Muscle Invasion Research Articles

Prospective Assessment of VI-RADS with Muscle Invasion in Urinary Bladder Cancer and Its Implication on Re-Resection/Restaging TURBT Patients.

Bladder cancer (BCa) diagnosis relies on distinguishing muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC) forms. Transurethral resection of the bladder tumor (TURBT) is a standard procedure for initial staging and treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) enhances diagnostic accuracy for muscle invasiveness through advanced imaging techniques, potentially reducing reliance on repeat TURBT and improving patient management. We aimed to evaluate the role of VI-RADS in predicting muscle invasiveness in BCa and its potential to predict adverse pathology in high-risk NMIBC to avoid unnecessary repeat TURBT procedures. In this prospective study, we included 62 patients over the age of 18years who underwent TURBT. In a secondary phase, patients selected for restaging TURBT (re-TURBT) were included, but those with T2 tumors or low-risk NMIBC were excluded. Multiparametric magnetic resonance imaging (MRI) examinations were scored by a radiologist using the VI-RADS 5 method, while a pathologist analyzed TURBT and re-TURBT samples for accurate staging. Statistical analysis evaluated the role of VI-RADS in BCa staging. The VI-RADS score was the only predictive factor for muscle invasion in multivariate analysis. Setting the VI-RADS score at >3 resulted in the highest sensitivity, specificity, and diagnostic accuracy, with values of 67.0%, 89.0%, and 78%, respectively. The receiver operating characteristic area under the curve score for VI-RADS for muscle invasion was 85% for stage Ta, 61% for stage T1, and 88% for stage T2, which shows the utility of VI-RADS in the predictiveness of MIBC/NMIBC. VI-RADS is effective in stratifying BCa patients by predicting muscle invasiveness and identifying NMIBC cases that may not need repeat TURBT.

Impact of virtual monochromatic images of different low-energy levels in dual-energy CT on radiomics models for predicting muscle invasion in bladder cancer.

The purpose of this study was to investigate the impact of different low-energy virtual monochromatic images (VMIs) in dual-energy CT on the performance of radiomics models for predicting muscle invasive status in bladder cancer (BCa). A total of 127 patients with pathologically proven muscle-invasive BCa (n = 49) and non-muscle-invasive BCa (n = 78) were randomly allocated into the training and test cohorts at a ratio of 7:3. Feature extraction was performed on the venous phase images reconstructed at 40, 50, 60 and 70-keV (single-energy analysis) or in combination (multi-energy analysis). Recursive feature elimination (RFE) and the least absolute shrinkage and selection operator(LASSO) were employed to select the most relevant features associated with BCa. Models were built using a support vector machine(SVM) classifier. Diagnostic performance was assessed through receiver operating characteristic curves, evaluating sensitivity, specificity, accuracy, precision, and the area-under-the curve (AUC) values. In the test cohort, the multi-energy model achieved the best diagnostic performance with AUC, sensitivity, specificity, accuracy, and precision of 0.917, 0.800, 0.833, 0.821, and 0.750, respectively. Conversely, the single-energy model exhibited lower AUC and sensitivity in predicting the muscle invasion status. By combining information from VMIs of various energies, the multi-energy model displays superior performance in preoperatively predicting the muscle invasion status of bladder cancer.

Long-term recurrence risk, metastatic potential and length of cystoscopic surveillance of low-grade non-muscle invasive bladder cancer.

Patients with Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) rarely develop metastases or die from it. Long-term data are scant and length of follow-up poorly defined. This retrospective study included 521 patients diagnosed with primary TaLG (n=491) or papillary urothelial neoplasm of low malignant potential (PUNLMP, n=30) from 1989-2019 at an Academic center. Patient data was acquired using patient records chart review and a bladder cancer informatics registry at the center. Risk of recurrence, progression in stage, to muscle invasion, metastases and death due to BC were analyzed. RNAseq assessed the transcriptomic profiles of four TaLG that metastasized. Interobserver variability in pathological grading (WHO 2004/2022 and 1973, n=80) was blindly assessed by three expert pathologists. Median follow-up was 9.6 (95%CI: 8.6-10.2) years. Among 521 patients (73% men, median age 67.0 years), 350 recurred, 57 progressed in stage, 20 developed metastases, and 15 died from BC (median of 9.6 years after diagnosis). Cancer-specific survival probabilities were 0.99, 0.98 and 0.96 at 5-, 10- and 15- years, respectively. Fifty patients who were recurrence-free for the first 5 years developed late recurrences and 2 of them died of BC. Metastatic TaLG had more adverse transcriptomic findings in keeping with higher grade tumors despite phenotypically similar to indolent tumors. Grading concordance for the 2004/2022 system and WHO 1973 was 0.78 (95%CI: 0.65-0.90) and 0.41 (95%CI: 0.32-0.50), respectively. This study with long-term data challenges the assumption that primary TaLG NMIBC nearly never progresses to lethal disease if followed long enough. However, the risk of BC-related mortality is extremely low in patients who are recurrence-free for the first 5 years. Minimizing variability in pathological grading remains an unmet need.

