Vesical Imaging-Reporting And Data System Research Articles

A Nomogram of MRI Features to Assess Muscle Invasion in VI-RADS 2 Tumors With Stalk.

Vesical Imaging-Reporting and Data System (VI-RADS) is widely used to assess the muscle-invasive status of bladder cancer. However, the current classification efficacy of VI-RASD 2 tumors of stalk is unsatisfactory. To develop a nomogram to assess muscle-invasive bladder cancer (MIBC) in VI-RADS 2 tumors with stalk. Retrospective. A total of 186 patients (age: 67.8 ± 12.7 years) with 15.1% females, divided randomly into a training cohort (N = 130) and validation cohort (N = 56). 3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin-echo), and dynamic contrast-enhanced imaging (gradient-echo). Twenty-one MRI features of tumors and stalks were developed from training cohort. The mean apparent diffusion coefficient (ADC) values of the tumor, stalk, and psoas muscles were calculated from the three circular regions of interest. The normalized T . The normalized ST . Three readers assessed the morphology of tumors and stalks. The final features of nomogram were selected by univariable logistic and the least absolute shrinkage and selection operator (LASSO) regression. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis. In VI-RADS 2 tumors with stalk, tumor size over 3 cm, increased stalk width, stalk morphology, decreased normalized T value, and increased normalized ST value were selected as the risk factors for MIBC. The AUC, accuracy, sensitivity, and specificity of the nomogram to assess MIBC were 0.969 (95% CI: 0.941-0.997), 92.3%, 94.1%, and 92.0% in training cohort and 0.940 (95% CI: 0.859-1.000), 89.3%, 75.0%, and 91.7% in validation cohort. This study constructed a nomogram for preoperative assessment of MIBC and modifying the current VI-RADS. 3 TECHNICAL EFFICACY: Stage 2.

Performance of pre- and post-pembrolizumab vesical imaging–reporting and data system (VI-RADS) to predict the pathological response and efficacy outcomes in muscle-invasive urothelial bladder cancer (MIBC): Full data analysis from the PURE-01 trial.

65 Background: The VI-RADS is a standardized reporting system that uses multiparametric magnetic resonance imaging (mpMRI) parameters to differentiate non muscle-invasive bladder cancer (NMIBC) from MIBC. Limited data on clinical response assessment to neoadjuvant therapy are currently available. In this study, we aimed to analyze the performance of VI-RADS to predict the pT0 or pT≤1 response post-neoadjuvant immunotherapy in MIBC. Methods: In PURE-01 study (NCT02736266) patients (pts) were staged with mpMRI before and after treatment (3 cycles of Pembrolizumab) prior to radical cystectomy (RC). Logistic regression models analyzed pre- and post-pembro VI-RADS, with clinical and tumor-related variables, against ypT≤1N0 (primary endpoint) and ypT0N0 (secondary endpoint). VI-RADS scores were dichotomized between 0-3 (0 = no evidence of disease) and 4-5 (5 = extension to extravescical fat). Event-free survival (EFS) and overall survival (OS) analyses based on VI-RADS were performed. Comprehensive genomic profiling and transcriptome-wide expression profiling data were matched with VI-RADS scores. Model performance was also tested in the ongoing NureCombo (nivolumab+nab-paclitaxel; NCT04876313) and SURE-01 (sacituzumab govitecan; NCT05226117) neoadjuvant studies. Results: In total, 110 patients treated with neoadjuvant pembrolizumab between 02/2017 and 07/2020 had centrally reviewed scans (N=220 mpMRI). Pre-pembrolizumab, 21 patients (19.1%) had no measurable disease (VI-RADS=0), 34 (30.9%) had a VI-RADS 1-3 score, and 55 (50%) had a VI-RADS 4-5 score. Both pre-pembrolizumab and post-pembrolizumab VI-RADS 0-3 scores were the only significant covariates that predicted the ypT≤1N0 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembrolizumab VI-RADS 0-3 predicting the ypT≤1N0 response (odds ratio [OR]: 23.4, 95%CI: 7-95.3, p<0.0001). The area-under-the-curve (AUC) of this model was 0.90. Post-pembrolizumab VI-RADS 0-3 also predicted longer EFS (p<0.001) and OS (p=0.044). The scores of several gene signatures from baseline tumors differed between pre-pembrolizumab VI-RADS 0-3 and 4-5 categories. RAF1 mutations were enriched in pre-pembrolizumab VI-RADS 0-3 group (p=0.045). Conclusions: VI-RADS scores post-pembrolizumab revealed a robust association with pathological downstaging and survival. VI-RADS scores were also characterized by distinct biomarker features. These results indicate that VI-RADS is emerging as an important tool to design next-generation trials in MIBC. Clinical trial information: NCT02736266 .

Differentiation of bladder cancer stages using the vesical imaging -reporting and data system and apparent diffusion coefficient.

T stage is closely related to the treatment and prognosis of patients with bladder cancer (BC). However, preoperative T staging is still challenging. Multiparametric magnetic resonance imaging (mpMRI) may be valuable. This study was performed to explore the value of the Vesical Imaging-Reporting and Data System (VI-RADS) and the volumetric apparent diffusion coefficient (ADC) histogram parameters in detecting T2 stage and below stage (≤T2 stage) from T3 stage and above stage (≥T3 stage) BCs. The study included 62 patients (mean age, males vs. females: 62.1±10.9 vs. 61.8±11.7 years) with BC pathologically confirmed by partial or radical cystectomy. All of the tumors were scored normatively by two radiologists using the VI-RADS scoring system by two radiologists. The volumetric ADC histogram of each lesion was obtained from the ADC maps. The Cochran-Armitage test was used to examine the relevance between VI-RADS scores and T stages. The Mann-Whitney U test was used to compare the histogram parameters between ≤T2 stage and ≥T3 stage BCs. A receiver operating characteristic (ROC) curve was used to assess the predictive power of each model. The minimum ADC; mean ADC; median ADC; maximum ADC; and 10th, 25th, 75th, and 90th percentile ADC of ≤T2 stage BCs were significantly higher than those of ≥T3 stage BCs, while skewness and kurtosis had opposite results. VI-RADS achieved the highest area under the curve (AUC) of 0.834 among all parameters. The combination of VI-RADS, skewness and kurtosis yield a significantly higher AUC than VI-RADS alone (0.915 vs. 0.834, P=0.0478). VI-RADS and volume ADC histogram analysis can effectively discriminate between ≤T2 stage and ≥T3 stage BCs, and the volumetric ADC histogram can provide further information to supplement VI-RADS.

