Upper tract urothelial carcinoma (UTUC) presents a significant recurrence risk following radical nephroureterectomy (RNU). Patients on dialysis may experience unique clinical trajectories due to uremic states and altered immune responses.

To evaluate the impact of dialysis on intravesical recurrence and survival outcomes in patients with UTUC undergoing RNU, and to identify predictive factors influencing prognosis.

A retrospective cohort study analyzed 402 patients with non-metastatic UTUC treated with RNU between 2001 and 2014. Patients were stratified into dialysis (n = 66) and non-dialysis (n = 336) groups. Survival and recurrence outcomes were assessed using Kaplan-Meier and Cox regression analyses.

Dialysis patients were predominantly female, younger, and exhibited less advanced pathological tumor stages. Dialysis was associated with higher intravesical recurrence rates (p = 0.009), which were largely attributable to a history of bladder cancer (42.4% vs. 26.5%; p = 0.009). After adjustment for bladder cancer history, dialysis was not an independent predictor of bladder recurrence-free survival (BRFS). Advanced pT stages (HR: 3.9, p = 0.012) and prior bladder cancer were the primary factors influencing BRFS.

Dialysis does not independently worsen surgical outcomes or BRFS in UTUC patients post-RNU when accounting for prior bladder cancer. Prognostic models should integrate these findings to enhance individualized surveillance and treatment strategies.

Metachronous bladder recurrences after prior treatment for primary upper tract urothelial carcinoma (UTUC) can occur in ∼3% to 50% of patients. Because UTUC demonstrated distinct molecular alterations, bladder recurrences in these patients may be molecularly and phenotypically different compared to primary bladder carcinoma. We aim to study the BCG efficacy in patients with primary high risk nonmuscle invasive bladder cancer (P-NMIBC) and metachronous bladder recurrences after previous nephroureterectomy for UTUC (M-NMIBC).

We reviewed an IRB-approved prospective uro-oncology database of patients who underwent resection followed by BCG therapy for high grade NMIBC from 2017 to 2021. Clinicopathological parameters, intravesical therapies and the oncological outcomes were analyzed. Patients in the P-NMIBC group were matched to patients in the M-NMIBC cohort (control) via propensity score matching (PSM) to adjust for potential clinicopathological confounders. Nearest-neighbor PSM targeting a 4:1 ratio of study to control subjects was performed using a caliper of 0.2, aiming for an absolute standardized mean difference of <0.1 across key covariates. Secondary outcomes were progression to distant metastasis and overall survival. Logistic and cox regression analyses were performed to elucidate independent variables associated with intravesical recurrences and disease progression.

Of the 183 patients diagnosed with NMIBC, 35 patients were identified to have a history of UTUC with radical nephroureterectomy. EAU risk stratification revealed 50 (27.3%) intermediate risk, 107 (58.5%) high risk and 26 (14.2%) very high risk groups. P-NMIBC patients were more likely to have symptomatic presentation (79.7% vs. 23.9%), and a larger mean tumor size (25.7 mm vs. 15.4 mm) than M-NMIBC. The mean follow-up duration for the study was 34.0 months. In the unmatched analysis, M-NMIBC was associated with increased risk of HG intravesical recurrence post BCG compared to P-NMIBC (54.3% vs. 28.4%, P = 0.006, HR 2.14, 95% CI: 1.25-3.65) and increased risk of progression to MIBC (28.6% vs. 4.7%, P = 0.007, HR 4.19, 95% CI: 1.47-11.95). For the propensity-matched analysis, the control group consisted of 35 M-NMIBC matched to 123 P-NMIBC patients for similar demographics, EAU risk score and BCG doses. M-NMIBC again demonstrated a higher HG intravesical recurrence rate (54.3% vs. 22.8%, P = 0.001, HR 2.67, 95% CI: 1.50-4.77), progression to MIBC (28.6% vs. 5.7%, P = 0.022, HR 3.42, 95% CI: 1.20-9.75) and progression to distant metastasis (20.0% vs. 6.5%, P = 0.033, HR 3.02, 95% CI: 1.09-8.35). Overall survival in both groups were not significantly different in both unmatched and matched analysis.

Our study indicates that BCG treatment may be less effective for NMIBC patients with a history of UTUC, with a higher risk of intravesical recurrences and disease progression. This is an important consideration when counselling patients for BCG treatment and overall prognostication.

ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1) plays a critical role in multiple cancers; however, its role in bladder cancer (BC) remains largely unexplored. This study investigates the impact of ENPP1 on tumor progression, apoptosis, and the immune microenvironment through bioinformatics and experimental validation.

ENPP1 expression and clinical significance were analyzed using TCGA-BLCA, GEO datasets, and a local clinical cohort of 36 BC patients. Immune infiltration and functional enrichment were assessed using ESTIMATE, CIBERSORT, and clusterProfiler. Single-cell RNA sequencing (scRNA-seq) data examined ENPP1 expression in BC tissues. Stable ENPP1-overexpressing (UMUC3) and ENPP1-knockdown (J82) cell lines were established. Functional assays, including proliferation, migration, and apoptosis marker analysis, were performed.

