Serum IgA as a Prognostic Beacon: Anticipating Systemic Therapy Efficacy in Metastatic Clear Cell Renal Cell Carcinoma.

OBJECTIVE: Immunotherapy-tyrosine kinase inhibitor (IO-TKI) therapy has revolutionized the treatment landscape for metastatic clear cell renal cell carcinoma (mccRCC); however, the absence of effective biomarkers poses a challenge in predicting the efficacy of these regimens. This study aims to explore the predictive and prognostic value of serum immunoglobulin A (IgA) in mccRCC patients undergoing IO-TKI therapy. METHODS: Ninety-six mccRCC patients treated with IO-TKI therapy from 2019 to 2023 were enrolled and serum IgA levels were assessed at the pretreatment baseline and after 3 months of treatment. RESULTS: Notably, baseline levels of IgA showed no correlation with the objective response rate. However, patients achieving complete or partial responses exhibited a remarkable decrease in IgA levels, while those with stable or progressive disease displayed an increase in IgA levels after 3 months of treatment. Furthermore, the dynamic alteration in IgA levels after 3 months of treatment demonstrated predictive value for both progression-free survival (PFS) and overall survival (OS). The time-dependent receiver operating characteristic curves exhibited outstanding performance in predicting PFS (AUC 0.793) and OS (AUC 0.738). CONCLUSION: Taken together, this study demonstrates that dynamic alteration of serum IgA after 3 months of treatment was significantly correlated with prognosis and therapeutic efficacy in mccRCC patients.

Development of Novel Paclitaxel-Loaded ZIF-8 Metal-Organic Framework Nanoparticles Modified with Peptide Dimers and an Evaluation of Its Inhibitory Effect against Prostate Cancer Cells.

Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) onto the surface of PTX@ZIF-8 to prepare a nanotargeted drug delivery system (Di-PEG@PTX@ZIF-8) for the treatment of prostate cancer. This study investigated the morphology, particle size distribution, zeta potential, drug loading, encapsulation rate, stability, in vitro release behavior, and cytotoxicity of this targeted drug delivery system, and explored the uptake of Di-PEG@PTX@ZIF-8 by human prostate cancer Lncap cells at the in vitro cellular level, as well as the proliferation inhibition and promotion of apoptosis of Lncap cells by the composite nanoparticles. The results suggest that Di-PEG@PTX@ZIF-8, as a zeolitic imidazolate frameworks-8-loaded paclitaxel nanoparticle, has promising potential for the treatment of prostate cancer, which may provide a novel strategy for the delivery system targeting prostate cancer.

Research Advances in Nucleic Acid Delivery System for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the lives of nearly 1% of the total population worldwide. With the understanding of RA, more and more therapeutic drugs have been developed. However, lots of them possess severe side effects, and gene therapy may be a potential method for RA treatment. A nanoparticle delivery system is vital for gene therapy, as it can keep the nucleic acids stable and enhance the efficiency of transfection in vivo. With the development of materials science, pharmaceutics and pathology, more novel nanomaterials and intelligent strategies are applied to better and safer gene therapy for RA. In this review, we first summarized the existing nanomaterials and active targeting ligands used for RA gene therapy. Then, we introduced various gene delivery systems for RA treatment, which may enlighten the relevant research in the future.

Dynamic alteration and prognostic significance of tumor-associated CD68+ and CD68+ PD-L1- macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

