Prevalencia del cáncer del tracto urinario. Análisis de la cohorte española del estudio IDENTIFY / Prevalence of urinary tract cancer in the Spanish cohort of the IDENTIFY study

Introducción Los tumores malignos del tracto urinario están asociados a gran morbimortalidad siendo su prevalencia variable a nivel global. Recientemente el estudio IDENTIFY ha publicado resultados sobre la prevalencia del cáncer del tracto urinario a nivel internacional. Este estudio evalúa la prevalencia de cáncer dentro de la cohorte española del estudio IDENTIFY para determinar si los resultados publicados son extrapolables a nuestra población. Material y métodos Se realizó un análisis de los datos de la cohorte de pacientes españoles del estudio IDENTIFY. Se trata de una cohorte prospectiva de pacientes derivados al hospital con sospecha de cáncer, predominantemente por hematuria. Los pacientes fueron reclutados entre diciembre de 2017 y diciembre de 2018. Resultados En total 706 pacientes procedente de 9 centros españoles fueron analizados. Doscientos setenta y siete pacientes (39,2%) fueron diagnosticados de cáncer, 259 (36,7%) de cáncer vejiga, 10 (1,4%) de tracto urinario superior, 9 (1,2%) renal y 5 (0,7%) de próstata. El aumento de la edad (OR: 1,05; IC 95%: 1,03-1,06; p<0,001), presencia de hematuria visible (OR: 2,19; IC 95%: 1,13-4,24; p=0,02) y el hábito tabáquico (exfumadores: OR: 2,11; IC 95%: 1,30-3,40; p=0,002; fumadores: OR: 2,36; IC 95%: 1,40-3,95; p=0,001) se asocia con mayor probabilidad de cáncer vesical. Conclusión Este estudio resalta el riesgo que existe en pacientes con HV y hábito tabáquico de presentar cáncer de vejiga. El cáncer de vejiga presentó la mayor prevalencia, siendo esta mayor que la expuesta en series previas y la presentada en el estudio IDENTIFY. Trabajos futuros deben evaluar otros factores asociados que permitan crear modelos de predicción de cáncer para seguir aumentando la detección de estos en nuestros pacientes. (AU)

Introduction Malignant tumors of the urinary tract are associated with high morbidity and mortality, and their prevalence can vary worldwide. Recently, the IDENTIFY study has published results on the prevalence of urinary tract cancer at a global level. This study evaluates the prevalence of cancer within the Spanish cohort of the IDENTIFY study to determine whether the published results can be extrapolated to our population. Patients and methods An analysis of the data from the Spanish cohort of patients in the IDENTIFY study was performed. This is a prospective cohort of patients referred to secondary care with suspected cancer, predominantly due to hematuria. Patients were recruited between December 2017 and December 2018. Results A total of 706 patients from 9 Spanish centers were analyzed. Of these, 277 (39.2%) were diagnosed with cancer: 259 (36.7%) bladder cancer, 10 (1.4%) upper tract urothelial carcinoma, 9 (1.2%) renal cancer and 5 (0.7%) prostate cancer. Increasing age (OR: 1.05; 95% CI: 1.03-1.06; P<.001), visible hematuria (VH) OR: 2.19; 95% CI: 1.13-4.24; P=.02)and smoking (ex-smokers: OR: 2.11; 95% CI: 1.30-3.40; P=.002); (smokers: OR: 2.36; 95% CI: 1.40-3.95; P=.001) were associated with higher probability of bladder cancer. Conclusion This study highlights the risk of bladder cancer in patients with VH and smoking habits. Bladder cancer presented the highest prevalence; higher than the prevalence reported in previous series and presented in the IDENTIFY study. Future work should evaluate other associated factors that allow us to create cancer prediction models to improve the detection of cancer in our patients. (AU)

Analysis of the Clinicopathological Characteristics and Prognosis of Patients with Nonurothelial Bladder Cancer

