Development and validation of a clinical and ultrasound features-based nomogram for preoperative differentiation of renal urothelial carcinoma and central renal cell carcinoma.

PURPOSE: This study aimed to develop and validate an ultrasound (US)-based nomogram for the preoperative differentiation of renal urothelial carcinoma (rUC) from central renal cell carcinoma (c-RCC). METHODS: Clinical data and US images of 655 patients with 655 histologically confirmed malignant renal tumors (521 c-RCCs and 134 rUCs) were collected and divided into training (n = 455) and validation (n = 200) cohorts according to examination dates. Conventional US and contrast-enhanced US (CEUS) tumor features were analyzed to determine those that could discriminate rUC from c-RCC. Least absolute shrinkage and selection operator regression was applied to screen clinical and US features for the differentiation of rUC from c-RCC. Using multivariate logistic regression analysis, a diagnostic model of rUC was constructed and visualized as a nomogram. The diagnostic model's performance was assessed in the training and validation cohorts by calculating the area under the receiver operating characteristic curve (AUC) and calibration plot. Decision curve analysis (DCA) was used to assess the clinical usefulness of the US-based nomogram. RESULTS: Seven features of both clinical features and ultrasound imaging were selected to build the diagnostic model. The nomogram achieved favorable discrimination in the training (AUC = 0.996, 95% CI: 0.993-0.999) and validation (AUC = 0.995, 95% CI: 0.974, 1.000) cohorts, and good calibration (Brier scores: 0.019 and 0.016, respectively). DCA demonstrated the clinical usefulness of the US-based nomogram. CONCLUSION: A noninvasive clinical and US-based nomogram combining conventional US and CEUS features possesses good predictive value for differentiating rUC from c-RCC.

Urothelial Carcinoma: Epidemiology and Imaging-Based Review.

Bladder cancer is the 6th most common malignancy in the United States, with urothelial carcinomas comprising over 95% of cases of bladder cancer, and commands a significant disease burden in Rhode Island. Imaging studies can provide valuable diagnostic information for urothelial carcinomas at initial presentation and are routinely used for noninvasive staging, treatment response monitoring, and post-treatment surveillance. This review aims to discuss and highlight three imaging modalities: ultrasonography, computed tomography, and magnetic resonance imaging, with particular focus on the notable features and appearance of urothelial carcinoma on each modality and their relative utility throughout the disease course. A general overview of disease epidemiology and treatment practices is also provided.

Practical Guide to VI-RADS: MRI Protocols, Lesion Characterization, and Pitfalls.

Urothelial carcinoma is the most common type of bladder cancer (BC), accounting for approximately 90% of all cases. Evaluating the depth of tumor invasion in the bladder wall (tumor staging) is essential for determining the treatment and prognosis in patients with BC. Neoadjuvant therapy followed by radical cystectomy is the most common treatment of localized muscle-invasive BC (MIBC). Therefore, it is vital to differentiate non-MIBC from MIBC. Transurethral resection of bladder tumor (TURBT) is the reference standard to determine the extent of tumor invasion into the bladder wall through tissue sampling. However, this diagnostic and therapeutic method may not adequately sample the muscularis propria, leading to a higher risk of residual disease, early recurrence, and tumor understaging in approximately 50% of patients during the initial TURBT. Multiparametric MRI can overcome some of the limitations of TURBT when evaluating BC, particularly regarding tumor staging. In this context, the Vesical Imaging Reporting and Data System (VI-RADS) classification was developed to establish standards for bladder multiparametric MRI and interpretation. It uses a 5-point scale to assess the likelihood of detrusor muscle invasion. T2-weighted MR images are particularly useful as an initial guide, especially for categories 1-3, while the presence of muscular invasion is determined with diffusion-weighted and dynamic contrast-enhanced sequences. Diffusion-weighted imaging takes precedence as the dominant method when optimal image quality is achieved. The presence of a stalk or a thickened inner layer and no evidence of interruption of the signal intensity of the muscular layer are central for predicting a low likelihood of muscle invasion. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Hoegger in this issue.

Application of contrast-enhanced ultrasound in diagnosis and grading of bladder urothelial carcinoma.

PURPOSE: To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC). METHODS: The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed. RESULTS: There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%. CONCLUSION: The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.