Tumor contact length with bladder wall provides effective risk stratification for lesions with a VIRADS score of 2-3.

To evaluate the diagnostic performance of the tumor contact length (TCL) in the prediction of MIBC (muscle-invasive bladder cancer) in lesions corresponding to the vesical imaging-reporting and data system (VIRADS) score 2-3. This is a single institution, retrospective study targeting 191 consecutive patients assigned of VIRADS score 2-3, who had pre-transurethral resection MRI from July 2019 to September 2021. Logistic regression analyses were performed to determine meaningful predictors of MIBC for this score group, and a nomogram was plotted with those variables. The diagnostic performance of each predictor was compared at predefined thresholds (VIRADS score 3 and TCL 3cm) using the generalized linear model and ROC analysis. Both VIRADS score and TCL remained independent predictors of MIBC for this score group (odds ratio 7.3 for VIRADS score, and 1.3 for TCL, p < 0.01 for both). The contribution of TCL to the probability of MIBC in the nomogram was greater than that of the VIRADS score. VIRADS score had a sensitivity of 0.54 (14/26), specificity of 0.92 (203/221), and diagnostic accuracy of 0.88 (217/247), and TCL showed a sensitivity of 0.89 (23/26), specificity of 0.95 (209/221), and diagnostic accuracy of 0.94 (232/247). The difference in sensitivity (p = 0.03) and accuracy (p = 0.04) was statistically significant. The AUC was also significantly wider for TCL than for VIRADS (0.97 vs. 0.73, p < 0.01). A simple index, TCL, may be helpful in further risk stratification for MIBC in patients with a score of VIRADS 2-3. For bladder cancer patients with insufficient qualitative evidence of muscle layer invasion using VIRADS categorization, TCL, a simple quantitative indicator defined as the curvilinear contact length between the bladder wall and the tumor, may be helpful in risk stratification. • Even when only lesions with score 2-3 were targeted, VIRADS was still a meaningful indicator of MIBC. • With a predefined threshold of 3cm applied, TCL outperformed VIRADS in the score 2-3 group, in predicting MIBC. • A longer TCL for a lesion with a VIRADS score 2 may warrant an additional warning for MIBC, whereas a shorter TCL for a lesion with a score 3 may indicate a lower risk of MIBC.

MRI-Based Radiomics in Bladder Cancer: A Systematic Review and Radiomics Quality Score Assessment.

(1): Background: With the recent introduction of vesical imaging reporting and data system (VI-RADS), magnetic resonance imaging (MRI) has become the main imaging method used for the preoperative local staging of bladder cancer (BCa). However, the VI-RADS score is subject to interobserver variability and cannot provide information about tumor cellularity. These limitations may be overcome by using a quantitative approach, such as the new emerging domain of radiomics. (2) Aim: To systematically review published studies on the use of MRI-based radiomics in bladder cancer. (3) Materials and Methods: We performed literature research using the PubMed MEDLINE, Scopus, and Web of Science databases using PRISMA principles. A total of 1092 papers that addressed the use of radiomics for BC staging, grading, and treatment response were retrieved using the keywords "bladder cancer", "magnetic resonance imaging", "radiomics", and "textural analysis". (4) Results: 26 papers met the eligibility criteria and were included in the final review. The principal applications of radiomics were preoperative tumor staging (n = 13), preoperative prediction of tumor grade or molecular correlates (n = 9), and prediction of prognosis/response to neoadjuvant therapy (n = 4). Most of the developed radiomics models included second-order features mainly derived from filtered images. These models were validated in 16 studies. The average radiomics quality score was 11.7, ranging between 8.33% and 52.77%. (5) Conclusions: MRI-based radiomics holds promise as a quantitative imaging biomarker of BCa characterization and prognosis. However, there is still need for improving the standardization of image preprocessing, feature extraction, and external validation before applying radiomics models in the clinical setting.

Evaluation of Whole-Tumor Texture Analysis Based on MRI Diffusion Kurtosis and Biparametric VI-RADS Model for Staging and Grading Bladder Cancer.

to evaluate the feasibility of texture analysis (TA) based on diffusion kurtosis imaging (DKI) in staging and grading bladder cancer (BC) and to compare it with apparent diffusion coefficient (ADC) and biparametric vesical imaging reporting and data system (VI-RADS). In this retrospective study, 101 patients with pathologically confirmed BC underwent MRI with multiple-b values ranging from 0 to 2000 s/mm2. ADC- and DKI-derived parameters, including mean kurtosis (MK) and mean diffusivity (MD), were obtained. First-order texture histogram parameters of MK and MD, including the mean; 5th, 25th, 50th, 75th, and 90th percentiles; inhomogeneity; skewness: kurtosis; and entropy; were extracted. The VI-RADS score was evaluated based on the T2WI and DWI. The Mann-Whitney U-test was used to compare the texture parameters and ADC values between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), as well as between low and high grades. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of each significant parameter and their combinations. The NMIBC and low-grade group had higher MDmean, MD5th, MD25th, MD50th, MD75th, MD90th, and ADC values than those of the MIBC and the high-grade group. The NMIBC and low-grade group yielded lower MKmean, MK25th, MK50th, MK75th, and MK90th than the MIBC and high-grade group. Among all histogram parameters, MD75th and MD90th yielded the highest AUC in differentiating MIBC from NMIBC (both AUCs were 0.87), while the AUC for ADC was 0.86. The MK75th and MK90th had the highest AUC (both 0.79) in differentiating low- from high-grade BC, while ADC had an AUC of 0.68. The AUC (0.92) of the combination of DKI histogram parameters (MD75th, MD90th, and MK90th) with biparametric VI-RADS in staging BC was higher than that of the biparametric VI-RADS (0.89). Texture-analysis-derived DKI is useful in evaluating both the staging and grading of bladder cancer; in addition, the histogram parameters of the DKI (MD75th, MD90th, and MK90th) can provide additional value to VI-RADS.