Background: Due to the low incidence of nonurothelial bladder cancer (NUBC), there is limited evidence in the field of evidence-based medicine regarding treatment modalities for such diseases. The purpose of our study was to explore the clinicopathological characteristics and prognostic factors of NUBC. Methods: We retrospectively analyzed the clinical data of 135 bladder squamous cell carcinoma (SqCC) and adenocarcinoma (AC) patients treated at the Second Hospital of Tianjin Medical University between October 2011 and February 2022, including 70 SqCC and 65 AC patients; We also analyzed 145 patients from the Surveillance, Epidemiology, and End Results (SEER) database from 2011 to 2020, including 108 SqCC and 37 AC patients. Clinicopathological characteristics and prognoses were compared between the SqCC and AC groups. Additionally, the Kaplan‒Meier method and log-rank tests were used to perform survival analysis, and the Cox proportional hazard model was applied to analyze clinical factors affecting prognosis. Results: Comparisons of clinicopathological characteristics between the SqCC and AC groups revealed that age at diagnosis (p < 0.001, p < 0.001), tumor diameter (p < 0.001), tumor location (p = 0.002), and surgical approach (p < 0.001) were significantly different. Univariate and multivariate Cox regression analyses indicated that lymph node metastasis (p = 0.031), advanced pT stage (p < 0.001), and SqCC (p < 0.001) were independent risk factors affecting the prognosis of NUBC patients, and comparisons of clinicopathological characteristics between the SqCC and AC groups from the SEER database revealed that tumor diameter (p < 0.001), tumor location (p = 0.033), tumor number (p = 0.004), surgical approach (p = 0.005), and lymph node metastasis (p = 0.017) were statistically significant... (AU)

The Prognostic Value of the Combination of the Prognostic Nutritional Index and the Lymphocyte: Monocyte Ratio for the Prediction of Patients with Muscle-Invasive Bladder Cancer

Objective: To explore the efficacy of combining the prognostic nutritional index (PNI) and the lymphocyte:monocyte ratio (LMR) for patients with muscle-invasive bladder cancer (MIBC). Methods: Of 172 patients who were diagnosed with MIBC in our hospital, 94 were eligible for the study. The clinical data of the 94 patients with MIBC were collected. The patients were divided according to the optimal cut-off values for the preoperative PNI and LMR into a low-PNI subgroup (PNI <44.15, 52 patients), a high-PNI subgroup (PNI ≥44.15, 42 patients), a low-LMR subgroup (LMR <2.98, 50 patients) and a high-LMR subgroup (LMR ≥2.98, 44 patients). The area under the receiver operating characteristic (ROC) curve (AUC) was used to analyse the efficacy of the PNI and the LMR in predicting the prognosis of patients with MIBC. Univariate and multivariate logistic regression analyses were performed to evaluate prognostic factors for patients with MIBC. Kaplan–Meier (K‒M) survival analysis was used for overall survival (OS) analysis to explore the ability of the PNI combined with the LMR to predict the prognosis of patients with MIBC. Results: The optimal cut-off values for the preoperative PNI and the preoperative LMR were 44.15 and 2.98, respectively, on the basis of ROC curves. ROC curve analysis revealed that the PNI (AUC = 0.720, sensitivity 65.9%, specificity 74.50%, Youden index 0.399) and the LMR (AUC = 0.724, sensitivity 65.9%, specificity 70.0%, Youden index 0.395) both had good prognostic efficacy for patients with MIBC. The results of univariate and multivariate logistic regression analyses showed that preoperative PNI <44.15 was an independent risk factor for OS in patients with MIBC (p = 0.027). Based on K‒M survival curve analysis, patients with PNI <44.15 and LMR <2.98 had the shortest OS (p = 0.00002). Conclusions: Low preoperative PNI and LMR values are indicative of poor prognosis in patients with MIBC...(AU)

Outcomes with atezolizumab in metastatic urothelial cancer: real-world data from a single institution

Purpose Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment of metastatic urothelial carcinoma (mUC) upon platinum-based chemotherapy according to the positive results of large clinical trials. Nevertheless, results from unselected populations reflecting real-world data (RWD) are highly informative to the clinician. We reviewed daily clinical practice outcomes in patients with mUC who received atezolizumab in our institution. Methods Here we evaluated the clinical activity and safety of atezolizumab in an unselected population of mUC patients who received atezolizumab between 2018 and 2022 reflecting RWD. Efficacy and safety information were retrospectively collected. Results A total of 63 patients were included. The mean age was 68 years and the objective response rate was 14.3%. The median progression-free survival was 3 months and the median overall survival 6 months. At 1 year, 42% of the patients were alive. ECOG (0 vs 1) and neutrophil–lymphocytes ratio < 2 at the start of ICI were positive prognostic factors that discriminated between long vs short survivors. Overall tolerance was good with no new safety signals. Five patients (17%) had treatment-related adverse events grade ≥ 2 that required corticosteroids. Conclusion In this retrospective study, atezolizumab was an effective and tolerable treatment option for patients with mUC after progression to platinum-based chemotherapy. Yet, patient selection remains critical to improve outcomes (AU)

Predictors of trimodality therapy in patients with muscle-invasive bladder cancer and effect on survival

