Diagnosis Of Muscle-invasive Bladder Cancer Research Articles

Diagnostic significance of peritumoral enhancement in distinguishing between muscle-invasive and non-muscle-invasive bladder cancer.

The aim of this study was to assess the prevalence of peritumoral enhancement (PTE) in patients with muscle-invasive bladder cancer (MIBC) and non-MIBC (NMIBC) and to propose a modified diagnostic criterion for Vesical Imaging Reporting and Data System (VI-RADS) that incorporates PTE. This retrospective study included 95 patients with bladder cancer (age, 72 ± 11; 77 men; 36 MIBCs and 59 Non-MIBCs) who underwent multiparametric MRI in our referral center between 2011 and 2023. The images were interpreted by four radiologists. The readers classified the possibility of muscle layer invasion into categories 1-5, based on the VI-RADS categorical diagnostic criterion. PTE was defined as a linear contrast enhancement observed at the edge of tumor invasion which is convex outward from the normal bladder wall and contrasts more than the normal muscle layer and tumor. A modified VI-RADS that upgrades the final VI-RADS category to 4 if PTE is present when the original VI-RADS category is 3 or less was proposed. The frequency of PTE in the MIBC and NMIBC groups was compared using the Fisher's exact test. Sensitivity and specificity for the diagnosis of MIBC were compared with the original VI-RADS using McNemar test. Pathologic diagnosis was used as the reference standard. PTE was present in 70-81% (25/36-29/36) of MIBC and absent in 92-98% (54/59-58/59) of non-MIBC. For all readers, the PTE was significantly more frequent (p < 0.001) in the MIBC group than the NMIBC group. The sensitivities of modified VI-RADS (75.0-86.1%) were significantly higher than those of original VI-RADS (41.7-55.6%) (p = 0.002-0.008). The specificity of modified VI-RADS (91.5-98.3%) were not statistically different from original VI-RADS (98.3-100%). In conclusion, PTE is a highly specific finding for MIBC. modified VI-RADS incorporating PTE increases sensitivity for MIBC.

Urinary diversion in old patients(80+ years)

With increasing life expectancy there is also an increased need for the management of older (≥ 80years) patients with the diagnosis of muscle-invasive bladder cancer. Radical cystectomy with urinary diversion is the state of the art treatment (with neoadjuvant chemotherapy, as long as the patient is fit enough). Choosing the best urinary diversion with respect to morbidity compared to functionality and quality of life remains achallenge in these patients. Physical age alone is not decisive for making a decision. A thorough preoperative assessment of medical features, physical and cognitive impairments is more important. Older patients are generally provided with an ileal conduit as an incontinent urinary diversion, as the intervention involves reduced operating times and complexity compared to continent urinary diversions; however, in the case of good health status with an adequate life expectancy and sufficient compliance, continent diversions may be considered even in aged candidates. In the case of multimorbid patients with a high perioperative risk, ureterostomy with permanent ureteric stents is an important alternative. Most importantly, a thorough preoperative counselling enables patients to reach an informed decision.

Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60mL/minute per 1.73 m2. Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59mL/minute exhibited a measured CrCI ≥ 60mL/minute. Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59mL/minute.

Pictorial review of the diagnosis of muscle-invasive bladder cancer using vesical imaging-reporting and data system (VI-RADS).

The Vesical Imaging-Reporting and Data System (VI-RADS) is a standard magnetic resonance imaging (MRI) and diagnostic method for muscle-invasive bladder cancer that was published in 2018. Several studies have demonstrated that VI-RADS has high diagnostic power and reproducibility. However, reading VI-RADS requires a certain amount of expertise, and radiologists need to be aware of the various pitfalls. MRI of the bladder includes T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCEI). T2WI is excellent for understanding anatomy. DWI and DCEI show high contrast between the tumor and normal anatomical structures and are suitable for staging local tumors. Bladder tumors are classified into five categories according to their size and morphology and their positional relationship to the bladder wall based on the VI-RADS diagnostic criteria. If the T2WI, DWI, and DCEI categories are the same, the category is the VI-RADS category. If the categories do not match, the DWI category is the VI-RADS category. If image quality of DWI is not evaluable, the DCEI category is the final category. In many cases, DWI is dominant, but this does not mean that T2WI and DCEI can be omitted from the reading of the bladder. In this educational review, typical and atypical teaching cases are demonstrated, and how to resolve misdiagnosis and the limitations of VI-RADS are discussed. The most important aspect of VI-RADS reading is to practice multiparametric reading with a solid understanding of the characteristics and role of each sequence and an awareness of the various pitfalls.

