Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999-2020.

Introduction: Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States. Methods: Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05. Results: Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West. Discussion: Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.

Factors influencing health-related quality of life in patients with bladder or kidney cancer: a prospective cohort study of the impact of nutritional status and frailty phenotype.

PURPOSE: This study aimed to investigate the impact of nutritional status and frailty phenotype and the predictors of temporal changes on health-related quality of life (HRQoL) of patients with bladder or kidney cancer. METHODS: Frailty phenotype, Patient-Generated Subjective Global Assessment, and Quality-of-life questionnaire Core-30 were applied twice to patients diagnosed with bladder or kidney cancer. Patients also completed a sociodemographic questionnaire, and clinical data were collected from records. RESULTS: Sixty-two individuals completed the study, mostly male, with a mean age of 62.5 (± 11.4) years. The median time of follow-up was 14.5 months. Role functioning, emotional functioning, and fatigue improved over time (p < 0.05). The factors that negatively affected the long-term quality of life summary score were being female, malnourished, pre-frail and frail, cancer treatment, performance status, and lower income. Using the multivariate model, being malnourished (ß = - 7.25; 95% CI, - 10.78 to - 3.71; p < 0.001), frail (ß = - 7.25; 95% CI, - 13.39 to - 1.11; p = 0.021), and each one-point increase in performance status (ß = - 6.9; 95% CI, - 9.54 to - 4.26; p < 0.001), were the ones that most negatively impacted the HRQoL between the two assessments. CONCLUSION: This study confirmed that frailty, nutritional status, and performance status are the main predictors of HRQoL of patients with bladder or kidney cancer over time. IMPLICATIONS FOR CANCER SURVIVORS: These findings may be the first step towards highlighting the importance of preventing malnutrition and frailty, in favor of a better long-term QoL for cancer patients.

Long-term consequences of positive surgical margin after partial nephrectomy for renal cell carcinoma: multi-institutional analysis.

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

Primary extrarenal papillary type II renal cell carcinoma presenting as a pelvic mass: a case report and review of the literature.

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

Surgical outcomes of novel retroperitoneal low anterior vs posterior and transperitoneal access in single-port partial nephrectomy.

PURPOSE: Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical outcomes for novel Retroperitoneal Low Anterior Access (LAA) in SP-RAPN. The study compared outcomes of the standard approach (SA), considering transperitoneal (TP) and posterior retroperitoneal (RP) access vs LAA in SP-RAPN series. METHODS: 102 consecutive patients underwent SP-RAPN between 2019 and 2023 at a tertiary referral robotic center were identified. Baseline characteristics, peri- and post-operative outcomes were collected. Patients were stratified according to surgical approach into standard (RP or TP) vs LAA and, subsequently, RP vs LAA. Multivariable logistic regression analysis was used to test the probability of the same-day discharge adjusting for comorbidity indexes. RESULTS: Overall, 102 consecutive patients were included in this study (68 SA - 26 TP and 42 posterior RP vs 34 LAA). Median age was 60 (IQR 51.5-66) years and median BMI was 31 (IQR 26.3-37.6). No baseline differences were observed. LAA exhibited significantly shorter length of stay (LOS) (median 10 [IQR 8-12] vs 24 [IQR 12-30.2.] hours, p < .0001), reduced post-operative pain (p < .0001) and decreased narcotic use on 0-1 PO Day (p < .001) compared to SA and RP only. Multivariate analysis, adjusting for comorbidities, identified LAA as a strong predictor for Same-Day Discharge. CONCLUSION: LAA is an effective approach as well as RP and TP, regardless of the renal mass location, whether it is anterior or posterior, upper/mid or lower pole, yielding favorable outcomes in LOS, post-operative pain and decreased narcotics use compared to SA in SP-RAPN.

Long-term Renal Function Outcomes After Stereotactic Ablative Body Radiotherapy for Primary Renal Cell Carcinoma Including Patients with a Solitary Kidney: A Report from the International Radiosurgery Oncology Consortium of the Kidney.