Background Due to its unique advantages over radical cystectomy (RC), trimodality therapy (TMT) is increasingly being utilized by patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not suitable for or refuse RC. However, achieving a satisfactory oncological outcome with TMT requires strict patient selection criteria, and the comparative oncological outcomes of TMT versus RC remain controversial. Methods Patients diagnosed with non-metastatic MIBC who underwent TMT or RC were identified from the SEER database during 2004–2015. Before one-to-one propensity score matching (PSM), logistic regression was utilized to identify predictors of TMT. After matching, K-M curves were generated to estimate cancer-specific survival (CSS) and overall survival (OS) with log-rank to test the significance. Finally, we conducted univariate and multivariate Cox analyses to identify independent prognostic factors for CSS and OS. Results The RC and TMT groups included 5812 and 1260 patients, respectively, and the TMT patients were significantly older than the RC patients. Patients with advanced age, separated, divorced, or widowed (SDW) or unmarried marital status (married as reference), and larger tumor size (< 40 mm as reference) were more likely to be treated with TMT. After PSM, TMT was found to be associated with worse CSS and OS, and it was identified as an independent risk factor for both CSS and OS. Conclusion MIBC patients may not be carefully evaluated prior to TMT, and some non-ideal candidates underwent TMT. TMT resulted in worse CSS and OS in the contemporary era, but these results may be biased. Strict TMT candidate criteria and TMT treatment modality should be required (AU)

A gene signature of cancer-associated fibroblasts predicts prognosis and treatment response in bladder cancer

Objective Due to the pivotal role cancer-associated fibroblasts (CAFs) play in tumor progression, our study aimed to develop a signature of CAFs-related gene (CRG) to predict the survival outcomes and treatment response of bladder cancer (BLCA). Methods The transcriptome data and relevant clinical information about BLCA were collected from publicly available databases, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Weighted gene co-expression network analysis was utilized to uncover CAFs-associated hub genes, and subsequently, a risk model for survival prognosis was constructed using LASSO-Cox regression. The immune microenvironment, immune infiltration, immunotherapy response, and drug sensitivity were explored using ESTIMATE, CIBERSORT, TIDE, and oncoPredict algorithms. To verify the expression of the CRGs, additional analyses were performed using online databases (HPA, CCLE, TIMER, cBioPortal, and TISCH). Results Our study developed a CRG signature and constructed a prognostic model. Significant differences in overall survival were observed between the two risk stratifications. The risk score increased with the infiltration of CAFs and tumor staging progression, while closely correlating with immune checkpoint expression and infiltration of CD8 T cells, follicular helper T cells, regulatory T cells, activated dendritic cells, M0 macrophages, M2 macrophages, and resting mast cells. Furthermore, a higher proportion of patients in the low-risk stratification exhibited responsiveness to immunotherapy, and significant variances in sensitivity to multiple chemotherapy medications were observed between the two risk stratifications. Conclusion The construction of the risk model based on the CRG signature offers new avenues for the prognosis evaluation and development of personalized treatment strategies for BLCA (AU)

Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience

Purpose Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. Materials and method In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. Results Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0–1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1–2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. Conclusions Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status (AU)

Comparison of different prediction tools for the risk of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a propensity-matched analysis

Objective To compare the predictive performance of the current clinical prediction models for predicting intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). Methods We retrospectively analysed upper tract urothelial carcinoma patients who underwent radical nephroureterectomy in our centre from January 2009 to December 2019. We used the propensity score matching (PSM) method to adjust the confounders between the IVR and non-IVR groups. Additionally, Xylinas’ reduce model and full model, Zhang’s model, and Ishioka’s risk stratification model were used to retrospectively calculate predictions for each patient. Receiver operating characteristic (ROC) curves were generated, and the areas under the curves (AUCs) were compared to identify the method with the highest predictive value. Zesults We included 217 patients with a median follow-up of 41 months, of which 57 had IVR. After PSM analysis, 52 pairs of well-matched patients were included in the comparative study. No significant difference was found in clinical indicators besides hydronephrosis. The model comparison showed that the AUCs of the reduced Xylinas’ model for 12 months, 24 months, and 36 months were 0.69, 0.73, and 0.74, respectively, and those of the full Xylinas’ model were 0.72, 0.75, and 0.74, respectively. The AUC of Zhang’s model for 12 months, 24 months, and 36 months was 0.63, 0.71, and 0.71, respectively, the performance of Ishioka’s model is that the AUC of 12 months, 24 months and 36 months was 0.66, 0.71, and 0.74, respectively. Conclusion The external verification results of the four models show that more comprehensive data and a larger sample size of patients are needed to strengthen the models’ derivation and updating procedure, to better apply them to different populations (AU)