BACKGROUND: The current study aimed to investigate the dynamic alteration and prognostic significance of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 status of immune cells in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC). METHODS: Multiplex immunofluorescence staining was performed to examine CD68+ TAM, CD4+ T cell, CD8+ T cell, FOXP3+ Treg cell, and PD-L1 expression in paired MIBC tissues (n = 54) before and after NAC. Patients were then divided into definite responders (DR), (≤pT1) and incomplete responders (IR). RESULTS: There was no significant difference between DR and IR cohorts for the immune cell infiltration levels at the baseline status. Tobacco history was identified to be associated with worse NAC efficacy. CD68+ (stroma area: p = 0.025; tumor area: p = 0.028; total area: p = 0.013) and CD68+ PD-L1- (stroma area: p = 0.035; tumor area: p = 0.013 total area: p = 0.014) TAMs infiltration levels decreased significantly after NAC, while there was no significant difference of CD68+ PD-L1+ and TILs. The infiltration of CD68+ (p = 0.033), CD68+ PD-L1- (p = 0.033), and CD68+ PD-L1+ (p < 0.001) TAMs in stroma area were significantly associated with poorer disease-free survival rate (DFS) of MIBC patients. CONCLUSION: CD68+ and CD68+ PD-L1- TAMs infiltration levels decreased significantly after NAC and pre-treatment TAM infiltration levels were independent prognostic factors for MIBC patients. While there was no sufficient evidence demonstrating that pre-treatment TILs or TAMs could predict response to NAC in MIBC patients.

Transmembrane Transporter Sema3D Serves as a Tumor Suppressor in Localized Clear Cell Renal Cell Carcinoma.

Background: The transmembrane transporter Sema3D is a vital molecule involved in axon guidance and carcinogenesis of variant malignancies. However, the relationship between Sema3D and clear cell renal cell carcinoma (ccRCC) is barely reported and remains unclear. Methods: Sema3D expression and the connection of clinical and histological characteristics were first analyzed with transcriptome data in the TCGA repository. We then located and examined the Sema3D expression in ccRCC patients by using immunofluorescence staining in the tissue microarray. The prognostic value of Sema3D in localized ccRCC was evaluated by Cox proportional hazard analysis. Functional and gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to describe the potential mechanisms of Sema3D in ccRCC. Correlation analysis between Sema3D and tumor-infiltrating lymphocytes was calculated by ssGSEA. Results: In 86 ccRCC patients, Sema3D mRNA and protein expression were downregulated in tumor tissues than the para-tumor tissues, and Sema3D was dominantly expressed in the extracellular space. Low expression of Sema3D was associated with advanced tumor stage, advanced histological grade, and poor prognosis in ccRCC. In the subgroup analysis of 81 localized ccRCC patients, Sema3D expression level was an independent protective prognostic factor for overall survival (OS) (HR = 0.125, p=0.043). Coagulation, complement, estrogen response, and KRAS signaling hallmark gene sets were identified as Sema3D-related signaling pathways. The expression level of Sema3D was significantly correlated with a high abundance of several immune cells (neutrophils, eosinophils, and T helper cells). Conclusions: Transmembrane transporter Sema3D is an efficient prognostic biomarker for localized ccRCC patients, by playing the role of tumor suppressor in ccRCC. Sema3D can be a novel therapeutic target for ccRCC.

Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment.

Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line chemotherapy for CRPC. Although the therapy is successful in prolonging the survival of patients with CRPC, chemotherapy resistance develops due to the abnormal activation of the androgen receptor (AR) signaling pathway. Thus, to optimize DTX efficacy, continued maximum suppression of androgen levels and AR signaling is required. Here, we designed a prostate-specific membrane antigen (PSMA)-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment. Specifically, DTX was encapsulated into the hydrophobic inner layer, and the AR siRNA was then condensed with the cationic PEI block in the hydrophilic outer layer of the PEI-PLGA polymeric micelles. The micelles were further coated with PSMA-targeted anionic polyethylene glycol-polyaspartic acid (Di-PEG-PLD). In vitro and in vivo results demonstrated that the resulting Di-PP/AR-siRNA/DTX exhibited prolonged blood circulation, selective targeting, and enhanced antitumor effects. Consequently, Di-PP/AR-siRNA/DTX holds great potential for efficient CRPC treatment by combining chemotherapy and siRNA silencing of androgen-related signaling pathways.