BACKGROUND AND OBJECTIVE: Renal function preservation is particularly important following nonoperative treatment of localized renal cell carcinoma (RCC) since patients are often older with medical comorbidities. Our objective was to report long-term renal function outcomes after stereotactic ablative radiotherapy (SABR) including patients with a solitary kidney. METHODS: Patients with primary RCC treated with SABR with ≥2 yr of follow-up at 12 International Radiosurgery Consortium for Kidney institutions were included. Renal function was measured by estimated glomerular filtration rate (eGFR). KEY FINDINGS AND LIMITATIONS: In total, 190 patients (56 with a solitary kidney) underwent SABR and were followed for a median of 5.0 yr (interquartile range [IQR]: 3.4-6.8). In patients with a solitary kidney versus bilateral kidneys, pre-SABR eGFR (mean [standard deviation]) was 61.1 (23.2) versus 58.0 (22.3) ml/min (p = 0.32) and the median tumor size was 3.65 cm (IQR: 2.59-4.50 cm) versus 4.00 cm (IQR: 3.00-5.00 cm; p = 0.026). At 5 yr after SABR, eGFR decreased by -14.5 (7.6) and -13.3 (15.9) ml/min (p = 0.67), respectively, and there were similar rates of post-SABR dialysis (3.6% [n = 2/56] vs 3.7% [n = 5/134]). A multivariable analysis demonstrated that increasing tumor size (odds ratio [OR] per 1 cm: 1.57; 95% confidence interval [CI]: 1.14-2.16, p = 0.0055) and baseline eGFR (OR per 10 ml/min: 1.30; 95% CI: 1.02-1.66, p = 0.034) were associated with an eGFR decline of ≥15 ml/min at 1 yr. CONCLUSIONS AND CLINICAL IMPLICATIONS: With long-term follow-up after SABR, kidney function decline remains moderate, with no observed difference between patients with a solitary kidney and bilateral kidneys. Tumor size and baseline eGFR are dominant factors predictive of long-term renal function decline. PATIENT SUMMARY: With long-term follow-up, stereotactic ablative radiotherapy (SABR) yields moderate long-term renal function decline and low dialysis rates even in patients with a solitary kidney. SABR thus represents a promising noninvasive, nephron-sparing option for patients with localized renal cell carcinoma.

Psychosocial distress after radical prostatectomy, radical cystectomy, or (partial) nephrectomy - a comprehensive analysis of 4,290 German cancer patients during the COVID-19 pandemic.

AIM: To evaluate and identify predictors of psychosocial distress (PD) in patients after surgical treatment for prostate cancer (PC), bladder cancer (BC), or kidney cancer (KC) during the COVID-19 pandemic in a large, multi-institutional cohort. MATERIAL AND METHODS: Patients undergoing inpatient rehabilitation (IR) after radical prostatectomy (RP), radical cystectomy (RC), or (partial) nephrectomy in one IR center in 2021 were included. PD was evaluated by the Questionnaire on Stress in Cancer Patients (QSC-R23) at the beginning (T1) and the end (T2) of IR. Regression analyses were performed to identify disease-specific predictors for high PD. RESULTS: A total of 4,290 patients (3,413 after RP, 563 after RC, 314 after (partial) nephrectomy) were included in this study. Median PD decreased significantly during IR across all tumor entities (each p < 0.001). The number of PC and BC patients suffering from high PD decreased significantly (each p < 0.001), but not in KC patients (p = 0.310). Younger age independently predicts high PD in all three malignancies, while additionally positive surgical margins (p = 0.016), ileal conduit (IC; p < 0.001), and nephrectomy (p = 0.032) independently predict high PD in PC, BC, and KC patients, respectively. During the Covid-19 pandemic the demand for individual psycho-oncologic counseling increased significantly in PC (p = 0.03) and KC (p = 0.001) patients. CONCLUSION: Younger age independently predicts high PD in the three main urological malignancies. Positive surgical margins in PCa, IC in BCa, and nephrectomy in KC are disease-specific independent predictors for high PD in the early period after surgical treatment. IMPLICATIONS FOR CANCER SURVIVORS: Disease-specific predictors for high PD may help clinicians identify patients at risk and may guide timely referrals to psycho-oncologic counseling in the early period after uro-oncologic surgery.