Longer time to radical cystectomy in patients treated with neoadjuvant chemotherapy is associated with worse oncological outcomes

BackgroundCurrent muscle-invasive bladder cancer (MIBC) guidelines recommend not delaying radical cystectomy (RC) >3 months after diagnosis as it decreases overall survival (OS). However, literature investigating the impact of delay in RC in patients who receive NAC is limited, especially on a population-based level. ObjectiveTo investigate the association between time from diagnosis of MIBC to RC (TTRC) in patients with urothelial bladder cancer (UBC) treated with NAC and RC and 1) 2-year OS and 2) pathological lymph node status (pN+) in a population-based cohort. MethodsPatients were selected from the Netherlands Cancer Registry. The study included 237 patients with cT2-T4aN0M0 UBC, treated with NAC and RC between November 2017 and October 2019. Association between TTRC and OS was assessed using multivariable Cox regression analyses. Schoenfeld and Martingale residuals were used to investigate the proportional hazards assumption and whether a cut-off in the TTRC could be identified. Association between TTRC and pN+ was assessed using multivariable logistic regression analyses. ResultsMedian TTRC was 23 weeks (interquartile range (IQR) 19–26). 2-year OS was 67% (95%CI 59%–74%). Each week of delay in the TTRC was independently associated with 2-year OS (HR 1.06; P = 0.03) in the Cox regression analysis. The sensitivity analyses, defining TTRC as the time between last cycle of NAC and RC, revealed that each week of delay between NAC and RC was associated with 2-year OS (Hazard ratio (HR) 1.13; P < 0.0001), and with pN+ (Odds ratio (OR) 1.21; P = 0.01) in the Cox and logistic regression analyses, respectively. ConclusionsA longer TTRC is associated with worse oncological outcomes in patients treated with NAC and RC.

Health-related Quality of Life During the First 4 Years After Non–Muscle-invasive Bladder Cancer Diagnosis: Results of a Large Multicentre Prospective Cohort

BackgroundThe health-related quality of life (HRQoL) of patients with non–muscle-invasive bladder cancer (NMIBC) may be impaired due to the chronic and burdensome disease course, but longitudinal data are limited. ObjectiveTo evaluate HRQoL outcomes during the first 4 yr after NMIBC diagnosis, and to compare HRQoL across patient characteristics and with a normative population. Design, setting, and participantsPatients with NMIBC (n = 1019) were included from the multicentre prospective cohort UroLife. Data were collected at 6 wk (baseline), and 3, 15, and 51 mo after diagnosis. Longitudinal reference data were obtained from an age- and sex-matched normative population (n = 490). Outcome measurements and statistical analysisCancer- and NMIBC-specific HRQoL outcomes (range 0–100) were evaluated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-NMIBC24 questionnaires, respectively. Linear mixed modelling was used to analyse within-group changes and between-group differences. Results and limitationsThe majority of HRQoL outcomes remained stable over time. Observed changes were only of small clinical relevance. Improvements were noted in insomnia, social functioning, and three NMIBC-specific symptoms, while minor deteriorations in appetite and diarrhoea lasted until 51 mo. HRQoL in some domains was worse for high-grade NMIBC, high European Association of Urology (EAU) risk group, initial Bacillus Calmette-Guérin (BCG) treatment, being female, and being younger (<65 yr); yet differences were few, small, and temporary. No differences were observed across recurrence status. Compared with a normative population, clinically relevant worse scores were observed for six of 15 outcomes, which mostly recovered at 51 mo, except for minor symptoms of appetite loss and diarrhoea. ConclusionsNo remarkable changes in HRQoL were observed during the first 4 yr after NMIBC diagnosis. Grade, EAU risk group, initial treatment, recurrence, sex, and age did not importantly affect HRQoL. HRQoL was largely comparable with that of the general population, especially after 4 yr. Patient summaryQuality of life is not largely affected during the first 4 yr after non–muscle-invasive bladder cancer diagnosis.

Immunohistochemical diagnosis of tumor-associated macrophages in patients with muscle-invasive bladder cancer after radical cystectomy