A multicenter bladder cancer MRI dataset and baseline evaluation of federated learning in clinical application

Bladder cancer (BCa), as the most common malignant tumor of the urinary system, has received significant attention in research on the clinical application of artificial intelligence algorithms. Nevertheless, it has been observed that certain investigations use data from various medical facilities to train models for BCa, which may pose a privacy risk. Given this concern, protecting patient privacy during machine learning algorithm training is a crucial aspect that requires substantial attention. One emerging machine learning paradigm that addresses this concern is federated learning (FL). FL enables multiple entities to collaboratively build machine learning models while preserving data privacy and security. In this study, we present a multicenter BCa magnetic resonance imaging (MRI) dataset. The dataset comprises 275 three-dimensional bladder T2-weighted MRI scans collected from four medical centers, and each scan includes diagnostic pathological labels for muscle invasion and pixel-level annotations of tumor contours. Four FL methods are used to assess the baseline of the dataset for both the task of diagnosing muscle-invasive bladder cancer and automatic bladder tumor lesion segmentation.

Urogenital schistosomiasis, a leading cause of bladder squamous cell carcinoma

Abstract Introduction/Objective Schistosoma, genus of trematodes, commonly known as blood flukes are parasitic flatworms responsible for a group of infections in humans termed schistosomiasis and hundreds of millions of people are infected worldwide. In areas where Shistosoma is not endemic to the region most cases of bladder malignancy are of urothelial origin. In areas where Shistosoma is endemic bladder malignancy is more commonly squamous cell carcinoma. However, with increased travel, migration and tourism it is important to potentially consider Shistosoma infection in areas that are not typically considered endemic regions. Methods/Case Report A 62-year-old male presented to our hospital and revealed through an interpreter he has had 1.5 years hematuria with “pieces of meat or brown dirt”. Cystoscopy was performed and showed a large necrotic mass. CT scan showed an 8.2 cm exophytic bladder dome mass. TURBT was performed and a diagnosis of invasive high-grade urothelial carcinoma with squamous differentiation and with multiple Schistosoma organisms identified.The patient received Schistosoma treatment and was scheduled for radical cystectomy and ileal conduct. A few days before the scheduled procedure the patient presented to our emergency department with acute abdominal pain. He was subsequently diagnosed with progressive bladder cancer with new left malignant ureteral obstruction, which lead to hydronephrosis, DVT, abdominopelvic ascites and intraperitoneal bladder perforation. Abdominal fluid cytology showed atypical keratinizing squamous cells suspicous for malignancy and marked acute inflammation. Patient underwent cystectomy with ileal conduit and the specimen was sent to pathology for examination. Results (if a Case Study enter NA) NA Conclusion Gross examination showed an irregular perforated bladder. Microscopic examination showed a high grade urothelial carcinoma with squamous and sarcomatoid differentiation with detrusor muscle invasion. Additionally, Schistosoma organisms with a terminal spine and calcified eggs were identified. Some of the calcified egg material was engulfed by giant cells. The organisms are surrounded by a prominent eosinophilic infiltrate. Lymphovascular invasion is also noted. Schistosomiasis is associated with the development of squamous cell carcinoma of the bladder. It is important to maintain high oncological alertness for squamous cell carcinoma, particularly for patients arriving from endemic areas. Such as in our case, a patient from Somalia living in Kansas City.

Tumor immune microenvironment dynamics and outcomes of prognosis in non-muscle-invasive bladder cancer.

Agents that target PD-1 and PD-L1 have been developed in the treatment of bladder cancer (BC). However, the diversity of immune cell infiltration in non-muscle-invasive BC (NMIBC) and the dynamics of the microenvironment as it progresses to muscle-invasive/metastatic disease remains unknown. To assess tumor immune activity, hierarchical clustering was applied to 159 BC samples based on cellular positivity for the defined immune cellular markers (CD3/CD4/CD8/FOXP3/CD20/PD-1/PD-L1/LAG3/TIGIT), divided into two clusters. There was a "hot cluster" (25%) consisting of patients with a high expression of these markers and a "cold cluster" (75%) comprising those without. The expression of CD39, CD44, CD68, CD163, IDO1, and Ki67 was significantly higher in tumors in the hot cluster. Immunologically, high-grade T1 tumors were significantly hotter, whereas tumors that had progressed to muscle invasion turned cold. However, a certain number of high-grade NMIBC patients were in the cold cluster, and these patients had a significantly higher risk of disease progression. Using an externally available TCGA dataset, RB1 and TP53 alterations were more frequently observed in TCGA hot cluster; rather FGFR3, KDM6A, and KMT2A alterations were common in TCGA cold/intermediate cluster. Analyses of recurrent tumors after BCG therapy revealed that tumor immune activity was widely maintained before and after treatment, and high FGFR3 expression was detected after recurrence in tumors initially classified into the cold cluster. Collectively, we revealed the dynamics of the tumor microenvironment in BC as a whole and identified candidate molecules as therapeutic targets for recurrent NMIBC, e.g., after BCG therapy.