MRI for risk stratification of muscle invasion by upper tract urothelial carcinoma: a feasibility study.

BACKGROUND: Magnetic resonance imaging (MRI) is recommended in patients with upper tract urothelial carcinoma (UTUC) only when computed tomography (CT) is contraindicated. However, CT does not allow distinguishing ureter wall layers, making impossible to assess muscle invasion, a factor contributing to differentiate high- from low-risk UTUCs, which require different therapeutic approaches. We investigated the feasibility of MRI assessment of UTUC muscle invasion. METHODS: From June 2022 to March 2023, we prospectively enrolled patients suspected of UTUC, i.e., with positive urinary tract ultrasound and/or ureteroscopy, or positive urinary cytology and/or hematuria but negative cystoscopy and bladder ultrasound at two Italian centers. They underwent CT followed by MRI (≤ 24 h apart), independently reported by two experienced radiologists, blinded from histopathology results. After imaging confirmation, they all underwent nephroureterectomy and histopathology analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: Thirty-nine lesions were detected in 30 patients on both CT and MRI. Muscle-invasive UTUC prevalence was 81% (21/26) among patients with MRI suspicion and 8% (1/13) among those without MRI suspicion (p < 0.001). Considering the assessment of muscle-layer invasion, the more experienced reader achieved 95% sensitivity (95% confidence interval 82-100), 71% specificity (47-88), 81% PPV (63-93), 92% NPV (70-100), 85% accuracy (67-96), and 0.84 AUC (0.70-0.98). Inter-reader agreement was substantial (κ = 0.73). CONCLUSIONS: MRI showed a promising diagnostic performance for the assessment of UTUC risk of muscle invasion. RELEVANCE STATEMENT: Resulting feasible both in technical and clinical terms, MRI could be helpful for upper tract urothelial carcinomas pre-operative risk stratification, to allow a personalized patients' management. These results play in favor of promoting preoperative MRI for UTUC, as already proven for bladder cancer. KEY POINTS: • Muscle invasion is a crucial information for tailored treatments of upper tract urothelial carcinomas. • CT does not distinguish ureter wall layers, making muscle invasion risk assessment not feasible. • MRI was shown to reliably diagnose muscle-layer invasion by upper tract urothelial carcinomas (sensitivity 95%, specificity 71%).

CT findings and clinical characteristics in distinguishing renal urothelial carcinoma mimicking renal cell carcinoma from clear cell renal cell carcinoma.

BACKGROUND: We aimed to characterize the clinical and multiphase computed tomography (CT) features, which can distinguish renal urothelial carcinoma (RUC) mimicking renal cell carcinoma (RCC) from clear cell renal cell carcinoma (ccRCC) with collecting system invasion (CSI). METHODS: Data from 56 patients with RUC (46 men and 10 women) and 366 patients with ccRCC (262 men and 104 women) were collected and assessed retrospectively. The median age was 65.50 (IQR: 56.25-69.75) and 53.50 (IQR: 42.25-62.5) years, respectively. Univariate and multivariate logistic regression analyses were performed on clinical and CT characteristics to determine independent factors for distinguishing RUC and ccRCC, and an integrated predictive model was constructed. Differential diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: The independent predictors for differentiating RUC from ccRCC were infiltrative growth pattern, hydronephrosis, heterogeneous enhancement, preserving reniform contour, and hematuria. The differential diagnostic performance of the integrated predictive model-1 (AUC: 0.947, sensitivity: 89.07%, specificity: 89.29%) and model-2 (AUC: 0.960, sensitivity: 92.1%, specificity: 89.3%) were both better than that of the infiltrative growth pattern (AUC: 0.830, sensitivity: 71.9%, specificity: 92.9%), heterogeneous enhancement (AUC: 0.771, sensitivity: 86.3%, specificity: 67.9%), preserving reniform contour (AUC = 0.758, sensitivity: 85.5%, specificity: 66.1%), hydronephrosis (AUC: 0.733, sensitivity: 87.7%, specificity: 58.9%), or hematuria (AUC: 0.706, sensitivity: 79.5%, specificity: 51.8%). CONCLUSION: The CT and clinical characteristics showed extraordinary discriminative abilities in the differential diagnosis of RUC and ccRCC, which might provide helpful information for clinical decision-making.

PET/Computed Tomography Transformation of Oncology: Kidney and Urinary Tract Cancers.

Renal cell carcinoma (RCC) and urothelial carcinoma (UC) are two of the most common genitourinary malignancies. 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) can play an important role in the evaluation of patients with RCC and UC. In addition to the clinical utility of 18F-FDG PET to evaluate for metastatic RCC or UC, the shift in molecular imaging to focus on specific ligand-receptor interactions should provide novel diagnostic and therapeutic opportunities in genitourinary malignancies. In combination with the rise of artificial intelligence, our ability to derive imaging biomarkers that are associated with treatment selection, response assessment, and overall patient prognostication will only improve.

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

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

Lymph Node Dissection in Upper Tract Urothelial Carcinoma: Current Status and Future Perspectives.

PURPOSE OF REVIEW: This narrative review aims to evaluate the role of lymph node dissection (LND) in upper tract urothelial carcinoma (UTUC) and its implications for staging and management outcomes, as well as future perspectives. RECENT FINDINGS: Multiple studies have demonstrated the limitations of conventional imaging techniques in accurately localizing lymph node metastasis (LNM) in UTUC. While 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) shows promise for preoperative LNM detection, its specificity is low. Alternative methods such as choline PET/CT and sentinel lymph node detection are under consideration but require further investigation. Additionally, various preoperative factors associated with LNM hold potential for predicting nodal involvement, thereby improving nodal staging and oncologic outcomes of LND. Several surgical approaches, including segmental ureterectomy and robot-assisted nephroureterectomy, provide a possibility for LND, while minimizing morbidity. LND remains the primary nodal staging tool for UTUC, but its therapeutic benefit is still uncertain. Advances in imaging techniques and preoperative risk assessment show promise in improving LNM detection. Further research and multi-center studies are needed to comprehensively assess the advantages and limitations of LND in UTUC, as well as the long-term outcomes of alternative staging and treatment strategies.

Pedal acrometastasis secondary to urothelial carcinoma masquerading as Charcot arthropathy in a patient with diabetes.

A woman in her 80s with known diabetes mellitus and bladder cancer presented to her general practitioner (GP) with pain and swelling in her left foot following trauma. Initial radiographs were reported as normal, prompting a diagnosis of a simple sprain and conservative management. Three months later, the patient was referred to the orthopaedic team due to progressively increasing pain and swelling. Repeat X-rays revealed lytic lesions in both the talus and navicular bones; MRI confirmed the presence of a lytic and proliferative defect in the mid-foot, which was reported as acute Charcot arthropathy with superimposed infection. This was also considered the most likely diagnosis when imaging was reviewed in two separate multidisciplinary team) meetings. However, biopsy demonstrated that the cause of the presentation was in fact acrometastasis from urothelial carcinoma, an infrequently described entity.

Primary high-grade urothelial carcinoma of prostate with prostatic hyperplasia: a rare case report and review of the literature.

BACKGROUND: Primary urothelial carcinoma in the prostate (UCP) is extremely rare and occurs most frequently in the bladder. There are only dozens of primary cases reported in the literature. Here, we describe a rare case of primary UCP and review the literature. CASE PRESENTATION: A 67-year-old widowed male, was referred to our hospital due to the frequency, and urgency of dysuria. Magnetic resonance imaging (MRI) examination revealed prostate size was about 57 mm × 50 mm × 54 mm, increased prostatic transitional zone, and surrounding of prostatic duct indicate bar isointense T1, short T2, hyperintense DWI, and hyposignal ADC (PI-RADS 3); posterior of peripheral zone indicate patchy isointense T1, short T2, hyperintense DWI, and hyposignal ADC (PI-RADS 5). Subsequently, the patient underwent a transrectal prostate biopsy. Histopathological and immunohistochemical (IHC) assessments showed prostatic high-grade urothelial carcinoma with benign prostatic hyperplasia. Finally, the patient underwent laparoscopic radical prostatectomy. Four months after surgery, CT plain and enhanced scan revealed thickening of the bladder wall. On further workup, cystoscopy revealed lymphoid follicular changes in the cut edge of the radical prostatectomy, and cystoscopic biopsies showed the malignant tumor. CONCLUSIONS: Prostatic urothelial carcinoma should always be considered if the patient with severe lower urinary tract symptoms or hematuria, PSA, and digital rectal examination without abnormalities, without a personal history of urothelial cancer, but contrast-enhanced MRI showed the lesion located in the prostate. As of right now, radical surgical resections remain the most effective treatment. The effectiveness of neoadjuvant or adjuvant chemotherapy is still controversial.

Effect of decreased renal function on poor oncological outcome after radical cystectomy.

PURPOSE: To evaluate the impact of preoperative renal impairment on the oncological outcomes of patients with urothelial carcinoma who underwent radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients with urothelial carcinoma who underwent radical cystectomy from 2004 to 2017. All patients who underwent preoperative 99mTc-diethylenetriaminepentaacetic acid renal scintigraphy (DTPA) were identified. We divided the patients into two groups according to their glomerular filtration rates (GFRs): GFR group 1, GFR≥90 mL/min/1.73 m²; GFR group 2, 60≤GFR<90 mL/min/1.73 m². We included 89 patients in GFR group 1 and 246 patients in GFR group 2 and compared the clinicopathological characteristics and oncological outcomes between the two groups. RESULTS: The mean time required for recurrence was 125.5±8.0 months in GFR group 1 and 85.7±7.4 months in GFR group 2 (p=0.030). The mean cancer-specific survival was 131.7±7.8 months in GFR group 1 and 95.5±6.9 months in GFR group 2 (p=0.051). The mean overall survival was 123.3±8.1 months in GFR group 1 and 79.5±6.6 months in GFR group 2 (p=0.004). CONCLUSIONS: Preoperative GFR values in the range of 60≤GFR<90 mL/min/1.73 m² are independent prognostic factors for poor recurrence-free survival, cancer-specific survival, and overall survival in patients after radical cystectomy compared with GFR values of ≥90 mL/min/1.73 m².

First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma.

PURPOSE: Nectin-4 is an emerging biomarker for cancer diagnosis and therapy. Recently, enfortumab vedotin (EV) was approved by the FDA as the first nectin-4 targeting antibody-drug conjugate for treating advanced urothelial carcinoma (UC). A PET imaging method to noninvasively quantify nectin-4 expression level would potentially help to select patients most likely to respond to EV and predict the response. EXPERIMENTAL DESIGN: In this study, we designed a bicyclic peptide-based nectin-4 targeting radiotracer 68Ga-N188. Initially, we performed preclinical evaluations of 68Ga-N188 in UC cell lines and xenograft mouse models. Next, we performed the translational study in healthy volunteers and a pilot cohort of patients with advanced UC on uEXPLORER total-body PET/CT. RESULTS: In the preclinical study, 68Ga-N188 showed high affinity to nectin-4, specific uptake in a nectin-4(+) xenograft mouse model, and suitable pharmacokinetic and safety profiles. In the translational study, 2 healthy volunteers and 14 patients with advanced UC were enrolled. The pharmacokinetic profile was determined for 68Ga-N188, and the nectin-4 relative expression level in different organs was quantitatively imaged. CONCLUSIONS: A clear correlation between PET SUV value and nectin-4 expression was observed, supporting the application of 68Ga-N188 PET as a companion diagnostic tool for optimizing treatments that target nectin-4. See related commentary by Jiang et al., p. 3259.

The efficacy of ultrasonography for the detection of upper tract urothelial carcinoma.

