BACKGROUND: In recent years, different urinary markers such as the Bladder Epicheck® have been developed in an attempt to reduce the number of cystoscopies in the follow-up of non-muscle invasive bladder cancer (NMIBC).
OBJECTIVE: To provide a systematic review of Bladder Epicheck® and its current clinical utility in the follow-up and detection of recurrence of NMIBC.
METHODS: Systematic review based on a literature search of PubMed, Web of Science and Scopus databases until October 2023, according to PRISMA and Quadas-2 criteria. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the marker were calculated. Diagnostic performance was evaluated by the area under the curve (AUC).
RESULTS: Fifteen studies were analyzed (n = 3761) including 86.7% prospective studies. Of the patient series, 53.2% had received previous intravesical instillations. The mean Se of the biomarker in the detection of recurrence varied according to tumor grade (87.9%-high grade/HG vs. 44.9%-low grade/LG, respectively). Their weighted mean Se and Sp were 71.6% and 84.5%, respectively. The mean recurrence rate was 29.1%. The weighted mean PPV and NPV were 56.4% and 92.8% (97.7% non-LG), respectively. The mean AUC was 85.63%.
CONCLUSIONS: Bladder Epicheck® is a useful urinary marker in the follow-up of NMIBC, with significantly high Se and NPV in the detection of recurrences, especially in cases of HG disease. Its use can reduce the number of cystoscopies required in the follow-up of NMIBC, improving the quality of life of patients and potentially increasing health economic savings.

BACKGROUND: Bladder cancer (BC) is the seventh most common cancer worldwide. Not every infection ends as cancer, although the HPV-induced carcinogenesis is a complex process consequence of inflammation. To determine the association between human papillomavirus (HPV) and the diagnosis of bladder cancer.
METHODS: We carried out a systematic review according to Cochrane and PRISMA recommendations. We searched in EMBASE, Medline (Ovid), and The Cochrane Central Register of Controlled Trials (CENTRAL), from inception to nowadays. We included case-control studies. The risk of bias assessment was performed based on QUADAS2. We performed a random effect Meta-analysis.
RESULTS: We included 14 studies in qualitative and quantitative analysis. There was mainly a low risk of bias. We finally found a strong association between the presence of HPV and bladder cancer diagnosis (OR 4.18 95%CI 2.63-6.66; I2 = 40%).
CONCLUSIONS: HPV is currently associated with the diagnosis of bladder cancer.

We propose to update bladder cancer mortality rates in Spain from 1980 to 2021, by sex and age-group, by autonomous community (AC).
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.
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 (≥75 years) 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).
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.

Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions.
A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes.
Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n = 14) were significantly younger than those who did not (p = 0.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (p = 0.032); however, none of the parameters were associated with histologically confirmed granuloma formation.
Genitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

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 (κ = 0.45).
CONCLUSIONS: VI-RADS is diagnostically powerful in differentiating MIBC from NMBIC prior to transurethral resection. The agreement between radiologists is moderate.