Unsupervised image-to-image translation in multi-parametric MRI of bladder cancer

Detection of muscular invasive bladder cancer (MIBC) is critical for surgical selection of bladder cancer (BCa) patients. Currently, multi-parameter magnetic resonance imaging (mp-MRI) is the predominant approach for identifying MIBC. However, mp-MRI is still insufficient due to the presence of noise and artifacts. Our research aims to synthesize images from the existing sequences of mp-MRI to substitute missing or low signal-to-noise ratio sequences through image-to-image (I2I) translation. Using mp-MRI images of 255 BCa patients collected in our department, we here propose a one-to-many unsupervised I2I translation network with region-wise semantic enhancement to synthesize virtual samples. We introduce an improved adaptive instance normalization module to support the generator for synthesizing multi-domain images. In addition, a branch for region-wise semantic segmentation helps the generator to enhance the quality of image translation for a specific region. A semantically consistent loss is applied to maintaining the consistency between the synthesized and the input images via region-wise semantic segmentation. Experiments on the BraTS and BCa datasets indicate that our I2I translation approach outperforms several state of the art methods. Additionally, we perform clinical feasibility tests using the synthesis images. The clinicians reach a consensus between the Vesical Imaging Reporting and Data System (VI-RADS) scoring results from the synthesized and the real mp-MRI images. In addition, after the BCa training set has been expanded using the proposed generation model, the accuracy of the BCa muscular invasion classification is improved from 77.78% to 85.19%.

Biology and performance of pre- and post-pembrolizumab (pembro) vesical imaging–reporting and data system (VI-RADS) to predict the pathological response in muscle-invasive urothelial bladder cancer (MIBC): Full data analysis from a clinical trials pipeline.

4591 Background: The VI-RADS is a standardized reporting system that uses multiparametric magnetic resonance imaging (mpMRI) parameters to predict the probability of MIBC. It has been also used in studies using standard neoadjuvant chemotherapy. No studies have analyzed the performance of VI-RADS to predict the pT0 or pT≤1 response post-immunotherapy (IO) in MIBC. Methods: In PURE-01 study patients (pts) were staged with mpMRI before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VI-RADS against pT≤1 (primary endpoint) and pT0 (secondary endpoint). VI-RADS scores were dichotomized between 0-3 (0=no evidence of disease) and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS) and tumor mutational burden (TMB). Model performance was also tested in the ongoing NureCombo (nivolumab+nab-paclitaxel; NCT04876313) and SURE-01 (sacituzumab govitecan; NCT05226117) studies. Transcriptome-wide expression profiling was matched with VI-RADS scores. Results: In PURE-01, 115 pts had centrally-reviewed MRI scans (N=230 mpMRI), treated between 02/17 and 08/18. In total, 32 (27.8%) had pure/predominant non-urothelial carcinoma (UC) histology, 54 (47%) had a cT3-4N0 MIBC. Pre-pembro: 21 pts (18.3%) had no measurable disease (VI-RADS=0), 37 (32.2%) a VI-RADS 1-3 score, and 57 (49.5%) had a VI-RADS 4-5 score. 20 pts (17.4%) had a downstage from VI-RADS 4-5 to VIRADS 0-3 post-pembro. Pre-pembro VIRADS 4-5 were associated with higher angiogenesis and epithelial-mesenchymal transition (EMT) activity vs VI-RADS 0-3 (p=0.011 and 0.033). Both pre-pembro and post-pembro VI-RADS 0-3 scores were the only significant covariates against pT≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VI-RADS 0-3 against pT≤1 response (OR: 23.4, 95%CI: 7-95.3, p&lt;0.0001). The AUC of this model was 0.90. Model-based decisions were supported in the range of threshold probabilities of 10-80%. Post-pembro VI-RADS 4-5 were characterized by higher stromal signature scores vs VI-RADS 0-3. When post-therapy VI-RADS were tested in evaluable pts from the combined NureCombo+SURE-01 cohort (N=17pts, 34 mpMRI): 90% of post-VI-RADS 0-3 revealed a pT≤1 stage at radical cystectomy. Conclusions: VI-RADS scores mirrored distinct biological features in MIBC, recapitulating tissue biomarkers of IO response. VI-RADS scores post-IO revealed a strong association with pathological downstaging and represented a robust feature based on which selecting pts for bladder-sparing strategies. Results seemed to be also applicable to other novel neoadjuvant therapies beyond IO monotherapy. Clinical trial information: NCT02736266 .

Integrating radiomics with the vesical imaging-reporting and data system to predict muscle invasion of bladder cancer.