BACKGROUND: Bladder cancer is a serious problem of oncourology. The gold standard of treatment for muscle-invasive bladder cancer is radical cystectomy with previous neoadjuvant chemotherapy. Unfortunately, the effectiveness of radical treatments is severely limited in the long term. For this reason, research in the field of predicting survival can significantly improve long-term oncological results. The determination of the levels of macrophages associated with the tumor appears promising.&#x0D; AIM: to determine the effect of the expression levels of macrophages associated with a tumor on survival rates in patients diagnosed with muscle-invasive bladder cancer after radical cystectomy.&#x0D; MATERIALS AND METHODS: the study was conducted on the basis of the Clinic of the Bashkir State Medical University in the period from 01.05.2021 to 01.07.2023. The study involved 66 patients with an established diagnosis of muscle-invasive bladder cancer. After surgical treatment, histological and immunohistochemical studies were performed to determine CD68 and CD163 levels. After 24 months, a survival analysis was performed to determine the levels of general, tumor-specific and relapse-free survival and the construction of Kaplan–Mayer graphs.&#x0D; RESULTS: According to the results of the analysis, there was a significant decrease in survival in groups with high CD68 and CD163 expression rates (p 0.05). In the study groups, there was a significantly significant correlation between high levels of CD68 and CD163 (p 0.05).&#x0D; CONCLUSIONS: CD68 and CD163 can act as independent markers of predicted survival in patients with muscle-invasive bladder cancer after radical cystectomy.

Magnetic resonance radiographic features which might lead to misdiagnosis of muscle-invasive bladder cancer based on vesical imaging reporting and data system: the application experience of a single center.

The Vesical Imaging Reporting and Data System (VI-RADS) has been widely used for diagnosing muscle-invasive bladder cancer (MIBC), yet instances of misdiagnosis persist. However, limited research discusses the factors affecting its accuracy. This study aimed to evaluate the diagnostic efficacy of the VI-RADS in our center and to preliminarily identify possible magnetic resonance imaging (MRI) characteristics of misdiagnosis. From January 2018 to February 2023, a consecutive series of 211 participants pathologically diagnosed with bladder cancer (BC) who underwent an MRI exam were retrospectively enrolled. MRI was interpreted by 2 radiologists with different levels of experience, the diagnostic performance was validated using the receiver operating characteristic (ROC) curve, and VI-RADS ≥4 was considered to indicate MIBC-positive status. The clinical and radiographic characteristics of the true-positive (TP), true-negative (TN), false-positive (FP), and false-negative (FN) groups were analyzed using Kruskal-Wallis test or Fisher exact test. With VI-RADS ≥4 as the cutoff value, the area under the ROC curves (AUCs) were 0.951 (0.912-0.976) and 0.847 (0.791-0.893) for the more-experienced reader and less-experienced reader, respectively, with good interobserver agreement (κ=0.74105). The median tumor size in the TP (more experienced: 57 cases; less experienced: 44 cases) and FP (more experienced: 8 cases; less experienced: 9 cases) groups was larger than that in the TN (more experienced: 141 cases; less experienced: 139 cases) group for the more-experienced reader (TP: 28 mm; FP: 31 mm; TN: 19 mm; P<0.001 and P=0.031, respectively) and the less-experienced reader (TP: 31 mm; FP: 28 mm; TN: 19 mm; P<0.001 and P=0.042, respectively). The tumor base in the TP and FP groups was larger than that in the TN group for the more-experienced reader (TP: 37 mm; FP: 48 mm; TN: 15 mm; both P<0.001) and for the less-experienced reader (FP: 42 mm; FP: 36 mm; TN: 15 mm; P<0.001 and P=0.022, respectively). The median tumor base in the TP group was larger than that in the FN group for the less-experienced reader (TP: 42 mm; FN: 17 mm; P=0.004). We observed good to excellent AUCs with good interobserver agreement among radiologists with different levels of expertise using VI-RADS. Large tumor size and wide tumor base affected the accuracy of VI-RADS in MIBC diagnosis.

Secondary Bladder Cancer After Prostate Cancer Treatment: An Age-matched Comparison Between Radiation and Surgery

BackgroundSecondary malignancy is a long-term risk of radiation. External beam radiation therapy (EBRT) for prostate cancer treatment has been associated with later development of bladder cancer and worse bladder cancer features. ObjectiveWe sought to provide an updated comparison of the long-term risk of bladder cancer after different localized prostate cancer treatments. Design, setting, and participantsUsing the Surveillance, Epidemiology, and End Results (SEER) cancer registry, we compared an age-matched subset of patients who underwent radical prostatectomy (RP) with those who underwent EBRT, brachytherapy (BT), EBRT + BT, and RP followed by EBRT (RPtoEBRT) between 2000 and 2018. Our final cohort included 261 609 patients with a median follow-up of 11.6 yr. Outcome measurements and statistical analysisOur primary outcomes were time to bladder cancer diagnosis, muscle-invasive bladder cancer diagnosis, and bladder cancer death. We used cause-specific hazard models considering death as a competing event. A similar analysis was performed on lung cancer, as a surrogate marker for smoking. We also compared proportions of variant histology, high-grade, and invasive disease among bladder cancers that occurred after radiation versus RP using chi-square testing. Results and limitationsAll radiation groups were associated with bladder cancer diagnosis; hazard ratios (HRs) were 1.72, 1.85, 1.80, and 1.53 for EBRT, BT, EBRT + BT, and RPtoEBRT, respectively, using RP as a referent (all p < 0.001). HRs for bladder cancer death were even higher: 2.39, 2.57, and 3.02 for EBRT, BT, and EBRT + BT, respectively (all p < 0.001), except for RPtoEBRT (HR 1.43, p = 0.28). Lung cancer diagnosis was also associated with radiation but at lower HRs—1.63, 1.32, 1.42, and 1.30 for EBRT, BT, EBRT + BT, and RPtoEBRT, respectively (all p < 0.001). There were a higher proportion of ≥T2, ≥T3, and sarcomatoid variant bladder cancers after radiation (all p < 0.01) ConclusionsThe risk of developing and dying from bladder cancer is increased in patients treated with radiation compared with those treated with RP. The risk was similar for BT and EBRT. Bladder cancers after radiation are more likely to be sarcomatoid variant and present as muscle invasive. Patient summaryWe observed the rates of bladder cancer after patients had undergone surgery or radiation for prostate cancer, and found higher rates of bladder cancer after radiation. We also observed that bladder cancers that occur after radiation tend to be more aggressive.

Biparametric versus Multiparametric Magnetic Resonance Imaging for Assessing Muscle Invasion in Bladder Urothelial Carcinoma with Variant Histology Using the Vesical Imaging-Reporting and Data System

BackgroundThe diagnostic performance of contrast medium–free biparametric magnetic resonance imaging (bpMRI; combining T2-weighted imaging [T2WI] and diffusion-weighted imaging [DWI]) for evaluating variant-histology urothelial carcinoma (VUC) remains unknown. ObjectiveTo compare the diagnostic performance of bpMRI and multiparametric MRI (mpMRI; combining T2WI, DWI, and dynamic contrast-enhanced MRI]) for assessing muscle invasion of VUC. Design, setting, and participantsThis multi-institution retrospective analysis included 118 patients with pathologically verified VUC who underwent bladder mpMRI before transurethral bladder tumor resection between 2010 and 2019. Outcome measurements and statistical analysisThree board-certified radiologists separately evaluated two sets of images, set 1 (bpMRI) and set 2 (mpMRI), in accordance with the Vesical Imaging Reporting and Data System (VI-RADS). The histopathology results were utilized as a reference standard. Receiver operating characteristic curve analysis, Z test, and Wald test were used to assess diagnostic abilities. Results and limitationsSixty-six (55.9%) and 52 (44.1%) of the 118 patients with VUC included in the analysis (mean age, 71 ± 10 yr; 88 men) had muscle-invasive bladder cancer (MIBC) and non-MIBC, respectively. For the diagnosis of MIBC, the areas under the curve for bpMRI were significantly smaller than those for mpMRI (0.870–0.884 vs 0.902–0.923, p < 0.05). The sensitivity of bpMRI was significantly lower than that of mpMRI for all readers with a VI-RADS cutoff score of 4 (65.2–66.7% vs 77.3–80.3%, p < 0.05). The specificity of bpMRI and mpMRI did not differ significantly for all readers (88.5–90.4 vs 88.5–92.3, p > 0.05). A limitation of the study is the limited sample size because of the rarity of VUC. ConclusionsIn patients with VUC, on applying VI-RADS, the diagnostic results of bpMRI were inferior to those of mpMRI for evaluating muscle invasion. Therefore, mpMRI-based methods are recommended for evaluating muscle invasiveness of VUC. Patient summaryContrast medium–free biparametric magnetic resonance imaging (bpMRI)-based Vesical Imaging Reporting and Data System (VI-RADS) can accurately diagnose pure urothelial carcinomas, similar to conventional multiparametric magnetic resonance imaging–based VI-RADS. However, bpMRI-based VI-RADS may misdiagnose muscle invasiveness of urothelial carcinoma with variant histology, particularly when its cutoff score is 4.

Survival outcomes in patients with muscle-invasive bladder cancer receiving neoadjuvant chemotherapy stratified by number of cycles.

4586 Background: Neoadjuvant cisplatin-based chemotherapy (NAC) prior to radical cystectomy is the standard of care for patients with muscle invasive bladder cancer (MIBC). Three or more cycles of NAC are commonly administered based on outcomes in prior prospective trials, however many patients are intolerant of 3 cycles of NAC due to toxicity. The prognosis of patients receiving fewer than 3 cycles of NAC has yet to be elucidated. Methods: This is a retrospective single-center study to quantify pathologic response, recurrence-free survival (RFS), and overall survival (OS) from time of first NAC in patients treated with &lt; 3 cycles of NAC compared to patients treated with ≥3 cycles of NAC. Inclusion criteria include: diagnosis of MIBC between 2004-2017, ≥5 years of follow up, deceased or had recurrence prior to 5 years follow up but with adequate follow-up data. Patients were excluded from the study if they were found to have metastatic disease prior to initiation of NAC, lost to follow up prior to 5 years with no evidence of recurrence or death, or had progression of disease during NAC. The primary objective of this study was to determine RFS and OS in patients stratified by cycles of NAC. Patient characteristics were compared using chi-square tests, Fisher’s exact tests, and Wilcoxon rank sum tests. Kaplan Meier curves and log-rank tests were used to compare RFS between subgroups, and Cox proportional hazards models were used to compare RFS adjusting for ECOG performance status, baseline GFR, stage, type of NAC regimen, and patient age at first dose of NAC. 5-year OS was calculated as a percentage of patients surviving at 5 years. Results: A total sample of 195 patients were treated with NAC for MIBC, of which 30 (15.3%) patients received &lt; 3 cycles and 165 (84.6%) patients received ≥3 cycles of NAC. 53 patients received gemcitabine and cisplatin (GC) and 142 patients received methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). Complete pathologic response (ypT0N0) was observed in 7.4% of patients receiving &lt; 3 cycles and in 26.8% of patient receiving ≥3 cycles of NAC (p = 0.024). Significant pathologic response ( &lt; ypT2) was obtained in 22.2% of patients receiving &lt; 3 cycles of NAC and in 41.8% of patients receiving ≥3 cycles (p &gt; 0.05). Median RFS in patients with &lt; 3 cycles of NAC was 8.8 months (95% CI 6.51, 13.4) and 54.5 months with ≥3 cycles of NAC (95% CI 29.8, 111.9). Based on a log-rank test there is a statistically significant difference in unadjusted RFS between the two groups (p &lt; 0.001). The 5-year OS in patients receiving &lt; 3 cycles of NAC was 13.3%, and the 5-year OS in those receiving ≥3 cycles was 53.3%. Conclusions: Early cessation of chemotherapy due to intolerance had significant implications on pathologic response, RFS and OS. Clinicians should prioritize administering at least 3 cycles of cisplatin-based chemotherapy when feasible to optimize outcomes.

Identification of biomarkers for early progression in muscle invasive bladder cancer (MIBC) using real-world data.

e16568 Background: MIBC accounts for ~25% of all newly diagnosed bladder cancers and is associated with a high rate of recurrence despite radical treatment. The time to progression (TTP) can vary significantly between patients and can affect their prognosis. We leveraged a real world clinico-genomics database to classify patients as early vs late progressors, understand its impact on their outcomes and identify genetic drivers of early progression. Methods: This retrospective study was executed using the deeply curated ConcertAI Genome360 bladder cancer dataset. Only patients with confirmed MIBC status with reported tumor progression after initial treatment were considered. Based on the distribution of TTP from MIBC diagnosis of this patient cohort, we subdivided the patients into early vs late progressors. Overall survival (OS) and progression free survival (PFS) analyses were performed between these 2 cohorts. The underlying deleterious genomic mutations were identified in each cohort and differential genomic enrichment analysis was performed to identify statistically significant biomarkers correlated with early progression (p-value &lt; = 0.05). Additionally, identified biomarkers were analyzed in the context of administered therapies. Results: The TTP exhibited a bimodal distribution with a break at around 500 days, so we chose this as the cut-off to define early (N = 203) vs late progressors (N = 51). As expected, there was a significant difference in the median PFS of early vs late progressors (0.62 vs 2.41 years (p &lt; 1e-6)). The OS was also significantly different (1.98 vs 4.36 years (p = 6e-6)). We further identified mutations in 6 biomarkers which were enriched in early vs late progressors. These were CDK12 (p = 0.05), EGFR (p = 0.034), LRP1B (p = 0.05), MET (p = 0.045), PTEN (p = 0.026) and SMAD4 (p = 0.047). These patients were primarily treated with platinum-based therapies +/- gemcitabine/PD-L1 therapies in-line with MIBC treatment guidelines. The identified driver genes activate PI3K-AKT-MTOR, JAK-STAT3, b-catenin and ERK pathways which are known to interfere with the mechanism of action of platinum-based therapies, thus potentially forming the basis of early progression. Conclusions: Using our Genome360 bladder dataset, we have identified prognostic biomarkers for early progression in MIBC. This may provide clinicians with a tool to identify and modify treatment for a subset of MIBC patients who are at risk of early progression on standard of care therapies.