OBJECTIVE: The COVID-19-induced effects of primary bladder cancer (BC) patients have not yet been clarified. The aim of this study was to investigate the effects of the pandemic on the diagnosis, treatment, and follow-up of primary BC patients.
METHODS: A retrospective single-center analysis was made of all patients who underwent diagnostic and surgical procedures due to primary BC between November 2018 and July 2021. A total of 275 patients were identified and allocated to one of the groups: Pre-COVIDBC (BC diagnosed before the COVID-19 pandemic) or COVIDBC (during the pandemic).
RESULTS: The BC patients diagnosed during the pandemic were mostly at higher stages (T2) (p = 0.04), the risk of non-muscle invasive BC (NMIBC) was higher (p = 0.02), and recurrence and progression scores were increased (p = 0.001) compared to patients diagnosed before the pandemic. The time to surgery from diagnosis (p = 0.001) and symptom duration (p = 0.04) were significantly prolonged during the pandemic and the rate of follow-up significantly decreased (p = 0.03).
CONCLUSIONS: The study results highlight the significant increase in muscle invasive BC and the very high risk of NMIBC in patients presenting during the COVID-19 pandemic.
BACKGROUND: Los efectos inducidos por la COVID-19 en pacientes con cáncer de vejiga primario no están aclarados actualmente.
OBJECTIVE: Investigar los efectos de la pandemia en el diagnóstico, el tratamiento y el seguimiento del cáncer de vejiga primario.
UNASSIGNED: Se realizó un análisis retrospectivo unicéntrico de todos los pacientes que se sometieron a procedimientos diagnósticos y quirúrgicos por cáncer primario de vejiga durante noviembre de 2018 y julio de 2021. Se incluyeron 275 pacientes en el estudio. Los pacientes fueron asignados a uno de dos grupos: pre-COVIDBC (antes de la pandemia) o COVIDBC (durante la pandemia).
RESULTS: Los pacientes con cáncer de vejiga diagnosticados durante la pandemia se encontraban en su mayoría en estadios más altos (T2) (p = 0.04), el grupo de riesgo era más alto en el cáncer de vejiga no invasivo del músculo (p = 0.02), y la recurrencia y las puntuaciones de progresión aumentaron (p = 0.001) en comparación con antes del período pandémico. Además, el tiempo hasta la cirugía desde el diagnóstico (p = 0.001) y la duración de los síntomas (p = 0.04) aumentaron considerablemente durante la pandemia, y la tasa de seguimiento disminuyó significativamente (p = 0.03).
CONCLUSIONS: Destaca el aumento significativo del cáncer de vejiga invasivo del músculo y del cáncer de vejiga no invasivo del músculo de muy alto riesgo durante la pandemia.

To perform the first investigation of the role of immune-inflammatory-nutritional status (INS) on oncological outcomes in patients undergoing open radical cystectomy (ORC) for urothelial carcinoma (UC).
The records of consecutive patients who underwent ORC for non-metastatic bladder cancer between 2009 and 2020 were retrospectively analyzed. Neoadjuvant chemotherapy, non-urothelial tumor biology, and absence of oncological follow-up were exclusion criteria. Systemic immune-inflammatory index (SII) and Prognostic Nutritional Index (PNI) values were calculated and optimal cut-off values for these were used to designate four subgroups: \"high SII-high PNI\", \"low SII-high PNI\", \"low SII-low PNI\", and \"high SII-low PNI\". The Low SII-high PNI INS group had best overall survival (OS) rate while the remainder were included in non-favorable INS group. Survival curves were constructed, and a multivariate Cox regression model was used for OS and recurrence-free survival (RFS).
After exclusions, the final cohort size was 173 patients. The mean age was 64.31 ± 8.35 and median follow-up was 21 (IQR: 9-58) months. Optimal cut-off values for SII and PNI were 1216 and 47, respectively. The favorable INS group (low SII-high PNI, n = 89) had the best OS rate (62.9%). Multivariate Cox regression analysis indicated that non-favorable INS (n = 84) was a worse independent prognostic factor for OS (HR: 1.509, 95%CI: 1.104-3.145, p = 0.001) and RFS (HR: 1.285; 95%CI: 1.009-1.636, p = 0.042).
Preoperative assessment of INS may be a useful prognostic panel for OS and RFS in patients who had ORC for UC.

Bladder cancer (BC) is a common malignancy in Spain. The aims of this study were: to identify the proportion of patients diagnosed with BC incidentally or after symptomatic presentation in a contemporary period in Spain; to compare demographic, clinical, and pathologic characteristics between these groups.
This was a retrospective analysis of a multi-centre observational study of 26 hospitals in the Spanish National Health System of all BCs newly diagnosed in 2011. The study represented 21.5% of the Spanish population and hospitals were selected in proportion to Spain\'s regions to ensure a representative sample. Patients were categorized by whether the cancer was diagnosed incidentally or after symptomatic presentation and baseline demographic, pathologic, and clinical characteristics were analyzed.
2472 were newly diagnosed with BC at the 26 participating Spanish hospitals with 308 (12.5%) of cases diagnosed incidentally and 2164 (87.5%) diagnosed after symptomatic presentation. No differences were observed between patients diagnosed incidentally vs. symptomatically in terms of demographics or measured co-morbidities. Compared to symptomatically diagnosed bladder tumours, those diagnosed incidentally were more likely to have a papillary appearance, to be significantly smaller, and less likely to have positive/suspicious cytology. Additionally, incidentally diagnosed bladder tumours were less likely to be muscle-invasive (11.7% vs. 25.0%, p < 0.01) nor aggressive at pathology, with 33.6% Grade 3 compared to 50.1%, (p < 0.01).
We identified a significant percentage (12.5%) of new bladder cancer diagnosis made incidentally in a representative sample of the Spanish population. These tumours exhibited less aggressive pathologic characteristics than their symptomatic counterparts.

