C-reactive protein may be overexpressed in kidney cancer tissue. We determined if urine C-reactive protein concentration is greater in patients with high grade renal cell carcinoma or greater than healthy controls, and compared to other urologic cancers and non-cancerous urologic disease. This observational study obtained pre-nephrectomy urine and plasma from 87 patients with a small imaged renal mass (≤4cm) undergoing partial nephrectomy. Postoperative pathology established clear cell or papillary renal cell cancer, angiomyolipoma, chromophobe, or oncocytoma, and tumor Fuhrman grade. Follow-up urine was collected from 52 clear cell/papillary cancer patients. Urine and/or plasma were from bladder or prostate cancer patients and matched healthy controls. C-reactive protein was measured by enzyme-linked immunosorbent assay. Urine C-reactive protein in grade 1-2 (n=41) and grade 3-4 (n=24) renal cancer was 17- and 80-fold greater than controls, respectively. This decreased 85% post-nephrectomy, suggesting origin from tumors and not systemic filtration from blood. Urine C-reactive protein in angiomyolipoma, chromophobe, or oncocytoma, bladder or prostate cancer was less than grade 3-4 renal cancer. C-statistic to differentiate grade 1-2 from 3-4 clear cell/papillary renal cancer was 0.98 (95% CI 0.95-1.00); sensitivity 1.00 (95% CI, 0.87-1.00), specificity 0.95 (95% CI 0.84-0.99). Two patients with remarkably high pre-nephrectomy urine C-reactive protein, but no others, developed late metastases. Pre-nephrectomy urine C-reactive protein was increased in patients with high grade clear cell and papillary renal cancer, but not other renal or urologic disease. Urine C-reactive protein may be used pre-surgically to noninvasively grade small renal masses, and may predict future renal cell cancer metastasis.
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma and accounts for 70-80% of all kidney tumors. It originates in the proximal convoluted tubules in the nephron and is characterized by cells with clear cytoplasm due to large intracellular lipid droplets and free cholesterol. The current study examined the impact of hypoxia on kidney carcinoma cells 786-0. MATERIAL AND METHODS: A publicly available dataset GSE225253 was analyzed, which contains RNA-seq transcriptomic data of kidney carcinoma cells 786-0 subject to normoxic and hypoxic conditions. Differential gene expression (DGE) analysis and gene ontology (GO) enrichment analysis were performed by R packages. RESULTS: Following hypoxia, 2366 genes were upregulated and 1799 were downregulated in 786-0 cells (FDR < 0.05). GO enrichment analysis revealed key upregulated pathways including upregulation of cell adhesion, gland development, and monosaccharide metabolic process, and downregulated pathways including ribonucleoprotein complex biogenesis, RNA splicing, and ribosome biogenesis. Hypoxia induced higher expression levels of growth factors (IGF2, CSF1, CSF2, TGFB1, TGFB2, VEGFA), inflammatory chemokines (CCL2, CXCL16) and cytokines (IL12A, IL32), and immune checkpoint ligands and receptors (CD274, PDCD1LG2, CD276, TNFRSF9, ADORA2A, TNFRSF14) in 786-0 cells. CONCLUSION: Hypoxia induced significant gene expression changes in kidney carcinoma cells, enhancing growth factor signaling, inflammation, immune checkpoint expression, and angiogenesis. These changes likely contribute to a tumor-supportive microenvironment, promoting cancer cell survival, proliferation, and immune evasion. Further in vitro and ex vivo studies are warranted to validate these findings and explore potential therapeutic strategies targeting hypoxia-induced pathways in ccRCC. in body composition features are associated with survival.