Phenotype remodelling of HNSCC cells in the muscle invasion environment

BackgroundTumour invading muscle in head and neck squamous cell carcinoma (HNSCC) is often associated with destructive growth and poor prognosis. However, the phenotypic functions and pathological mechanisms of muscle-invasive cancer cells in tumour progress remains unknown. In this study, we aimed to investigate the phenotypic functions of muscle-invasive cancer cells of HNSCC and their potential crosstalk with tumour microenvironment.MethodsWe obtained scRNA-seq data (SC) from GSE103322 (N = 18) and GSE181919 (N = 37), spatial RNA-seq data (ST) from GSE208253 and GSE181300 (N = 4), transcriptomics of human HNSCC samples from GSE42743 (N = 12) and GSE41613 (N = 97). Utilizing the TCGA-HNSC dataset, we conducted univariate and multivariate Cox analyses to investigate the prognostic impact of muscle-invasion in HNSCC, with validation in an additional cohort. Through Stutility and AUCell approaches, we identified and characterized muscle-invasive cancer cell clusters, including their functional phenotypes and gene-specific profiles. Integration of SC and ST data was achieved using Seurat analysis, multimodal intersection analysis, and spatial deconvolution. The results were further validated via in vitro and in vivo experiments.ResultsOur analyses of the TCGA-HNSC cohort revealed the presence of muscle-invasion was associated with a poor prognosis. By combining ST and SC, we identified muscle-invasive cancer cells exhibiting epithelial-to-mesenchymal transition (EMT) and myoepithelial-like transcriptional programs, which were correlated with a poor prognosis. Furthermore, we identified G0S2 as a novel marker of muscle-invasive malignant cells that potentially promotes EMT and the acquisition of myoepithelium-like phenotypes. These findings were validated through in vitro assays and chorioallantoic membranes experiments. Additionally, we demonstrated that G0S2-overexpressing cancer cells might attract human ECs via VEGF signalling. Subsequent in vitro and in vivo experiments revealed G0S2 plays key roles in promoting the proliferation and invasion of cancer cells.ConclusionsIn this study, we profiled the transcriptional programs of muscle-invasive HNSCC cell populations and characterized their EMT and myoepithelial-like phenotypes. Furthermore, our findings highlight the presence of muscle-invasion as a predictive marker for HNSCC patients. G0S2 as one of the markers of muscle-invasive cancer cells is involved in HNSCC intravasation, probably via VEGF signalling.

Performance and Clinical Implications of VI-RADS in detecting muscle invasion in bladder tumors: A prospective observational study

ABSTRACT Introduction: Bladder cancer staging is pivotal for guiding therapeutic decisions. In this study, the primary objective was to assess the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI), The study aimed to classify bladder tumors as either nonmuscle-invasive bladder cancers or muscle-invasive bladder cancers (MIBC) using the Vesical Imaging Reporting and Data System (VI-RADS) scoring. A secondary objective of the study focused on the accuracy of biparametric magnetic resonance imaging (bpMRI) in comparison to mpMRI. Methods: Thirty-three patients with bladder tumors were enrolled and underwent both mpMRI and bpMRI scoring assessments. VI-RADS scores were assigned and subsequently compared with histopathological findings posttransurethral resection of bladder tumor., Statistical measures included sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for VI-RADS scores at cutoff thresholds of ≥4 and 5. Results: MpMRI at a VI-RADS cutoff of ≥4 yielded an 83.33% sensitivity and 100% specificity, with a diagnostic accuracy of 90.91%. At a cutoff of 5, sensitivity was 100%, specificity was 77.27%, and diagnostic accuracy was 84.85%. bpMRI at a cutoff of ≥4 showed an 80% sensitivity and 100% specificity, with diagnostic accuracy matching mpMRI at 90.91%. Conclusions: This prospective analysis demonstrates that VI-RADS scoring with mpMRI provides reliable diagnostic accuracy for bladder cancer staging. mpMRI exhibits high sensitivity and specificity at a cutoff of ≥ 4, making it a robust tool for MIBC detection. bpMRI is an effective alternative in select patients. The study validates the use of VI-RADS scoring in clinical practice for effective treatment planning.