Can the Vesical Imaging Reporting and Data System (VI-RADS) score be applied in conventional ultrasound and contrast-enhanced ultrasound to differentiate muscle-invasive bladder cancer?

To investigate the value of vesical imaging reporting and data system (VI-RADS) score based on conventional ultrasound and contrast-enhanced ultrasound (CEUS) in differentiating muscle-invasive bladder cancer (MIBC). Thirty-eight patients who underwent conventional ultrasound and CEUS examinations at our ultrasound department between March 2021 and June 2022 were retrospectively included in this study. Two sonographers analyzed the conventional ultrasound and CEUS images of each patient separately and scored them in strict accordance with VI-RADS scoring system based on conventional ultrasound and CEUS. The VI-RADS score of each lesion was compared with the pathological findings to assess the diagnostic performance of VI-RADS. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the VI-RADS score in the diagnosis of MIBC were analyzed when the cutoff values were 3 and 4, respectively. Interobserver agreement was evaluated using the weighted-kappa coefficient (κ). The final pathological results evidenced 25 (65.8%) non-muscle-invasive bladder cancers (NMIBCs) and 13 (34.2%) MIBCs. When the VI-RADSscore ≥ 4, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the VI-RADS score for predicting muscle-invasive bladder cancer were 92.3%, 84.0%, 75.0%, 95.5%, and 86.8%, respectively. The area under the receiver operating curve for the VI-RADS score was 0.882 (95%CI:0.761-1). Inter-reader agreement for VI-RADS scoreswas good. The VI-RADS score based on conventional ultrasound and CEUS is useful in differentiating muscleinvasive bladder cancer.

Health-related quality of life after curative treatment for muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which the gold-standard treatment is radical cystectomy (RC) in combination with cisplatin-based neoadjuvant chemotherapy. Bladder-sparing strategies such as trimodal therapy (TMT) have also emerged to improve health-related quality of life (HRQoL) of patients. However, an improved understanding of the effect of all these treatment modalities on HRQoL is essential to provide personalized patient care. Different combinations of generic, cancer-specific and bladder cancer-specific questionnaires can be used as instruments for HRQoL evaluation in patients with MIBC before and after curative treatments, which can largely affect multiple domains of HRQoL including general health as well as physical, functional, social and emotional well-being. However, diagnosis of MIBC per se is also likely to affect HRQoL, and the perspective of cure after RC or TMT could induce a return to baseline HRQoL values for most of these domains. A considerable amount of data on HRQoL after RC is available, but conflicting results have been reported regarding the effect of urinary diversion (ileal conduit or orthotopic neobladder) and surgical approach (open or robotic surgery) on patient quality of life. Data on HRQoL after TMT are scarce, and additional comparative studies including patients receiving RC (especially using ileal orthotopic neobladder) are needed.

Is high accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) sufficient for its implementation in the urological practice?

Currently, the only method used to differentiate between MIBC and NMIBC is transurethral resection of the bladder tumour (TURBT). Magnetic resonance and Vesical Imaging-Reporting and Data System (VI-RADS) would allow for discrimination between NMIBC and MIBC. We evaluate the sensitivity and specificity of VI-RADS in the diagnosis of muscle-invasive bladder cancer and discuss its value in everyday urological practice. 64 patients with bladder cancer (BC) were enrolled into this prospective study. Multiparametric magnetic resonance imaging (mpMRI) was performed before transurethral resection of the bladder tumour (TURBT) and evaluated using the VI-RADS score. Score were compared to histopathology results. We evaluated the sensitivity, specificity, positive and negative predictive value of this system using both cut-off VI-RADS ≥ 3 and ≥ 4. Sensitivity of 92.3% (95%CI: 64.0; 99.8), specificity of 81.4% (95%CI: 69.1; 90.3), positive predictive value of 52.2% (95%CI: 30.6; 73.2) and negative predictive value of 98.0% (95%CI: 89.1; 99.9) was determined using cut off VI-RADS ≥ 3, while sensitivity of 76.9% (95%CI: 46.2; 95.0), specificity of 91.5% (95%CI: 81.3; 97.2), positive predictive value of 66.7% (95%CI: 38.4; 88.2), and negative predictive value of 94.7% (95%CI: 85.4; 98.9) was determined using cut-off VI-RADS ≥ 4. Based on our results, we consider the optimal cut-off point to be VI-RADS ≥ 3 with the overall prediction accuracy of 83.3% (95%CI: 72.7; 91.1). We acknowledge that mpMRI provides valuable information with regard to BC staging, however, despite its high overall accuracy, we do not consider the VI-RADS could replace TURBT in discrimination between non-muscle invasive and MIBC.

