higher pathological stage (p= 0.002), larger tumors (7.2 vs. 4.7 cm, p = 0.004), and higher pathological grade (grade 3-4 vs. grade 1-2; p=0.035) (Table 1). All the patients with renal vein or inferior vena cava involvement had detectable ctDNA (n=8). Conclusions: In our cohort, preoperative ctDNA was detectable in 50% of patients with suspected clinically localized RCC. Detectable ctDNA preoperatively correlated with clinically relevant features. The ability of preoperative ctDNA to predict recurrence and survival in patients with clinically localized RCC warrants further evaluation. [Table: see text]

Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma.

Renal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investigation, in silico multiepitope vaccines were constructed by linking specific CD70 protein epitopes for helper T lymphocytes and CD8+ T lymphocytes. To enhance immunogenicity, sequences of cell-penetrating peptide (CPP), penetratin (pAntp), along with the entire sequence of tumor necrosis factor-α (TNF-α), were attached to the N-terminal and C-terminal of the CD70 epitopes. Computational assessments were performed on these chimeric vaccines for antigenicity, allergenicity, peptide toxicity, population coverage, and physicochemical properties. Furthermore, refined 3D constructs were subjected to a range of analyses, encompassing structural B-cell epitope prediction and molecular docking. The chosen vaccine construct underwent diverse assessments such as molecular dynamics simulation, immune response simulation, and in silico cloning. All vaccines comprised antigenic, nontoxic, and nonallergenic epitopes, ensuring extensive global population coverage. The vaccine constructs demonstrated favorable physicochemical characteristics. The binding affinity of chimeric vaccines to the TNF receptor remained relatively stable, influenced by the alignment of vaccine components. Molecular docking and dynamics analyses predicted stable interactions between CD70-CPP-TNF and the TNF receptor, indicating potential efficacy. In silico codon optimization and cloning of the vaccine nucleic acid sequence were accomplished using the pET28a plasmid. Furthermore, this vaccine displayed the capacity to modulate humoral and cellular immune responses. Overall, the results suggest therapeutic potential for the chimeric CD70-CPP-TNF vaccine against RCC. However, validation through in vitro and in vivo experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.

Correlation between PD-L1 and Ki-67 Expression at various T-stage Clear Cell Renal Cell Carcinomas

Renal cell carcinoma (RCC) is a malignant neoplasm originating from renal epithelium, with the clear cell renal cell carcinoma (ccRCC)being the most common type (80%) and the most common cause of death among other types of kidney cancer. Pathological stage is an important parameter that affects ccRCC survival, followed by nuclear grade. Pathological staging of RCC according to the AJCC (American Joint Committee on Cancer) TNM system 8th edition is based on local extension of the main tumor (T), involvement of lymph node (N), and metastasis (M). Ki-67 is a marker of proliferation used to assess tumor grade. High Ki-67 correlates with poor prognosis, advanced clinical and pathological features, thus Ki-67 can be used as a biomarker in the management of RCC.Ki-67 is routinely used to see the proliferation index in various cases of malignancy, but not in kidney malignancy. Programmed death ligand 1 (PD-L1) acts as a negative regulator of T cell-mediated anti-tumor immune responses. PD-L1 is expressed on T cells, B cells, macrophages, dendritic cells, endothelial cells and in various tumor cells including ccRCC. This study aims to determine the correlation between the expression of PD-L1 and Ki-67 in various T-stage clear cell renal cell carcinomas. Material and Method: This was an observational analytical study with cross-sectional approach toward 52 cases of ccRCC whose diagnosis was made histopathologically at the Anatomical Pathology Installation of Dr. Soetomo General Academic Hospital Surabaya from January 2014 to December 2020. Immunohistochemical stainingwas carried out using Ki-67 and PD-L1 antibodies, followed by an assessment using a scoring system. T-stage data were obtained from the patients’ medical recordswhich were then analyzed statistically with the Spearman test. Result: The study included 52 cases of ccRCC obtained from nephrectomy specimens at RSUD dr. Soetomo between 2014–2020. The age distribution of the subjects was 29–69 years and the mean and median age was 53 years. The ratio of male patients compared to female patients was 2.5:1. The majority was stage T2 (50%). Statistical test results showed no correlation between the expression of PD-L1 and Ki-67 in various T-stage clear cell renal cell carcinomas (p=0.965 and p=0.680). Conclusion: This study showed no correlation between the expression of PD-L1 and Ki-67 in various T-stage clear cell renal cell carcinomas. Nonetheless PD-L1 can be considered as an important biomarker with a poorer prognosis and aggressive clinicopathological findings in patients with RCC.