Assessing muscle invasion in bladder cancer via virtual biopsy: a study on quantitative parameters and classical radiomics features from dual-energy CT imaging

ObjectiveTo evaluate the prediction value of Dual-energy CT (DECT)-based quantitative parameters and radiomics model in preoperatively predicting muscle invasion in bladder cancer (BCa).Materials and methodsA retrospective study was performed on 126 patients with BCa who underwent DECT urography (DECTU) in our hospital. Patients were randomly divided into training and test cohorts with a ratio of 7:3. Quantitative parameters derived from DECTU were identified through univariate and multivariate logistic regression analysis to construct a DECT model. Radiomics features were extracted from the 40, 70, 100 keV and iodine-based material-decomposition (IMD) images in the venous phase to construct radiomics models from individual and combined images using a support vector machine classifier, and the optimal performing model was chosen as the final radiomics model. Subsequently, a fusion model combining the DECT parameters and the radiomics model was established. The diagnostic performances of all three models were evaluated through receiver operating characteristic (ROC) curves and the clinical usefulness was estimated using decision curve analysis (DCA).ResultsThe normalized iodine concentration (NIC) in DECT was an independent factor in diagnosing muscle invasion of BCa. The optimal multi-image radiomics model had predictive performance with an area-under-the-curve (AUC) of 0.867 in the test cohort, better than the AUC = 0.704 with NIC. The fusion model showed an increased level of performance, although the difference in AUC (0.893) was not statistically significant. Additionally, it demonstrated superior performance in DCA. For lesions smaller than 3 cm, the fusion model showed a high predictive capability, achieving an AUC value of 0.911. There was a slight improvement in model performance, although the difference was not statistically significant. This improvement was observed when comparing the AUC values of the DECT and radiomics models, which were 0.726 and 0.884, respectively.ConclusionThe proposed fusion model combing NIC and the optimal multi-image radiomics model in DECT showed good diagnostic capability in predicting muscle invasiveness of BCa.

Development and Validation of a Contrast-Enhanced US VI-RADS for Evaluating Muscle Invasion in Bladder Cancer.

Background Contrast-enhanced US (CEUS) can be used preoperatively for evaluating muscle invasion in bladder cancer, which is important for determining appropriate treatment. However, diagnostic criteria for assessing this at CEUS have not been standardized. Purpose To develop and validate a CEUS Vesical Imaging Reporting and Data System (VI-RADS) for evaluating muscle invasion in bladder cancer. Materials and Methods This single-center prospective study consecutively enrolled patients with suspected bladder cancer. Participants underwent transabdominal or intracavity CEUS between July 2021 and May 2023. Participants were divided into a training set and a validation set at a 2:1 ratio based on the chronologic order of enrollment. The training set was used to identify major imaging features to include in CEUS VI-RADS, and the likelihood of muscle invasion per category was determined using a pathologic reference standard. The optimal VI-RADS category cutoff for muscle invasion was determined with use of the maximum Youden index. The validation set was assessed by novice and expert readers and used to validate the diagnostic performance and interreader agreement of the developed system. Results Overall, 126 participants (median age, 64 years [IQR, 57-71 years]; 107 male) and 67 participants (median age, 64 years [IQR, 56-69 years]; 49 male) were included in the training and validation set, respectively. In the training set, the optimal CEUS VI-RADS category cutoff for muscle invasion was VI-RADS 4 or higher (Youden index, 0.77). In the validation set, CEUS VI-RADS achieved good performance for both novice and expert readers (area under the receiver operating characteristic curve, 0.80 [95% CI: 0.70, 0.90] vs 0.88 [95% CI: 0.80, 0.97]; P = .09). The interreader agreement regarding the evaluation of CEUS VI-RADS category was 0.77 (95% CI: 0.65, 0.85) for novice readers, 0.87 (95% CI: 0.79, 0.92) for expert readers, and 0.78 (95% CI: 0.70, 0.84) for all readers. Conclusion The developed CEUS VI-RADS showed good performance and interreader agreement for the assessment of muscle invasion in bladder cancer. Chinese Clinical Trial Registry no. ChiCTR2100049435 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Morrell in this issue.