RT-qPCR, Western blotting, and immunohistochemistry confirmed differential ENPP1 expression between BC tissues and adjacent normal tissues. High ENPP1 expression was associated with worse overall survival (OS), advanced T and N stages, and poor pathological grades. Functional assays demonstrated that ENPP1 overexpression enhanced proliferation, migration, and apoptosis resistance, while knockdown suppressed these processes. Mechanistically, ENPP1 overexpression reduced pro-apoptotic markers BAX and Caspase-3 while increasing anti-apoptotic Bcl-2. Immune infiltration analysis revealed a positive correlation between ENPP1 expression and M2 macrophage infiltration, alongside decreased CD8+ T cell infiltration. scRNA-seq identified high ENPP1 expression in cancer-associated fibroblasts and epithelial cells. Drug sensitivity analysis linked elevated ENPP1 expression to resistance against chemotherapies like gemcitabine and cytarabine.

ENPP1 drives tumor progression, modulates immune infiltration, and contributes to chemotherapy resistance in BC, underscoring its potential as a therapeutic target.

To evaluate the effects of adjuvant chemotherapy (AC) and adjuvant immunotherapy (AI) on the prognosis of patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU). A systematic review and meta-analysis was conducted using studies identified from PubMed, Cochrane Library, Embase, CENTRAL, and ClinicalTrials.gov up to September 2024. We performed pair-wise and network meta-analyses to evaluate survival outcomes, focusing on overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), recurrence-free survival, and metastasis-free survival. A total of 43 studies involving 13,132 patients were included. Pair-wise meta-analysis showed that AC significantly improved OS (HR 0.74, 95% CI 0.63-0.86, P = 0.0001), CSS (HR 0.74, 95% CI 0.60-0.90, P < 0.00001), and DFS (HR 0.61, 95% CI 0.51-0.75, P < 0.00001). A pooled analysis of three RCTs with 384 UTUC patients showed that AI did not significantly improve DFS (HR 1.19, 95% CI 0.87-1.64, P = 0.28) or OS (HR 1.28, 95% CI 0.81-2.03). Network meta-analysis suggested that combining AC with AI could offer better DFS than AC alone, with AC outperforming AI. Ranking analysis indicated that MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) was the most effective for OS and CSS improvement, followed by GC (gemcitabine and cisplatin). AC improves the prognosis of UTUC patients, whereas the results with AI are less promising. AC shows better outcomes than AI after RNU. Preliminary evidence suggests that combining AC with AI may enhance DFS, but further research is needed to confirm its effectiveness.

Neddylation, as a type of post-translational modification, plays a key role in cancer development. However, the biological characteristics and clinical prognosis value of Neddylation-related genes (NRGs) signatures in clear cell renal cell carcinoma (ccRCC) remain undetermined. Here, we identified two subtypes of NRGs in ccRCC based on TCGA data and constructed a NRGs risk signature (NRGS). Survival analysis, ROC curves, and nomograms showed that NRGS was an important predictor of prognosis in patients with clear cell renal cell carcinoma. We further revealed important correlations between NRGS and clinicopathological features, gene mutations, drug sensitivity, and immune cell infiltration. High NRGS indicates a poorer prognosis for kidney cancer, but higher remission rates with immunotherapy. Drug sensitivity also varies across risk groups. UBB was identified as a hub gene for NRGS and was downregulated in ccRCC, which is associated with poor prognosis. In conclusion, this study provides strategies for predicting prognosis and individualizing treatment for ccRCC.

To development of a preoperative CT-based radiomics model for predicting muscle invasion in patients with upper tract urothelial carcinoma below T3 stage.

163 consecutive patients who underwent radical nephroureterectomy for stage pT1-2 UTUC were retrospectively enrolled two medical centers (116 patients in training data and 47 patients in external validation data). Lesion segmentation, extraction and selection of radiomic features on pre-surgical CT urography, development and validation of predictive models were performed. Risk stratification of UTUC was evaluated. The diagnostic performance of the radiomics model and risk stratification was analyzed. Reference standard was histopathological analysis.

Among 163 patients (mean age, 52 years ± 9 [standard deviation], 97 men), 61.5% had pT2 grade tumors. 1165 features with intraclass coefficients > 0.75 were retained for least absolute shrinkage and selection operator (LASSO) regression. Nine radiomic features with non-zero coefficients on LASSO regression were selected from the training dataset and used for constructing the radiomics model. Good discrimination capability of the predictive model was observed, as AUCs were 0.859 (95% CI, 0.782-0.917) in the training dataset and 0.821 (95% CI, 0.682-0.918) in the validation dataset, respectively. Based on judgement by the model, When the tumor length diameter > 3 cm, combining ureteroscopy biopsy would improve sensitivity and NPV to 0.86 (95% CI, 0.776-0.922), 0.81 (95% CI, 0.714-0.903).

The preoperative radiomics model showed promising diagnostic performance in predicting UTUC muscle invasion. This could help patients receive more accurate risk classification, especially help patients avoiding radical nephroureterectomy.