Molecular mechanisms and clinical relevance of endothelial cell cross-talk in clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer in adults and stands out as one of the most vascularized and immune-infiltrated solid tumors. Overproduction of vascular endothelial growth factor A promotes uncontrolled growth of abnormal vessels and immunosuppression, and the tumor microenvironment (TME) has a prominent role in disease progression, drug targeting and drug response, and for patient outcome. Methods: Studies of experimental models, large-scale omics approaches, and patient prognosis and therapy prediction, using gene expression signatures and tissue biomarker analysis, have been reviewed for enhanced understanding of the endothelium in ccRCC and the interplay with the surrounding TME. Results: Preclinical and clinical studies have discovered molecular mechanisms of endothelial cross-talk of relevance for disease progression, patient prognosis, and therapy prediction. There is, however, a lack of representative ccRCC experimental models. Omics approaches have identified clinically relevant subsets of angiogenic and immune-infiltrated tumors with distinct molecular signatures and distinct endothelial cell and immune cell populations in patients. Conclusions: Recent genetically engineered ccRCC mouse models together with emerging evidence from single cell RNA sequencing data open up for future validation studies, including multiplex imaging of ccRCC patient cohorts. These studies are of importance for therapy benefit and personalized treatment of ccRCC patients.

Hippo signaling modulation and its biological implications in urological malignancies.

Although cancer diagnosis and treatment have rapidly advanced in recent decades, urological malignancies, which have high morbidity and mortality rates, are among the most difficult diseases to treat. The Hippo signaling is an evolutionarily conserved pathway in organ size control and tissue homeostasis maintenance. Its downstream effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are key modulators of numerous physiological and pathological processes. Recent work clearly indicates that Hippo signaling is frequently altered in human urological malignancies. In this review, we discuss the disparate viewpoints on the upstream regulators of YAP/TAZ and their downstream targets and systematically summarize the biological implications. More importantly, we highlight the molecular mechanisms involved in Hippo-YAP signaling to improve our understanding of its role in every stage of prostate cancer, bladder cancer and kidney cancer progression. A better understanding of the biological outcomes of YAP/TAZ modulation will contribute to the establishment of future therapeutic approaches.

A highly sensitive SERS substrate of porous membrane-Ag NPs for kidney cancer detection.

BACKGROUND: The substrate employed in surface-enhanced Raman spectroscopy (SERS) constitutes an essential element in the cancer detection methodology. In this research, we introduce a three-dimensional (3D) structured SERS substrate that integrates a porous membrane with silver nanoparticles to enhance SERS spectral signals through the utilization of the aggregation effect of silver nanoparticles. This enhancement is crucial because accurate detection results strongly depend on the intensity of specific peaks in Raman spectroscopy. A highly sensitive SERS substrate can significantly improve the accuracy of detection results. RESULTS: We collected 66 plasma samples from individuals with kidney cancer and control individuals, including both bladder cancer patients and healthy individuals. Then, we utilized substrates with and without porous membranes to acquire the SERS spectra of the samples, enabling us to evaluate the enhancement effect of our SERS substrate. The spectral analysis demonstrated enhanced peak intensities in the experimental group (with porous substrate) compared to the control group (without porous substrate). The uniformity and reproducibility of the SERS substrate are also significantly enhanced, which is very helpful for improving the accuracy of detection results. Additionally, the Principal Component Analysis-Linear Discriminant Analysis algorithm (PCA-LDA) was employed to classify the SERS spectra of both groups. In the experimental group, the classification accuracy was 98.5 % for kidney cancer, and 83.3 % for kidney and bladder cancer. Compared to the control group, it improved by 3 % and 12.6 % respectively. SIGNIFICANT: This indicates that our 3D structured SERS substrate combined with multivariate statistical algorithms PCA-LDA can not only improve the accuracy of SERS detection technology in single cancer detection, but also has great potential in multiple cancer detection. This 3D structured SERS substrate is expected to become a new auxiliary means for cancer detection.