To develop predictive models based on the integration of radiomics with the Vesical Imaging-Reporting and Data System (VI-RADS) for determining muscle invasion of bladder cancer. One hundred ninety-one patients were retrospectively included in this study from January 2015 to March 2022. Of these, 121 data were randomly divided into training and validation sets at a ratio of 7:3. The remaining data (n = 70) served as the independent testing set. The radiomics features were extracted from bladder cancer on high-b-value DWI images. The pipelines of radiomics models were trained in the training set. One optimal model was selected based on the performance in the validation set. Then, the selected model was tested in the independent testing set. Two radiologists evaluated the VI-RADS based on T2WI and DWI. Reader 1 was an experienced reader, and Reader 2 was an inexperienced reader. A clinical-radiomics model was built by integrating the radiomics signature and VI-RADS. The performance was assessed using receiver operating characteristic curve analysis. The histopathological results were used as the standard reference to assess the diagnostic accuracy of muscle invasion. The radiomics model had area under the curve (AUC) values of 0.801, 0.867, and 0.806 in the training, validation, and testing sets, respectively. The VI-RADS scores of Readers 1/2 yielded AUC values of 0.831/0.781, 0.909/0.815, and 0.871/0.776 in the training, validation, and testing sets, respectively. The clinical-radiomics model for Readers 1/2 revealed AUC values of 0.889/0.854, 0.961/0.919, and 0.881/0.844 in the training, validation, and testing sets, respectively. The performance of the clinical-radiomics model was improved compared to the VI-RADS score for inexperienced Reader 2 (P < 0.05). The radiomics model was useful in the diagnosis of muscle invasion of bladder cancer. The clinical-radiomics model integrating radiomics and VI-RADS further improved the performance compared to VI-RADS alone, which was helpful for readers with less diagnostic experience.

Diagnostic validity of the vesical imaging-reporting and data system (VI-RADS): a real-world study

ObjectivesPreoperative 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. MethodsBetween 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. ResultsAmong 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). ConclusionVI-RADS is diagnostically powerful in differentiating MIBC from NMBIC prior to transurethral resection. The agreement between radiologists is moderate.

Validez diagnóstica del sistema vesical imaging-reporting and data system (VI-RADS): estudio con datos de la vida real

ObjectivePreoperative 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. MethodsBetween 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. ResultsAmong 96 patients, 20 (20.8%) had MIBC, and 76 (79.2%) had NMIBC. Both radiologists had great diagnostic performance in diagnosing MIBC. The first radiologist had an area under curve (AUC) of 0.83 and 0.84, the sensitivity of 85% and 80%, and the specificity of 80.3% and 88.2% for VI-RADS≥3 and≥4, respectively. The second radiologist had an area under curve (AUC) of 0.79 and 0.77, the sensitivity of 85% and 65%, and the specificity of 73.7% and 89.5% for VI-RADS≥3 and≥4, respectively. The overall VI-RADS score agreement between the two radiologists was moderate (K=0.45). ConclusionVI-RADS is diagnostically powerful in differentiating MIBC from NMBIC prior to transurethral resection. The agreement between radiologists is moderate.

Novel utility of Vesical Imaging-Reporting and Data System in multimodal treatment for muscle-invasive bladder cancer.

To examine the clinical significance of the Vesical Imaging-Reporting and Data System (VI-RADS) in predicting outcome of multimodal treatment (MMT) in muscle-invasive bladder cancer (MIBC) patients. We reviewed 78 pathologically proven MIBC patients who underwent MMT including transurethral resection and chemoradiotherapy, followed by partial or radical cystectomy. Treatment response was assessed through histologic evaluation of cystectomy specimens. Two radiologists categorized the index lesions of pretherapeutic MRI according to the 5-point VI-RADS score. The associations of VI-RADS score with the therapeutic effect of MMT were analyzed. The diagnostic performance of VI-RADS scores with a cut-off VI-RADS scores  ≤ 2 or ≤ 3 for predicting pathologic complete response to MMT (MMT-CR) was evaluated. MMT-CR was achieved in 2 (100%) of VI-RADS score 1 (n = 2), 16 (84%) of score 2 (n = 19), 12 (86%) of score 3 (n = 14), 7 (64%) of score 4 (n = 11), and 14 (44%) of score 5 (n = 32). VI-RADS score was inversely associated with the incidence of MMT-CR (p = 0.00049). The cut-off VI-RADS score  ≤ 2 and  ≤ 3 could predict the favorable therapeutic outcome of MMT with high specificity (0.89 with 95% confidence interval [CI]: 0.71-0.98 and 0.82 with 95% CI: 0.62-0.94, respectively) and high positive predictive value (0.86 with 95% CI: 0.64-0.97 and 0.86 with 95% CI: 0.70-0.95, respectively). VI-RADS score may serve as an imaging marker in MIBC patients for predicting the therapeutic outcome of MMT. Muscle-invasive bladder cancer patients with a lower Vesical Imaging-Reporting and Data System score can be a good candidate for bladder-sparing treatment incorporating multimodal treatment. • Vesical Imaging-Reporting and Data System (VI-RADS) score was potentially valuable for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The likelihood of achieving complete response of multimodal treatment (MMT) decreased with increasing VI-RADS score. • VI-RADS score could serve as an imaging marker that optimizes patient selection for MMT.

LBA03-12 BIOLOGY AND PERFORMANCE OF PRE- AND POST-PEMBROLIZUMAB (PEMBRO) VESICAL IMAGING-REPORTING AND DATA SYSTEM (VI-RADS) TO PREDICT THE PATHOLOGICAL RESPONSE IN MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER (MIBC): FULL DATA ANALYSIS FROM A CLINICAL TRIALS PIPELINE

