Diagnosis Of Muscle-invasive Bladder Cancer Research Articles

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.

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.

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

The 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. To evaluate HRQoL outcomes during the first 4 yr after NMIBC diagnosis, and to compare HRQoL across patient characteristics and with a normative population. Patients 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). Cancer- 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. The 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. No 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. Quality of life is not largely affected during the first 4 yr after non-muscle-invasive bladder cancer diagnosis.

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.

Cascade Path Augmentation Unet for bladder cancer segmentation in MRI

Treatment choices for patients with bladder cancer (BCa) are determined by the presence of muscular invasion. The precise segmentation of the inner and outer walls (IW and OW), as well as the bladder tumor (BT), is crucial for improving computer-aided diagnosis of muscle-invasive bladder cancer (MIBC). To propose a novel deep learning-based model to improve the segmentation accuracy of the IW, OW, and BT, which can be useful in clinical practice. We proposed a Cascade Path Augmentation Unet (CPA-Unet) network to conduct multi-regional segmentation of the bladder using 1545 T2-weighted MRI scans. The model employs a cascade strategy to eliminate the redundant information in the background. Unet is used to segment the bladder from the background in the rough segmentation. The path augmentation structure is used in the fine segmentation to mine multi-scale features. Additionally, the partial dense connection is adopted as the skip connection module to concatenate the low- and high-level sematic features. The CPA-Unet is trained using 1391 T2WI slices and tested using 154 T2WI slices. In comparison to previous deep learning-based methods, the CPA-Unet achieves superior segmentation results in terms of Dice similarity coefficient (DSC) and Hausdorff distance (HD) (IW: DSC =98.19%, HD =2.07mm; OW: DSC =82.24%, HD =2.62mm; BT: DSC =87.40%, HD =0.76mm). Our proposed CPA-Unet network is capable of segmenting the bladder into its IW and OW, as well as tumors. The segmentation results provide a reliable and effective foundation for computer-assisted clinical diagnosis of MIBC.

Malignant Central Nervous System Lymphoma after Radical Total Cystectomy : A Diagnostic Challenge

We report a case of primary central nervous system lymphoma (PCNSL) in an 81-year-old man who had undergone radical cystectomy with an ileal conduit urostomy due to a diagnosis of muscle-invasive bladder cancer. The postoperative diagnosis was invasive urothelial carcinoma (pT2bN1M0, stage IV). Gemcitabine-cisplatin therapy was provided as adjuvant chemotherapy, and there was no recurrence during follow-up. Four years after surgery, he visited the emergency department because of weakness of the lower extremities and stuttering. He was found to have a parietal lobe mass on magnetic resonance imaging (MRI) and hospitalized with suspicion of brain metastasis. Despite examination by a neurosurgeon, it was not possible to make a clinical diagnosis, and the patient gradually deteriorated and died 21 days later. The pathology results were diagnostic of PCNSL.

Diet Quality and Survival in a Population-Based Bladder Cancer Study

Nutrition may impact bladder cancer survival. We examined the association between diet quality and overall and bladder cancer-specific survival. Bladder cancer cases from a population-based study reported pre-diagnosis diet. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010). Vital status was ascertained from the National Death Index. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards and competing risks regression models. Overall AHEI-2010 adherence was not associated with overall or bladder cancer-specific survival among non-muscle invasive bladder cancer (NMIBC) cases (HR, 1.00; 95% CI, 0.98-1.01; HR, 1.00; 95% CI, 0.97-1.02) or muscle invasive bladder cancer (MIBC) cases (HR, 0.99; 95% CI, 0.96-1.03; HR, 1.01, 95% CI 0.97-1.06). AHEI-2010 sugar-sweetened beverages adherence was associated with poorer overall survival (HR, 1.04; 95% CI, 1.01-1.08) and AHEI-2010 sodium adherence was associated with better overall and bladder cancer-specific survival after NMIBC diagnosis (HR, 0.92, 95% CI, 0.85-1.00; HR, 0.82; 95% CI, 0.68-0.98). AHEI-2010 fruit adherence was associated with poorer overall and bladder cancer-specific survival after MIBC diagnosis (HR, 1.17; 95% CI, 1.02-1.33; HR, 1.26; 95% CI, 1.03-1.55). Consumption of sugar-sweetened beverages, sodium, and fruit, not overall AHEI-2010 adherence, may be associated with bladder cancer survival.