Copy number variation of urine exfoliated cells by low-coverage whole genome sequencing for diagnosis of prostate adenocarcinoma: a prospective cohort study.

BACKGROUND: Non-invasive, especially the urine-based diagnosis of prostate cancer (PCa) remains challenging. Although prostate cancer antigen (PSA) is widely used in prostate cancer screening, the false positives may result in unnecessary invasive procedures. PSA elevated patients are triaged to further evaluation of free/total PSA ratio (f/t PSA), to find out potential clinically significant PCa before undergoing invasive procedures. Genomic instability, especially chromosomal copy number variations (CNVs) were proved much more tumor specific. Here we performed a prospective study to evaluate the diagnostic value of CNV via urine-exfoliated cell DNA analysis in PCa. METHODS: We enrolled 28 PSA elevated patients (≥ 4 ng/ml), including 16 PCa, 9 benign prostate hypertrophy (BPH) and 3 prostatic intraepithelial neoplasia (PIN). Fresh initial portion urine was collected after hospital admission. Urine exfoliated cell DNA was analyzed by low coverage Whole Genome Sequencing, followed by CNV genotyping by the prostate cancer chromosomal aneuploidy detector (ProCAD). CNVs were quantified in absolute z-score (|Z|). Serum free/total PSA ratio (f/t PSA) was reported altogether. RESULTS: In patients with PCa, the most frequent CNV events were chr3q gain (n = 2), chr8q gain (n = 2), chr2q loss (n = 4), and chr18q loss (n = 3). CNVs were found in 81.2% (95% Confidence Interval (CI) 53.7-95.0%) PCa. No CNV was identified in BPH patients. A diagnosis model was established by incorporating all CNVs. At the optimal cutoff of |Z|≥ 2.50, the model reached an AUC of 0.91 (95% CI 0.83-0.99), a sensitivity of 81.2% and a specificity of 100%. The CNV approach significantly outperformed f/t PSA (AUC = 0.62, P = 0.012). Further analyses showed that the CNV positive rate was significantly correlated with tumor grade. CNVs were found in 90.9% (95% CI 57.1-99.5%) high grade tumors and 60.0% (95% CI 17.0-92.7%) low grade tumors. No statistical significance was found for patient age, BMI, disease history and family history. CONCLUSIONS: Urine exfoliated cells harbor enriched CNV features in PCa patients. Urine detection of CNV might be a biomarker for PCa diagnosis, especially in terms of the clinically significant high-grade tumors.

Deaths and adverse events from adjuvant therapy with immune checkpoint inhibitors in solid malignant tumors: A systematic review and network meta-analysis.

Background: By prolonging overall survival and reducing disease recurrence rates, immune checkpoint inhibitors (ICIs) are an emerging adjuvant therapy option for patients with resectable malignant tumors. However, the safety profile (deaths and adverse events [AEs]) of adjuvant ICIs has not been fully described. Methods: We searched the literature for phase III randomized clinical trials that compared PD-1, PD-L1, and CTLA-4 inhibitors in solid malignant tumors. Incidences of death, discontinuation, AEs of any cause, treatment-related adverse events (TRAEs), and immune-related adverse events (IRAEs) were extracted for the network meta-analysis. Network meta-analyses with low incidence and poor convergence are reported as incidences with 95% confidence intervals (95% CIs). Results: Ten randomized clinical trials that included 9243 patients who received ICI adjuvant therapy were eligible. In total, 21 deaths due to TRAEs were recorded, with an overall incidence of 0.40% (95% CI: 0.26-0.61). The treatment-related mortality rates for ipilimumab (0.76%, 95% CI: 0.31-1.55) and atezolizumab (0.56%, 95% CI: 0.18-1.31) were higher than for pembrolizumab (0.24%, 95% CI: 0.10-0.56) and nivolumab (0.30%, 95% CI: 0.08-0.77). The most frequent causes of death were associated with the gastrointestinal (0.10%, 95% CI: 0.04-0.24) and pulmonary (0.08%, 95% CI: 0.03-0.21) systems. Compared with the control arm, we found that nivolumab (odds ratio [OR]: 2.73, 95% CI: 0.49-15.85) and atezolizumab (OR: 12.43, 95% CI: 2.42-78.48) caused the fewest grade ≥3 TRAEs and IRAEs. Commonly reported IRAEs of special interest were analyzed, and two agents were found to have IRAEs with incidences >10%, i.e., hepatitis for atezolizumab (14.80%, 95% CI: 12.53-17.32) and hypophysitis for ipilimumab (13.53%, 95% CI: 11.38-15.90). Conclusions: Ipilimumab and atezolizumab were correlated with higher treatment-related death rates than pembrolizumab and nivolumab, in which the gastrointestinal and pulmonary systems were mostly involved. Regarding severe TRAEs and IRAEs, nivolumab and atezolizumab are likely to be the safest agent, respectively. This study will guide clinical practice for ICI adjuvant therapies.