You have accessJournal of UrologyCME1 Apr 2023LBA03-12 BIOLOGY AND PERFORMANCE OF PRE- AND POST-PEMBROLIZUMAB (PEMBRO) VESICAL IMAGING-REPORTING AND DATA SYSTEM (VI-RADS) TO PREDICT THE PATHOLOGICAL RESPONSE IN MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER (MIBC): FULL DATA ANALYSIS FROM A CLINICAL TRIALS PIPELINE Andrea Necchi, Giuseppe Basile, Ewan Gibb, Giuseppina Calareso, Tiago Padua, Damiano Patanè, Emanuele Crupi, Chiara Mercinelli, Andrea Del Prete, Patrizia Giannatempo, Marco Moschini, Jeffrey Ross, Alberto Briganti, Francesco Montorsi, Antonella Messina, Francesco De Cobelli, and Giorgio Brembilla Andrea NecchiAndrea Necchi More articles by this author , Giuseppe BasileGiuseppe Basile More articles by this author , Ewan GibbEwan Gibb More articles by this author , Giuseppina CalaresoGiuseppina Calareso More articles by this author , Tiago PaduaTiago Padua More articles by this author , Damiano PatanèDamiano Patanè More articles by this author , Emanuele CrupiEmanuele Crupi More articles by this author , Chiara MercinelliChiara Mercinelli More articles by this author , Andrea Del PreteAndrea Del Prete More articles by this author , Patrizia GiannatempoPatrizia Giannatempo More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Jeffrey RossJeffrey Ross More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Antonella MessinaAntonella Messina More articles by this author , Francesco De CobelliFrancesco De Cobelli More articles by this author , and Giorgio BrembillaGiorgio Brembilla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003426.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The VI-RADS is a standardized reporting system that uses multiparametric magnetic resonance imaging (mpMRI) parameters to predict the probability of MIBC. It has been also used in studies using standard-of-care perioperative or bladder-sparing therapies. No studies have analyzed the performance of VI-RADS to predict the pT0 or pT ≤1 response post-immunotherapy (IO) in MIBC. METHODS: In PURE-01 study patients (pts) were staged with mpMRI before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VI-RADS against pT ≤1 (primary endpoint) and pT0 (secondary endpoint). VI-RADS scores were dichotomized between 0-3 (0=no evidence of disease) and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS) and tumor mutational burden (TMB). Model performance was also tested in the ongoing NureCombo (nivolumab+nab-paclitaxel; NCT04876313) and SURE-01 (sacituzumab govitecan; NCT05226117) studies. Transcriptome-wide expression profiling was matched with VI-RADS scores. RESULTS: In PURE-01, 115 pts had centrally-reviewed MRI scans (N=230 mpMRI), treated between 02/17 and 08/18. In total, 32 (27.8%) had pure/predominant non-urothelial carcinoma (UC) histology, 54 (47%) had a cT3-4N0 MIBC. Pre-pembro: 21 pts (18.3%) had no measurable disease (VI-RADS=0), 37 (32.2%) a VI-RADS 1-3 score, and 57 (49.5%) had a VI-RADS 4-5 score. 20 pts (17.4%) had a downstage from VI-RADS 4-5 to VIRADS 0-3 post-pembro. Pre-pembro VIRADS 4-5 were associated with higher angiogenesis and epithelial-mesenchymal transition (EMT) activity vs VI-RADS 0-3 (p=0.011 and 0.033).Both pre-pembro and post-pembro VI-RADS 0-3 scores were the only significant covariates against pT ≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VI-RADS 0-3 against pT ≤1 response (OR: 23.4, 95% CI: 7-95.3, p<0.0001). The AUC of this model was 0.90. Model-based decisions were supported in the range of threshold probabilities of 10-80%. Post-pembro VI-RADS 4-5 were characterized by higher stromal signature scores vs VI-RADS 0-3.When post-therapy VI-RADS were tested in evaluable pts from the combined NureCombo+SURE-01 cohort (N=17; 34 total mpMRI scans): 90% of post-VI-RADS 0-3 revealed a pT ≤1 stage at radical cystectomy. CONCLUSIONS: VI-RADS scores mirrored distinct biological features in MIBC, recapitulating tissue biomarkers of IO response. VI-RADS scores post-IO revealed a strong association with pathological downstaging and represented a robust feature based on which selecting pts for bladder-sparing strategies. Results seemed to be also applicable to other novel neoadjuvant therapies beyond IO monotherapy. Source of Funding: AIRC (Associazione Italiana per la Ricerca sul Cancro).Merck Inc.Gilead Biosciences Inc.Bristol-Myers Squibb (BMS) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1196-e1197 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrea Necchi More articles by this author Giuseppe Basile More articles by this author Ewan Gibb More articles by this author Giuseppina Calareso More articles by this author Tiago Padua More articles by this author Damiano Patanè More articles by this author Emanuele Crupi More articles by this author Chiara Mercinelli More articles by this author Andrea Del Prete More articles by this author Patrizia Giannatempo More articles by this author Marco Moschini More articles by this author Jeffrey Ross More articles by this author Alberto Briganti More articles by this author Francesco Montorsi More articles by this author Antonella Messina More articles by this author Francesco De Cobelli More articles by this author Giorgio Brembilla More articles by this author Expand All Advertisement PDF downloadLoading ...

PD36-04 UTILITY OF PRE- AND POST-PEMBROLIZUMAB VESICAL IMAGING – REPORTING AND DATA SYSTEM (VIRADS) TO PREDICT THE PATHOLOGICAL RESPONSE IN MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER (MIBC): AN ANALYSIS OF THE PURE-01 COHORT

