Atsunari Kawashima

Background: Belzutifan, a hypoxia‐inducible factor 2α (HIF‐2α) inhibitor, is effective for metastatic renal cell carcinoma (mRCC), although its cardiovascular safety profile remains unclear. Case Presentation: A 52‐year‐old woman with mRCC developed progressive dyspnea and a 6.7‐kg weight gain 27 days after initiating belzutifan as third‐line therapy. Chest radiography revealed marked cardiomegaly (cardiothoracic ratio 63.4%), and echocardiography showed preserved left ventricular ejection fraction (67.1%) with mild diastolic dysfunction and findings consistent with congestive heart failure. Intensive diuretic therapy led to rapid improvement, with the cardiothoracic ratio decreasing to 42.7% and NT‐proBNP declining from 912 to 203 pg/mL. After belzutifan rechallenge at a reduced dose, NT‐proBNP increased again and subsequently normalized after discontinuation due to disease progression. Conclusion: Belzutifan may be associated with reversible congestive heart failure with preserved ejection fraction. Cardiac evaluation should be considered in patients who develop dyspnea during belzutifan therapy.

Objective: To evaluate the prognostic significance of the Fib-4 index, ALBI and NLR (FAN) score, a composite score comprising the fibrosis-4 index, albumin-bilirubin score, and neutrophil-to-lymphocyte ratio, in patients with advanced urothelial carcinoma treated with enfortumab vedotin (EV) monotherapy. Methods: This multicenter retrospective study included 164 patients with advanced urothelial carcinoma who received EV monotherapy following prior systemic therapy. Patients were classified into three groups (0, 1, and 2–3) based on the FAN score, and progression-free, cancer-specific, and overall survival (OS) outcomes were evaluated. Results: The proportion of patients with FAN scores of 0, 1, and 2–3 were 26.8% (n = 44), 40.2% (n = 66), and 32.9% (n = 54), respectively. Median progression-free survival (PFS) was 8.1, 5.7, and 3.8 months across FAN score groups. A significant difference was observed between the FAN 0 and 2–3 groups (Holm-adjusted P = .025). Median cancer-specific survival (CSS) was 17.5, 12.2, and 7.2 months and differed significantly across groups (Holm-adjusted P = .012). OS showed a similar significant decline (Holm-adjusted P = .013). Multivariable analysis confirmed the FAN score as an independent prognostic factor for OS, CSS, and PFS. Furthermore, adding the FAN score to a model comprising conventional clinical factors improved prognostic accuracy for both CSS and OS (ΔC-index for CSS = 0.067, bootstrap P < .001; ΔC-index for OS = 0.057, bootstrap P < .001). Conclusions: The FAN score is a simple and clinically useful prognostic tool that may improve risk stratification in patients receiving EV monotherapy for advanced urothelial carcinoma.

Objectives: Prostate‐specific membrane antigen positron emission tomography (PSMA‐PET) is a sensitive imaging modality for detecting recurrent prostate cancer following definitive local therapy. However, evidence on ¹⁸ F‐labeled PSMA tracers in Japanese patients with biochemical recurrence (BCR) remains limited. The aim of this study was to examine the recurrence site distribution by [ ¹⁸ F]PSMA‐1007 PET in patients with BCR and identify factors associated with metastatic disease. Methods: We retrospectively analyzed 129 patients with prostate cancer who developed BCR after definitive local therapy and underwent [ ¹⁸ F]PSMA‐1007 PET. The primary endpoint was the distribution of recurrence sites detected by PSMA‐PET. Secondary endpoints included clinicopathological factors associated with metastatic disease. Exploratory endpoints involved outcomes of lesion‐directed therapy following PSMA‐PET. Results: PSMA‐PET identified recurrent lesions in 83% ( n = 107), including local recurrence in 40% ( n = 51), lymph node metastasis in 43% ( n = 55), and bone metastasis in 26% ( n = 33); sites were not mutually exclusive. Metastatic lesions were detectable even at low prostate‐specific antigen (PSA) levels (≤ 1.0 ng/mL). In multivariate analysis, Grade Group ≥ 4 was independently associated with metastatic disease (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.06–6.77), whereas a PSA doubling time ≥ 8.7 months was independently associated with a lower likelihood of metastasis (OR, 0.12; 95% CI, 0.05–0.27). Among 55 patients who underwent lesion‐directed therapy, PSA declines ≥ 90% were observed in 60% of cases. Conclusions: In this Japanese cohort with BCR, [ ¹⁸ F]PSMA‐1007 PET delineated recurrence patterns and identified clinicopathological factors associated with metastatic disease. PSMA‐PET may provide clinically relevant information to support individualized salvage treatment strategies.