Self-Assembled Hyperbranched Gold Nanoarrays Decode Serum United Urine Metabolic Fingerprints for Kidney Tumor Diagnosis.

Serum united urine metabolic analysis comprehensively reveals the disease status for kidney diseases in particular. Thus, the precise and convenient acquisition of metabolic molecular information from united biofluids is vitally important for clinical disease diagnosis and biomarker discovery. Laser desorption/ionization mass spectrometry (LDI-MS) presents various advantages in metabolic analysis; however, there remain challenges in ionization efficiency and MS signal reproducibility. Herein, we constructed a self-assembled hyperbranched black gold nanoarray (HyBrAuNA) assisted LDI-MS platform to profile serum united urine metabolic fingerprints (S-UMFs) for diagnosis of early stage renal cell carcinoma (RCC). The closely packed HyBrAuNA afforded strong electromagnetic field enhancement and high photothermal conversion efficacy, enabling effective ionization of low abundant metabolites for S-UMF collection. With a uniform nanoarray, the platform presented excellent reproducibility to ensure the accuracy of S-UMFs obtained in seconds. When it was combined with automated machine learning analysis of S-UMFs, early stage RCC patients were discriminated from the healthy controls with an area under the curve (AUC) > 0.99. Furthermore, we screened out a panel of 9 metabolites (4 from serum and 5 from urine) and related pathways toward early stage kidney tumor. In view of its high-throughput, fast analytical speed, and low sample consumption, our platform possesses potential in metabolic profiling of united biofluids for disease diagnosis and pathogenic mechanism exploration.

The Value of Radiological Imaging in Assessing Extrarenal Fat and Renal Vein Invasion in Renal Cell Carcinoma.

Renal cell carcinoma with extrarenal fat (perinephric or renal sinus fat) and renal vein invasion is the main evidence for the T3a stage according to the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. Extrarenal fat invasion of renal cell carcinoma is defined as the presence of perinephric fat invasion or renal sinus fat invasion. Renal vein invasion is defined as the presence of main or segmental (branch) renal vein invasion. Accurate assessment of extrarenal fat and renal vein invasion is crucial for urologists to adopt the optimal therapeutic schedule, including radical nephrectomy or nephron-sparing treatments. Currently, imaging is still the most widely used means of examination for diagnosis and staging of renal cell carcinoma, especially multidetector computed tomography (MDCT). Therefore, we have, herein, summarized the latest progress and the future direction regarding imaging for assessing perinephric or renal sinus fat and renal vein invasion of renal cell carcinoma to assist clinical treatment selection and patient risk stratification.

Association between CT-based adipose variables, preoperative blood biochemical indicators and pathological T stage of clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is corelated with tumor-associated material (TAM), coagulation system and adipocyte tissue, but the relationships between them have been inconsistent. Our study aimed to explore the cut-off intervals of variables that are non-linearly related to ccRCC pathological T stage for providing clues to understand these discrepancies, and to effectively preoperative risk stratification. MethodsThis retrospective analysis included 218 ccRCC patients with a clear pathological T stage between January 1st, 2014, and November 30th, 2021. The patients were categorized into two cohorts based on their pathological T stage: low T stage (T1 and T2) and high T stage (T3 and T4). Abdominal and perirenal fat variables were measured based on preoperative CT images. Blood biochemical indexes from the last time before surgery were also collected. The generalized sum model was used to identify cut-off intervals for nonlinear variables. ResultsIn specific intervals, fibrinogen levels (FIB) (2.63–4.06 g/L) and platelet (PLT) counts (>200.34 × 109/L) were significantly positively correlated with T stage, while PLT counts (<200.34 × 109/L) were significantly negatively correlated with T stage. Additionally, tumor-associated material exhibited varying degrees of positive correlation with T stage at different cut-off intervals (cut-off value: 90.556 U/mL). ConclusionPreoperative PLT, FIB and TAM are nonlinearly related to pathological T stage. This study is the first to provide specific cut-off intervals for preoperative variables that are nonlinearly related to ccRCC T stage. These intervals can aid in the risk stratification of ccRCC patients before surgery, allowing for developing a more personalized treatment planning.