ABSTRACT Artificial intelligence (AI) tools are increasingly being adopted across a wide range of scientific disciplines, offering transformative potential in data analysis and interpretation and can enhance the understanding and optimization of medical databases. Specifically, in the context of renal cell carcinoma (RCC), prognostic models such as UISS, SSIGN, and ASSURE scores are commonly utilized to estimate recurrence risk and overall survival. However, these models rely heavily on conventional statistical methods and predefined clinical parameters. Our aim was to investigate the feasibility of leveraging readily available AI tools to identify novel prognostic factors for overall survival in RCC patients undergoing surgery and to aid in developing an enhanced, data-driven prognostic scoring system. MATERIAL AND METHODS Data from 1,273 consecutive patients who underwent surgery for renal cell carcinoma between 2010 and 2020 at a German tertiary care center were analyzed. The de-identified dataset included demographics, clinical and pathologi- cal variables, surgical details, clinical scores such as R.E.N.A.L. score, and time to event endpoints such as recurrence and overall survival. Five publicly accessible AI tools (chatGPT, Tableau, Julius AI, Microsoft Power BI, Polymer) were utilized to identify key prognostic parameters and develop a prognostic scoring system for overall survival in RCC pa- tients. These bots were asked to first identify prognostic parameters and then develop a multi-variate prognostic model in response to the question: “Build a prognostic score for overall survival based on a multivariate analysis of the most predictive parameters”. The dataset was divided into a training (n=746) and test (n=527) subsets for score development and validation. Kaplan-Meier survival analysis and log rank testing were performed to evaluate the prognostic accuracy of the generated scoring systems. RESULTS Julius AI proved to be the simplest assistant to utilize, with workflows and programming derived from natural speech that are automatically converted into code. Key factors in predicting outcomes with this AI included duration until recurrence (r=0.75), surgery duration (r=0.35), initial metastasis status (r=0.34), tumor size (r=0.28), female gender (r=0.27), presence of necrosis (r=0.25), T-stage (r=0.24), grading (r=0.24), surgeon (r=0.24), and histology type (clear cell versus non-clear cell) at r=0.21. The AI automatically selected fields to construct a score, incorporating age, gender, ECOG performance status, surgical duration, surgeon, histology, pT stage, tumor size, necrosis presence, resection status, grading, type of nephrectomy (partial vs radical), and R.E.N.A.L. score. Patients were stratified into high-, intermediate-, and low-risk groups, and Kaplan-Meier analysis demonstrating significant survival differences among the groups (log-rank test p < 0.0001). However, one major limitation of the tools was that repeated analyses often yielded varying results, indicating that human judgment remains necessary. CONCLUSIONS AI displays potential in identifying parameters that predict survival outcomes in renal cell carcinoma (RCC) patients based on clinical factors. Nonetheless, human oversight remains crucial. In addition to established scoring systems like SSIGN, UISS, and ASSURE, key factors such as surgeon expertise, surgical duration, and the RENAL score, which have been historically underutilized, should be integrated into future prognostic models. These factors, combined with tumor characteristics such as histology, size, grading, and necrosis, offer an opportunity to enhance the accuracy and utility of prognostic tools. Refining AI systems for greater reliability and reproducibility is critical for advancing their application in clinical decision-making and personalized patient care.
Reflecting on the 25th anniversary of the Kidney Cancer Association’s (KCA’s) International Kidney Cancer Sympo- sium (IKCS), held recently in Louisville, KY with the theme "Bridges to Cure: Innovating Kidney Cancer Care," fills me with pride and optimism. For a quarter-century, IKCS has served as a cornerstone event, uniting leading researchers, clinicians, and advocates in a shared mission to revolutionize kidney cancer care.
Dear fellow clinicians and researchers, It is with immense pleasure and a profound sense of shared purpose that we present to you the proceedings of the International Kidney Cancer Symposium (IKCS) 2024. This year's symposium holds particular significance, resonating deeply within our community, as it coincides with the momentous 25th anniversary of our esteemed partner, the Kidney Cancer Association (KCA). This milestone is not merely a marker of time but a testament to a quarter-century of unwavering dedication to the fight against kidney cancer. The convergence of IKCS and this anniversary creates a unique opportunity to reflect on the remarkable journey we've undertaken together, celebrating the triumphs achieved and acknowledging the challenges that remain.
BACKGROUND The incidence of Renal Cell Cancer (RCC) is on the rise globally. In the period 1994-2003, the relative five-year survival after RCC in Denmark was 39 percent for men and 44 percent for women. We aimed to describe whether the establishment of a nationwide clinical quality database for RCC was followed by improved care and survival. PURPOSE The purpose of the nationwide quality register in Denmark is to standardize treatment and improve prognosis by documenting the quality of healthcare treatment and contribute to improving prevention, diagnostics, treatment and rehabilitation MATERIAL AND METHOD In Denmark it is mandatory for all departments treating RCC to report relevant quality data on all patients. Every Danish resident has a unique Civil Registration (CPR) number which allow linkage to the national patient register and the pathology register. These registers contain information about all examinations and treatments in Danish hospitals. In a national steering group of the clinical register for RCC, different quality indicators have been selected for monitoring the quality of the treatment. The group chose nine indicators to be measured each year. The group meet several times a year to prepare an annual quality report, which is published and sent to hospitals, healthcare regions and the Danish Health Authority. RESULTS The register was established 1 August 2010 and contains 12.193 new cases of RCC, including 1 091 from the current year (the period 1 August 2022 to 31 July 2023). Over the years, a clear improvement has been observed both nationally and differences between regions and hospital departments decreased and thereby the equality of treatment and outcomes in the country has improved. CONCLUSION Through systematic work with quality results, interdisciplinary collaboration and the introduction of new treatments, we have observed a uniform treatment and increased survival in patients with renal cancer, which is at an international level.
BACKGROUND Renal Cell Carcinoma (RCC) is one of the most frequently diagnosed malignancies, yet non-invasive biomarkers for early detection and prognosis in RCC remain scarce. This study aims to identify serum protein markers predictive of clear cell RCC (ccRCC) development and prognostic of survival outcomes. METHODS Using the UK Biobank, a prospective cohort of >500,000 individuals, we analyzed serum proteomic data from participants who developed ccRCC after serum collection (Group 2), those diagnosed prior to serum collection (Group 1), and controls (Group 3). Proteomic measurements were performed using the Olink Proximity Extension Assay (PEA). Cox proportional hazards regression models estimated hazard ratios (HRs) for cancer risk and survival, adjusting for age, sex, BMI, smoking status, and renal function. Kaplan-Meier survival analysis evaluated prognostic markers. RESULTS: Five serum proteins—HAVCR1, REN, INHBB, NCR3LG1, and PGF—were significantly associated with future ccRCC development. HAVCR1 exhibited the strongest predictive performance (HR 5.1, 95% CI: 3.6–7.3, p<0.001; AUC 0.8756). Among all patients with ccRCC, NCR3LG1 (HR 2.6, 95% CI: 1.4–5.1, p<0.002), PGF (HR 2.2, 95% CI: 1.3–3.8, p<0.001), and GDF15 (HR 1.8, 95% CI: 1.1–2.8, p<0.02) were associated with reduced survival. CONCLUSION This study identifies HAVCR1 as a promising diagnostic biomarker for early ccRCC detection, with NCR3LG1, PGF, and GDF15 serving as potential prognostic markers. Further validation in independent cohorts is needed to facilitate clinical translation into diagnostic and prognostic tools for ccRCC. https://doi.org/10.52733/IKCS24-Proc-or3 KEYWORDS
BACKGROUND: Poor muscle health is an adverse prognostic factor in clear cell renal cell cancer (ccRCC), but mechanisms are unknown. We examined associations among six body composition features, ClearCode34 tumor molecular subtype, and survival. METHODS: In a cohort of 837 patients with localized ccRCC, we segmented pre-surgical CT scans for cross-sectional areas and radiodensities of skeletal muscle, visceral adiposity, and subcutaneous adiposity. RNA was extracted from archived tumor specimens and run on a custom Nanostring array. A centroid- based classification categorized tumors as ccA (less aggressive) or ccB (more aggressive) ClearCode34 subtype. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body composition and ClearCode34 subtype. Hazard ratios (HRs) and 95% CIs were estimated for individual and joint effects of body composition features and ClearCode34 subtype on 5-year disease-free survival (DFS). RESULTS: The cohort was predominantly male, white, and had Stage I disease; 26% of tumors were ccB subtype. 95 DFS events occurred over 3532.2 person-years of follow-up. Patients with lower skeletal muscle radiodensity (SMD) were more likely to harbor ccB tumors (OR per 10-unit decrease in SMD: 1.30, 95% CI: 1.00-1.69). Exploratory joint effects analyses suggested patients with lower SMD and ccB subtype experienced the lowest DFS compared to patients without those characteristics (HR 2.68, 95% CI: 1.43-5.00). CONCLUSIONS: ccRCC patients with lower SMD (more fat- infiltrated skeletal muscle) at diagnosis may experience worse survival because they harbor more aggressive tumors. Future studies should determine how post-nephrectomy changes in body composition features are associated with survival.
I appreciate the opportunity to reflect on the last 25 years of kidney cancer research, having seen my first kidney cancer patients as a second-year fellow at the University of Chicago exactly 25 years ago under the mentorship of Drs. Nicholas Vogelzang and Walter Stadler; from day one, I found the biology of the disease interesting, even though at the time there were almost no therapeutics and most of our patients received clinical trial therapy. I remember one early patient encounter of a young man with advanced disease where, after delivering my rehearsed speech about interferon, interleukin-2, and clinical trial options, his wife's poignant question, "Do you mean that's all you've got?", brought me back to earth and has driven my personal journey of kidney cancer drug development ever since. I learned from Dr. Vogelzang to always appreciate and advocate for the patient perspective and to do everything possible to optimize patient outcomes.