Relationship between Changes of Serum Vascular Endothelial Growth Factor and Folate Receptor-α Levels and Clinical Efficacy of Toripalimab in Patients with Bladder Cancer

Objective: This study aims to explore the changes of serum vascular endothelial growth factor (VEGF) and folate receptor-α (FR-α) levels in patients with bladder cancer before and after treatment with toripalimab and to analyse the relationship between the changes of VEFG and FR-α and the clinical efficacy of patients. Methods: A total of 176 patients with bladder cancer admitted to our hospital from January 2020 to January 2022 were selected as the research subjects. All patients were treated with toripalimab. The clinical efficacy and changes of serum VEGF and FR-α levels before and after treatment were observed. Logistic regression was used to analyse the relationship between serum VEGF and FR-α levels and the therapeutic effect of toripalimab, and receiver operating characteristic curve was used to evaluate the predictive value of serum VEGF and FR-α on the efficacy. Results: The objective response rate and disease control rate after treatment were 31.82% and 70.45%, respectively. The serum VEGF and FR-α levels in patients after treatment were significantly lower than those before treatment (p < 0.001). The patients were divided into an effective group (n = 124) and an ineffective group (n = 52) according to clinical efficacy. The serum VEGF and FR-α levels of patients in the effective group were significantly lower than those of the ineffective group (p < 0.001). Logistic regression analysis showed that the elevated levels of serum VEGF (odds ratio = 1.226) and FR-α (odds ratio = 1.384) were the risk factors affecting the therapeutic effect of toripalimab (p < 0.05). The area under curve of the combined prediction of VEGF and FR-α was 0.920, the Youden index was 0.722, the sensitivity was 89.52%, the specificity was 82.69%, and the predictive value was higher than the single detection of VEGF or FR-α (p = 0.001, p < 0.001)(AU)

HER2 Affects the Biological Behaviours of Bladder Cancer Cells and is Closely Associated with the Progression and Prognosis of Bladder Cancer

Objective: Given the growing recognition of molecular targets in oncology, this study aimed to examine the expression pattern and prognostic significance of human epidermal growth factor receptor-2 (HER2) in bladder cancer (BC) and the effects of HER2 knockdown on the biological behaviours of BC cells. Methods: A total of 126 BC tissue samples and 20 samples of normal bladder mucosa were collected for immunohistochemical staining. The clinicopathological data were obtained from patients with BC. HER2 was knocked down in two BC cell lines (T24 and 5637) using lentiviral delivery of short hairpin RNA (shRNA), referred to as shHER2, with a blank control group (shCtrl) for comparison. A range of assays, including cell counting kit-8, colony formation, transwell, wound healing, and flow cytometry, were performed to assess the effects of HER2 knockdown on the proliferation, migration, cell cycle entry, and apoptosis of BC cells. Results: The study revealed a notable overexpression rate of HER2 in BC tissues (57.1%) than in normal bladder mucosa (0%) (p < 0.001). HER2 overexpression was associated with tumour number (p < 0.0001), pathological grade (p < 0.0001), lymph node metastasis (p = 0.040), distant metastasis (p = 0.037), overall survival (p = 0.0006), and recurrence-free survival (RFS) (p < 0.0001). In contrast, no significant association was identified between HER2 overexpression and demographic factors such as sex (p = 0.687), age (p = 0.430), tumour size (p = 0.053), or T stage (p = 0.134). Furthermore, the experimental knockdown of HER2 in BC cells inhibited the proliferation and migration and promoted their apoptosis and cell cycle arrest in the G1 phase. Conclusions: The findings suggest HER2 as a potential therapeutic target for BC and underscore the promise of developing anti-HER2-targeting strategies for BC management (AU)

Validez diagnóstica del sistema vesical imaging-reporting and data system (VI-RADS): estudio con datos de la vida real / Diagnostic validity of the vesical imaging-reporting and data system (VI-RADS): A real-world study