Preserving Renal Function without Compromising Oncological Outcomes: A Comparative Study of Partial and Total Nephrectomies in T3 Stage Renal Cell Carcinoma.

The utility of partial nephrectomy (PN) in locally advanced, stage T3 renal cell carcinoma (RCC) is controversial. This retrospective study aimed to review the oncological and functional outcomes of patients with T3a RCC who underwent PN. We included all patients with pT3a stage RCC undergoing either open, laparoscopic, or robotic PN at our center between January 2015 and 2023. A Wilcoxon rank sum test was utilized to compare nephrectomy types (radical nephrectomy [RN] vs PN). Survival analysis was conducted using Kaplan-Meier plots and a log-rank test. P-value < 0.05 indicated statistical significance. There were no significant differences in demographic characteristics between the RN and PN groups, except age (53.0 vs 6.5, respectively; P = 0.012) and body mass index (28.7 vs 34.3, respectively; P = 0.020). Furthermore, there were also no significant differences in the rates of local recurrence (P = 0.597), metastatic progression (P = 0.129), and chemotherapy use (P = 0.367) between nephrectomy types. Patient survival did not differ significantly based on the type of nephrectomy (log-rank P-value = 0.852). Together, our findings indicated that PN and RN yield near-equivalent oncological outcomes in terms of local recurrence, metastasis, and overall survival rates among pT3a RCC patients during a nearly 3-year follow-up period.

Impact of the COVID-19 pandemic on diagnosis of renal cell carcinoma and disease stage at presentation.

Renal cell carcinoma (RCC) is often associated with significant morbidity and mortality, with overall survival contingent on multiple factors - most importantly, disease stage at diagnosis. Disruptions in healthcare delivery during the COVID-19 pandemic have resulted in various reported diagnostic and treatment delays, which have had detrimental impacts on malignancies such as RCC. Surgically managed cases of RCC at our center were identified using a retrospective chart review of all nephrectomies conducted from March 1, 2018, to February 28, 2023. Examination of disease characteristics in three time period cohorts (before, during, and following the COVID-19 pandemic) was undertaken. Timeframes were consistent with implementation and abolition of public health restrictions in the province of Newfoundland and Labrador. A total of 483 surgically managed RCC cases were identified during the study period. The median age was 65 years (interquartile range [IQR] 56-71), and 62.3% of patients were male. Demographics did not vary across timeframes. Before and during the pandemic, pathologic stage 3 (pT3) disease was reported in 38.9% and 35.4% of cases, respectively, whereas the post-pandemic period saw this presentation in 50.0% of patients. Surgical wait times increased significantly across study timeframes (p=0.003). The first year following the COVID-19 pandemic saw an 11.1% increase in patients presenting with pT3 RCC. These findings are suggestive of a clinically significant stage migration, which paired with prolonged wait times for surgery, provide critical consideration in the urgency of diagnostic and treatment decisions for RCC in the immediate future.

Long-Term Survival of Patients with Stage T1N0M1 Renal Cell Carcinoma.