Upper tract urothelial carcinoma (UTUC) is a rare malignancy, representing only 5-10% of urothelial carcinoma. The mainstay of treatment for high-risk patients is radical nephroureterectomy. Given the aggressive behavior of this disease, additional treatments could be required perioperatively in terms of chemotherapy (CHT), either in a neoadjuvant or adjuvant setting. On the other hand, low-risk and selected cases can be managed with kidney-sparing surgery (KSS). The ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST) is an ongoing international, multicenter registry of patients undergoing surgery for UTUC. After conducting a literature search in February 2025 using the MEDLINE (via PubMed) and Embase databases, we identified 14 studies based on the ROBUUST data analyses. There are several key topics concerning UTUC that remain under debate and were therefore addressed in these studies, focusing on preoperative evaluation and planning, surgical techniques and intraoperative procedures, additional perioperative treatments, and outcomes. The ROBUUST registry has served as a valuable source for a growing body of investigations focusing on various aspects of UTUC treatment planning, decision-making, and outcomes, providing innovative tools and enabling large-scale, novel analyses.

To evaluate the impact of tumour location on the survival outcomes of patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU).

Patients with ureteral urothelial carcinoma (UUC) or renal pelvic urothelial carcinoma (RPUC) of the Clinical Research Office of the Endourology Society (CROES)-UTUC registry were analyzed. Study outcomes included overall survival (OS), cancer-specific survival (CSS), intravesical recurrence-free survival (IRFS), and progression-free survival (PFS), which were compared using Kaplan-Meier method with log-rank test. Propensity score matching (PSM) was performed to balance the differences in tumour features between the two groups.

The UUC and RPUC groups consisted of 309 (41.9%) and 429 (58.1%) patients, respectively. RPUC group had larger tumour size (77.9% ≥ 2 cm vs 67.0% in UUC, p < 0.01), and more T3/T4 tumours (36.4% vs. 22. 0%, p < 0.01). The UUC group exhibited worse PFS compared to the RPUC group ( p = 0.029 for the initial analysis and p = 0.013 after PSM). However, there were no significant differences in OS (p = 0.088 before PSM and p = 0.255 after PSM), CSS (p = 0.106 before PSM and p = 0.101 after PSM), or IRFS (p = 0.112 before PSM and p = 0.28 after PSM) between the two groups.

Patients with ureteral urothelial carcinoma exhibited worse PFS compared to those with renal pelvic urothelial carcinoma. However, no significant differences were observed in OS, CSS, or IRFS between the two tumour locations. UTUC patients should be counselled about their individualized prognosis accordingly.

NCT02281188.

The protective role of marriage has been identified in various cancers, but its effect on the overall urological system remains unclear. Patients diagnosed with bladder cancer (BCa), renal cell carcinoma (RCC), and upper tract urothelial carcinoma (UTUC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into married and unmarried groups based on their marital status. A binary multivariable logistic regression was used to explore the effect of marriage on the diagnosis of urological cancers. One-to-one propensity score matching (PSM) was employed to reduce baseline differences between the two groups. Multivariable Cox regression analysis and subgroup analysis were conducted to investigate the impact of marriage on cancer-specific survival (CSS). A total of 162,544 patients were included in the study, with a median follow-up period of 6.2 years (IQR 2.3-9.8 years). Among them, 104,706 (64.4%) were married, and 57,838 (35.6%) were unmarried. Married patients had a lower risk of being diagnosed with stage III/IV disease compared to unmarried patients (OR 0.94, 95% CI 0.92-0.96, p < 0.001), but this trend was only significant in BCa (OR 0.88, 95% CI 0.84-0.91, p < 0.001), but not in RCC (OR 0.98, 95% CI 0.94-1.01, p = 0.172) or UTUC (OR 1.03, 95% CI 0.95-1.12, p = 0.523). After PSM, 47,975 patients were included in each group, and marriage was found to be an independent protective prognostic factor for CSS (HR 0.81, 95% CI 0.79-0.83, p < 0.001), but this was not significant in UTUC (HR 0.95, 95% CI 0.88-1.03, p = 0.244). Across the entire urological system, marriage is an independent protective predictor for both diagnosis and survival, but the effect varies among different types of cancers.

To evaluate the role of extirpative surgery for the primary tumor in metastatic upper tract urothelial carcinoma (mUTUC).

The PubMed, Web of Science, and Cochrane Library were searched on July 2024 to identify relevant studies according to the Preferred Reporting Items for Systematic Review (PRISMA) statement. Studies were eligible for analysis if they compared oncologic outcomes between mUTUC patients who underwent surgical resection of the primary tumor and patients who did not. Cancer-specific survival (CSS) and overall survival (OS) were assessed using multivariate logistic regression analyses. We identified 2686 reports, of which 11 articles comprising 12 833 records were selected for this systematic review. Eight and three studies used Surveillance Epidemiology and End Results (SEER) and National Cancer Database (NCDB) databases, respectively. Surgical resection of the primary tumor was significantly associated with better CSS and OS in patients with mUTUC. Among the 5353 mUTUC patients included in our meta-analysis, radical nephroureterectomy (RNU) was independently associated with better OS with a pooled hazard ratio (HR) of 0.62 [95% confidence interval (CI) 0.54-0.72, P  < 0.05]. Subgroup analyses of studies restricted to mUTUC patients with distant lymph node metastasis ( n  = 1372) revealed RNU to be independently associated with better OS with pooled HR: 0.44 (95% CI 0.28-0.67, P  < 0.05) together with systemic chemotherapy, primary tumor site in the ureter, lower T stage, and no locoregional lymph node involvement.

Surgical resection of the primary tumor offers oncologic survival benefits in select patients with mUTUC. However, in the absence of data from prospective randomized studies, it is essential to evaluate each patient individually as part of a collaborative multidisciplinary shared decision working with the patient.

Renal cell carcinoma (RCC) is the third most common malignant tumor in the urinary system, often presenting with distant metastases at diagnosis. Approximately one-quarter of patients undergoing nephrectomy experience distant recurrence. Despite the recent advancements in combination-targeted and immune checkpoint inhibitor therapies, the development of new therapeutic strategies and the identification of biomarkers for metastatic risk remain crucial. The study found that high SPC25 expression is closely associated with poor clinical outcomes, and knocking down SPC25 significantly inhibits tumor cell proliferation and migration. Non-targeted metabolomics analysis also revealed that SPC25 knockdown reduces tumor cell activity, resulting in a low-invasive state. Additionally, this study utilized high-throughput molecular docking to screen small molecule drugs targeting SPC25, aiming to find drugs that inhibit RCC metastasis. The research discovered that mefloquine, at concentrations that do not significantly kill tumor cells, can markedly inhibit RCC metastasis. It was the first to report that mefloquine achieves its anti-metastatic effects by binding to SPC25 and inhibiting epithelial-mesenchymal transition. These results suggest that SPC25 has the potential to serve as an early biomarker for metastatic risk in RCC and highlight a novel strategy where mefloquine inhibits RCC metastasis through SPC25 binding, offering new avenues to improve the prognosis of RCC patients.

To investigate the risk of upper urinary tract urothelial carcinoma (UTUC) in patients with non-muscle-invasive bladder cancer (NMIBC), in relation to the primary NMIBC tumour risk categories, calendar time trends and intravesical Bacillus Calmette-Guerin (BCG) treatment.

All patients with primary NMIBC diagnosed 1997-2019 registered in Bladder Cancer Data base Sweden (BladderBaSe) 2.0 were included in the study. Risk of UTUC was calculated by cumulative incidence proportion using competing risk analysis. Associations with risk of UTUC by tumour stage category, calendar time, and intravesical BCG treatment was estimated by hazard ratios from multivariable Cox regression analyses.

Of 36 038 NMIBC patients, 537 (1.5%) were diagnosed with UTUC during a mean time of 7 years in follow-up. The risk of UTUC within 10 years from NMIBC diagnosis was 1.7% (95% 1.6-1.9) with highest estimates for TaG3/CIS. Stage T1 and TaG3/CIS, as compared with TaG1-2 was associated to risk, with stronger associations during later calendar times. Within high-risk NMIBC patients (CIS/TaG3/T1), intravesical BCG treatment was associated with higher risk of UTUC.

This large study of more than 36 000 patients with NMIBC found 1.7% (95% 1.6-1.9) risk of UTUC within 10 years of diagnosis. Differences by tumour stage category indicate the need for refined studies accounting for tumour characteristics, location in the bladder and given treatment to optimise follow-up routines in NMIBC.

To investigate the pattern and risk factors of local recurrence and intravesical recurrence of ureteral upper tract urothelial carcinoma (UTUC) following segmental ureterectomy (SU).

From February 2012 to August 2021, a retrospective analysis was conducted on patients following SU. Univariate and multivariate Cox regression analysis were used to evaluate the risk factors. Kaplan-Meier curves were employed to illustrate survival outcomes.

Among 88 patients, 50 (57%) were male, with a median age of 71 (IQR: 62-77) years. The procedures of ureteral reconstruction included ureteral reimplantation in 77 (88%) cases, ureteroureteral anastomosis in 9 (10 %) cases, Boari flap ureteroplasty with psoas hitch in 1 (1%) case, and cutaneous ureterostomy in 1 (1%) case. The median follow-up time was 44.5 months. The 3-year rate of local recurrence, lymph node metastasis, ipsilateral upper urinary tract recurrence and intravesical recurrence was 31.6%, 19.0%, 22.2% and 35.7%, respectively. G3 (HR = 3.355, 95% CI 1.375-8.184, P = 0.008), and lymphatic vascular infiltration (HR = 3.127, 95% CI 1.043-9.373, P = 0.042) were independent risk factors for local recurrence. G3 (HR = 3.782, 95% CI 1.036-13.812, P = 0.044) was an independent risk factor for lymph node metastasis. Sarcomatoid differentiation (HR = 3.943, 95% CI 1.087-14.308, P = 0.037) was an independent risk factor for ipsilateral upper urinary tract recurrence. Previous or concurrent bladder cancer (HR = 3.280, 95% CI 1.667-6.453, P = 0.001) and sarcomatoid differentiation (HR = 4.442, 95% CI 1.317-14.989, P = 0.016) were independent risk factor for intravesical recurrence. The most common regions for bladder recurrence were posterior wall (21%), same lateral wall (16%) and trigon (16%).

SU is a feasible treatment for selected UTUC patients, yet it is associated with a considerable risk of local and intravesical recurrence. Careful monitoring and active adjuvant therapy are essential to minimize the recurrence rate for patients with risk factors.

Bladder cancer development is closely associated with the dynamic interaction and communication between M2 macrophages and tumor cells. However, specific biomarkers for targeting M2 macrophages in immunotherapy remain limited and require further investigation.