Objetivo: Recientemente se ha generalizado el uso del sistema vesical imaging-reporting and data (VI-RADS). Nos propusimos validar el rendimiento diagnóstico del VI-RADS para diferenciar el cáncer vesical músculo-iinvasivo (CVMI) del cáncer vesical no músculo-invasivo (CVNMI) en un contexto de práctica clínica real. Métodos Entre diciembre de 2019 y febrero de 2022 se revisaron los pacientes con sospecha de cáncer vesical primario. Se incluyeron los pacientes con un protocolo de RM multiparamétrica adecuado para VI-RADS antes de cualquier tratamiento invasivo. La estadificación local de los pacientes se realizó mediante resección transuretral, segunda resección o cistectomía radical como tratamiento de referencia. Dos expertos en radiología genitourinaria cegados a los datos clínicos e histopatológicos evaluaron las imágenes de RM multiparamétrica de forma independiente y retrospectiva. Se analizó el rendimiento diagnóstico de ambos radiólogos y la concordancia entre lectores. Resultados De los 96 pacientes, 20 (20,8%) tenían CVMI y 76 (79,2%) tenían CVNMI. La exactitud diagnóstica del CVMI fue alta para los dos radiólogos. El primer radiólogo tenía un área bajo la curva (ABC) de 0,83 y 0,84, una sensibilidad de 85% y 80% y una especificidad de 80,3% y 88,2% para VI-RADS≥3 y≥4, respectivamente. El segundo radiólogo tenía un área bajo la curva (ABC) de 0,79 y 0,77, una sensibilidad del 85% y el 65% y una especificidad del 73,7% y el 89,5% para VI-RADS≥3 y≥4, respectivamente. La concordancia de la puntuación VI-RADS global entre los dos radiólogos fue moderada (K=0,45). Conclusión El sistema VI-RADS tiene un alto poder diagnóstico para diferenciar el CVMI de CVNMI antes de la resección transuretral. La concordancia entre los radiólogos es moderada. (AU)

Objective: Preoperative Vesical Imaging-Reporting and Data System (VI-RADS) becomes widespread. We aimed to validate the diagnostic performance of VI-RADS in differentiating muscle-invasive (MIBC) from non-muscle-invasive bladder cancer (NMIBC) in a real-world setting. Methods Between December 2019 and February 2022 suspected primary bladder cancer patients were reviewed. Those with proper multiparametric MRI (mpMRI) protocol for VI-RADS before any invasive treatment were included. Patients were locally staged according to transurethral resection, second resection, or radical cystectomy as the reference standard. Two experienced genitourinary radiologists who were blinded to clinical and histopathological data evaluated the mpMRI images independently and retrospectively. The diagnostic performance of both radiologists and the interreader agreement were analyzed. Results Among 96 patients, 20 (20.8%) had MIBC, and 76 (79.2%) had NMIBC. Both radiologists had great diagnostic performance in diagnosing MIBC. The first radiologist had an area under curve (AUC) of 0.83 and 0.84, the sensitivity of 85% and 80%, and the specificity of 80.3% and 88.2% for VI-RADS≥3 and≥4, respectively. The second radiologist had an area under curve (AUC) of 0.79 and 0.77, the sensitivity of 85% and 65%, and the specificity of 73.7% and 89.5% for VI-RADS≥3 and≥4, respectively. The overall VI-RADS score agreement between the two radiologists was moderate (K=0.45). Conclusion VI-RADS is diagnostically powerful in differentiating MIBC from NMBIC prior to transurethral resection. The agreement between radiologists is moderate. (AU)

Resultados perioperatorios y oncológicos a largo plazo de los pacientes con variantes histológicas de cáncer vesical sometidos a cistectomía radical: un análisis de emparejamiento por índices de propensión con carcinoma urotelial puro / The perioperative and long-term outcomes of patients with variant histology bladder cancer undergoing radical cystectomy: A propensity score-matched analysis with pure urothelial carcinoma

Objetivos Evaluar los resultados perioperatorios y a largo plazo de la cistectomía radical en los pacientes con variantes histológicas frente a los pacientes con patrón histológico de carcinoma urotelial puro. Métodos Los pacientes diagnosticados de carcinoma vesical con variantes histológicas fueron emparejados con aquellos diagnosticados de carcinoma urotelial puro en una proporción de 1:3 mediante un análisis de puntuación de propensión. Los 2 grupos se compararon en términos de resultados perioperatorios y morbimortalidad a largo plazo. Resultados En el presente estudio retrospectivo se incluyeron 148 individuos (37 con variantes histológicas de CU y 111 con carcinoma urotelial puro). Un total de 107 (72,3%) individuos presentaron al menos una complicación perioperatoria según la clasificación de Clavien-Dindo. Esta proporción fue similar entre los pacientes con carcinoma urotelial frente a aquellos con variante histológica (p=0,22). En cuanto a las complicaciones a largo plazo, el número de pacientes con hernia incisional clínicamente significativa que requirió cirugía (14 [12,7%] frente a 3 [8,3%]; p=0,68], estenosis uretero-intestinal/uretero-cutánea o cualquier otra complicación relacionada con la derivación urinaria aplicada (15 [13,6%] frente a 7 [19,4%]; p=0,56], o el número de pacientes que presentaron septicemia (17 [15,5%] frente a 10 [27,8%]; p=0,16] u obstrucción del tracto urinario (12 [10,9%] frente a 4 [11,1%]; p>0,99] durante el seguimiento fue similar para el grupo carcinoma urotelial y el de variante histológica. Según el análisis de supervivencia con curvas de Kaplan-Meier y el modelo de regresión de Cox univariante, el riesgo de muerte por cualquier causa era mayor en los pacientes con variante histológica que en los de patrón histológico puro (log-rank test=0,045; hazard ratio: 1,7; intervalo de confianza del 95%: 1,01-2,87; p=0,047). Conclusiones La morbimortalidad perioperatorias son comparables . (AU)