You have accessJournal of UrologyCME1 Apr 2023PD36-04 UTILITY OF PRE- AND POST-PEMBROLIZUMAB VESICAL IMAGING – REPORTING AND DATA SYSTEM (VIRADS) TO PREDICT THE PATHOLOGICAL RESPONSE IN MUSCLE-INVASIVE UROTHELIAL BLADDER CANCER (MIBC): AN ANALYSIS OF THE PURE-01 COHORT Giuseppe Basile, Giorgio Brambilla, Marco Bandini, Daniele Raggi, Laura Marandino, Tiago Costa De Padua, Emanuele Crupi, Renzo Colombo, Maurizio Colecchia, Roberta Lucianò, Marco Moschini, Jeffrey S Ross, Alberto Briganti, Francesco Montorsi, Francesco De Cobelli, and Andrea Necchi Giuseppe BasileGiuseppe Basile More articles by this author , Giorgio BrambillaGiorgio Brambilla More articles by this author , Marco BandiniMarco Bandini More articles by this author , Daniele RaggiDaniele Raggi More articles by this author , Laura MarandinoLaura Marandino More articles by this author , Tiago Costa De PaduaTiago Costa De Padua More articles by this author , Emanuele CrupiEmanuele Crupi More articles by this author , Renzo ColomboRenzo Colombo More articles by this author , Maurizio ColecchiaMaurizio Colecchia More articles by this author , Roberta LucianòRoberta Lucianò More articles by this author , Marco MoschiniMarco Moschini More articles by this author , Jeffrey S RossJeffrey S Ross More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Francesco De CobelliFrancesco De Cobelli More articles by this author , and Andrea NecchiAndrea Necchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003334.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The possibility to predict the pathologic complete response (pT0) or downstaging (pT≤1) after neoadjuvant therapy may have profound impact on the management of MIBC and orient next-generation bladder-sparing trials. The VIRADS is a standardized reporting system that uses mpMRI parameters to predict the probability of MIBC. No studies have analyzed the ability of VIRADS to predict the pT0 or pT≤1 response post-immunotherapy (IO). METHODS: In PURE-01 patients (pts) were staged with bladder multiparametric magnetic resonance imaging (mpMRI: T2-weighted imaging, diffusion-weighted imaging, dynamic contrast enhancement) before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VIRADS against pT≤1 (primary endpoint) and pT0 (secondary endpoint). VIRADS scores were dichotomized between 0-3 and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS), tumor mutational burden (TMB) and molecular subtype (Decipher). RESULTS: Overall, 58 pts had MRI scans (N=116 mpMRI), treated between 02/17 and 08/18. Median age was 65 years, 25 (43.1%) had cT3-4N0 MIBC. Pre-pembro: 8 pts (13.8%) had no measurable disease (VIRADS=0), 20 (34.5%) a VIRADS 1-3 score, and 30 (51.7%) had a VIRADS 4-5 score. Six pts (10.3%) had a downstage from VIRADS 4-5 to VIRADS 0-3 post-pembro. Both pre-pembro and post-pembro VIRADS 0-3 scores were significantly associated with pT≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VIRADS 0-3 against pT≤1 response (OR: 30.2, 95%CI: 6.2-223.2, p<0.0001, AUC: 0.92). Regarding pre-pembro VIRADS 0-3: (OR: 4.35, 95%CI: 1.1-19.7, p=0.04; AUC: 0.83). CPS was another significant variable for pT≤1 endpoint only in MVA using pre-pembro VIRADS 0-3 (OR: 1.02, 95%CI: 1-1.05, p=0.02). Post-pembro VIRADS 0-3 was also associated with pT0 on MVA (OR: 4.59, 95%CI: 1.2-19.6, p=0.02; AUC: 0.78), whereas pre-pembro VIRADS was not (p=0.13). An enrichment of basal-type tumors was seen in VIRADS 0-3 cases and of luminal tumors in VIRADS 4-5 cases post-pembro. CONCLUSIONS: To our knowledge, this is the first evidence establishing the predictivity of the VIRADS score towards the pathological downstaging, both in the pre and post IO settings. Post-pembro VIRADS emerged as an important feature by which selecting pts for bladder-sparing strategies. Source of Funding: No © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e981 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giuseppe Basile More articles by this author Giorgio Brambilla More articles by this author Marco Bandini More articles by this author Daniele Raggi More articles by this author Laura Marandino More articles by this author Tiago Costa De Padua More articles by this author Emanuele Crupi More articles by this author Renzo Colombo More articles by this author Maurizio Colecchia More articles by this author Roberta Lucianò More articles by this author Marco Moschini More articles by this author Jeffrey S Ross More articles by this author Alberto Briganti More articles by this author Francesco Montorsi More articles by this author Francesco De Cobelli More articles by this author Andrea Necchi More articles by this author Expand All Advertisement PDF downloadLoading ...

PD36-03 VESICAL IMAGING REPORTING AND DATA SYSTEM (VI-RADS) COULD PREDICT THE PROGNOSIS OF BLADDER CANCER PATIENTS RECEIVED RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 Apr 2023PD36-03 VESICAL IMAGING REPORTING AND DATA SYSTEM (VI-RADS) COULD PREDICT THE PROGNOSIS OF BLADDER CANCER PATIENTS RECEIVED RADICAL CYSTECTOMY Qiang Lv, Xiao Yang, Qiang Cao, and Juntao Zhuang Qiang LvQiang Lv More articles by this author , Xiao YangXiao Yang More articles by this author , Qiang CaoQiang Cao More articles by this author , and Juntao ZhuangJuntao Zhuang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003334.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Vesical Imaging Reporting and Data System (VI-RADS) has shown a good potential in determining muscle-invasive bladder cancer (MIBC) patients. However, whether the VI-RADS could predict the prognosis of radical cystectomy (RC) patients has not been reported. METHODS: We retrospectively analyzed the information of bladder cancer patients admitted to our center from June 2012 to June 2022. All patients who underwent multiparametric magnetic resonance imaging (mpMRI) and underwent RC were included. The exclusion criteria were: 1) Pathology was not urothelial carcinoma. 2) Receive neoadjuvant chemotherapy. 3) VI-RADS could not be evaluated. 4) The follow-up data was incomplete. VI-RADS were scored by two radiologists, blinded to clinical data. Patients’ clinical features, pathology data and imaging information were recorded. All statistical analyses were performed in SPSS26.0 and R software. RESULTS: Overall, 219 patients were finally included in the study. There were 188 males and 31 females with a median age of 66 (IQR: 61-74) years. Pathology showed 23 patients of low grade and 196 cases of high grade. Among them, 126 patients were MIBC. Patients with VI-RADS≥3 had worse progression-free survival (PFS) and overall survival (OS) than those with VI-RADS <3. In addition, we divided into two groups with a cut-off of VI-RADS 4, and found the same trends. The AUC of VI-RADS predicting 3-year PFS was 0.822 (sensitivity=0.832 and negative predictive value=0.923). Multivariate COX regression analysis showed that VI-RADS≥3 and lymph node metastasis were independent risk factors for PFS (HR=2.871, p=0.029 and HR=3.886, p<0.001, respectively). The results of COX regression are shown in Table 1. In the MIBC subgroup, patients with VI-RADS≥4 had worse PFS and OS. In the NMIBC subgroup, the prognosis of patients with VI-RADS≥3 is still worse. VI-RADS was no significance to distinguish the prognosis if patients had multi-walled. CONCLUSIONS: The prognosis of RC patients with VI-RADS≥3 is worse than those with VI-RADS <3. Even if the pathology is NMIBC, the prognosis of them is still worse. In patients with multi-walled tumors, VI-RADS was less valuable in predicting prognosis. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e980 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qiang Lv More articles by this author Xiao Yang More articles by this author Qiang Cao More articles by this author Juntao Zhuang More articles by this author Expand All Advertisement PDF downloadLoading ...