Fatal Bladder Carcinoma in Woman with Human Immunodeficiency Virus: A Case Report

Background: Chronic human immunodeficiency virus (HIV) infection is associated with an increased incidence of Non-Acquired Immunodeficiency Syndrome (non-AIDS) defining cancers. To date, only a limited number of cases of bladder cancer have been linked with HIV infection in women. We sought to describe the clinical characteristics of HIV-associated bladder cancer. Methods: A 54-year-old female patient presented with symptoms of an occlusive syndrome. Medical examination was followed by a CT scan. The imaging revealed a significant finding. There was a noticeable process within the bladder. Further evaluation and management were recommended. Results: Spontaneous urinary cytology revealed the presence of malignant cells. An endoscopy was performed under spinal anesthesia, uncovering a large sessile tumor with necrotic areas located on the ventral aspect and dome of the bladder. Due to the severity of the condition, a palliative resection was carried out. Subsequent histological examination identified the tumor as a high-grade urothelial carcinoma, with evidence of muscle invasion. This diagnosis confirmed the aggressive nature of the disease, highlighting the necessity for further medical management and intervention. Conclusion: Bladder cancers in HIV-infected patients are rare but can occur in relatively young individuals with a low nadir CD4 cell count. These cancers often exhibit aggressive pathological features and can be fatal.

Palatoglossus Muscle and T4 Category in the Eighth Edition of TNM Staging System for OPSCC.

The present study challenges the appropriateness of considering invasion of the palatoglossus muscle (PGM) as a criterion for staging oropharyngeal squamous cell carcinoma (OPSCC) as T4. Retrospective observational study. Tertiary University Hospital. This retrospective study included nonmetastatic OPSCC patients treated with curative intent at the University of Trieste, Italy from 2015 to 2021. Patients were categorized into 4 groups: (1) tumors classified as T1-T2 by both International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC)-TNM; (2) T1-T2 tumors upgraded to T4 solely by UICC due to oropharyngeal PGM infiltration; (3) T1-T2 tumors upgraded to T4 by both UICC and AJCC due to oral PGM infiltration; (4) tumors classified as T3-T4 by both UICC and AJCC. Kaplan-Meier analysis estimated overall survival (OS) and disease-free survival (DFS). Multivariable Cox models, adjusted for clinical factors, assessed the impact of palatoglossus invasion on outcomes over 5 years. A total of 121 consecutive patients with primary OPSCC were included (median [interquartile range] age 65 years [58-74]; 63% male). While patients with upgraded T4 category due to infiltration of the oral portion of the PGM exhibited a prognosis superimposable on that of other patients with advanced stage disease, those with upgraded T4 category due to infiltration of the oropharyngeal portion of the PGM displayed OS and DFS comparable to T1-T2 patients. Our findings highlight that invasion of the oropharyngeal portion of the PGM may not be a suitable criterion for staging OPSCC as T4. Further research involving larger and independent patient cohorts is strongly encouraged to corroborate these observations.

Multi-DECT image-based intratumoral and peritumoral radiomics for preoperative prediction of muscle invasion in bladder cancer

ObjectivesTo assess the predictive value of intratumoral and peritumoral radiomics based on Dual-energy CT urography (DECTU) multi-images for preoperatively predicting the muscle invasion status of bladder cancer (BCa). Material and methodsThis retrospective analysis involved 202 BCa patients who underwent DECTU. DECTU-derived quantitative parameters were identified as risk factors through stepwise regression analysis to construct a DECT model. The radiomic features from the intratumoral and 3mm outward peritumoral regions were extracted from the 120 kVp-like, 40 keV, 100 keV, and iodine-based material-decomposition (IMD) images in the venous-phase and were screened using Mann-Whitney U test, Spearman correlation analysis, and LASSO. Radiomics models were developed using the Multilayer Perceptron for the intratumoral, peritumoral and intra- and peritumoral (IntraPeri) regions. Subsequently, a nomogram was created by integrating the multi-image IntraPeri radiomics and DECT model. Model performance was evaluated using area-under-the-curve (AUC), accuracy, sensitivity, and specificity. ResultsNormalized iodine concentration (NIC) was identified as an independent predictor for the DECT model. The IntraPeri model demonstrated superior performance compared to the intratumoral and peritumoral models both in 40 keV (0.830 vs. 0.766 vs. 0.763) and IMD images (0.881 vs. 0.840 vs. 0.821) in the test cohort. In the test cohort, the nomogram exhibited the best predictability (AUC=0.886, accuracy=0.836, sensitivity=0.737, and specificity=0.881), outperformed the DECT model (AUC=0.763, accuracy=0.754, sensitivity=0.632, and specificity=0.810) in predicting muscle invasion status of BCa with a statistically significant difference (p< 0.05). ConclusionThe nomogram, incorporating IntraPeri radiomics and NIC, serves as a valuable and non-invasive tool for preoperatively assessing the muscle invasion status of BCa.

Urothelial Carcinoma with Trophoblastic Differentiation-A Report with Review.

Urothelial carcinoma with trophoblastic differentiation is a rare type of urothelial carcinoma that poses a diagnostic challenge. A 50-year-old man presented with hematuria for 4 months duration. Ultrasonography examination showed polypoidal lesions along the right lateral wall and near the right vesicoureteric junction of the urinary bladder. The transurethral resection of the bladder tumor (TURBT) specimen showed marked necrosis and urothelial tumor cells arranged in nests, sheets, and papillae, admixed with multinucleated large cells. Deep muscle and extensive lymphovascular invasion were noted. The tumor cells were diffuse immunopositive for GATA3 and focal positive for p63 and SALL4. Large multinucleated tumor cells were immunopositive for β-hCG, GATA3, inhibin-α, and PLAP, focally positive for SALL4 while negative for p63. The patient denied further treatment and succumbed to the disease after 8 months of the TURBT procedure. We report a rare invasive urothelial carcinoma with trophoblastic differentiation and discuss the differential diagnosis and literature review.

Sex bias in FGFR3 somatic mutations in bladder cancer

Abstract Background Strong sex disparities have been observed among patients with bladder cancer (BCa). FGFR3 is one of the most frequently mutated genes in bladder cancer, and there are inconsistencies in its frequency in male and female patients. Methods Here, we conducted a meta-analysis comparing the FGFR3 somatic mutation frequency in men and women among 7351 patients with BCa from 18 cohorts. Results We showed that female patients had a 1.32 times higher risk of having FGFR3 somatic mutations than males. This difference was attributed to mutations occurring at the 2 most frequently mutated sites, S249 and Y375. Additionally, nonsense mutations were more likely to be found in women, whereas indel/frameshift mutations were almost exclusively found in men; however, no difference was noted for missense mutations. Conclusions A female sex bias in FGFR3 somatic mutations was observed in BCa. Well-powered individual participant data analyses addressing the possible confounding effects of other factors (eg, age, ethnicity, smoking status, muscle invasiveness, and molecular subtype), as well as analyses integrating omics and functional investigations, are warranted to further validate and explain the mechanisms of the current findings.

Impact of diabetes mellitus on oncologic outcomes in patients receiving robot-assisted radical cystectomy for bladder cancer.

Aim of this study is to investigate the association between DM and oncological outcomes among patients with muscle-invasive (MI) or high-risk non-muscle invasive (NMI) bladder cancer (BC) who underwent robot-assisted radical cystectomy with intracorporeal urinary diversion (RARC). An IRB approved multi-institutional BC database was queried, including patients underwent RARC between January 2013 and June 2023. Patients were divided into two groups according to DM status. Baseline, clinical, perioperative, pathologic data were compared. Chi-square and Student t tests were performed to compare categorical and continuous variables, respectively. Kaplan-Meier method and Cox regression analyses were performed to assess the association between DM and oncologic outcomes. Out of 547 consecutive patients, 97 (17.7%) had DM. The two cohorts showed similar preoperative features, except for ASA score (p = 0.01) and Hypertension rates (p < 0.001). No differences were detected for perioperative complications, pT stage, pN stages and surgical margins status (all p > 0.12). DM patients displayed significantly lower 5-yr disease-free survival (DFS) (44.6% vs. 63.3%, p = 0.007), 5-yr cancer-specific survival (CSS) (45.1% vs. 70.1%, p = 0.001) and 5-yr Overall survival (OS) (39.9% vs. 63.8%, p = 0.001). At Multivariable Cox-regression analyses DM status was identified as independent predictor of worse cancer-specific survival (CSS) (HR 2.1; p = 0.001) and overall survival (OS) (HR 2.05; p < 0.001). Among BC patients who underwent RARC, DM patients showed worse oncologic outcomes than the non-DM patients, with DM status playing an independent negative predicting role in CSS and OS. Future prospective studies are awaited, stimulating basic and translational research to identify possible mechanisms of interaction between DM and BC.