Cystoscopy and cauterization performed in the operating room is expensive and exposes patients to anesthesia risks. Patient tolerability during office cystoscopy and cauterization is critical to the office management of bladder cancer (BC) and other urologic diseases. We evaluated the risk factors for pain of flexible cystoscopy in the office-setting with emphasis on a sub-group of BC patients who underwent cauterization.
Retrospective analyses of 110 anonymous patient surveys completed after cystoscopy and/or cauterization. Survey information included age, gender, indication for cystoscopy, number of prior cystoscopies, number of prior office-based cauterizations, anxiety prior/during cystoscopy, and pain during cystoscopy and/or cauterization. Univariate/multivariate and linear-regression analyses were performed to evaluate the association of pain with clinical parameters.
Average pain during cystoscopy (1.75 ± 1.331) was not significantly different when cauterization was also performed (2.37 ± 2.214) (p < 0.001) (p = 0.2840). Patients in the lower age group (<66 years) indicated higher anxiety levels (p = 0.0005), more pain at cystoscopy (P = 0.004) and cauterization (p < 0.001). Although the patients\' overall anxiety level was low (1-3/10), it was associated with some pain during cystoscopy (p = 0.0005) and cauterization (p < 0.000). In multivariate analysis, anxiety was the only independent predictor of pain during cystoscopy (p = 0.03, OR: 6.52,95% CI: 1.2-35.6) and cauterization (p = 0.0012, OR: 3.4, 95%CI: 1.6-7.0). In BC patients, pain scores during cystoscopy and cauterization were not significantly different (p = 0.4772) but associated with anxiety.
Office-based cystoscopy and cauterization are tolerable with minimal pain. Higher pain levels during cystoscopy were associated with procedure anxiety, and pain during cauterization was associated with procedure anxiety and younger age. Younger and more anxious patients may need more counseling before cystoscopy.

Bladder cancer (BLCA) is a malignant urothelial carcinoma with a high mortality rate. Ferroptosis is a new type of programmed cell death and functions in suppressing tumor growth and progression. However, few studies focus on ferroptosis and BLCA.
We explored the potential oncogenic roles of ferroptosis-related genes in BLCA based on multiple public datasets. We then used univariate and multivariate cox regression to build a new survival model based on ferroptosis-related genes to predict the survival of BLCA.
We found that 23 ferroptosis-related genes had a strong correlation with each other in BLCA. Eight ferroptosis-related genes, CDKN1A, HSPA5, NFE2L2, MT1G, FANCD2, CISD1, TFRC, NCOA4, had a significantly different expression and heat-map. HSPA5 and CISD1 have a statistically significant difference in OS and DFS. Besides, CISD1 had an ideal nomogram to predict the 1-3-5-year OS (C-index: 0.701, P < .001). Furthermore, HSPA5 and CISD1 had a lower DNA methylation rate than normal tissue and HSPA5 had a positive connection with TMB (P = .02). In addition, HSPA5 participated in the DNA replication and P53 signaling pathway, and CISD1 mediated the oxidative phosphorylation and positive regulation of the intrinsic apoptotic signaling pathway.
Ferroptosis-related genes had a strong correlation with BLCA, notably, HSPA5 and CISD1 may play a role in inducing ferroptosis to suppress bladder tumorigenesis and CISD1 can be a novel prognostic biomarker as well as an effective target for diagnosis and treatment in BLCA.