PD44-01 ACCURACY OF ACTUAL STAGE PREDICTION USING VESICAL IMAGING-REPORTING AND DATA SYSTEM (VI-RADS) BEFORE RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023PD44-01 ACCURACY OF ACTUAL STAGE PREDICTION USING VESICAL IMAGING-REPORTING AND DATA SYSTEM (VI-RADS) BEFORE RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA Si Hyun Kim, Jang Hee Han, Seung-Hwan Jeong, Hyeong Dong Yuk, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, and Ja Hyeon Ku Si Hyun KimSi Hyun Kim More articles by this author , Jang Hee HanJang Hee Han More articles by this author , Seung-Hwan JeongSeung-Hwan Jeong More articles by this author , Hyeong Dong YukHyeong Dong Yuk More articles by this author , Chang Wook JeongChang Wook Jeong More articles by this author , Cheol KwakCheol Kwak More articles by this author , Hyeon Hoe KimHyeon Hoe Kim More articles by this author , and Ja Hyeon KuJa Hyeon Ku More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003354.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies using the vesical imaging reporting and data system (VI-RADS) to predict muscle-invasive bladder cancer had some limitations. Most studies were performed with transurethral resection of bladder tumor specimens with few samples. This study was conducted to address these shortcomings and confirm the accuracy of VI-RADS for bladder cancer. METHODS: This study used data from the Seoul National University Prospectively Enrolled Registry for Urothelial Cancer–Radical Cystectomy (SUPER-UC-Cx). Patients who underwent multiparametric magnetic resonance imaging (mp-MRI) before radical cystectomy were included in this study between March 2020 and March 2022. All images were reported by radiologists and reviewed by two urologists. The patient characteristics and clinical information were blinded during the review. The performance of qualitative and quantitative variables in predicting muscle layer invasion or perivesical fat infiltration was verified by receiver operating characteristic (ROC) curve analysis. RESULTS: Of 208 patients, 182 (87.5%) underwent mp-MRI before radical cystectomy. Twenty-three patients with non-urothelial carcinoma, inappropriate MRI scans, and bladder filling were excluded. Cut-off for muscle invasion, VI-RADS score of 4 had the highest area under the curve (AUC) (sensitivity 0.84; specificity 0.93; accuracy 0.90; positive predictive value (PPV) 0.84; negative predictive value (NPV) 0.93, and AUC 0.88). Cut-off for perivesical fat invasion and VI-RADS score of 5 had the highest AUC (sensitivity, 0.78; specificity, 0.99; accuracy, 0.95; PPV, 0.96; NPV, 0.95; and AUC, 0.89). CONCLUSIONS: VI-RADS is a good predictor of bladder cancer staging before radical cystectomy and is especially helpful in predicting muscle invasion and perivesical fat infiltration. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1124 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Si Hyun Kim More articles by this author Jang Hee Han More articles by this author Seung-Hwan Jeong More articles by this author Hyeong Dong Yuk More articles by this author Chang Wook Jeong More articles by this author Cheol Kwak More articles by this author Hyeon Hoe Kim More articles by this author Ja Hyeon Ku More articles by this author Expand All Advertisement PDF downloadLoading ...

MP32-17 PREDICTING THE MIBC IN STALKED TUMOR OF VI-RADS 2 USING NOMOGRAM OF MRI CHARACTERISTICS

You have accessJournal of UrologyCME1 Apr 2023MP32-17 PREDICTING THE MIBC IN STALKED TUMOR OF VI-RADS 2 USING NOMOGRAM OF MRI CHARACTERISTICS Qiang Lv, Xiao Yang, Qiang Cao, and Lingkai Cai Qiang LvQiang Lv More articles by this author , Xiao YangXiao Yang More articles by this author , Qiang CaoQiang Cao More articles by this author , and Lingkai CaiLingkai Cai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003265.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Background: The vesical imaging-reporting and data system (VI-RADS) scores was created to report the staging of bladder cancer (BCa). A proportion of BCa with stalk pathologized as MIBC. Purpose: To measure the MRI characteristics of the tumor and the stalk and establish a model for predicting muscle-invasive bladder cancer (MIBC) in VI-RADS 2. METHODS: From November 2012 and May 2022, a total of 178 patients with bladder cancer with stalk were included in this study and divided into training and validation cohorts by a ratio of 7:3. The univariable logistic regression analysis and Lasso regression were utilized to select the most useful predictive features from among 22 variables. Then, a logistic regression analysis was used to develop the prediction model with a nomogram. The area under the curves (AUCs) of receiver operating characteristic (ROC) curves and calibration curves were performed to demonstrate the performance and accuracy of the nomogram. The decision curve analyses were applied to assess the clinical benefit of the nomogram. RESULTS: Four variables as potential risk factors for MIBC of the stalk were selected, including the size of the tumor over 3cm, the increased width of the stalk, the morphology of the stalk and the decreased normalized T value. The AUCs of the model for predicting MIBC were 0.95 (95%CI: 0.91-0.99) in the training cohort and 0.91 (95%CI: 0.79-1.00) in the validation cohort. The calibration curve of the nomogram suggested excellent agreement. The decision curve analyses curve indicated that using the nomogram to predict MIBC added more net benefit than the all or none strategies. CONCLUSIONS: In this study, we constructed the MIBC prediction model by combining clinical data and MRI features of the stalk and tumor in VI-RADS 2. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e448 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qiang Lv More articles by this author Xiao Yang More articles by this author Qiang Cao More articles by this author Lingkai Cai More articles by this author Expand All Advertisement PDF downloadLoading ...