Objectives To assess the perioperative and long-term outcomes after open radical cystectomy in patients with histological variants versus pure urothelial carcinoma. Methods Patients with a variant histology carcinoma of the urinary bladder were matched through a propensity score analysis with those with pure urothelial carcinoma on a 1:3 ratio. The two groups were compared in terms of perioperative and long-term morbidity and mortality. Results Overall, 148 individuals were included in the present retrospective study (37 with variant histology and 111 with pure urothelial carcinoma). A total of 107 (72.3%) individuals presented at least one perioperative complication based on the Clavien-Dindo classification. This proportion was similar between patients with urothelial versus variant histology carcinoma (P=.22). In the long term, the number of patients with clinically significant incisional hernia requiring surgery [14 (12.7%) vs 3 (8.3%), P=.68], uretero-intestinal/uretero-cutaneous strictures or any other complication related to the applied urinary diversion [15 (13.6%) vs 7 (19.4%), P=.56], as well as the number of patients presenting with septicemia [17 (15.5%) vs 10 (27.8%), P=.16] or with urinary tract obstruction [12 (10.9%) vs 4 (11.1%), P>.99] at follow-up did not differ between urothelial versus variant histology carcinoma. The survival analysis with Kaplan-Meier curves and the univariate Cox regression model suggested that the risk of death from any cause was increased in patients with variant compared to pure urothelial histology (log-rank test=.045, hazard ratio: 1.7, 95% confidence interval: 1.01-2.87, P=.047). Conclusions Perioperative morbidity and mortality are comparable in patients with variant histology versus pure urothelial carcinoma. (AU)

Prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitor treatment

Purpose We evaluated the prevalence of immune-related adverse events and anti-tumor efficacy in advanced/metastatic urothelial carcinoma following immune-checkpoint inhibitors (ICIs) treatment. Methods We conducted a multicenter retrospective study of patients with advanced/metastatic urothelial carcinoma treated with ICIs in four Spanish institutions. irAEs were classified using Common Terminology Criteria for Adverse Event (CTCAE) v.5.0 guidelines. The primary endpoint was overall survival (OS). Other endpoints were overall response rate (ORR) and progression-free survival (PFS). irAEs were evaluated as a time-dependent covariate to avoid immortal time bias. Results A total of 114 patients were treated with ICIs between May 2013 and May 2019, 105 (92%) of whom received ICIs as monotherapy. irAEs of any grade were experienced in 56 (49%) patients and 21 (18%) patients had grade ≥ 3 toxicity. The most frequent irAEs were gastrointestinal and dermatological toxicities, reported in 25 (22%) and 20 (17%) patients, respectively. Patients with grade 1–2 irAEs had significantly longer OS compared to those without grade 1–2 irAEs (median 18.2 vs. 8.7 months, HR = 0.61 [95% CI 0.39–0.95], p = 0.03). No association with efficacy was observed for patients with grade ≥ 3 irAEs. No difference in PFS was observed after adjusting for the immortal time bias. ORR was higher in patients who developed irAEs (48% vs 17%, p < 0.001). Conclusions Our findings suggest that development of irAEs was associated with higher ORR, and patients who developed grade 1–2 irAEs had longer OS. Prospective studies are necessary to confirm our findings (AU)

Clinical Effect of the Combination of Compound Kushen Injection and Gemcitabine on Postoperative Patients with Non-Muscle Invasive Bladder Cancer and Its Influence on Serum-Related Factors