Renal cell carcinoma and risk of second primary cancer: A Danish nationwide cohort study.

AIM: To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). METHODS: We identified all patients diagnosed with incident RCC during 1995-2019, using population-based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population. RESULTS: The absolute 1- and 20-year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person-years (PY) (SIR, 2.3; 95% CI: 2.1-2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow-up (SIR, 1.3; 95% CI: 1.2-1.4), and 6 per 1000 PY beyond 5 years of follow-up (SIR, 1.4; 95% CI: 1.3-1.5). The sustained elevated cancer risk beyond 1 year of follow-up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006-2019 than in 1995-2005, but only during the first year of follow-up. CONCLUSION: Patients with incident RCC have a sustained 40% elevated long-term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer.

Robot-assisted Partial Nephrectomy for Hilar and Nonhilar Renal Masses: Comparison of Perioperative, Oncological, and Functional Results in a Multicentre Prospective Cohort (NEPRAH Study, UroCCR 175).

BACKGROUND AND OBJECTIVE: A hilar location for a renal tumour is sometimes viewed as a limiting factor for safe partial nephrectomy. Our aim was to evaluate perioperative, oncological, and functional outcomes of robot-assisted partial nephrectomy (RAPN) for hilar tumours (RAPN-H) in comparison to RAPN for nonhilar tumours (RAPN-NH). METHODS: We conducted an observational, multicentre cohort study using prospectively collected data from the French Research Network on Kidney Cancer (UroCCR). The registry includes data for 3551 patients who underwent RAPN for localised or locally advanced renal masses between 2010 and 2023 in 29 hospitals in France. We studied the impact of a hilar location on surgery, postoperative renal function, tumour characteristics, and survival. We also compared rates of trifecta achievement (warm ischaemia time [WIT] <25 min, negative surgical margins, and no perioperative complications) between the groups. Finally, we performed a subgroup analysis of RAPN without vascular clamping. Variables were compared in univariable analysis and using multivariable linear, logistic, and Cox proportional-hazards models adjusted for relevant patient and tumour covariates. KEY FINDINGS AND LIMITATIONS: The analytical population included 3451 patients, of whom 2773 underwent RAPN-NH and 678 underwent RAPN-H. Longer WIT (ß = 2.4 min; p < 0.01), longer operative time (ß = 11.4 min; p < 0.01) and a higher risk of postoperative complications (odds ratio 1.33; p = 0.05) were observed in the hilar group. Blood loss, the perioperative transfusion rate, postoperative changes in the estimated glomerular filtration rate, and trifecta achievement rates were comparable between the groups (p > 0.05). At mean follow-up of 31.9 mo, there was no significant difference in recurrence-free survival (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.58-1.2; p = 0.3), cancer-specific survival (HR 1.1, 95% CI 0.48-2.6; p = 0.79), or overall survival (HR 0.89, 95% CI 0.52-1.53; p = 0.69). CONCLUSIONS AND CLINICAL IMPLICATIONS: Patient and tumour characteristics rather than just hilar location should be the main determinants of the optimal surgical strategy for hilar tumours. PATIENT SUMMARY: We found that kidney tumours located close to major kidney blood vessels led to a longer operation and a higher risk of complications during robot-assisted surgery to remove the tumour. However, tumours in these locations were not related to a higher risk of kidney function loss, cancer recurrence, or death.

Immunotherapy Applications for Thymine Dimers and WT1 Antigen in Renal Cancers: A Comparative Statistical Analysis.