Vigor of bi-parametric MRI with MR segmentation unity in valuation of UB neoplasm mural invasion

BackgroundThe urinary bladder neoplasm is considered the second most frequent kind of neoplasm globally, after prostate cancer. Bladder neoplasm clinical management strategies and prognosis depend on the extent of loco-regional disease. MRI is increasingly being employed for preoperative, local staging of BC. The aim of this study was to expose the mastery of bi-parametric MRI (MRDWI and T2WI conjunction) with signal intensity-based MR segmentation in evaluation of UB neoplasm mural invasion if unaccompanied by contrast-enhanced MRI with special concern to Vesical Imaging Reporting and Data System (VIRADS) score taking the histopathological diagnosis as a reference.ResultsThis prospective study was conducted on 99 patients (with 100 UB lesions), who were referred from the urology department with bladder neoplasm suspicion. The mean age of the patients was 64.8 years. About 66.6% of the cases were smokers. The most common pathology of the UB neoplastic lesions was urothelial carcinoma. ADC in muscle-invasive bladder cancer (MIBC) was significantly lower than in non-invasive bladder cancer (NMIBC), with the minimum to maximum value of the ADC in all cases about 0.01–2.0. Also, we have done DWI at different b values, where b 1000 turned out to be the most accurate in detection of muscle invasion. Sensitivity, specificity, PPV, NPV and accuracy were calculated for T2WI only VIRADS, DWI only VIRADS, bi-parametric MR (T2WI and DWI)-based VIRADS, signal intensity-based MR segmentation VIRADS and for bi-parametric and MR segmentation conjunction-based VIRADS. The diagnostic performance for the combination of the bi-parametric MRI and signal intensity-based MR segmentations attained the highest values in sensitivity, specificity, PPV and NPV as well as accuracy.ConclusionsBi-parametric MRI (MRDWI with T2WI) and signal intensity MR segmentation conjunction have proven to be efficacious in accurately determining the UB neoplasm mural invasion allowing for the dispensability of CE-MRI in the event of contrast contraindications, unavailability or even its high cost.

Malignant Hip Flexion Failure Syndrome: An Oncologic Disease Compared to Malignant Psoas Syndrome.

Malignant psoas syndrome (MPS) causes painful hip immobilization when a malignant tumor reaches the psoas muscle. However, there exists a different condition in which a malignant tumor invades the psoas muscle, leading to hip flexion failure without painful hip immobilization. This study aimed to define malignant hip flexion failure syndrome (MHFFS) as tumors located in the upper lumbar region or at the lesser trochanter of the femur, near the origin or termination of the psoas muscle, and to compare its prevalence, characteristics, and outcomes with those of classical MPS. We analyzed 291 patients who received palliative radiotherapy (RT) in the lumbar, pelvic, and lower leg regions from 2013 to 2023. The prevalence of MPS and MHFFS, pathological features, distinctive clinical presentations, treatment modalities, and treatment outcomes have been summarized. We also defined the 'Clinical sign reported by Ishikawa and Teramura (IT sign)' to describe the characteristic action of lifting the affected lower leg with both hands in MHFFS cases and assessed its clinical significance. Among the 291 patients, 6 (2.1%) had MHFFS and 11 (3.8%) had MPS. MHFFS resulted from metastatic tumors in the 11th and 12th thoracic vertebrae, as well as the 1st and 2nd lumbar vertebrae or the lesser trochanter of the femur, and it was characterized by hip and groin pain along with hip flexion dysfunction. All cases showed a positive IT sign. The response to RT varied, with symptomatic improvement observed in 50% of the patients. MPS is characterized by tumor invasion of the psoas muscle, causing severe lumbosacral nerve pain. Strong opioids were used for pain management in all patients, and epidural anesthesia was required in some patients. The median survival time of patients with MPS and MHFFS was 13.2 months. MPS required opioids more potently than MHFFS, but MHFFS responded relatively well to early RT.

MRI and frozen section evaluation of mylohyoid muscle in determining surgical approach for T2-T3 floor of the mouth cancer.

The choice of surgical approach for floor of the mouth (FOM) cancer, particularly for intermediate-stage tumors (cT2-cT3), remains controversial. This study aims to evaluate a method considering mylohyoid muscle (MM) invasion as a determinant for surgical approach selection, utilizing magnetic resonance imaging (MRI) preoperatively and frozen section (FS) analysis intraoperatively. This observational retrospective cohort study analyzed patients undergoing surgical resection of cT2 and cT3 FOM squamous cell carcinoma (SCC) between January 2013 and June 2023. MM infiltration assessed by preoperative MRI determined the surgical approach: clear infiltration led to compartmental surgery (CS), while doubtful or absent infiltration led to transoral surgery (TOS). Conversion from TOS to CS occurred intraoperatively based on macroscopic evidence or positive FS. Data collected included demographic, clinical, surgical, and pathological variables. Survival analysis was conducted using Kaplan-Meier method. Among 44 patients included, majority had cT2 tumors (59.1%). MM resection was necessary in 22.7% of cases. Overall survival (OS) and progression-free survival (PFS) did not significantly differ between TOS and CS groups. Radiological depth of invasion (rDOI) < 10mm is correlated with MM preservation in 89% of cases, while rDOI > 10mm is correlated with MM resection only in 23.8% of cases. Pathological depth of invasion (pDOI) discrepancies were observed in the two groups: in CS group is shown a higher pDOI (> 10mm) confirmation (90%). Surgical complications and functional outcomes differed between TOS and CS groups. Considering MM invasion for surgical approach selection in cT2-cT3 FOM tumors appears oncologically safe, with better functional outcomes in muscle preservation. Preoperative MRI for MM assessment combined with intraoperative FS analysis provides reliable guidance for surgical decision-making.