Nomogram based on baseline clinicopathological characteristics for predicting bladder cancer-specific survival to neoadjuvant chemotherapy in muscle-invasive bladder cancer.

To develop a risk score based on a prognostic model and a nomogram integrating baseline clinicopathological variables to predict bladder cancer-specific survival (BCSS) to neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) patients. We retrospectively identified a consecutive sample of 247 MIBC patients treated with cisplatin-based NAC-plus-cystectomy in two Spanish hospitals between 2000 and 2019. Age at MIBC diagnosis, sex, histology, lymphovascular invasion, previous non-MIBC, hydronephrosis, and clinical TNM were included in the initial Cox regression model. A risk score was computed based on the final prognostic model and a nomogram was used to estimate BCSS at 2 and 5years. Median age was 66years; 89% were males; 83% had pure urothelial carcinoma; 16.2% had previous non-MIBC. Clinical stage was T2N0, T3-4aN0, and Tx-4N + in 24%, 57%, and 19% of patients, respectively. Complete pathological response was seen in 29.4% and downstaging to non-MIBC (ypT1, ypTa, ypTis) in 12.5% of patients. Overall 5-year BCSS was 59%. Four prognostic factors were identified: variant histology, previous non-MIBC, female sex and hydronephrosis. By adding the points attributed to each of these factors, we categorized patients in three groups: low-risk (0 points); intermediate-risk (1-9 points); high-risk (≥ 10 points). Five-year BCSS was 72%, 53%, and 15%, respectively (p < 0.0001). We developed a nomogram and risk score based on four baseline clinicopathological characteristics to predict BCSS to NAC-plus-cystectomy in MIBC patients. If validated in prospective studies, this nomogram can be useful for selecting patients likely to benefit from NAC.

Diagnostic Value of the Vesical Imaging-Reporting and Data System in Bladder Urothelial Carcinoma with Variant Histology

The value of the Vesicle Imaging-Reporting and Data System (VI-RADS) in the diagnosis of muscle-invasive bladder cancer (MIBC) for urothelial carcinoma with variant histology (VUC) remains unknown. We retrospectively evaluated 360 consecutive patients with bladder cancer (255 pure urothelial carcinoma [PUC] and 69 VUC) who underwent multiparametric magnetic resonance imaging between 2011 and 2019. VI-RADS scores assigned by four readers were significantly higher for the VUC group than for the PUC group (p < 0.05). In the cohort of 122 pair-matched patients, there was no significant difference in VI-RADS score distribution between the PUC and VUC groups for all readers (p > 0.05). The area under the receiver operating characteristic curve for MIBC diagnosis via overall VI-RADS score was 0.93–0.94 for PUC and 0.89–0.92 for VUC, with no significant difference between the PUC and VUC groups (p = 0.32–0.60). These data suggests that VI-RADS scores achieved high diagnostic performance for detection of muscle invasion in both PUC and VUC. Patient summaryThe Vesical Imaging-Reporting and Data System (VI-RADS) is a standardized system for reporting on detection of muscle-invasive bladder cancer via magnetic resonance imaging (MRI) scans. Our study shows that VI-RADS is also highly accurate for diagnosis for different variants of muscle-invasive bladder cancer, with good inter-reader agreement.

A novel pathway to detect muscle-invasive bladder cancer based on integrated clinical features and VI-RADS score on MRI: results of a prospective multicenter study

PurposeTo determine the clinical, pathological, and radiological features, including the Vesical Imaging-Reporting and Data System (VI-RADS) score, independently correlating with muscle-invasive bladder cancer (BCa), in a multicentric national setting.Method and MaterialsPatients with BCa suspicion were offered magnetic resonance imaging (MRI) before trans-urethral resection of bladder tumor (TURBT). According to VI-RADS, a cutoff of ≥ 3 or ≥ 4 was assumed to define muscle-invasive bladder cancer (MIBC). Trans-urethral resection of the tumor (TURBT) and/or cystectomy reports were compared with preoperative VI-RADS scores to assess accuracy of MRI for discriminating between non-muscle-invasive versus MIBC. Performance was assessed by ROC curve analysis. Two univariable and multivariable logistic regression models were implemented including clinical, pathological, radiological data, and VI-RADS categories to determine the variables with an independent effect on MIBC.ResultsA final cohort of 139 patients was enrolled (median age 70 [IQR: 64, 76.5]). MRI showed sensitivity, specificity, PPV, NPV, and accuracy for MIBC diagnosis ranging from 83–93%, 80–92%, 67–81%, 93–96%, and 84–89% for the more experienced readers. The area under the curve (AUC) was 0.95 (0.91–0.99). In the multivariable logistic regression model, the VI-RADS score, using both a cutoff of 3 and 4 (P < .0001), hematuria (P = .007), tumor size (P = .013), and concomitant hydronephrosis (P = .027) were the variables correlating with a bladder cancer staged as ≥ T2. The inter-reader agreement was substantial (k = 0.814).ConclusionsVI-RADS assessment scoring proved to be an independent predictor of muscle-invasiveness, which might implicate a shift toward a more aggressive selection approach of patients’ at high risk of MIBC, according to a novel proposed predictive pathway.