Development of Mitomycin C-Loaded Nanoparticles Prepared Using the Micellar Assembly Driven by the Combined Effect of Hydrogen Bonding and π-π Stacking and Its Therapeutic Application in Bladder Cancer.

Micelle is mainly used for drug delivery and is prepared from amphiphilic block copolymers. It can be formed into an obvious core-shell structure that can incorporate liposoluble drugs. However, micelles are not suitable for the encapsulation of water-soluble drugs, and it is also difficult to maintain stability in the systemic circulation. To solve these problems, a type of polymer material, Fmoc-Lys-PEG and Fmoc-Lys-PEG-RGD, was designed and synthesized. These copolymers could self-assemble into micelles driven by π-π stacking and the hydrophobic interaction of 9-fluorenylmethoxycarbony (Fmoc) and, at the same time, form a framework for a hydrogen-bonding environment in the core. Mitomycin C (MMC), as a water-soluble drug, can be encapsulated into micelles by hydrogen-bonding interactions. The interaction force between MMC and the polymers was analyzed by molecular docking simulation and Fourier transform infrared (FTIR). It was concluded that the optimal binding conformation can be obtained, and that the main force between the MMC and polymers is hydrogen bonding. Different types of MMC nanoparticles (NPs) were prepared and the physicochemical properties of them were systematically evaluated. The pharmacodynamics of the MMC NPs in vitro and in vivo were also studied. The results show that MMC NPs had a high uptake efficiency, could promote cell apoptosis, and had a strong inhibitory effect on cell proliferation. More importantly, the as-prepared NPs could effectively induce tumor cell apoptosis and inhibit tumor growth and metastasis in vivo.

Neoadjuvant Chemotherapy-Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study.

PURPOSE: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. MATERIALS AND METHODS: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. RESULTS: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. CONCLUSION: After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Enhancing anti-melanoma outcomes in mice using novel chitooligosaccharide nanoparticles loaded with therapeutic survivin-targeted siRNA.

Melanoma anti-tumor therapy remains a challenge. SiRNA-based therapies provide a powerful means, but limitations remain in its pharmaceutical applications owing to the lack of highly efficient delivery systems. In this study, to improve the siRNA delivery efficiency of chitooligosaccharide (COS), phenylboronic acid (PBA)-modified COS was synthesized and structurally characterized. PBA-modified COS was used to deliver survivin-targeted siRNA for melanoma treatment. The siRNA-loaded nanoparticles were prepared by a synergetic assembly of electrostatic complexation and chemical cross-linking. The particle size and zeta potential were characterized by dynamic light scattering, and transmission electron microscopy was utilized to observe the morphology of the nanoparticles. The cellular uptake of nanoparticles on B16F10 cells was studied by flow cytometry and confocal laser scanning microscopy. A luciferase reporter gene assay determined the gene silencing efficiency of different nanoparticles. As a result, the novel nanoparticles remarkably inhibited the proliferation of B16F10 cells in vitro and significantly inhibited the growth and metastasis of melanoma in vivo. In conclusion, PBA-modified COS can serve as a promising carrier for siRNA delivery in the field of anti-tumor therapy.