Image directed redesign of bladder cancer treatment pathways: the BladderPath RCT.

Transurethral resection of bladder tumour has been the mainstay of bladder cancer staging for >60 years. Staging inaccuracies are commonplace, leading to delayed treatment of muscle-invasive bladder cancer. Multiparametric magnetic resonance imaging offers rapid, accurate and non-invasive staging of muscle-invasive bladder cancer, potentially reducing delays to radical treatment. To assess the feasibility and efficacy of the introducing multiparametric magnetic resonance imaging ahead of transurethral resection of bladder tumour in the staging of suspected muscle-invasive bladder cancer. Open-label, multistage randomised controlled study in three parts: feasibility, intermediate and final clinical stages. The COVID pandemic prevented completion of the final stage. Fifteen UK hospitals. Newly diagnosed bladder cancer patients of age≥18 years. Participants were randomised to Pathway 1 or 2 following visual assessment of the suspicion of non-muscle-invasive bladder cancer or muscle-invasive bladder cancer at the time of outpatient cystoscopy, based upon a 5-point Likert scale: Likert 1-2 tumours considered probable non-muscle-invasive bladder cancer; Likert 3-5 possible muscle-invasive bladder cancer. In Pathway 1, all participants underwent transurethral resection of bladder tumour. In Pathway 2, probable non-muscle-invasive bladder cancer participants underwent transurethral resection of bladder tumour, and possible muscle-invasive bladder cancer participants underwent initial multiparametric magnetic resonance imaging. Subsequent therapy was determined by the treating team and could include transurethral resection of bladder tumour. Feasibility stage: proportion with possible muscle-invasive bladder cancer randomised to Pathway 2 which correctly followed the protocol. Intermediate stage: time to correct treatment for muscle-invasive bladder cancer. Between 31 May 2018 and 31 December 2021, of 638 patients approached, 143 participants were randomised; 52.1% were deemed as possible muscle-invasive bladder cancer and 47.9% probable non-muscle-invasive bladder cancer. Feasibility stage: 36/39 [92% (95% confidence interval 79 to 98%)] muscle-invasive bladder cancer participants followed the correct treatment by pathway. Intermediate stage: median time to correct treatment was 98 (95% confidence interval 72 to 125) days for Pathway 1 versus 53 (95% confidence interval 20 to 89) days for Pathway 2 [hazard ratio 2.9 (95% confidence interval 1.0 to 8.1)], p = 0.040. Median time to correct treatment for all participants was 37 days for Pathway 1 and 25 days for Pathway 2 [hazard ratio 1.4 (95% confidence interval 0.9 to 2.0)]. For participants who underwent chemotherapy, radiotherapy or palliation for multiparametric magnetic resonance imaging-diagnosed stage T2 or higher disease, it was impossible to conclusively know whether these were correct treatments due to the absence of histopathologically confirmed muscle invasion, this being confirmed radiologically in these cases. All patients had histological confirmation of their cancers. Due to the COVID-19 pandemic, we were unable to realise the final stage. The multiparametric magnetic resonance imaging-directed pathway led to a substantial 45-day reduction in time to correct treatment for muscle-invasive bladder cancer, without detriment to non-muscle-invasive bladder cancer participants. Consideration should be given to the incorporation of multiparametric magnetic resonance imaging ahead of transurethral resection of bladder tumour into the standard pathway for all patients with suspected muscle-invasive bladder cancer. The improved decision-making accelerated time to treatment, even though many patients subsequently needed transurethral resection of bladder tumour. A proportion of patients can avoid transurethral resection of bladder tumour completely, reducing costs and morbidity, given the much lower cost of magnetic resonance imaging and biopsy compared to transurethral resection of bladder tumour. Further work to cross-correlate with the recently developed Vesical Imaging-Reporting and Data System will improve accuracy and aid dissemination. Longer follow-up to examine the effect of the pathway on outcomes is also required. Incorporation of liquid deoxyribonucleic acid-based biomarkers may further improve the quality of decision-making and should also be investigated further. This study is registered as ISRCTN 35296862. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135775) and is published in full in Health Technology Assessment; Vol. 28, No. 42. See the NIHR Funding and Awards website for further award information.