A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL).

BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. METHODS: This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. DISCUSSION: This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358.

Patterns of recurrence in genuine and induced oligometastatic castration-resistant prostate cancer treated with progressive site-directed therapy.

OBJECTIVES: To describe oncological outcomes after progressive site-directed therapy (PSDT) in genuine and induced oligometasatic (OM)-castration-resistant prostate cancer (CRPC). METHODS: Thirty-seven patients with OM-CRPC treated with PSDT were retrospectively analyzed, and oncological outcomes and recurrence patterns on whole-body diffusion-weighted MRI (WB-DWI) were evaluated. RESULTS: Twenty-two (59%) were classified as genuine OM-CRPC and 15 (41%) as induced OM-CRPC. A 50% decline in PSA after PSDT was observed in 21 (95%) genuine OM-CRPCs and 7 (47%) induced OM-CRPCs (p = 0.0005). At a median observation period of 7.3 months, median PSA progression-free survival were 10.9 months in the genuine OM-CRPCs and 4.8 months in the induced OM-CRPCs (p = 0.015). Among the patients who developed PSA progression after PSDT, 11 of 15 in the genuine OM-CRPCs (73%) and 11 of 14 in the induced OM-CRPCs (79%) underwent WB-DWI at PSA progression. The median numbers of newly detected metastases were 2 (range: 1-5) in the genuine OM-CRPCs and 4 (range: 1-40) in the induced OM-CRPCs (p = 0.049). Only one new metastasis appeared in 5 patients from the genuine OM-CRPCs (46%) and 1 from the induced OM-CRPCs (9.1%, p = 0.048). In 7 of 9 patients from the genuine OM-CRPCs (78%) and 7 of 8 patients from the induced OM-CRPCs (88%) who had bone metastases alone, the newly detected metastasis limited to the bone. CONCLUSIONS: Genuine OM-CRPC had better oncological outcomes after PSDT than induced OM-CRPC, and the number of lesions detected at recurrence was limited. Induced OM-CRPC might be a disseminated condition with micrometastases at OM diagnosis.

Metastatic Diffusion Volume Based on Apparent Diffusion Coefficient as a Prognostic Factor in Castration-Resistant Prostate Cancer.

BACKGROUND: Whole-body diffusion-weighted MRI (WB-DWI) is useful for assessing disease activity in castration-resistant prostate cancer (CRPC). MET-RADS-P is a subjective assessment-based reporting system proposed to standardize the interpretation of WB-DWI. However, a quantitative evaluation of WB-DWI has not been fully investigated. PURPOSE: To investigate the validity, and analyze the prognostic value, of quantitative evaluation of WB-DWI based on apparent diffusion coefficient (ADC) values for CRPC. STUDY TYPE: Retrospective. POPULATION: Sixty-six patients with CRPC. The median age was 75 years. During the median follow-up period of 25.2 months, 23 of 66 patients (34.8%) died of prostate cancer. FIELD STRENGTH/SEQUENCE: A 1.5 T WB-DWI was used with two b-values (0 s/mm2 -1000 s/mm2 ). A single-shot echo-planar imaging sequence was used. ASSESSMENT: WB-DWI were evaluated by three readers according to MET-RADS-P scoring system. Using imaging software, Attractive BDScore, tumor diffusion volume (mDV) and ADC value of metastatic lesion (mADC) was calculated by two readers. The mDV was calculated with ADC values (×10-3  mm2 /sec) of 0.4-0.9 (mDV0.4-0.9 ), 0.9-1.4 (mDV0.9-1.4 ), and 1.4-1.8 (mDV1.4-1.8 ), respectively. STATISTICAL TESTS: Spearman's rank correlation coefficient was used to assess the correlation. The relationships between the variables with cancer-specific survival (CSS) were evaluated. Multivariate analysis was performed using the Cox proportional hazards model. RESULTS: mDVs showed a strong positive correlation with MET-RADS-P scores (r = 0.90/0.87, P < 0.05 for both). mDV showed a statistically significant association with CSS (hazard ratio [HR]: 1.01, P < 0.05). When the mDVs calculated based on the ADC values were included, mDV0.4-0.9 (HR: 1.02, P < 0.05) and the number of therapeutic lines (HR: 1.35, P < 0.05) were significant independent indicators of CSS shortening. CONCLUSION: Assessment of metastatic tumor volume based on ADC values can be used in the prognostic evaluation of patients with CRPC. WB-DWI might be a potential prognostic imaging biomarker for CRPC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Clinical utility of the Vesical Imaging-Reporting and Data System for muscle-invasive bladder cancer between radiologists and urologists based on multiparametric MRI including 3D FSE T2-weighted acquisitions.