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.

Utility of pre- and post-pembrolizumab (Pembro) Vesical Imaging–Reporting and Data System (VIRADS) to predict the pathological response in muscle-invasive urothelial bladder cancer (MIBC): An analysis of the PURE-01 cohort.

552 Background: The possibility to predict the pathologic complete response (pT0) or downstaging (pT≤1) after neoadjuvant therapy may have profound impact on the management of MIBC and orient next-generation bladder-sparing trials. The VIRADS is a standardized reporting system that uses mpMRI parameters to predict the probability of MIBC. No studies have analyzed the ability of VIRADS to predict the pT0 or pT≤1 response post-immunotherapy (IO). Methods: In PURE-01 patients (pts) were staged with bladder multiparametric magnetic resonance imaging (mpMRI: T2-weighted imaging, diffusion-weighted imaging, dynamic contrast enhancement) before and after treatment (3 cycles of pembro) prior to radical cystectomy (RC). All mpMRI scans were centrally reviewed. Logistic regression models analyzed pre- and post-pembro VIRADS against pT≤1 (primary endpoint) and pT0 (secondary endpoint). VIRADS scores were dichotomized between 0-3 and 4-5. Covariates included cT-stage, age, gender, PD-L1 combined positive score (CPS) and tumor mutational burden (TMB). Results: In total, 58 pts were had centrally-reviewed MRI scans (N=116 mpMRI), treated between 02/17 and 08/18. Demographic characteristics and outcomes were generally similar between the all-treated and VIRADS-evaluable populations of PURE-01. Median age was 65 years, 52 (89%) had pure/predominant urothelial carcinoma (UC) histology, 25 (43.1%) had cT3-4N0 MIBC. Pre-pembro: 8 pts (13.8%) had no measurable disease (VIRADS=0), 20 (34.5%) a VIRADS 1-3 score, and 30 (51.7%) had a VIRADS 4-5 score. Six pts (10.3%) had a downstage from VIRADS 4-5 to VIRADS 0-3 post-pembro. Both pre-pembro and post-pembro VIRADS 0-3 scores were significantly associated with pT≤1 endpoint on multivariable analyses (MVA): the strongest effect was seen with post-pembro VIRADS 0-3 against pT≤1 response (OR: 30.2, 95%CI: 6.2-223.2, p&lt;0.0001). The AUC of this model was 0.92. Regarding pre-pembro VIRADS 0-3: OR: 4.35, 95%CI: 1.1-19.7, p=0.04; AUC: 0.83. CPS was another significant variable for pT≤1 endpoint only in MVA using pre-pembro VIRADS 0-3 (OR: 1.02, 95%CI: 1-1.05, p=0.02). Post-pembro VIRADS 0-3 was also associated with pT0 on MVA (OR: 4.59, 95%CI: 1.2-19.6, p=0.02; AUC: 0.78), whereas pre-pembro VIRADS was not (p=0.13). Mean apparent diffusion coefficients (ADC) were similar between pre- and post-pembro lesions (0.86 vs 0.87). Conclusions: To our knowledge, this is the first evidence establishing the predictivity of the VIRADS score towards the pathological downstaging, both in the pre and post IO settings. Post-pembro VIRADS, along with the combination of pre-pembro VIRADS and CPS, emerged as the strongest features based on which selecting pts for bladder-sparing strategies. Clinical trial information: NCT02736266 .

Co-primary endpoint analysis of HCRN GU 16-257: Phase 2 trial of gemcitabine, cisplatin, plus nivolumab with selective bladder sparing in patients with muscle-invasive bladder cancer (MIBC).

447 Background: Transurethral resection of bladder tumor (TURBT) plus systemic therapy has been known for decades to achieve durable bladder-intact survival in a subset of patients with MIBC but efforts to advance this paradigm have been complicated by a lack of (a) prospective studies, (b) rigorous approaches to assess and define clinical complete response (cCR), and (c) integration of novel therapies. Methods: Eligible patients were cisplatin-eligible with cT2-T4aN0M0 urothelial bladder cancer. Patients received 4 cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging including urine cytology, MRI/CT of the bladder, cystoscopy and bladder biopsies. Patients achieving a cCR (normal cytology, imaging, and cT0/Ta) were eligible to proceed without cystectomy and receive nivolumab q2 weeks x 8 followed by surveillance. Patients not achieving cCR were recommended to undergo cystectomy. Coprimary endpoints included (1) cCR rate and (2) association between cCR and 2-year outcomes. The key secondary endpoint was the impact of pre-specified baseline genomic alterations on outcomes. Additional biomarkers to refine patient selection were also explored. Results: Between 8/2018-11/2020, 76 patients were enrolled at 7 sites (male 79%, median age 69; cT2 = 56%, cT3 = 32%, cT4 = 12%). Median follow-up is 27 months. 72/76 patients underwent clinical restaging and a cCR was achieved in 33/76 (43%; 95% CI: 32%, 55%). One cCR patient opted for immediate cystectomy (ypTaN0M0). Outcomes are summarized in the Table. Baseline ERCC2, ATM, FANCC, or RB1 alterations were not, but tumor mutational burden ≥ 10 mutations/mb was, significantly associated with the composite endpoint of ypT0 (immediate cystectomy) or 2-year bladder-intact metastasis-free survival (BIMFS). On landmark analysis, VI-RADS (Vesical Imaging–Reporting and Data System) score (3-5 versus 1-2) on restaging MRI (central blinded review) was associated with inferior BIMFS (HR 4.5; p = &lt;0.01) and MFS (HR 19.3; p &lt;0.01). Circulating tumor DNA data will be presented at the meeting. Conclusions: TURBT followed by gemcitabine, cisplatin, plus nivolumab achieves stringently defined cCR in a substantial subset of patients with MIBC. ≥2-year bladder-intact survival is achieved in the majority of patients with a cCR. Clinical trial information: NCT03558087 . [Table: see text]