Metastatic renal cell carcinoma (RCC) is among the most lethal urological malignancies. However, small, localized RCCs (≤7 cm, stage T1) have an excellent prognosis. There is a rare patient subgroup diagnosed with synchronous distant metastasis (T1N0M1), of which very little is known in terms of survival outcomes and underlying disease biology. Herein, we examined the long-term survival of 27 patients with clear cell RCC (ccRCC) stage T1N0M1 in comparison to 18 patients without metastases (T1N0M0). Tumor tissue was stained by immunohistochemistry for CD8+ tumor infiltrating lymphocytes (TILs). As expected, patients with stage T1N0M1 showed a significantly worse median cancer specific survival (CSS; 2.8 years) than patients with stage T1N0M0 (17.7 years; HR 0.077; 95% CI, 0.022-0.262). However, eight patients (29.6%) with ccRCC stage T1N0M1 survived over five years, and three of those patients (11.1%) survived over a decade. Some of these patients benefitted from an intensified, multimodal treatment including metastasis-directed therapy. The number of CD8+ TILs was substantially higher in stage T1N0M1 ccRCCs than in stage T1N0M0 ccRCCs, suggesting a more aggressive tumor biology. In conclusion, long-term survival is possible in patients with ccRCC stage T1N0M1, with some patients benefitting from an intensified, multimodal treatment approach.

LONG TERM OUTCOME OF LAPAROSCOPIC RADICAL NEPHRECTOMY FOR PATHOLOGICAL T1, T2 RENAL CELL CANCER AT VIET DUC HOSPITAL

Background: To evaluation of the long term outcome of laparoscopic radical nephrectomy for pathological T1, T2 renal cell cancer at Viet Duc Hospital. Methods: We retrospectively identified 73 patients who underwent RN between 2015 and 2022. We divided patients into three groups based on tumour size: &lt;4 cm, 4– 7 cm, &gt;7 cm. Clinical and paraclinical characteristics include age, gender, back pain, tumor size, tumor location, disease stage on computed tomography scans, histopathological results, postoperative outcomes and complications, postoperative survival time, and accumulated survival time. Results: the average age was 53.52 ± 12.17 years. CT scans classified renal cell carcinoma stages preoperatively according to IUAC 2009: 53.4% were stage T1a, 42.4% were stage T1b, 2.8% were stage T2a, and 1.4% were stage T2b, 2 patients experienced infection at the trocar site used for kidney extraction, 4 patients developed postoperative fever, and 1 patient had postoperative bleeding requiring a blood transfusion. One patient underwent emergency open surgery immediately after discharge due to bleeding through the drainage. The postoperative complication rate according to the Clavien-Dindo classification was 11% (8 patients). The results show that 63 patients are still alive, 5 patients have passed away due to the disease, and 5 patients have died from other causes such as traffic accidents, cardiovascular diseases, and cerebral vascular accidents. The average follow-up time is 46.7±26.5 months. The cumulative survival rates at 3, 4, 5, 6, and 7 years after radical nephrectomy for the treatment of renal cell carcinoma were 100%, 97.6%, 94.8%, 90.9%, and 83.3%, respectively. The average additional survival time after surgery was 84.11 ± 1.80 months. Conclusions: Laparoscopic radical nephrectomy for early-stage renal cell carcinoma (T1 and T2) demonstrates high surgical safety and absolute efficacy in oncology.

Role of Immunotherapy in Renal Cell Carcinoma; A Case Study

Introduction: The most common cancer of kidney is- renal cell carcinoma. Early diagnosis can make a hope from the recovery of the disease. The incidence of renal cell carcinoma is commonly found in elderly aged patients. Sometimes it occurs in one kidney whereas, sometimes it effects both kidneys. Smoking, overweight, taking excessive painkillers can increase the chance of renal cell carcinoma. Case Presentation: A 57 years old Bangladeshi diabetic male patient, was diagnosed as right sided renal cell carcinoma (stage pT3cN0G2) along with the chief complaint of recurrent gross hematuria came to outdoor in April 2020. After confirmed diagnosis surgery had done followed by medications. From 10/03/2022, patient started 1 cycle of oral therapy with tablet Sunitinib. After that, immunotherapy and targeted therapy were advised to start with injection Pembrolizumab 200mg every three weeks followed by tablet Axitinib 5mg for every two weeks. Patient received 17 cycles of Pembrolizumab followed by Axitinib and got the last cycle at 24/02/2024. Conclusion: With the minimal side effects, it is evident that, Pembrolizumab has shown a positive response to the patient. It has added the new standard care of treatment of renal cell carcinoma at intermediate-high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions.