Three-dimensional imaging of upper tract urothelial carcinoma improves diagnostic yield and accuracy.

Upper tract urothelial carcinoma (UTUC) is a rare form of urothelial cancer with a high incidence of recurrence and a low survival rate. Almost two-thirds of UTUCs are invasive at the time of diagnosis; therefore, improving diagnostic methods is key to increasing survival rates. Histopathological analysis of UTUC is essential for diagnosis and typically requires endoscopy biopsy, tissue sectioning, and labeling. However, endoscopy biopsies are minute, and it is challenging to cut into thin sections for conventional histopathology; this complicates diagnosis. Here, we used volumetric 3-dimensional (3D) imaging to explore the inner landscape of clinical UTUC biopsies, without sectioning, revealing that 3D analysis of phosphorylated ribosomal protein S6 (pS6) could predict tumor grade and prognosis with improved accuracy. By visualizing the tumor vasculature, we discovered that pS6+ cells were localized near blood vessels at significantly higher levels in high-grade tumors than in low-grade tumors. Furthermore, the clustering of pS6+ cells was associated with shorter relapse-free survival. Our results demonstrate that 3D volume imaging of the structural niches of pS6 cells deep inside the UTUC samples improved diagnostic yield, grading, and prognosis prediction.

Radiomics-based machine learning approach for the prediction of grade and stage in upper urinary tract urothelial carcinoma: a step towards virtual biopsy.

OBJECTIVES: Upper tract urothelial carcinoma (UTUC) is a rare, aggressive lesion, with early detection a key to its management. This study aimed to utilise computed tomographic urogram data to develop machine learning models for predicting tumour grading and staging in upper urothelial tract carcinoma patients and to compare these predictions with histopathological diagnosis used as reference standards. METHODS: Protocol-based computed tomographic urogram data from 106 patients were obtained and visualised in 3D. Digital segmentation of the tumours was conducted by extracting textural radiomics features. They were further classified using 11 predictive models. The predicted grades and stages were compared to the histopathology of radical nephroureterectomy specimens. RESULTS: Classifier models worked well in mining the radiomics data and delivered satisfactory predictive machine learning models. The multilayer panel showed 84% sensitivity and 93% specificity while predicting UTUC grades. The Logistic Regression model showed a sensitivity of 83% and a specificity of 76% while staging. Similarly, other classifier algorithms [e.g. Support Vector classifier (SVC)] provided a highly accurate prediction while grading UTUC compared to clinical features alone or ureteroscopic biopsy histopathology. CONCLUSION: Data mining tools could handle medical imaging datasets from small (<2 cm) tumours for UTUC. The radiomics-based machine learning algorithms provide a potential tool to model tumour grading and staging with implications for clinical practice and the upgradation of current paradigms in cancer diagnostics. CLINICAL RELEVANCE: Machine learning based on radiomics features can predict upper tract urothelial cancer grading and staging with significant improvement over ureteroscopic histopathology. The study showcased the prowess of such emerging tools in the set objectives with implications towards virtual biopsy.

Is the excretory phase necessary to identify upper tract urothelial neoplasms at CT urography? A 10-year population-based study.

PURPOSE: To assess the proportion of upper tract urothelial carcinomas (UTUC) that are evident without the excretory phase at CT urography (CTU), and the proportion of potentially avoidable radiation. METHODS: UTUCs diagnosed between January 2008-December 2017 were retrospectively identified from a population-based cancer registry. For each patient, US, non-urographic CT, and MRI exams were assessed for a primary mass and secondary imaging findings (hydronephrosis, urinary tract thickening, luminal distention, fat stranding, and lymphadenopathy/metastatic disease). CTUs were assessed for primary and secondary findings, and whether the tumor was evident as a filling defect on excretory phase. The dose-length product (DLP) of potentially avoidable excretory phases was calculated as a fraction of total DLP. RESULTS: 288 patients (mean age, 72±11 years, 165 males) and 545 imaging examinations were included. Of 192 patients imaged with 370 non-urographic CTs, a primary mass was evident in 154 (80.2%), secondary findings were evident in 172 (89.6%), and primary or secondary findings were evident in 179 (93.2%). Of 175 CTUs, primary and secondary findings were evident in 157 (89.7%) and 166 (94.9%) examinations, respectively, and primary or secondary findings were evident in 170/175 (97.1%). 131/175 (74.9%) UTUCs were evident as a filling defect, including the 5/175 (2.9%) UTUCs without primary or secondary findings. Of 144 CTUs with available DLP data, the proportion of potentially avoidable radiation was 103.7/235.8 (44.0%) Gy⋅cm. CONCLUSION: In our population, almost all UTUCs were evident via primary or secondary imaging findings without requiring the excretory phase. These results support streamlining protocols and pathways.

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.

A computed tomography urography-based machine learning model for predicting preoperative pathological grade of upper urinary tract urothelial carcinoma.

OBJECTIVES: Development and validation of a computed tomography urography (CTU)-based machine learning (ML) model for prediction of preoperative pathology grade of upper urinary tract urothelial carcinoma (UTUC). METHODS: A total of 140 patients with UTUC who underwent CTU examination from January 2017 to August 2023 were retrospectively enrolled. Tumor lesions on the unenhanced, medullary, and excretory periods of CTU were used to extract Features, respectively. Feature selection was screened by the Pearson and Spearman correlation analysis, least absolute shrinkage and selection operator algorithm, random forest (RF), support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost). The logistic regression (LR) was used to screen for independent influencing factors of clinical baseline characteristics. Machine learning models based on different feature datasets were constructed and validated using algorithms such as LR, RF, SVM, and XGBoost. By computing the selected features, a radiomics score was generated, and a diverse feature dataset was constructed. Based on the training set, 16 ML models were created, and their performance was evaluated using the validation set for metrics including sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC), and others. RESULTS: The training set consisted of 98 patients (mean age: 64.5 ± 10.5 years; 30 males), whereas the validation set consisted of 42 patients (mean age: 65.3 ± 9.78 years; 17 males). Hydronephrosis was the best independent influence factor (p < 0.05). The RF model had the best performance in predicting high-grade UTUC, with AUC of 0.914 (95% Confidence Interval [95%CI] 0.852-0.977) and 0.903 (95%CI 0.809-0.997) in the training set and validation set, and accuracy of 0.878 and 0.857, respectively. CONCLUSIONS: An ML model based on the RF algorithm exhibits excellent predictive performance, offering a non-invasive approach for predicting preoperative high-grade UTUC.

AI-powered radiomics: revolutionizing detection of urologic malignancies.

PURPOSE OF REVIEW: This review aims to highlight the integration of artificial intelligence-powered radiomics in urologic oncology, focusing on the diagnostic and prognostic advancements in the realm of managing prostate, kidney, and bladder cancers. RECENT FINDINGS: As artificial intelligence continues to shape the medical imaging landscape, its integration into the field of urologic oncology has led to impressive results. For prostate cancer diagnostics, machine learning has shown promise in refining clinically-significant lesion detection, with some success in deciphering ambiguous lesions on multiparametric MRI. For kidney cancer, radiomics has emerged as a valuable tool for better distinguishing between benign and malignant renal masses and predicting tumor behavior from CT or MRI scans. Meanwhile, in the arena of bladder cancer, there is a burgeoning emphasis on prediction of muscle invasive cancer and forecasting disease trajectory. However, many studies showing promise in these areas face challenges due to limited sample sizes and the need for broader external validation. SUMMARY: Radiomics integrated with artificial intelligence offers a pioneering approach to urologic oncology, ushering in an era of enhanced diagnostic precision and reduced invasiveness, guiding patient-tailored treatment plans. Researchers must embrace broader, multicentered endeavors to harness the full potential of this field.

The Role of Dual-Energy CT in the Study of Urinary Tract Tumors: Review of Recent Literature.

Urothelial cancers are often detected incidentally because of an exponential growth in medical cross-sectional imaging. Nowadays there is the need for improved lesion characterization to distinguish clinically significant tumors from benign conditions. The gold standard for diagnosis of bladder cancer is cystoscopy, while for upper tract urothelial cancer computed tomographic urography and flexible ureteroscopy are more appropriate modalities. Computed tomography (CT) is the cornerstone in the assessment of locoregional and distant disease, using a protocol with precontrastographic and postcontrastographic phases. In particular, renal pelvis, ureter and bladder lesions can be assessed during the urography phase in the acquisition protocol of the urothelial tumors. Multiphasic CT is associated with overexposure to ionising radiation and repeated infusion of iodinated contrast media, which can be problematic especially in certain types of patients (allergic, nephropathic, pregnant women and in paediatric age). Dual-energy CT can overcome these difficulties with a number of methods, for example, by reconstructing virtual noncontrast images from a single-phase examination with contrast medium. In this review of the recent literature, we would like to highlight the role of Dual-energy CT in the diagnosis of urothelial cancer, its potential in this setting and possible advantages related to it.

Diagnostic Imaging in the Evaluation of Asymptomatic Microhematuria: Systematic Review and Meta-analysis.

PURPOSE: Microhematuria is a highly prevalent condition with a low associated risk of urothelial and upper tract malignancy. The AUA Guidelines recently changed recommendations for imaging favoring renal ultrasound for low- and intermediate-risk patients with microhematuria. We summarize the diagnostic test characteristics of computed tomography urography, renal ultrasound, and magnetic resonance urography in comparison with surgical pathology for the diagnosis of upper urinary tract cancer in microhematuria and gross hematuria patients. MATERIALS AND METHODS: This study is a systematic review and meta-analysis using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from evidence collected for the 2020 AUA Microhematuria Guidelines report, including studies assessing imaging following diagnosis of hematuria published from January 2010 through December 2019. RESULTS: The search identified 20 studies which reported the prevalence of malignant and benign diagnoses in relation to imaging modality, of which 6 were included in the quantitative analysis. For the detection of renal cell carcinoma and upper urinary tract carcinoma in patients with microhematuria and gross hematuria, computed tomography urography had a sensitivity of 94% (95% CI, 84%-98%) and a specificity of 99% (95%CI, 97%-100%) with a certainty of evidence rating of very low and low, respectively when 4 studies were pooled. In comparison, ultrasound demonstrated a sensitivity ranging from 14%-96% (low certainty of evidence) and a specificity of 99%-100% in 2 studies (moderate certainty of evidence), while magnetic resonance urography demonstrated a sensitivity of 83% and specificity of 86% in 1 study with a low certainty of evidence. CONCLUSIONS: In a limited data set for each individual imaging modality, computed tomography urography appears the most sensitive imaging modality for the diagnostic evaluation of microhematuria. Future studies will be needed to evaluate the clinical and health system financial impacts of the change in guideline recommendations from computed tomography urography to renal ultrasound in evaluating low- and intermediate-risk patients with microhematuria.

CT of the urinary tract revisited.

Computed tomography (CT) of the abdomen is usually appropriate for the initial imaging of many urinary tract diseases, due to its wide availability, fast scanning and acquisition of thin slices and isotropic data, that allow the creation of multiplanar reformatted and three-dimensional reconstructed images of excellent anatomic details. Non-enhanced CT remains the standard imaging modality for assessing renal colic. The technique allows the detection of nearly all types of urinary calculi and the estimation of stone burden. CT is the primary diagnostic tool for the characterization of an indeterminate renal mass, including both cystic and solid tumors. It is also the modality of choice for staging a primary renal tumor. Urolithiasis and urinary tract malignancies represent the main urogenic causes of hematuria. CT urography (CTU) improves the visualization of both the upper and lower urinary tract and is recommended for the investigation of gross hematuria and microscopic hematuria, in patients with predisposing factors for urologic malignancies. CTU is highly accurate in the detection and staging of upper tract urothelial malignancies. CT represents the most commonly used technique for the detection and staging of bladder carcinoma and the diagnostic efficacy of CT staging improves with more advanced disease. Nevertheless, it has limited accuracy in differentiating non-muscle invasive bladder carcinoma from muscle-invasive bladder carcinoma. In this review, clinical indications and the optimal imaging technique for CT of the urinary tract is reviewed. The CT features of common urologic diseases, including ureterolithiasis, renal tumors and urothelial carcinomas are discussed.

Targeted Molecular Imaging as a Biomarker in Urologic Oncology.

Urologic malignancies constitute a large portion of annually diagnosed cancers. Timely diagnosis, accurate staging, and assessment of tumor heterogeneity are essential to devising the best treatment strategy for individual patients. The high sensitivity of molecular imaging allows for early and sensitive detection of lesions that were not readily detectable using conventional imaging techniques. Moreover, molecular imaging enables the interrogation of molecular processes used in targeted cancer therapies and predicts cancer response to treatment. Here we review the current advancements in molecular imaging of urologic cancers, including prostatic, vesical, renal testicular, and ureteral cancers.

Dual-Energy CT applications in urinary tract cancers: an update.

Urothelial tumours are the fourth most common cancer in the world and account for the majority of tumours involving the bladder. The symptom that often leads to diagnosis is the presence of haematuria. Diagnosis is made by cystoscopy, which is currently the gold standard in bladder cancer. Computed tomography (CT) performed with pre- and post-contrastographic phases is essential in order to assess the loco-regional and distant extension of disease. The diagnosis and staging of upper tract urothelial cancer (UTUC) are best done with computed tomography urography and flexible ureteroscopy (URS). In the acquisition protocol of this type of tumour, a urographic phase is mandatory, which allows for an accurate diagnostic assessment of the renal pelvis, ureter and bladder, especially in papillary forms. The use of multiple acquisition phases, especially in this type of patient who will have to perform follow-up CTs, leads to the problem of overexposure to ionising radiation, as well as the frequent administration of iodinated contrast medium. For this reason, in recent year, the focus has been put on advanced technologies such as dual-energy CT (DECT), that is a method that can offer some advantages for both radiologist and patient, in the diagnosis of cancer and, in particular, urinary tract disease.

Magnetic Resonance Imaging-guided Adaptive Radiotherapy for Urological Cancers: What Urologists Should Know.

Magnetic resonance imaging (MRI)-guided radiotherapy allows for online adaptation of the radiation plan on the basis of anatomical and functional changes during treatment. MRI-guided radiotherapy holds significant promise for broadening the therapeutic window for multiple urological cancers.

CT findings and diagnostic performance of upper urinary tract carcinoma in situ.

OBJECTIVES: To evaluate the CT characteristics and detectability of carcinoma in situ (CIS) of the upper urinary tract. METHODS: Between January 2007 and March 2020, 28 patients (mean age: 73 years, 25 male and 3 female) with 29 pure CIS lesions of the upper urinary tract (i.e., without concomitant non-CIS lesion) who underwent nephroureterectomy were identified. The most recent CT scan performed before ureteroscopy, systemic neoadjuvant chemotherapy, or nephroureterectomy was selected for analysis. Twenty-eight patients without upper tract malignancy were selected as a control group. All images were evaluated for presence of upper urinary tract CIS using confidence levels ranging from 1 to 100 by two radiologists. The confidence level of 75 was used as a cutoff threshold for calculating sensitivity and specificity. RESULTS: The median interval between CT scan and nephroureterectomy was 96 days. The number of true-positive lesions (per-lesion sensitivity) was 41% (12/29) and 52% (15/29) by readers 1 and 2. The true-positive lesion appeared as wall thickening in 83% (10/12) by reader 1 and 80% (12/15) by reader 2, and as a mass in 17% (2/12) by reader 1 and 20% (3/15) by reader 2. All mass-forming lesions were located in the renal collecting system. The per-patient sensitivity and specificity were 42% and 100% in reader 1, and 54% and 96% in reader 2. CONCLUSIONS: The common abnormal finding of pure CIS in the upper urinary tract was wall thickening. Pure CIS could also appear as a mass-forming lesion when it is located in the renal collecting system. KEY POINTS: • The common abnormal finding of pure CIS in the upper urinary tract is wall thickening. Gradually progressive urothelial wall thickening and/or worsening symptoms should raise the suspicion of CIS. • Pure CIS in the upper urinary tract also appears as a mass-forming lesion when it is located in the renal collecting system. • Hydronephrosis and fat stranding play an auxiliary role in detecting pure CIS in the upper urinary tract.

[Imaging of oligometastatic disease in selected urologic cancers]. / Bildgebung oligometastasierter Tumoren des Harntraktes.

BACKGROUND: Local treatment of the primary or metastatic sites in urologic malignancies is promising when compared to systemic therapy alone, leading to the definition of a potentially curative oligometastatic state. OBJECTIVES: Comparison of imaging modalities regarding local and metastatic tumor sites in urologic cancers. METHODS: Review of comparative trials addressing quality criteria of imaging modalities. RESULTS: Depending on primary tumor and metastatic site, conventional imaging modalities such as computer tomography (CT) and bone scintigraphy still represent the standard of care in Germany. Due to superior quality criteria, hybrid-imaging techniques were widely adopted for oncological staging and particular due to the new PSMA-ligand (PSMA-PET/CT) in prostate cancer imaging. The development of new radioisotopes as well as their clinical application remains a focus of current research. CONCLUSIONS: High-quality diagnostic imaging modalities lay the groundwork for a precise definition of an oligometastatic state. By enabling treatment of the entire tumor burden, a delay of systemic therapy, longer progression-free survival, or even curative treatment may become achievable.

Effects of psoas major muscle volume in predicting the prognosis of patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

BACKGROUND: This study evaluated the impact of sarcopenia and psoas major muscle volume on the survival of patients with upper urinary tract urothelial carcinoma who had undergone radical nephroureterectomy. METHODS: We reviewed data from 110 patients treated with radical nephroureterectomy in our department between June 2007 and February 2017. Psoas major muscle volume was quantified based on computed tomography data using Synapse Vincent software. The psoas major muscle volume index was calculated as psoas major muscle volume/height squared (cm3/m2). We analysed relapse-free survival, cancer-specific survival and overall survival after radical nephroureterectomy to identify factors that predicted patient survival. RESULTS: The median psoas major muscle volume index was 121.5 cm3/m2, and the psoas major muscle volume index was <100 cm3/m2 in 34 of 110 patients (30.9%). Multivariate analysis indicated that ≥pT3-stage cancer, lymphovascular invasion and a psoas major muscle volume index of <100 cm3/m2 were independent predictors of shorter relapse-free survival, cancer-specific survival and overall survival. Using these factors, patients were stratified into three groups: low, intermediate and high risks for relapse-free survival, cancer-specific survival and overall survival. CONCLUSIONS: Low psoas major muscle volume resulting from sarcopenia, high T stage and the presence of lymphovascular invasion was associated with poor survival in patients with urinary tract urothelial carcinoma who had undergone radical nephroureterectomy, supporting the use of psoas major muscle volume as a new objective prognostic marker.