In this study, we identified key co-expressed genes in M2 macrophages and developed gene signatures to predict prognosis and immunotherapy response in patients. Public database provided the bioinformatics data used in the analysis. We created and verified an M2 macrophage-related gene signature in these datasets using Lasso-Cox analysis.

The predictive value and immunological functions of our risk model were examined in bladder cancer patients, and 158 genes were found to be significantly positively correlated with M2 macrophages. Moreover, we identified two molecular subgroups of bladder cancer with markedly different immunological profiles and clinical prognoses. The five key risk genes identified in this model were validated, including CALU, ECM1, LRP1, CYTL1, and CCDC102B, demonstrating the model can accurately predict prognosis and identify unique responses to immunotherapy in patients with bladder cancer.

In summary, we constructed and validated a five-gene signature related to M2 macrophages, which shows strong potential for forecasting bladder cancer prognosis and immunotherapy response.

After radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), prognosis is poor for high-risk patients. This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients.

This phase II trial (ClinicalTrials.gov identifier: NCT04617756) included patients with nonmetastatic, high-grade UTUC, on the basis of the ureteroscopic biopsy or urine cytology, and/or infiltrative aspect of the renal pelvis/ureteral wall by computed tomography imaging. Before RNU, patients received durvalumab plus gemcitabine/cisplatin (cohort 1) or durvalumab plus gemcitabine/carboplatin (cohort 2) once every 3 weeks for a total of four cycles (cohort choice on the basis of the glomerular filtration rate). The primary objective was the pathologic complete response (ypT0) rate in each cohort.

Fifty patients were enrolled between 2021 and 2024 (31 in cohort 1; 19 in cohort 2). Median age was 68 years (range, 38-79), and 59% were men. Forty-five patients received four cycles of treatment, three patients three cycles, and one patient two cycles. Five patients switched to carboplatin during treatment. At surgery (N = 45 patients), rates of pT0 were 13% (4/29) in cohort 1 and 5% (1/19) in cohort 2. Fifty percent (15/29) of patients were pTa/pT1 in cohort 1, and 42% (8/19) in cohort 2. No severe immunotherapy-mediated toxicity was observed. Four patients had chemotherapy-related grade 3 neutropenia, one grade 4; one patient had grade 3 thrombopenia, one grade 4; and four patients had grade 3 anemia.

Although our negative study did not meet its primary end point in either cohort, the combination of durvalumab and platin-based chemotherapy, especially cisplatin, showed promising results in terms of downstaging. The safety profile was good and the surgical risk was not increased.

Urinary actinomycosis is a rare condition, often mimicking a urinary tract tumor. Due to its low prevalence, it can be challenging to diagnose and may be mistaken for malignancies. A 33-year-old female patient with a history of type 2 Diabetes Mellitus and recurrent urinary tract infections presented to the emergency room with right renal fossa pain radiating to the right hypochondrium, fever with chills, nausea, and vomiting. Physical examination revealed a positive Giordano sign and tenderness at the ipsilateral middle and upper ureteral points. A contrast-enhanced CT scan showed a mass infiltrating the distal third of the right ureter, causing retrograde dilatation and hydronephrosis. Additionally, a liver injury with both liquid and solid components was observed. Therefore, given the suspicion of a urothelial tumor, a diagnostic cystoscopy and ureteroscopy were performed. Using interventional radiology, an abscessed liver lesion was drained, yielding purulent fluid. The histopathological examination revealed no evidence of malignancy. However, due to the strong suspicion of upper urinary tract urothelial carcinoma, a right radical nephroureterectomy with bladder cuff excision and retroperitoneal lymphadenectomy was performed. Histopathological examination ultimately confirmed urinary actinomycosis. Consequently, antibiotic therapy with oral amoxicillin 2 g every 12 h was initiated, leading to a good clinical response. Despite its low incidence, urinary actinomycosis should be considered as a differential diagnosis in cases suspected of urothelial tumors in the upper urinary tract. Increased awareness of this rare condition may help prevent unnecessary surgical interventions.

Given the conflicting evidence currently available in the literature, our aim was to assess the prognostic and predictive values of the deficient mismatch repair (dMMR) phenotype in a large cohort of upper tract urothelial carcinoma (UTUC) patients.

Based on our national network, we performed a retrospective multicenter study including 281 UTUC patients treated with radical nephroureterectomy between 2000 and 2015 at ten French hospitals. The dMMR phenotype as well as PD-L1 and PD-1 expression were determined using immunohistochemistry analyses based on 2-mm-core tissue microarrays. Multivariable Cox regression models were fitted to assess the impact of the dMMR phenotype on recurrence-free (RFS), cancer-specific (CSS), and overall (OS) survival using interaction terms to test the heterogeneity of the treatment effect of adjuvant chemotherapy (AC). Multivariable logistic regression models were also fitted to assess the impact of the dMMR phenotype on PD-L1 and PD-1 expression.