Minimally invasive kidney tumor surgery has evolved over the last 33 years beginning with laparoscopic radical and later partial nephrectomy and with more recent progression to robotic assisted laparoscopic operations. The principal advantages of minimally invasive surgery (MIS), also reported widely in other surgical specialties, include less painful and more cosmetic incisions and faster return to normal activities and work when compared to similar open surgical operations. In addition, reports of oncological outcomes that were noninferior to similar open surgical operations led to worldwide expansion of these approaches. However, from the earliest experience with MIS utilized in oncological surgery to the present, reports of atypical tumor recurrences (ATR) in locations not usually part of the natural history of a specific cancer, including port sites, tumor resection beds, and carcinomatosis, raised concerns amongst surgeons and oncologists in many specialties. Surgeons performing MIS techniques for kidney tumors reported similar ATR. Although ATR is an uncommon clinical event, the impact on the individual patient who experiences it usually leads to a heavy treatment burden of surgical salvage with or without additional systemic therapies and a low likelihood of complete remission. The mechanisms by which ATR occur and its precise incidence are unknown, but a more complete understanding of its etiology and means of prevention is currently an unmet research need. Surgeons in Europe and the United State have taken initial steps to coordinate consortium data to address aspects of this serious surgical problem.
BACKGROUND: Microwave ablation (MWA) is an emerging treatment modality for clinical T1a (cT1a) small renal masses (SRM) with studies showing it has comparable oncological outcomes to partial nephrectomy (PN). However, more research is needed to the impact of each treatment on kidney function decline. OBJECTIVE: To compare the progression of kidney function decline in patients with cT1a SRM treated with MWA or PN. Methods: This study included prospective data on patients treated between 2015-2021 with kidney function data collected from 2015-2024 from a single institutional database. Three outcomes for kidney function decline were examined: 30% decline in estimated glomerular filtration rate (eGFR) compared to pre-treatment, chronic kidney disease (CKD) upstaging compared to pre-treatment and eGFR <60 mL/min/1.73m2, and the composite endpoint of the previous two events. Cox proportional hazards models were used to compare outcomes between the two treatments. RESULTS: Among 97 MWA and 49 PN included, MWA patients were older, had lower baseline eGFR, and higher rates of CKD prior to treatment. Univariate Cox proportional hazard model showed treatment modality was not significantly associated with reaching kidney decline endpoints. After adjusting for patient characteristics (age, race, baseline eGFR, Charlson Comorbidity Index), only baseline eGFR was associated with reaching kidney function endpoints. CONCLUSION: There was no statistically significant difference in kidney function decline between PN and MWA treatments for cT1a SRM. After adjusting for patient factors, the higher hazard for MWA was attenuated.
The 25th Anniversary International Kidney Cancer Symposium (IKCS 2024) in Louisville, Kentucky, brought together leading experts to discuss the latest advancements in kidney cancer research and treatment. Key highlights included presentations on novel therapeutic approaches, including emerging immunotherapies and targeted therapies. The symposium also emphasized the importance of multidisciplinary care, patient-centered outcomes, and the role of supportive care in improving the overall patient experience. This meeting summary provides a comprehensive overview of the key findings and discussions presented at IKCS 2024.
These recommended abstracts from 2024 IKCSNA Annual Meeting highlight some of the most important trends in ongoing trials chosen by Dr. Hutson and reflect the foremost research and strategies from latest clinical trials that impact the current standard of care in renal cancer.
BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is one of the most common types of renal cell carcinoma, and there is often a poor prognosis for advanced KIRC patients. C1QTNF1 plays a key role in inflammatory signaling. However the prognostic value of C1QTNF1 in KIRC remains unknown. METHODS: Our study investigated the potential function of C1QTNF1 in KIRC comprehensively. RESULTS: The expression of C1QTNF1 was upregulated significantly in KIRC. Moreover, a higher level of expression of C1QTNF1 was associated with a poor prognosis and an advanced stage of cancer. In addition, KIRC showed a significant association between C1QTNF1 expression and the numbers of NK cells, DC, Tam, and Th1/Th2 cells infiltrating the tumor. It has been shown that a nomogram model based on C1QTNF1, and several clinical factors is effective at predicting overall survival. CONCLUSIONS: C1QTNF1 may participate in carcinogenesis of KIRC and contribute to immune cell infiltration, as evidenced by these observations.