MP13-20 LONG TERM OUTCOMES IN PATIENTS WITH MUSCLE INVASIVE BLADDER CANCER WHO ARE MISCLASSIFIED AS ACHIEVING A COMPLETE CLINICAL RESPONSE TO NEOADJUVANT CHEMOTHERAPY: HOW COSTLY ARE MISTAKES?

You have accessJournal of UrologyBladder Cancer: Invasive I (MP13)1 Sep 2021MP13-20 LONG TERM OUTCOMES IN PATIENTS WITH MUSCLE INVASIVE BLADDER CANCER WHO ARE MISCLASSIFIED AS ACHIEVING A COMPLETE CLINICAL RESPONSE TO NEOADJUVANT CHEMOTHERAPY: HOW COSTLY ARE MISTAKES? Jane Kurtzman, Rainjade Chung, Helena Vila-Reyes, Guarionex Decastro, Christopher Anderson, Charles Drake, and James McKiernan Jane KurtzmanJane Kurtzman More articles by this author , Rainjade ChungRainjade Chung More articles by this author , Helena Vila-ReyesHelena Vila-Reyes More articles by this author , Guarionex DecastroGuarionex Decastro More articles by this author , Christopher AndersonChristopher Anderson More articles by this author , Charles DrakeCharles Drake More articles by this author , and James McKiernanJames McKiernan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001994.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Correctly classifying patients with muscle invasive bladder cancer (MIBC) as achieving a complete response to neoadjuvant chemotherapy (NAC) is challenging without radical cystectomy (RC) pathology. The accuracy of clinical staging following NAC is debated and the risk of occult residual MIBC is real. In this study, we present the survival outcomes of patients who were misclassified as having achieved a complete clinical response (CCR) to NAC. METHODS: We retrospectively reviewed our prospective database of patients with MIBC who achieved a CCR to NAC and elected active surveillance (AS). CCR criteria includes: negative cytology, benign TUR pathology and negative cross-sectional imaging. We defined misclassified CCR (mCCR) as a patient found to have intravesical MIBC within 6 months of meeting CCR criteria. Kaplan-Meier curves were used to assess overall (OS), cancer-specific (CSS) and metastasis-free (MFS) survival and log-rank tests to evaluate differences between cohorts. RESULTS: We included 54 patients, with a median age of 70 years (IQR 62-75) and median follow-up of 49 months (IQR 26-77) since MIBC diagnosis. 6/54 patients (11%) were mCCR. All 6 underwent RC at a mean of 129 days after CCR classification. Five-year OS, CSS and MFS for mCCR patients was 63%, compared to 80%, 89% and 93%, respectively, for the remaining patients (Figure 1). Log-rank tests revealed a significantly higher OS and MFS in CCR compared to mCCR patients (p=0.03 and p=0.05, respectively), but no difference in CSS (p=0.07). However, this lack of significance was likely due to lack of power. CONCLUSIONS: We observed an 11% rate of occult MIBC in patients who elect AS following a CCR to NAC. Delayed RC in this cohort resulted in a 63% 5-year OS, CSS and MFS. These survival outcomes for mCCR patients are comparable to those previously published for patients who undergo immediate RC following NAC and are found to have residual intravesical MIBC on specimen review. Our findings are useful when describing the risk of occult MIBC to patients contemplating AS. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e251-e251 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jane Kurtzman More articles by this author Rainjade Chung More articles by this author Helena Vila-Reyes More articles by this author Guarionex Decastro More articles by this author Christopher Anderson More articles by this author Charles Drake More articles by this author James McKiernan More articles by this author Expand All Advertisement Loading ...