Improving glioblastoma therapeutic outcomes via doxorubicin-loaded nanomicelles modified with borneol.

Glioblastoma is a grade IV malignant glioma with high recurrence and metastasis and faces a therapeutic obstacle that the blood-brain barrier (BBB) severely hinders the brain entry and efficacy of therapeutic drugs. Previous studies suggest that borneol (BO) has been used to enhance interested drugs to penetrate the BBB. In this study, a borneol-modified nanomicelle delivery system was established to facilitate the brain entry of doxorubicin for glioblastoma therapy. Herein, we firstly conjugated borneol molecules with DSPE-PEG2000-COOH to synthesize a novel carrier DSPE-PEG2000-BO and also characterized its structure. Doxorubicin-loaded nanomicelles (DOX BO-PMs) were prepared using DSPE-PEG2000-BO via electrostatic interaction and the physicochemical properties were investigated. The average particle size and zeta potential of DOX BO-PMs were respectively (14.95 ±â€¯0.17)nm and (-1.27 ±â€¯0.06)mV, and the drug encapsulation efficiency and loading capacity in DOX BO-PMs were (95.69 ±â€¯0.49)% and (14.62 ±â€¯0.39)%, respectively. The drug release of the DOX BO-PMs exhibited a both time- and pH-dependent pattern. The results demonstrated that DOX BO-PMs significantly enhanced the transport efficiency of DOX across the BBB and also exhibited a quick accumulation in the brain tissues. The in vitro anti-proliferation assay results suggested that DOX BO-PMs exerted a strong inhibitory effect on proliferation of glioblastoma cells. Importantly, in vivo antitumor results demonstrated that DOX BO-PMs significantly inhibited the tumor growth and metastasis of glioblastoma. In conclusion, DOX BO-PMs can improve the glioblastoma therapeutic outcomes and become a promising nanodrug candidate for the application of doxorubicin in the field of glioblastoma therapy.

Reninoma coexisting with adrenal adenoma during pregnancy: A case report.

Reninoma is a rare form of secondary hypertension. The present study reported a case of reninoma that coexisted with an adrenal adenoma in a young female with secondary hypertension during pregnancy. The patient, a 31-year-old female exhibiting hypertension for >1 year, developed a mass in the right adrenal gland, which was detected by an ultrasound scan in the 33rd gestational week. In addition, a well-defined solid mass on the left kidney was detected by a magnetic resonance imaging scan1 month subsequent to the termination of the pregnancy. The blood pressure (BP) of the patient did not change subsequent to the laparoscopic right adrenalectomy. The patient subsequently underwent laparoscopic left partial nephrectomy 2 months later. The BP levels demonstrated a significant reduction from 177/115 to 125/80 mmHg in the same day postoperatively, and stabilized to be within the normal range. The BP level of the patient remained within the normal range subsequent to a 6-month follow-up. Pathological analysis revealed reninoma on the left kidney. The present study aimed to provide information for radiologists who may encounter this type of benign tumor in the future, which exhibits elevated BP levels.

Urologic cancer in China.