Overall, 76 (27.0%) patients had a dMMR phenotype, which was an independent predictor of prolonged RFS (hazard ratio [HR] = 0.41; 95% confidence interval [CI] = [0.21-0.83]; p = 0.01), CSS (HR = 0.38; 95% CI = [0.18-0.83]; p = 0.02), and OS (HR = 0.44; 95% CI = [0.22-0.89]; p = 0.02), with a significant interaction with the use of AC in multivariable Cox regression models (all pinteraction < 0.05). Subgroup analyses showed that the use of AC was significantly associated with prolonged RFS (HR = 0.14; 95% CI = [0.06-0.30]; p < 0.001), CSS (HR = 0.10; 95% CI = [0.03-0.29]; p < 0.001), and OS (HR = 0.23; 95% CI = [0.10-0.54]; p = 0.001) in non-dMMR patients only, without any significant benefit in dMMR patients (all p > 0.05). In multivariable logistic regression analyses, the dMMR phenotype was significantly associated with inverse PD-L1 (OR = 0.20; 95% CI = [0.10-0.80]; p = 0.001) and PD-1 (OR = 0.36; 95% CI = [0.16-0.79]; p = 0.01) expression.

We observed that the dMMR phenotype was associated with favorable pathological characteristics and prognosis in UTUC patients, despite conferring decreased sensitivity to AC and lower PD-L1 or PD-1 expression.

ATPase H+ transporting V0 subunit b (ATP6V0B) is an essential component of the vacuolar ATP multi-protein complex (V-ATPase) associated with energy metabolism. However, information on its role and mechanism of action in bladder cancer (BCa) and other tumors is not clear.

In this study, we evaluated the expression of ATP6V0B in BCa and its correlation with patient survival outcomes by performing public database analysis, as well as, RT-qPCR and Western blotting assays. We also investigated the effect of altering the level of expression of ATP6V0B on the malignant behavior of BCa cells at the cellular level by conducting the CCK-8 assay and Transwell assay. In vivo experiments involved subcutaneous injection of stable ATP6V0B-knockdown BCa cells into nude mice to assess the influence of ATP6V0B on tumorigenesis. Additionally, bioinformatics analysis was combined with other methods to predict that ATP6V0B may modulate signaling pathways.

The findings showed that the expression of ATP6V0B increased in BCa tissues, and patients exhibiting high levels of this protein had a poorer prognosis. Additionally, our results showed that ATP6V0B functions as an oncogene and stimulates the proliferation, invasion, and migration of BCa cells in vitro. In vivo animal studies showed that downregulating ATP6V0B hindered the growth of BCa. Regarding the mechanism of action of ATVP60VB, we found that ATVP60VB can activate the PI3K/AKT signaling pathway through Progestin and AdipoQ Receptor Family Member 4 (PAQR4) -mediated upregulation.

To summarize, the results of this study indicated that an increase in the level of expression of ATP6V0B in BCa tissues and cells is associated with unfavorable patient prognosis due to its tumor-promoting effects via upregulation of the PAQR4/PI3K/AKT signaling pathway.

Upper tract urothelial carcinoma (UTUC) is a rare yet aggressive malignancy, representing 5-10% of urothelial cancers. While radical nephroureterectomy (RNU) has traditionally offered excellent oncological control, it compromises renal function. Recent advancements have shifted the paradigm toward kidney-sparing strategies in select cases. This review highlights innovations in UTUC diagnosis and conservative management, focusing on emerging imaging techniques, noninvasive biomarkers, and minimally invasive treatments.

Advances in multiparametric MRI and radiomics have improved diagnostic accuracy and risk stratification. Moreover, noninvasive biomarkers - including circulating tumor DNA, microRNAs, and urinary methylation assays - provide promising tools for early detection and surveillance. Kidney-sparing approaches such as endoscopic laser ablation and segmental ureterectomy have demonstrated comparable oncologic outcomes in low-risk patients. Moreover, topical therapies, including intracavitary treatments like UGN-101, offer a promising minimally invasive option.

The conservative management of UTUC is evolving, driven by advancements in imaging, molecular diagnostics, and minimally invasive treatments. While kidney-sparing approaches are increasingly utilized in low-risk patients, further prospective studies are needed to validate their efficacy.

Guidelines recommend endoscopic ablation in select upper urinary tract urothelial carcinoma (UTUC) patients. To test for differences in cancer-specific mortality (CSM) and other-cause mortality (OCM) in localized non-invasive low-grade UTUC with tumor size < 2 cm treated with endoscopic ablation vs. radical nephroureterectomy.

Within Surveillance, Epidemiology, and End Results database (2000-2020), we identified UTUC patients treated with either endoscopic ablation or radical nephroureterectomy. After propensity score matching (ratio 1:1), cumulative incidence plots, and competing risks regression models addressed CSM and OCM.

Of 249 included UTUC patients, 66 (27%) were treated with endoscopic ablation vs. 183 (73%) with radical nephroureterectomy. Over the study period, endoscopic ablation use increased from 10 to 45% (p = 0.01). After 1:1 propensity score matching, 66 of 66 (100%) endoscopic ablation and 66 of 183 (36%) radical nephroureterectomy patients were included. Ten-year CSM rates were 15.7% after endoscopic ablation vs. 13.9% after radical nephroureterectomy (p = 0.9). Ten-year OCM rates were 46.3% after endoscopic ablation vs. 57.9% after radical nephroureterectomy (p = 0.5). In multivariable competing risks regression models, CSM (hazard ratio 1.10; p = 0.9) and OCM (hazard ratio 0.83; p = 0.5) did not differ according to use of endoscopic ablation vs. radical nephroureterectomy.

Endoscopic ablation of localized non-invasive low-grade UTUC with tumor size < 2 cm results in absence of cancer-control outcome differences relative to radical nephroureterectomy. This observation validates the current guideline recommendations.