OBJECTIVES: To investigate the clinical utility of the Vesical Imaging-Reporting and Data System (VI-RADS) by comparing its diagnostic performance for muscle-invasive bladder cancer (MIBC) between radiologists and urologists based on multiparametric MRI, including three-dimensional (3D) fast spin-echo (FSE) T2-weighted acquisitions. METHODS: This study included 66 treatment-naïve patients (60 men, 6 women; mean age 74.0 years) with pathologically proven bladder cancer who underwent multiparametric MRI, including 3D FSE T2-weighted imaging, before transurethral bladder tumour resection between January 2010 and November 2018. The MRI scans were categorised according to the five-point VI-RADS score by four independent readers (two board-certified radiologists and board-certified urologists each), blinded to the histopathological findings. The VI-RADS scores were compared with the postoperative histopathological diagnosis. Interobserver agreement was assessed using weighted kappa coefficients. ROC analysis and generalised estimating equations were used to evaluate the diagnostic performance. RESULTS: Forty-nine (74.2%) and 17 (25.8%) tumours were confirmed to be non-MIBC and MIBC, respectively, based on pathological examination. The interobserver agreement was good-to-excellent between all pairs of readers (range, 0.73-0.91). The urologists' sensitivity/specificity values for DCE-MRI VI-RADS scores were significantly lower than those of radiologists. No significant differences were observed for the overall VI-RADS score. The AUC for the overall VI-RADS score was 0.94, 0.92, 0.89, and 0.87 for radiologists 1 and 2 and urologists 1 and 2, respectively. CONCLUSIONS: The VI-RADS score, based on multiparametric MRI including 3D FSE T2-weighted acquisitions, can be useful for radiologists and urologists to determine the bladder cancer muscle invasion status preoperatively. KEY POINTS: • VI-RADS (using multiparametric MRI including 3D FSE T2-weighted acquisitions) achieves good to excellent interobserver agreement and has similar diagnostic performance for detecting muscle invasion by both radiologists and urologists. • The diagnostic performance of the overall VI-RADS score is high for both radiologists and urologists, particularly due to the dominant effect of diffusion-weighted imaging on the overall VI-RADS score. • The sensitivity and specificity values of the T2WI VI-RADS scores for four readers in our study (using 3D FSE T2-weighted acquisitions) were similar (with slightly higher specificity values) to previously published results (using 2D FSE T2-weighted acquisitions).

Potential of Perfusion Magnetic Resonance Imaging to Predict Residual Renal Function after Radical Nephroureterectomy.

INTRODUCTION: The diffusion-weighted imaging (DWI) technique with intravoxel incoherent motion model enables the estimation of capillary blood volume as a perfusion-related parameter- (PP-) value. Therefore, the PP-value of the kidney theoretically reflects renal capillary blood volume. We analyzed the usefulness of the PP-value in estimating postoperative renal function in upper-tract urothelial carcinoma (UTUC) patients. METHODS: Forty-eight consecutive patients who underwent magnetic resonance imaging before radical nephroureterectomy from 2011 to 2018 were analyzed. A PP-map displaying PP-values on a pixel-by-pixel basis was created from DWI signals (b-values of 0, 500, and 1,000 s/mm2). Two readers independently analyzed the renal PP-value. DWI-based split renal function (SRF) of the intact kidney was calculated by splitting serum Cr-based preoperative estimated glomerular filtration rates (eGFRs). The predictive accuracy of the method was evaluated using renography as the reference standard. RESULTS: Interobserver analysis revealed an excellent correlation value of 0.97. The SRF value showed a good linear correlation with the observed postoperative eGFR (r = 0.76, p < 0.001). The predictive accuracy of the DWI-based method was similar to that of the nuclear-based method. CONCLUSION: This DWI-based evaluation of capillary blood volume provides a noninvasive tool for predicting the postoperative renal function, thereby facilitating the management of UTUC patients.