Renal cell carcinoma (RCC) remains incurable in advanced stages. Biomarkers have proven to be quite useful in cancer therapeutics. Herein, we provide a comparative/integrative statistical analysis of seminal immunohistochemistry (IHC) findings for Wilms' Tumor 1 antigen (WT1) and thymine dimers (TDs), emerging as atypical, yet promising, potential biomarkers for RCCs. We assessed WT1/TD reactivity in adult RCC tumor cells, tumor microenvironment (TME), and tumor-adjacent healthy renal tissue (HRT). WT1 positivity was scarce and strictly nuclear in tumor cells, whereas TD-reactive tumor tissues were prevalent. We report statistically significant positive correlations between the density of reactive RCC cellularity and the intensity of nuclear staining for both biomarkers (WT1 - rho = 0.341, p-value = 0.036; TDs - rho = 0.379, p-value = 0.002). RCC stromal TME TD-positivity was much more frequent than WT1 reactivity, apparently proportional to that of the proper RCC cellularity and facilitated by extensive RCC inflammatory infiltration. TDs exhibited nuclear reactivity for most TME cell lines, while RCC TME WT1 expression was rare and inconsistent. In HRTs, TDs were entirely restricted to renal tubular cells, the likely cellular progenitor of most conventional RCC subtypes. In lieu of proper validation, these early findings have significant implications regarding the origins/biology of RCCs and may inform RCC therapeutics, both accounting for the high frequency of immunotherapy-permissive frameshift indels in RCCs, but also hinting at novel predictive clinical tools for WT1-targeted immunotherapy. Overall, the current study represents a meek yet hopefully significant step towards understanding the molecular biology and potential therapeutic targets of RCCs.

Purely Off-Clamp Sutureless Robotic Partial Nephrectomy for Novice Robotic Surgeons: A Multi-Institutional Propensity Score-Matched Analysis.

Objectives: To compare perioperative outcomes of patients treated with sutureless off-clamp robotic partial nephrectomy (sl-oc RAPN) by either a novice or an expert robotic surgeon at two different institutions. Methods: Data concerning two continuous series of patients with cT1-2N0M0 renal tumors treated with sl-oc RAPN either by a novice or an expert surgeon were extracted from prospectively populated institutional databases over the last 4 years. Perioperative outcomes as well as the baseline characteristics of patients and tumors were compared by using χ2 and Mann-Whitney tests for categorical and continuous variables, respectively. A 1:1 propensity match score analysis (PMSa) generated two homogeneous cohorts. Logistic regression analysis was performed to assess predictors of trifecta outcomes, defined as negative surgical margins, no Clavien-Dindo ≧ 3 grade complications, and no ≧ 30% postoperative eGFR reduction. Results: Overall, 328 patients were treated by an expert surgeon, while 40 were treated by a novice surgeon. After PMSa analysis, two cohorts of 23 patients each were generated, homogeneous for all baseline variables (p ≥ 0.07). Hospital stay was the only significantly different outcome observed between the two groups (5 days vs. 2 days; p < 0.001). No statistically significant differences were recorded when comparing trifecta outcomes (expert: 100% vs. novice: 87%; p = 0.07). In the logistic regression analysis, no statistically significant predictors of trifecta outcomes were recorded. Conclusions: sl-oc RAPN is a feasible and safe nephron sparing technique, even when performed by a novice robotic surgeon.

Volumetric imaging of the tumor microvasculature reflects outcomes and genomic states of clear cell renal cell carcinoma.

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

Kidney Cancer and Potential Use of Urinary Extracellular Vesicles.

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

Blood cell indices and inflammation-related markers with kidney cancer risk: a large-population prospective analysis in UK Biobank.

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

Emerging Strategies in Adjuvant Immunotherapy: A Comparative Review of Bladder Cancer and Renal Cell Carcinoma Treatments.

Recent progress in adjuvant immunotherapy offers hope for improving disease-free survival in high-risk bladder cancer (BC) and renal cell carcinoma (RCC). This review focuses on key trials such as CheckMate 274 and KEYNOTE-564, which show promising results with nivolumab in BC and pembrolizumab in RCC, including a 30% reduction in progression risk. Pembrolizumab also demonstrated overall survival (OS) benefit in RCC. The review also explores the potential of circulating tumor DNA (ctDNA) as a biomarker for better therapy selection and patient stratification. It emphasizes the need for ongoing research to establish survival benefits and suggests integrating biomarkers and risk stratification to optimize adjuvant immunotherapy in BC and RCC.