Efficacy and safety of atezolizumab concurrent with radiotherapy in patients with muscle-invasive bladder cancer: An interim analysis of the ATEZOBLADDERPRESERVE phase II trial (SOGUG-2017-A-IEC(VEJ)-4).

4588 Background: Combined-modality treatments are bladder-preserving alternatives for patients (pts) who are not candidates for radical cystectomy by medical reasons, refusal, or patient´s choice. Immune therapies seem to potentiate tumor-specific immune response induced by radiotherapy (RT). Combination of RT with anti-PD-1/PD-L1 therapy appears safe and there are signs of promising activity. The aim of this study is to assess the efficacy and safety of atezolizumab (ATZ) concurrent with external beam radiotherapy (EBRT) for the treatment of muscle-invasive bladder cancer (MIBC) with bladder preservation intent. Here we present an interim analysis. Methods: This is an open, multicenter, and phase II trial, sponsored by SOGUG, in pts with confirmed diagnosis of MIBC in clinical stages cT2-T4a N0 M0 who are not candidates for radical cystectomy. Treatment consists of 6 doses of ATZ 1200 mg IV every 3 weeks, starting on day 1 of EBRT, and 60 Gy of RT in 30 fractions over 6 weeks at 2 Gy/day. The primary endpoint of the study is pathological complete response (pCR) defined as a response of grade 5 according to Miller and Payne criteria, 1 to 2 months after the last dose of ATZ. A planned interim analysis has been performed (data cut-off date: November 2021) on the primary endpoint to avoid exposure to ineffective treatment according to the minimax two-stages Simon’s design (stopping rule: 9 out of the first 13 evaluable pts should achieve pCR). Incidence of adverse events (AE) and serious AE (SAE) has been also secondarily assessed. Results: From September 2019 to November 2021, 39 pts were screened, of whom 13 were excluded due to non-compliance with eligibility criteria. Thus, the evaluable population consisted of 26 pts. The safety analysis was performed in 22 pts who had received at least one dose of ATZ. 14 pts were assessed pathologically and, thus, included in interim efficacy analysis (median age: 78.6 years; clinical stage: 71.4% T2a, 14.3% T2b, 7.1% T3a, 7.1% T3b). All 14 pts had achieved pCR at the cut-off date. 20/22 (91%) pts experienced at least one AE, with asthenia (11 pts), diarrhea (9 pts), and urinary tract infection (4 pts) being the most common. 9 SAEs were reported in 7 (32%) pts (bacteriemia, COVID-19 infection, depressed LVEF, unknown origin fever, hepatic toxicity, kidney failure, rectorrhagia, respiratory infection, and urinary sepsis). 6 (27%) pts suffered AEs leading to treatment discontinuation. No AEs leading to death occurred. 17 pts with available data on survival were alive at the cut-off date. Conclusions: Interim results suggest that ATZ combined with EBRT is a feasible and effective treatment in terms of pCR, with a manageable safety profile. The final results from this trial will provide information about its effects on clinical outcome, including survival and updated safety findings. Clinical trial information: NCT04186013.

The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy

BackgroundThere might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non–muscle-invasive disease. ObjectiveTo investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2–4N0M0 MIBC. Design, setting, and participantsOncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysisThe outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitationsThe primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26–0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19–0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84–3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66–3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p < 0.001). ConclusionsPatients with primary MIBC have better pathologic response rates to NAC in comparison to patients with secondary MIBC. Chemoresistance might be related to the different genomic profile of primary versus secondary MIBC. Patient summaryWe investigated the treatment response to neoadjuvant chemotherapy (NAC; chemotherapy received before the primary course of treatment) and survival for patients with a primary diagnosis of muscle-invasive bladder cancer (MIBC) in comparison to patients with a history of non–muscle-invasive bladder cancer that progressed to MIBC. Patients with primary MIBC had a better response to NAC but this did not translate to better survival after accounting for other tumor characteristics.