Whole-body diffusion-weighted magnetic resonance imaging: Diagnosis and follow up of prostate cancer and beyond.

The diffusion-weighted imaging signal is derived from the motion of water molecules. It represents the physiological characteristics of tissue and is an essential imaging sequence for prostate cancer. Whole-body diffusion-weighted imaging facilitates the assessment of pathological conditions throughout the body. The concept of diffusion-weighted whole-body imaging with background body signal suppression and technological advances has led to routine clinical deployment of whole-body diffusion-weighted imaging as a one-step staging tool for prostate cancer. Furthermore, whole-body diffusion-weighted imaging has the potential to reveal the state of osseous lesions, for which conventional imaging techniques are suboptimal for monitoring the response to therapy, and extraosseous lesions, and holds promise as a new imaging-based therapeutic approach. This article reviews the basics of whole-body diffusion-weighted imaging, and focuses on application of whole-body diffusion-weighted imaging in the clinical management of prostate cancer at various stages in the course of the disease.

Renal epithelioid angiomyolipoma: Incidence in a Japanese cohort and diagnostic utility of diffusion-weighted magnetic resonance imaging.

OBJECTIVES: To show the epidemiological characteristics of epithelioid angiomyolipoma in a Japanese population, and to establish the preoperative diagnosis method of epithelioid angiomyolipoma. METHODS: Among the 855 tumors of patients who underwent partial/radical nephrectomy or renal biopsy for presumed renal cell carcinoma between 2007 and 2018, 39 renal tumors were diagnosed as nonclassical angiomyolipoma, including epithelioid angiomyolipoma and fat-poor angiomyolipoma. We retrospectively evaluated the incidence of epithelioid angiomyolipoma. Furthermore, we analyzed computed tomography and magnetic resonance imaging results, including diffusion-weighted magnetic resonance imaging findings of epithelioid angiomyolipoma and fat-poor angiomyolipoma. RESULTS: The incidence of epithelioid angiomyolipoma (n = 7) was 17.9% of surgically resected non-classical angiomyolipoma. The radiological appearance of epithelioid angiomyolipoma was hyperattenuating on unenhanced computed tomography images with iso or low intensity on T2-weighted magnetic resonance imaging. The mean apparent diffusion coefficient value of the solid component in epithelioid angiomyolipoma was significantly lower than that in fat-poor angiomyolipoma (median 0.79 × 10-3 vs 1.07 × 10-3 mm2 /s, P = 0.0019). CONCLUSIONS: The proportion of epithelioid angiomyolipoma in our Japanese cohort was equivalent to that of the reported series in the USA. The apparent diffusion coefficient value is potentially useful to differentiate between epithelioid angiomyolipoma and fat-poor angiomyolipoma. Further research is required to establish the imaging diagnostic criteria for epithelioid angiomyolipoma.

Usefulness of the inchworm sign on DWI for predicting pT1 bladder cancer progression.

OBJECTIVE: To evaluate the significance of the presence or absence of an "inchworm sign" on DWI for the recurrence and progression of T1 bladder cancer. MATERIALS AND METHODS: We retrospectively analyzed 91 patients with pT1 urothelial carcinoma who underwent DWI prior to transurethral resection between 2007 and 2016. DWI of the dominant tumors was scrutinized for inchworm signs at b = 1000 s/mm2. The association of the presence of the inchworm sign with progression and recurrence was analyzed; progression was defined as recurrence to stage T2 or higher and/or N+, and/or M1. RESULTS: An inchworm sign was seen in 65 cases (71%), while it was absent in 26 cases. Among the 65, 25 (38%) had confirmed tumor recurrence, while in the remaining 26, 14 (54%) had confirmed recurrence (median time post TURB = 7.9 and 10.1 months for each). At the time of recurrence, the tumor had progressed in one (2%) inchworm-sign-positive and seven (27%) inchworm-sign-negative cases. The progression rate of inchworm-sign-negative cases was significantly higher than that of inchworm-sign-positive cases (hazard ratio = 17.2, p = 0.0017), whereas there was no significant difference in the recurrence rate between two groups. The absence of an inchworm sign and histological grade 3 were independent risk factors for progression (p < 0.001 and 0.010, respectively). CONCLUSIONS: The absence of an inchworm sign on DWI was a significant prognostic factor for progression of T1 bladder cancer. Morphological evaluation of DWI signals may therefore be a useful adjunct to preoperative assessment of biological aggressiveness. KEY POINTS: • An inchworm sign is a simple diagnostic criterion that characterizes only the shape of the tumor signal on DWI, and potentially serves as an imaging biomarker to predict clinical aggressiveness. • The absence of an inchworm sign on DWI is a significant indicator of progression of T1 bladder cancer.

Acute generalized pustular bacterid concomitant with erythema nodosum, polyarthritis, and Achilles tendinitis.

We report a case of acute generalized pustular bacterid (AGPB) concomitant with erythema nodosum (EN), polyarthritis, and Achilles tendinitis. The patient was admitted with a complaint of fever, widespread plural pustules, erythema, and polyarthralgia. Histopathological examination of the skin lesions demonstrated features of AGBP and EN. Although arthralgia and AGPB can be recognized together, EN and Achilles tendinitis are rare manifestations seen in patients with AGPB. In this case report, we suggest arthralgia, EN, and Achilles tendinitis could coexist with AGPB.

Pneumocystis jirovecii pneumonia developed in a patient with rheumatoid arthritis after 14 weeks of iguratimod add-on to treatment with methotrexate and etanercept.

A 66-year-old woman who had rheumatoid arthritis and underwent a long-term treatment with methotrexate and etanercept developed Pneumocystis jirovecii pneumonia (PCP) 3 months after iguratimod add-on. Although most rheumatologists might have the impression that iguratimod has less toxicity and immunosuppressive effect compared with methotrexate and biologic disease-modifying antirheumatic drugs, this case suggests that iguratimod may increase the risk of PCP, especially in combination with other drugs.

[A Case of Leptospirosis in which the Causative Pathogen was Detected Using Cerebrospinal Fluid PCR Eight Days after Onset].

We report a patient with leptospirosis caused by infection with Leptospira interrogans serovar Rachmati. A 30-year-old Japanese man took part in a survival camp on Iriomote Island, Okinawa, from July 9 to July 15, 2014. During the camp, he swam in the river and kayaked. He developed a high fever and fatigue 7 days after completing his trip and was admitted to our hospital on July 22. On admission, he complained of a posterior cervical pain and a loss of appetite. Laboratory findings revealed granulocytosis, mildly elevated AST and ALT levels, elevated BUN and Cr levels, and a significantly elevated CRP level. No pathogenic bacteria were isolated from blood, urine, or cerebrospinal fluid cultures. We included leptospirosis in the differential diagnosis because of the patient's history of participating in a survival camp on Iriomote Island. Minocycline 200 mg, p.o. showed an excellent efficacy. The Leptospira flagellar gene FlaB was detected using a cerebrospinal fluid PCR. A microscopic agglutination test (MAT) during the convalescent stage demonstrated significant increases in antibodies against L. interrogans serovar Rachmati, confirming the diagnosis of leptospirosis. A medical history including occupation and recent travel history, and an adequate specimen sampling are crucial for the accurate and early diagnosis of leptospirosis.

Evaluation of the clinical behavior of unclassified renal cell carcinoma and its imaging findings on computed tomography and magnetic resonance imaging based on World Health Organization (WHO) 2022.

OBJECTIVES: To ascertain the clinical behaviors of unclassified renal cell carcinoma (RCC) and its characteristic imaging findings on CT and MRI. METHODS: Subjects in this retrospective study were 10 patients who had received a histological diagnosis of unclassified RCC based on World Health Organization (WHO) 2022 and who had undergone CT and/or MRI prior to surgery. In terms of clinical behaviors, TNM classification, stage, postoperative recurrence, time to recurrence, and postoperative survival were evaluated. In terms of imaging findings, tumor size, growth pattern, CT density, dynamic contrast-enhancement (DCE) pattern, internal appearance, presence of a pseudocapsule, and signal intensity on MRI were evaluated. We compared clinical behaviors and imaging findings, and investigated associations between them. RESULTS: One patient could not be followed-up due to death from other causes. Postoperative recurrence was observed in 4 patients, all of whom had Stage 3 RCC. In the remaining 5 patients without recurrence, all 5 patients showed Stage 2 or below. On imaging, unclassified RCC tended to be large (58.7 mm) and solid (100%), and heterogeneous interiors (80%), cystic degeneration (80%) and high intensity on diffusion-weighted imaging (DWI) (71.4%) were common. Comparing patients with and without recurrence, the following findings tended to differ between recurrence and recurrence-free groups: tumor size (73.4 ± 33.9 mm vs. 50.2 ± 33.9 mm, P = 0.286), growth pattern (invasive: 100% vs. 0%, expansive: 0% vs. 100%, P = 0.008 each), DCE pattern (progressive enhancement pattern, 66.7% vs. 0%, washout pattern, 0% vs. 66.7%, P = 0.135 each) and presence of a pseudocapsule (25% vs. 80%, P = 0.167). CONCLUSION: The clinical behavior of unclassified RCC varies widely. Although imaging findings are also variable, findings of large, heterogeneous tumors with cystic degeneration and high intensity on DWI were common. Several imaging findings such as large size, invasive growth, progressive enhancement pattern and no pseudocapsule may enable prediction of prognosis in unclassified RCC.

Inguinal lymph node metastases from prostate cancer: clinical, pathology, and multimodality imaging considerations.

Objective: To investigate clinical, pathology, and imaging findings associated with inguinal lymph node (LN) metastases in patients with prostate cancer (PCa). Materials and Methods: This was a retrospective single-center study of patients with PCa who underwent imaging and inguinal LN biopsy between 2000 and 2023. We assessed the following aspects on multimodality imaging: inguinal LN morphology; extrainguinal lymphadenopathy; the extent of primary and recurrent tumors; and non-nodal metastases. Imaging, clinical, and pathology features were compared between patients with and without metastatic inguinal LNs. Results: We evaluated 79 patients, of whom 38 (48.1%) had pathology-proven inguinal LN metastasis. Certain imaging aspects- short-axis diameter, prostate-specific membrane antigen uptake on positron-emission tomography, membranous urethra involvement by the tumor, extra-inguinal lymphadenopathy, and distant metastases-were associated with pathology-proven inguinal LN metastases (p < 0.01 for all). Associations with long-axis diameter, fatty hilum, laterality, and uptake of other tracers on positronemission tomography were not significant (p = 0.09-1.00). The patients with metastatic inguinal LNs had higher prostate-specific antigen levels and more commonly had castration-resistant PCa (p < 0.01), whereas age, histological grade, and treatment type were not significant factors (p = 0.07-0.37). None of the patients had inguinal LN metastasis in the absence of locally advanced disease with membranous urethra involvement or distant metastasis. Conclusion: Several imaging, clinical, and pathology features are associated with inguinal LN metastases in patients with PCa. Isolated metastasis to inguinal LNs is extremely rare and unlikely to occur in the absence of high-risk imaging, clinical, or pathology features.

Objetivo: Investigar achados clinicopatológicos e de imagem associados a metástases linfonodais inguinais em pacientes com câncer de próstata (CaP). Materiais e Métodos: Estudo retrospectivo de uma única instituição de pacientes com CaP submetidos a exames de imagem e biópsia inguinal de linfonodos em 2000­2023. A imagem multimodalidade foi avaliada para morfologia inguinal do linfonodo, linfadenopatia fora da região inguinal, extensão do CaP primário/recorrente e sítios metastáticos não nodais. Características de imagem e clinicopatológicas foram comparadas entre pacientes com e sem linfonodos inguinais metastáticos pela patologia. Resultados: Entre 79 pacientes estudados, 38 (48,1%) apresentaram metástase inguinal de linfonodo comprovada patologicamente. Certos achados de imagem ­ diâmetro do eixo curto, captação do antígeno de membrana prostático específico na tomografia por emissão de pósitrons, envolvimento da uretra membranosa pelo tumor, linfadenopatia fora da região inguinal e metástases a distância ­ foram associados com metástases inguinais no linfonodo pela patologia (p < 0,01). Diâmetro de eixo longo, hilo gorduroso, lateralidade, captação em outros traçadores de tomografia por emissão de pósitrons não foram significativos (p = 0,09­1,00). Clinicopatologicamente, os pacientes com linfonodos inguinais metastáticos apresentaram maior antígeno prostático específico e foram mais resistentes à castração (p < 0,01); idade, grau histológico e tipo de tratamento não foram estatisticamente significantes (p = 0,07­0,37). Nenhum paciente apresentou metástase inguinal isolada no linfonodo na ausência de doença localmente avançada com envolvimento da uretra membranosa ou metástase a distância. Conclusão: Várias características de imagem e clinicopatológicas foram associadas a metástases em LNs inguinais em pacientes com CaP. A metástase isolada para os LNs inguinais é extremamente rara e é improvável que ocorra na ausência de características de imagem e clinicopatológicas de alto risco.

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.

Pictorial review of multiparametric MRI in bladder urothelial carcinoma with variant histology: pearls and pitfalls.

Bladder cancer (BC), predominantly comprising urothelial carcinomas (UCs), ranks as the tenth most common cancer worldwide. UCs with variant histology (variant UC), including squamous differentiation, glandular differentiation, plasmacytoid variant, micropapillary variant, sarcomatoid variant, and nested variant, accounting for 5-10% of cases, exhibit more aggressive and advanced tumor characteristics compared to pure UC. The Vesical Imaging-Reporting and Data System (VI-RADS), established in 2018, provides guidelines for the preoperative evaluation of muscle-invasive bladder cancer (MIBC) using multiparametric magnetic resonance imaging (mpMRI). This technique integrates T2-weighted imaging (T2WI), dynamic contrast-enhanced (DCE)-MRI, and diffusion-weighted imaging (DWI) to distinguish MIBC from non-muscle-invasive bladder cancer (NMIBC). VI-RADS has demonstrated high diagnostic performance in differentiating these two categories for pure UC. However, its accuracy in detecting muscle invasion in variant UCs is currently under investigation. These variant UCs are associated with a higher likelihood of disease recurrence and require precise preoperative assessment and immediate surgical intervention. This review highlights the potential value of mpMRI for different variant UCs and explores the clinical implications and prospects of VI-RADS in managing these patients, emphasizing the need for careful interpretation of mpMRI examinations including DCE-MRI, particularly given the heterogeneity and aggressive nature of variant UCs. Additionally, the review addresses the fundamental MRI reading procedures, discusses potential causes of diagnostic errors, and considers future directions in the use of artificial intelligence and radiomics to further optimize the bladder MRI protocol.

Profiling Fibroblast Growth Factor Receptor 3 Expression Based on the Immune Microenvironment in Upper Tract Urothelial Carcinoma.