Objective: To observe the clinical effect of the combination of compound Kushen injection (CKI) and gemcitabine on postoperative patients with non-muscular invasive bladder cancer (NMIBC) and its influence on serum-related factors. Methods: A total of 150 patients with NMIBC were randomly divided into two groups. The patients in the control group (n = 75) received gemcitabine therapy; They were given 0.2 g gemcitabine once a week for 8 weeks after surgery and then changed to once every 2 weeks for eight times. The patients in the observation group (n = 75) were given CKI treatment on the basis of the control group for 10 days. The treatment was continued for three courses. After continuous follow-up for 2 years, the blood biochemistry, serum-related factors and immune T cell subsets and the safety and immune function changes, total effective rate, recurrence rate and occurrence of adverse reactions were evaluated. Results: The interferon-γ, interleukin (IL)-2, clusters of differentiation (CD)8+, serum cell adhesion molecules (CAMs), hepatocyte CAM and cysteine proteinase-8 levels in the two groups after treatment significantly increased compared with those before treatment (p < 0.05), with the observation group showing more increase (p < 0.05). However, the tumour necrosis factor-α, C-reactive protein (CRP), IL-6, CD3+, CD4+, matrix metalloproteinase (MMP)-9, MMP-2, epithelial-specific CAM, soluble CAM-1, liver CAM, E-cadherin, vascular endothelial growth factor and fibroblast growth factor levels decreased significantly after treatment (p < 0.05), with the observation group exhibiting more decrease (p < 0.05). The adverse reactions and recurrence rate in the observation group obviously decreased in comparison to those in the control group (p < 0.05) (AU)

Exploring the Shared Gene Signatures and Molecular Mechanisms between Bladder Urothelial Carcinoma and Metabolic Syndrome

Background: The aim of this study was to investigate the common gene signatures and potential molecular mechanisms of bladder urothelial carcinoma (BLCA) and metabolic syndrome (MS). Methods: Transcriptome data for BLCA and MS were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was utilized to identify co-expression networks associated with BLCA and MS, and five hub genes were further screened and validated using logistic least absolute shrinkage and selection operator (LASSO) regression models and receiver operating characteristic (ROC) curve, and external dataset for validation. The relationship between the hub genes and the clinicopathological characteristics and prognosis of BLCA patients was explored in the GEO and The Cancer Genome Atlas (TCGA)-BLCA cohorts, respectively. Differences in the immune microenvironment of BLCA and MS were analyzed using the database CIBERSORT and the R package “ssGSEA”, and the correlation between hub genes and tumor microenvironment, immune score and targeted drugs was analyzed with the help of the TCGA-BLCA cohort. Finally, BLCA single-cell RNA (scRNA) data were used to analyze the expression levels of the hub genes in various cell types of BLCA and molecular mechanisms. Results: Five hub genes were screened by WGCNA and LASSO regression analysis, namely AP2-associated protein kinase 1 (AAK1), ATP-binding cassette subfamily F member 2 (ABCF2), Mitochondrial ribosomal protein L42 (MRPL42), La-related protein 3 (SSB) and TATA-box binding protein-associated factor 10 (TAF10). Analyzed in the GEO and TCGA-BLCA cohorts, we found that the hub genes (TAF10 and ABCF2) were closely associated with the clinicopathological characteristics and prognosis of BLCA patients (AU)

Postoperative Metachronous Metastasis of Bladder Cancer to Penis: A Case Report

Background: Penile metastases are extremely rare events, originating primarily from primary pelvic tumours of the prostate, bladder, and gastrointestinal tract. The underlying mechanism of bladder cancer metastasis to the penis remains unclear. Metastasis to the penis is usually considered a late manifestation of systemic spread. Therefore, the prognosis of patients with penile metastasis remains poor and their survival period is short. Therefore, reporting this rare case will help to better understand the characteristics, diagnosis, and treatment processes of the disease, with the aim of improving the accuracy and efficiency of diagnosis and treatment. Case Description: A 65-year-old male received transurethral resection of a bladder tumor. One year later, he underwent radical cystectomy because of the recurrence and progression of bladder cancer. Postoperative pathology demonstrated that the stage of bladder cancer was T3N0M0. One year later, he discovered a penile mass that gradually grew and became hard, accompanied by urinary retention, but without other clinical symptoms. The patient underwent a complete penectomy. Histopathology and immunohistochemistry results demonstrated the tumour’s origin as a bladder urothelial carcinoma. The patient received systemic chemotherapy after surgery, but died 7 months later. Conclusions: Although penile metastasis of bladder cancer typically indicates an advanced stage of the malignant tumour and poor prognosis, we recommend that male patients with a history of bladder cancer should undergo a regular clinical examination of the penis to rapidly detect the disease and receive early treatment. In this case, despite treatment measures such as systemic chemotherapy and penectomy, the patient’s prognosis remained poor (AU)

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group

Purpose Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. Methods/patients Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. Results 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01–34.2 vs. 27 months, 95% CI 22.6–31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4–37.6 vs 25 months, 95% CI 20.7–29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). Conclusions There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer (AU)

Tendencias de la mortalidad por cáncer de vejiga en España, 1980-2021 / Bladder cancer mortality trends in Spain: 1980-2021

Objetivo Nos proponemos actualizar las tasas de mortalidad por cáncer de vejiga en España de 1980 a 2021, estandarizadas por sexo, grupo de edad y comunidades autónomas (CC. AA.). Materiales y métodos Se utilizaron las bases de datos públicas en línea del Instituto Nacional de Estadística para obtener datos sobre población y mortalidad por cáncer de vejiga. Se calcularon las tasas de mortalidad estandarizadas por edad (TMEE) para todas las edades y las truncadas (<75 y ≥75 años) y se presentaron como tasas por cada 100.000 personas. Se utilizó el modelo de regresión Joinpoint para el cálculo y análisis de las tendencias de las TMEE por cáncer de vejiga. Resultados En la última década, las TMEE por cáncer de vejiga (todas las edades,<75 años y ≥75 años) disminuyeron significativamente en España para ambos sexos. Esta tendencia se observó en 12 CC. AA. para los hombres y en 4 CC. AA. (Andalucía, Canarias, Cataluña y Madrid) para las mujeres, aunque en proporciones diferentes. Para los hombres, la TMEE permaneció estable en Castilla-León y La Rioja (<75 años), Cantabria, Castilla-La Mancha y Valencia (≥75 años) y las 2 regiones castellanas (todas las edades). En el caso de las mujeres, las TMEE también disminuyeron en Valencia (<75 y ≥75), Castilla-León (≥75), Galicia (≥75 y todas las edades) y Navarra (<75 y todas las edades). Conclusión Nuestros resultados revelan variaciones significativas en las tendencias por CC. AA., sexo y grupo de edad, enfatizando la necesidad de un seguimiento continuado e intervenciones específicas para reducir aún más las tasas de mortalidad por cáncer de vejiga en España (AU)

Objective We propose to update bladder cancer mortality rates in Spain from 1980 to 2021, by sex and age-group, by autonomous community (AC). Materials and methods The public online databases of the National Statistical Institute were used to obtain data on population and bladder cancer mortality. Age-standardised mortality rates (ASMRs), all ages and truncated (<75 and ≥75) were estimated and reported as rates per 100,000 persons. Joinpoint regression software was used for estimation and trend analysis of ASMRs bladder cancer. Results In the last decade, the ASMR for bladder cancer (all ages,<75 years and ≥75 years) decreased significantly in Spain for both sexes. This trend was observed in 12 ACs for men and in 4 ACs (Andalusia, Canary Islands, Catalonia and Madrid) for women, although to different degrees. For men, ASMR remained stable in Castilla-León and La Rioja (<75 years), Cantabria, Castilla-La Mancha and Valencia (≥75years) and the 2 Castilian regions (all ages). For women, ASMR also decreased in Valencia (<75 and ≥75), Castilla-León (≥75), Galicia (≥75 and all ages) and Navarre (<75 and all ages). Conclusion Our results reveal significant variations in trends by AC, sex and age group, emphasizing the need for continued follow-up and targeted interventions to further reduce bladder cancer mortality rates in Spain (AU)

Systemic Immune Inflammation Index and T-Staging Predict Prognosis in Patients with Muscle-Invasive Bladder Cancer

Objective: To explore the effect of combining the preoperative systemic immune inflammation index (SII) and T-staging to predict the prognosis of patients with muscle-invasive bladder cancer (MIBC). Methods: The clinical data of 94 MIBC patients who met the inclusion criteria of our hospital from September 01, 2012, to August 31, 2022, were collected. Data included sex, age, smoking history, tumour size, tumour number, pathology, P-grading, T-staging, SII, and overall survival (OS). The optimal cut-off of SII (863.62) was selected by obtaining the receiver operating characteristic (ROC) curve. Then, the samples were divided into the low-SII group (SII <863.62, 51 cases) and the high-SII group (SII ≥863.62, 43 cases). T-staging could be divided into T2 (61 cases) and T3 and higher stages (33 cases) according to the findings on depth of tumour invasion. Furthermore, the role of combined SII and T-staging for prognosis prediction was evaluated by performing Kaplan–Meier survival analysis and Cox proportional hazards modelling in the OS analysis. Results: MIBC patients with higher SII (≥863.62) were associated with shorter OS (p = 0.00005). Patients with more advanced T-stages had shorter OS than those with early T-stages (p = 0.00006). Furthermore, patients who had both higher SII and more advanced T-stages had markedly shorter OS (p = 0.00001). Conclusions: In patients with MIBC, a higher SII and increasing T-stage indicate a worse prognosis and shorter OS. Therefore, the combined SII and T staging approach is a reliable prognostic predictor for patients with MIBC (AU)