Cancer remains to be the second most common cause of death, and its incidence and mortality rates are increasing in China. According to the 2015 National Central Cancer Registry (NCCR) of China, the incidence of bladder cancer and prostate cancer ranked sixth and seventh, respectively, in male cancers. The majority of prostate cancer patients were diagnosed at an advanced stage. Early diagnosis of prostate cancer is the key to improve prostate cancer survival in China. Radical prostatectomy or radical radiotherapy is the main treatment for localized prostate cancer, and a comprehensive therapy based on androgen deprivation therapy is the treatment for advanced disease. The most common histologic types of bladder cancer in China were urothelial carcinoma, followed by adenocarcinoma and squamous carcinoma. The majority of patients were diagnosed using white-light cystoscopy with biopsy. Fluorescence and narrow-band imaging cystoscopy had additional detection rates and are becoming more popular. Following Chinese guidelines, most non-muscle invasive bladder cancer patients were treated with diagnostic transurethral resection and more than half of the muscle invasive bladder cancer patients were treated with radical cystectomy. Due to the increased detection rate of kidney tumors by ultrasound in physical examination, the number of incidentally diagnosed renal cell carcinoma has increased. Localized kidney cancers are more and more often treated by nephron-sparing surgery. Radical nephrectomy is still the main treatment option for patients with locally advanced renal cell carcinoma. Both laparoscopic and robotic-assisted laparoscopic surgeries have been used in big medical centers. Both testicular cancer and penile cancer have lower incidence levels than that in Europe. As we have an enormous population base, the absolute patient number is big. The diagnosis and treatment follows the Chinese guidelines. In China, both medical professionals and public should concern more on the early diagnosis, as there is not enough cancer prevention information available. Urologists should also take a more active role in educating the population.

[Clinical significance of serum levels of endostatin in patients with clear cell renal cell carcinoma].

OBJECTIVE: To assess serum levels of endogenous endostatin in patients with clear cell renal cell carcinoma (CCRCC) and to determine the relationship of these levels to tumor stage, grade. METHODS: From March 2004 to October 2008, preoperative serum were obtained from 138 consecutive patients with CCRCC (73 patients in T1, 39 patients in T2, 20 patients in T3, and 6 patients in T4) and 40 healthy controls. Serum levels of endostatin were measured by sandwich-ELISA. Associations between circulating endostatin levels and clinicopathologic factors and clinical outcome were determined. RESULTS: Endostatin levels did not differ significantly between the patients with CCRCC (93.1 microg/L) and healthy controls (78.9 microg/L, P > 0.05). Serum levels of endostatin were significantly higher in the T2-4 CCRCC patients (107.2 microg/L) than those of the T1 patients (80.4 microg/L, P < 0.01). No significant difference was found in the endostatin levels among the T2-4 patients, or between healthy controls and the T1 patients. The serum endostatin concentration was significantly higher in the metastasis group (118.4 microg/L) than in the no metastasis group (89.5 microg/L, P < 0.05), but there was no significant difference between patients with distant metastasis group (122.0 microg/L) and lymph nodes metastasis (110.0 microg/L, P > 0.05). Patients with G3-4 tumors had significantly higher endostatin levels (111.8 microg/L) than those of patients with G1 (80.4 microg/L) and G2 tumors (86.2 microg/L, P < 0.01), but endostatin levels did not differ significantly between the two groups (P > 0.05). CONCLUSION: Preoperative serum levels of endostatin elevated in patients with CCRCC and associated with higher stage and grade.

[Study of prognostic factors of ureter cancer].

OBJECTIVE: To evaluate the prognostic factors of ureter transitional cell carcinoma (TCC). METHODS: Between January 2001 and December 2005 133 TCC patients were treated. And the data was retrospectively analyzed. RESULTS: A mean age of the 133 patients was 68 years (range 43 - 87 years) at diagnosis. Altogether the non-invasive ureter TCC was found in 42 patients (31.6%) and the invasive ureter TCC in 91 patients (68.4%). Invasive ureter TCC growth was more common in distally located tumors (82.5%) compared to mid (62.5%) and proximal ureter (47.1%). Tumor stage, grade and location of the tumor were all correlated with disease specific survival in a univariate analysis. In a multivariate Cox analysis, tumor stage and grade were significantly associated with disease specific survival. CONCLUSIONS: More invasive tumors are found in ureter than in bladder. Ureter cancer is more frequently found in the distal part. Distally located ureteral tumors are more likely invading into the muscular cell layers compared to proximally located tumors. Tumor stage and grade are still the more important prognostic factors for ureter TCC.