Tumor de vías excretoras urinarias superiores. Presentación de caso / Upper urinary excretory tract tumor. A case report

RESUMEN Los tumores del tracto urinario superior representan menos del 5 % de todas las neoplasias uroteliales, con un porcentaje de recurrencia superior al 90 % y una supervivencia a los 5 años que oscila entre el 30-60 %. Por tales razones se presenta el caso de un paciente de 79 años que fue ingresado en el Hospital General Universitario Dr. Gustavo Aldereguía Lima de Cienfuegos, con un cuadro clínico caracterizado por hematuria, sin otra sintomatología. Mediante estudios imagenológicos le fue diagnosticado un tumor en la pelvis del riñón derecho. Se realizó tratamiento quirúrgico, practicándose una nefrectomía total, cuyo resultado histológico fue un carcinoma de células transicionales grado II con infiltración a planos musculares. La evolución clínica fue favorable luego de un año de la cirugía. Podemos concluir que en el diagnóstico precoz tienen un papel fundamental las imágenes tomográficas, pues permitieron identificar un tumor de las vías excretoras urinarias superiores en pelvis renal derecha. Se trazó una estrategia terapéutica inicialmente quirúrgica y a continuación quimioterapia; se logró una evolución satisfactoria y contribuir a la sobrevida de este paciente.

ABSTRACT Upper urinary tract tumors represent less than 5% of all urothelial neoplasms, with a recurrence rate greater than 90% and a 5-year survival that ranges from 30-60%. Therefore a 79-years-old patient was admitted to the Dr. Gustavo Aldereguía Lima University General Hospital in Cienfuegos, with a medical history characterized by hematuria, without other symptoms. Through imaging studies, he was diagnosed with a tumor in the pelvis of the right kidney. Surgical treatment was performed and a total nephrectomy was performed, the histological result of which was a grade II transitional cell carcinoma with infiltration to the muscular planes. The clinical evolution was favorable one year after surgery. We conclude that tomographic images play a fundamental role in early diagnosis, since they allowed the identification of a tumor of the upper urinary excretory tract in the right renal pelvis. A therapeutic strategy was initially designed for surgery and then chemotherapy; a satisfactory evolution was achieved and contributes to the survival of this patient.

Efficacy and Safety of the 64Cu(II)Cl2 PET/CT for Urological Malignancies: Phase IIa Clinical Study.

PURPOSE OF THE REPORT: The aim of this study was to evaluate safety and efficacy of copper-64(II)dichloride (64Cu(II)Cl2) as a new PET tracer for urological malignancies (UMs). METHODS: Patients with UM were enrolled in a prospective study. All patients were staged with preoperative CT and 64Cu(II)Cl2 PET/CT. Patient characteristics, anatomical and functional imaging, and final histopathology were recorded. Surgical specimens for histopathological examination were collected. To determine time-activity curves for 64Cu(II)Cl2 uptake in UM and normal tissues, SUVs were calculated. The safety of 64Cu(II)Cl2 was assessed. RESULTS: Twenty-three patients were included. An administered activity of 174.7 MBq (4.72 mCi) for 64Cu(II)Cl2 was equal to 9.80 mSv of the effective dose. The median SUVmax values were 5.7, 0.9, 1.8, and 9.8 for the prostate, bladder, penis, and kidney, respectively. Median SUVmax values were higher in organs with a malignancy in comparison with healthy tissue (prostate [11.5 vs 5.3, P < 0.001], bladder [6.2 vs 0.9, P = 0.007], and penis [3.9 vs 1.3, P = 0.027]), but not in the kidneys (5.0 vs 10.4, P = 0.998). The highest area under the curve (AUC) was reported for prostate cancer (AUC, 0.978), and the lowest for penile cancer (AUC, 0.775). The detection rates based on the best suggested cutoff according to the SUVmax were 85.7% (6/7) for prostate and bladder and 83.3% (5/6) for penile cancer. Neither drug-related effects nor physiologic responses occurred, nor adverse reactions. CONCLUSIONS: 64Cu(II)Cl2 is an effective and well-tolerated tracer in patients with UM. Our results show higher SUVmax in cancer patients than in healthy subjects. Our findings suggest that 64Cu(II)Cl2 PET/CT is useful in patients affected by prostate, bladder, and penis cancer.