BACKGROUND: Although several studies have shown favorable outcomes in upper tract urothelial carcinoma (UTUC) with fibroblast growth factor receptor 3 (FGFR3) mutations and/or expression, the relationship between immune cell markers and FGFR3 expression remains unknown. OBJECTIVE: To clarify the FGFR3-based immune microenvironment and investigate biomarkers to predict the treatment response to pembrolizumab (Pem) in patients with UTUC. DESIGN, SETTING, AND PARTICIPANTS: We conducted immunohistochemical staining in 214 patients with UTUC. The expression levels of FGFR3, CD4, CD8, CD68, CD163, CD204, and programmed cell death ligand 1 (PD-L1) were examined. INTERVENTION: All UTUC patients underwent radical nephroureterectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the relationship between these immune markers and patient prognosis. RESULTS AND LIMITATIONS: A total of 109 (50.9%) patients showed high FGFR3 expressions and a favorable prognosis compared with the remaining patients. Among the six immune markers, CD8 high expression was an independent favorable factor, whereas CD204 expression was an independent prognostic factor for cancer death. From the FGFR3-based immune clustering, three immune clusters were identified. Cluster A showed low FGFR3 with tumor-associated macrophage-rich components (CD204+) followed by a poor prognosis due to a poor response to Pem. Cluster B showed low FGFR3 with an immune hot component (CD8+), followed by the most favorable prognosis owing to a good response to Pem. Cluster C showed high FGFR3 expression but an immune cold component, followed by a favorable prognosis due to the high FGFR3 expression, but a poor response was confirmed with Pem. CONCLUSIONS: Although most patients exhibit a poor response to Pem, individuals with low FGFR3 expression and immune hot status may benefit clinically from Pem treatment. PATIENT SUMMARY: We conducted immunohistochemical staining to evaluate fibroblast growth factor receptor 3 (FGFR3)-related immune microenvironment by evaluating the expressions of CD4, CD8, CD68, CD163, CD204, and PD-L1 in 214 upper tract urothelial carcinoma patients. We identified three distinct immune clusters based on FGFR3 expressions and found that patients with a low FGFR3 expression but immune hot status received the maximum benefit from an immune checkpoint inhibitor.

Evaluating residual tumor after neoadjuvant chemotherapy for muscle-invasive urothelial bladder cancer: diagnostic performance and outcomes using biparametric vs. multiparametric MRI.

BACKGROUND: Neoadjuvant chemotherapy (NAC) before radical cystectomy is standard of care in patients with muscle-invasive bladder cancer (MIBC). Response assessment after NAC is important but suboptimal using CT. We assessed MRI without vs. with intravenous contrast (biparametric [BP] vs. multiparametric [MP]) for identifying residual disease on cystectomy and explored its prognostic role. METHODS: Consecutive MIBC patients that underwent NAC, MRI, and cystectomy between January 2000-November 2022 were identified. Two radiologists reviewed BP-MRI (T2 + DWI) and MP-MRI (T2 + DWI + DCE) for residual tumor. Diagnostic performances were compared using receiver operating characteristic curve analysis. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with disease-free survival (DFS). RESULTS: 61 patients (36 men and 25 women; median age 65 years, interquartile range 59-72) were included. After NAC, no residual disease was detected on pathology in 19 (31.1%) patients. BP-MRI was more accurate than MP-MRI for detecting residual disease after NAC: area under the curve = 0.75 (95% confidence interval (CI), 0.62-0.85) vs. 0.58 (95% CI, 0.45-0.70; p = 0.043). Sensitivity were identical (65.1%; 95% CI, 49.1-79.0) but specificity was higher in BP-MRI compared with MP-MRI for determining residual disease: 77.8% (95% CI, 52.4-93.6) vs. 38.9% (95% CI, 17.3-64.3), respectively. Positive BP-MRI and residual disease on pathology were both associated with worse DFS: hazard ratio (HR) = 4.01 (95% CI, 1.70-9.46; p = 0.002) and HR = 5.13 (95% CI, 2.66-17.13; p = 0.008), respectively. Concordance between MRI and pathology results was significantly associated with DFS. Concordant positive (MRI+/pathology+) patients showed worse DFS than concordant negative (MRI-/pathology-) patients (HR = 8.75, 95% CI, 2.02-37.82; p = 0.004) and compared to the discordant group (MRI+/pathology- or MRI-/pathology+) with HR = 3.48 (95% CI, 1.39-8.71; p = 0.014). CONCLUSION: BP-MRI was more accurate than MP-MRI for identifying residual disease after NAC. A negative BP-MRI was associated with better outcomes, providing complementary information to pathological assessment of cystectomy specimens.