PURPOSE: Ultrasonography and computed tomography urography are two commonly used modalities to image the upper tracts for the evaluation of hematuria. This study evaluated the efficacy of ultrasonography for the detection of upper tract urothelial carcinoma compared to computed tomography urography as a standard reference. METHODS: This retrospective study included patients with urothelial carcinoma of the renal pelvis and/or ureter who were diagnosed using computed tomography urography and underwent surgical treatment. We calculated the sensitivity of ultrasonography in upper tract urothelial carcinoma diagnosis, further classified the degree of hydronephrosis on ultrasonography, and analyzed the relationship between the sensitivity and the degree of hydronephrosis and tumor location. Additionally, the usefulness of the combination of the screening ultrasonography findings, the presence of gross hematuria, and/or urine cytology was analyzed. RESULTS: This study included 136 patients with upper urothelial carcinoma. Ultrasonography in the diagnosis had 45.6% sensitivity, and ultrasonography findings, including the detection of hydronephrosis, were present in 72.8%. The presence of hydronephrosis and tumor location were associated with detection by ultrasonography. The tumor was identified in a total of 134 (98.5%) patients by combining tumor detection and hydronephrosis using ultrasonography with gross hematuria and positive urine cytology as screening. CONCLUSION: Ultrasonography showed acceptable sensitivity for upper tract urothelial carcinoma diagnosis. Considering the hydronephrosis findings, ultrasonography is a useful screening tool for upper tract urothelial carcinoma. Additionally, excessive computed tomography examinations can be reduced by adding gross hematuria and positive urine cytology.

Current methods facilitating diagnosis of upper tract urothelial carcinoma: a comprehensive literature review.

PURPOSE OF REVIEW: Currently, kidney-sparing surgeries are considered the preferred approach in low-risk tumours and in selected high-risk patients. Therefore, accurate diagnosis of UTUC is crucial for further management. The purpose of this review is to summarize available methods facilitating the diagnosis of upper tract urothelial carcinoma (UTUC). RECENT FINDINGS: Recent articles propose numerous techniques of UTUC diagnosis. In this review, imaging, as well as, urine-based and endoscopic methods have been described and assessed. SUMMARY: Regarding imaging, computed tomography urography remains a gold standard, while PET is superior in search for small lesions and nodal metastases. However, contrast-enhanced ultrasonography also shows promise. On the contrary, available urine tests, such as urinary cytology, fluorescent in-situ hybridization, Xpert, DNA methylation analysis, urine-based liquid biopsy, p16/Ki-67 dual immunolabelling, ImmunoCyt and NMP22 are either poorly researched, or not accurate enough to use solely. Finally, during ureterorenoscopy, photodynamic diagnosis and narrow-band imaging can facilitate proper visualization of the tumor. Endoluminal ultrasonography and confocal laser endomicroscopy can potentially improve staging and grading of UTUC. Also, the 'form tackle' biopsy should be performed using a basket in papillary lesions and cold-cup biopsy of flat or sessile lesions. Even though cryobiopsy shows promise in UTUC diagnosis, in-vivo studies are necessary before it is introduced into clinical practice.

The comparison between contrast-enhanced ultrasound and contrast-enhanced magnetic resonance imaging in diagnosing bladder urothelial carcinoma.

PURPOSE: The surgical treatment of bladder urothelial carcinoma depends on whether the tumor has invaded the bladder muscular layer. Normal ultrasound and contrast-enhanced magnetic resonance imaging (contrast-enhanced MRI) are widely used in patients bear bladder tumors; the latter is also widely used in estimating the muscularis invasion of bladder cancer (BC). However, contrast-enhanced ultrasound (CEUS) is rarely used in this aspect. As the gold standard in diagnosing muscularis invasion remains being pathological examination, this study was set to find out whether there are differences between CEUS and contrast-enhanced MRI in diagnosing bladder malignant tumors and in diagnosing the muscularis invasion of the bladder urothelial carcinoma under the guide of the pathological results. METHODS: 160 patients from Yongchuan Hospital of Chongqing Medical University and The Second Affiliated Hospital of Chongqing Medical University were recruited from July 1st, 2021, to June 30th, 2022. Patients are arranged to undergo CEUS, contrast-enhanced MRI and then take a surgery. After surgery, we compare the results of CEUS, MRI and the pathological results, using software to run the statistical examinations. RESULTS: The accuracies of CEUS and contrast-enhanced MRI in diagnosing malignant bladder tumors were 85.90 and 84.62%, and they had no differences (P > 0.05). While the accuracies of CEUS and contrast-enhanced MRI in diagnosing the muscularis invasion were 84.62 and 76.92%, in which CEUS had a better sensitivity (P < 0.05). CONCLUSIONS: We found that CEUS and contrast-enhanced MRI had no differences in diagnosing the different pathological types (benign or malignant) of BC, but CEUS holds a better sensitivity in diagnosing muscularis invasions of bladder urothelial carcinoma than the contrast-enhanced MRI.