BACKGROUND: Renal cell carcinoma (RCC) is the most common kidney malignancy, often associated with poor prognosis due to late-stage diagnosis and metastasis. Recent research has identified PIWI-interacting RNAs (piRNAs) and PIWI-like proteins as potential biomarkers and therapeutic targets in cancer, including RCC. This systematic review aims to evaluate the role of piRNAs and PIWI-like proteins in RCC pathogenesis, prognosis, and treatment. METHODS: A systematic search of PubMed and ScienceDirect databases from 2014 to 2024 was conducted according to PRISMA guidelines. Eligible studies included randomized controlled trials, cohort studies, and case-control studies investigating piRNAs and PIWI-like proteins in RCC. A total of 13 studies were included, with the quality of studies assessed using the Newcastle-Ottawa Scale. RESULTS: Several piRNAs, such as piR-1742, piR-31115, and piR-57125, were found to be dysregulated in RCC, contributing to tumor proliferation, invasion, and metastasis through pathways like PI3K/AKT and epithelial-mesenchymal transition (EMT). PIWI-like proteins, particularly Piwi-like 1, were associated with advanced tumor stages and poor survival outcomes, making them significant prognostic markers. Mitochondrial piRNAs, including piR-34536 and piR-51810, were identified as novel biomarkers for RCC prognosis. CONCLUSION: piRNAs and PIWI-like proteins show great promise as emerging diagnostic and prognostic biomarkers, as well as therapeutic targets in RCC. While these molecules have demonstrated potential in RCC management, further research is needed to confirm their clinical relevance and mechanisms of action. Future studies should focus on larger, well-structured cohorts to validate these findings and explore therapeutic interventions targeting piRNAs and PIWI-like proteins.
The recent 2024 International Kidney Cancer Symposium (IKCS) marked its 25th anniversary, a significant milestone in its journey of fostering collaboration and innovation in the fight against kidney cancer. The symposium showcased a wealth of groundbreaking research and clinical advancements, offering fresh perspectives on the evolving landscape of kidney cancer. From novel therapeutic approaches to improved prognostic markers, the event highlighted the relentless pursuit of better outcomes for patients with this challenging disease.
INTRODUCTION:Performing surgery for renal cell carcinoma (RCC) in patients with horseshoe kidneys presents unique anatomic challenges. The complexities of clinical decision-making and technical challenges are further compounded by the presence of both IVC tumor thrombus extension and metastatic disease. CASE PRESENTATION:We encountered the unique case of a 66-year-old woman with a horseshoe kidney who presented with a 14cm mass in her right kidney with level II tumor thrombus extension into the IVC, retroperitoneal lymphadenopathy, and pulmonary nodules that were biopsy-proven to be consistent with metastatic clear cell RCC (cT3aN1M1). She was treated with combination immune checkpoint inhibition (ICI) and targeted therapy upfront. Given her durable response to systemic therapy, we elected to perform a consolidative cytoreductive nephrectomy for residual ypT3aN0 disease, and she has since remained disease-free radiographically. Using step-by-step illustrative photographs obtained intraoperatively, we detail our surgical approach and highlight technical pearls to manage similar cases of advanced RCC arising from horseshoe kidneys. CONCLUSION:We present a complex case of metastatic RCC with IVC tumor thrombus arising from a horseshoe kidney. We share our clinical and technical approach to overcoming the medical and surgical challenges inherent to her case. The optimal role and timing of cytoreductive nephrectomy relative to ICI administration continue to evolve based on both tumor- and patient-related factors. Indeed, we favor a multidisciplinary approach to optimize patient outcomes.
The 2024 American Society of Clinical Oncology (GU ASCO 2024) Genitourinary Cancers Symposium brought together leading cancer specialists from around the world to discuss the latest breakthroughs in treating genitourinary cancers, especially kidney cancer. The focus was on immunotherapy and combination treatments, offering promising new options for patients with advanced and high-risk tumors. The symposium also highlighted advancements in patient care, including a new tool to assess quality of life in people with metastatic kidney cancer.
Prior to the development of new cancer technologies, metastatic Renal Cell Carcinoma (mRCC) had a poor prognosis. Fortunately, advances in treatment are allowing a growing population of patients to live with advanced or mRCC. While quality of life has been an area of investigation in this population as treatments advance, relatively little is known about the specific survivorship needs experienced by these patients in the modern treatment era. Using the five survivorship domains defined by the National Cancer Institute, this narrative review explores the literature addressing the survivorship needs of patients living with mRCC. Significant physical, mental, emotional, social and financial effects of mRCC are herein discussed. By comparing literature from the pre-combination treatment period to the modern era, this narrative review of the published literature highlights the significant gaps in our survivorship knowledge for this unique and expanding population. Specifically, this review identifies gaps in understanding of symptom burden, psychological impact, financial effects, and the particular impact of immune-checkpoint inhibitor based combination therapies. Here, we highlight these areas for further research with the hope of finding strategies to alleviate the effects of mRCC and improve the quality of life of patients living with metastatic disease.