A percutaneous biopsy of suspected upper tract urothelial carcinoma (UTUC) is considered contraindicated due to potential safety concerns. This study evaluated the risk of tumor seeding along the needle track following a percutaneous needle-core biopsy for UTUC, along with diagnostic yield and oncological outcomes.

We conducted a retrospective multicenter study involving 53 patients who underwent a percutaneous biopsy for upper urinary tract urothelial carcinoma between 2012 and 2022. The primary endpoint was tumor recurrence along the biopsy needle track, assessed through a centralized review of follow-up cross-sectional imaging. The secondary endpoints included biopsy yield, histological concordance in tumor stage and grade compared with final histology in cases of nephroureterectomy, complication rates, and overall oncological outcomes.

The cohort consisted of 60% male patients with a mean age of 69 yr. At diagnosis, 32% had metastatic disease. A biopsy was performed due to diagnostic uncertainty regarding renal cell carcinoma or other diseases, distant metastases, or failed endoscopic biopsy. The median follow-up imaging time was 8.3 mo. Tumor track seeding occurred in one case (1.9%) 5 mo after the procedure. Biopsy yield was 94%, with histological concordance rates of 78% for tumor stage and 100% for grade. Complications occurred in 14.8% of cases, including two (3.7%) cases of obstructive pyelonephritis requiring endoscopic management.

A percutaneous biopsy is a useful diagnostic tool for high-grade invasive upper urinary tract urothelial carcinoma, with a low risk of tumor track seeding. It provides critical histological confirmation, facilitating future research on neoadjuvant systemic therapies.

In this study, we report that KIF26B is upregulated in bladder cancer and acts as an independent prognostic factor. Knockdown of kif26b blocks the proliferation, metastasis, and cisplatin resistance of bladder cancer cells. Mechanistically, TCF4 potently stimulates kif26b transcription by directly binding to its promoter. KIF26B activates the Wnt/β-catenin signaling pathway through association with TRAF2 and thus promotes the formation of the TCF4/β-catenin complex. KIF26B promotes the protein stability of TRAF2 by facilitating the OTUB2-mediated de-ubiquitination of TRAF2. Importantly, KIF26B promotes the nuclear translocation of TRAF2 through enhancing its association with IPO11, a process that is dependent on the C-terminal domain of β-catenin. Additionally, phosphorylation of tyrosine 78 in TRAF2 is essential for its binding to KIF26B in response to Wnt3a signaling. Furthermore, a KIF26B/TRAF2/PD-L1 axis is identified in bladder cancer, and combined therapy of anti-B7-H3 antibody with kif26b knockdown yields superior anti-tumor effects.

The efficacy of combined neoadjuvant and adjuvant therapy (CNAT) in upper tract urothelial carcinoma (UTUC) remains unclear despite its demonstrated potential in bladder urothelial carcinoma. High-risk features- clinical stage ≥ T3, node-positive disease, multifocality, high-grade pathology, hydronephrosis, and large tumor size - are associated with poor prognosis in UTUC. We investigated the oncological outcomes of CNAT versus adjuvant therapy (AT) alone in high-risk UTUC patients.

We analyzed perioperative data from 2433 patients with UTUC (2015-2023) across 17 centers in the US, Europe, and Asia. Propensity score matching was performed using preoperative clinical T and N stages. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS).

Among 285 high-risk UTUC patients, 76 matched patients (38 CNAT, 38 AT) were analyzed after matching, with a median follow-up of 15 months. CNAT and AT groups had comparable oncological outcomes: 2-year OS (72.9% vs. 71.8%; p = 0.89), CSS (76.7% vs. 75.3%; p = 0.92), RFS (30.1% vs. 39%; p = 0.97), or MFS (45.5% vs. 44.7%; p = 0.91), respectively. Cox regression showed no significant survival benefit of CNAT over AT after adjusting for clinical and pathological factors (HR for OS: 1.06; p = 0.9).

In this large multicenter international cohort, our findings suggest that CNAT does not provide a clear advantage over AT alone in patients with high-risk UTUC. Prospective randomized trials are needed to clarify the role of multimodal therapy in UTUC management.

The aim of this study was to determine the impact of the preoperative creatinine-cystatin C ratio (CCR) on the survival prognosis of patients following radical nephrectomy (RNU) for upper tract urothelial carcinoma (UTUC).

The retrospective analysis was conducted on UTUC patients who underwent radical nephrectomy (RNU) at West China Hospital between January 2009 and December 2019. The endpoint of the study was cancer-specific survival (CSS). Kaplan-Meier curves were used to estimate survival, and Cox proportional hazards modelling was used to assess risk. Nomograms were developed to predict CSS at 3 and 5 years of age, and the predictive power was assessed.

A critical CCR of 59.61 µmol/mg was demonstrated to affect 504 patients with UTUC who had undergone RNU. A correlation was identified between a lower preoperative CCR and a considerably worse CSS. In patients with UTUC, CCR was identified as an independent risk factor for CSS, particularly in patients with locally advanced UTUC (pT ≥ 3) (HR: 1.84, 95% CI: 1.14, 2.97). Moreover, the CCR-based nomogram exhibited robust predictive capacity, with areas under the curve for the 3- and 5-year CSS reaching 0.823 and 0.793, respectively.

Preoperative CCR is an independent predictor of CSS in UTUC patients receiving RNU treatment. As such, it should be viewed as a potentially useful customized tool in therapeutic decision-making.

Urothelial carcinoma (UC) is a common malignancy that imposes a significant health care burden. Current diagnostic methods are limited by their invasiveness and low sensitivity, particularly for detecting low-grade tumors. Noninvasive, accurate, and reliable diagnostic tests for an early diagnosis of UC are urgently needed.

UC-specific DNA methylation biomarkers were identified by combining public datasets from The Cancer Genome Atlas and Gene Expression Omnibus with a cohort from Renji Hospital (n = 50). Using the Least Absolute Shrinkage and Selection Operator regression, we developed a diagnostic model, termed the UriMee model, by selecting key biomarkers from a model cohort (n = 322) and subsequently validating it in an independent cohort (n = 131). The diagnostic performance of the assay was evaluated and compared with that of urine cytology.

At 30% threshold probability, the UriMee model demonstrated high sensitivity (92%) and specificity (92%) in distinguishing UC cases, with particularly strong performance in early-stage tumors (83% sensitivity for Ta, 93% for T1, and 100% for Tis). It significantly outperformed urine cytology, offering greater sensitivity (90% vs 25%, p < 0.001) while maintaining comparable specificity. Additionally, the model was highly effective in identifying upper tract urothelial carcinoma (UTUC), achieving sensitivity of 96%. The study's limitations include the necessity for larger multicenter studies and long-term follow-up to validate the findings and assess the test's effectiveness across diverse populations, as well as its utility in monitoring disease progression and recurrence.

The UriMee test demonstrated high sensitivity and specificity, particularly in detecting early-stage tumors and UTUC, significantly outperforming traditional methods.

Conventional robotic-assisted laparoscopic radical nephroureterectomy (RARNU) with bladder cuff excision (BCE) often requires changes in patient position, trocar placement, or robotic docking, increasing procedural complexity. Retroperitoneal single-position surgeries are rare and primarily focus on lateral and supine positions, which still present constraints. This study aims to investigate the safety and the feasibility of prone retroperitoneal RARNU (prRARNU) with BCE in single position, and to compare the results with clinical data on retroperitoneal RARNU (rRARNU) reported in the literature. From August 2023 to April 2024, four patients [mean age: 68.8 years; BMI: 24.3 kg/m2] with upper urinary tract urothelial carcinoma (UTUC) underwent prRARNU with BCE. Demographic, perioperative, and follow-up data were collected. Two patients had American Society of Anesthesiology score ≥ 3. All surgeries were successfully completed without open surgery conversions and blood transfusions. Mean operation time was (165 ± 6.7) minutes, estimated blood loss was (87.5 ± 41.5) mL, intraoperative PaCO2 was (39.5 ± 3.0) mmHg, drainage tube removal time was (3.3 ± 0.4) days, postoperative hospital stay was (3.8 ± 0.8) days, and postoperative 3-dayHb and eGFR decreased by (11.3 ± 4.0) g/L and (13.1 ± 20.5) mL/min/1.73 m2 respectively. After a median follow-up of 15.1 months, the mean eGFR at postoperative month 3 was (45.2 ± 15.9) mL/min/1.73 m2, with no complications or tumor recurrence. One patient died of acute heart failure unrelated to UTUC. Compared to published data on rRARNU, prRARNU with BCE demonstrated satisfactory outcomes, suggesting its safety, feasibility, with short operation time, and quick recovery.

Upper tract urothelial carcinoma (UTUC) is associated with poor survival. Recent studies have evaluated whether the presence of histological subtypes or divergent differentiation (HS/DD) is associated with worse UTUC prognosis. Our aim was to assess the relationship between HS/DD and clinicopathological features and oncological outcomes for patients with UTUC undergoing radical nephroureterectomy (RNU) without investigating causal pathways.

A literature search was conducted in September 2024. Patients with UTUC who underwent RNU were included. The main outcomes were differences in clinicopathological features and oncological outcomes between HS/DD and pure urothelial carcinoma (PUC) groups.

We included 22 studies involving 14 407 patients in our review. HS/DD was present in 14% of tumours. In comparison to PUC, the HS/DD group had significantly higher rates of ≥pT3 stage, high-grade tumours, lymph node invasion (LNI), lymphovascular invasion (LVI), and receipt of adjuvant chemotherapy. Pooled results revealed that the HS/DD group had significantly worse cancer-specific survival (CSS) (hazard ratio [HR] 1.65, 95% confidence interval CI] 1.39-1.96), overall survival (OS; HR 1.84, 95% CI 1.52-2.22) ,and recurrence-free survival (RFS; HR 1.64, 95% CI 1.43-1.87). Intravesical RFS (IVRFS) and urothelial RFS (URFS) were comparable between the groups.

Our findings suggest that UTUC with HS/DD is associated with more advanced/aggressive features, such as higher pathological stage and grade, LNI, and LVI. HS/DD is associated with significantly worse CSS, OS, and RFS, but does not predict worse IVRFS or URFS. Therefore, HS/DD detection should prompt extensive treatment and closer follow-up. To improve the quality of recommendations and patient care, well-designed studies with central pathological review are needed.