Introduction: Persistent urinary extravasation after high‐grade renal trauma is uncommon but may require intervention. Minimally invasive, kidney‐preserving options are particularly desirable in young patients. Case Presentation: An 18‐year‐old man sustained blunt trauma in a motorcycle accident. Contrast‐enhanced computed tomography revealed renal injury with urinary extravasation. Emergency transcatheter arterial embolization was performed for hemorrhage control. Despite subsequent ureteral stenting and percutaneous drainage, urinary leakage persisted. Fistulography demonstrated a small fistulous tract between the urinoma cavity and the lower calyx. Selective embolization using N‐butyl‐2‐cyanoacrylate (NBCA) was performed, resulting in immediate resolution without complications. Conclusion: Selective NBCA embolization is a safe and minimally invasive treatment option for persistent urinary fistula after renal trauma.

Objective: This study aimed to evaluate the short-term efficacy and safety of enfortumab vedotin plus pembrolizumab (EV + P) as a first-line systemic therapy for patients with advanced urothelial carcinoma (UC) in real-world practice, with a focus on cisplatin (CDDP) eligibility. Methods: Seventy-six patients who received EV + P treatment for advanced UC at 13 institutions between November 2024 and March 2025 were retrospectively included in this study. We collected the clinical characteristics and treatment data of the patients and assessed treatment response, progression-free survival (PFS), and adverse events (AEs). Patients were divided into two groups based on CDDP eligibility, and both efficacy and safety were compared between the groups. Results: The median observation period was 5.56 (IQR, 4.77–6.21) months. Complete response was achieved in 6 (7.9%) patients receiving EV + P, partial response in 40 (52.6%), stable disease in 20 (26.3%), and progressive disease in 10 (13.2%). Six-month and median PFS rates were 80.6% and not reached, respectively. AEs of any grade and grade ≥3 occurred in 59 (77.6%) and 25 (32.9%) patients, respectively. The most frequently observed AE was skin disorders, which occurred in 36 (47.4%) patients; no grade 5 AEs were observed. Treatment response, PFS, and the cumulative incidence of AEs did not differ between CDDP-ineligible and CDDP-eligible patients. Conclusions: The short-term efficacy of EV + P treatment seemed comparable to that in previous reports, and the safety profile was acceptable, regardless of CDDP eligibility.

Introduction: Primary mediastinal seminoma is rare with a favorable prognosis when appropriately treated, and surgical resection after chemotherapy is the standard treatment. However, refusal of blood transfusion for religious reasons can limit curative surgical management. Case Presentation: A 47‐year‐old Jehovah's Witness man was found to have a 10.8‐cm anterior mediastinal tumor. Biopsy confirmed seminoma. As the patient refused transfusion, definitive chemotherapy followed by radiotherapy was selected. Three cycles of chemotherapy (etoposide, ifosfamide, and cisplatin) resulted in 44% tumor reduction and partial response. Intensity‐modulated radiotherapy of the residual tumor (36 Gy in 20 fractions) achieved complete response, maintained for 11 months without recurrence or late toxicity. Conclusion: Sequential chemotherapy followed by consolidative radiotherapy appeared to be a safe and effective option for primary mediastinal germ cell tumor in the short term when surgical resection was not feasible for religious reasons.

Introduction: Enfortumab vedotin is a Nectin‐4‐directed antibody–drug conjugate approved for metastatic urothelial carcinoma. Cardiac adverse events such as pericardial effusion or tamponade associated with enfortumab vedotin are extremely rare. Case Presentation: A 50‐year‐old man with metastatic UC developed chest pain and dyspnea 3 days after the first EV infusion, followed by rapid progression to cardiac tamponade on Day 9. Emergency pericardiocentesis and thoracoscopic pericardial fenestration drained 2400 mL of pericardial and pleural fluid. Pericardial cytology revealed inflammatory cells without malignancy, while pleural nodules confirmed urothelial carcinoma. Infectious causes were excluded, and an acute EV‐related inflammatory reaction was suspected. EV was safely resumed on postoperative Day 20, achieving a sustained partial response for 8 months without recurrence of pericardial effusion. Conclusion: This rare case highlights the potential for acute, enfortumab vedotin‐related inflammatory pericardial effusion and emphasizes the importance of early recognition and prompt surgical intervention.

The microbiome is increasingly recognized as a regulator of carcinogenesis, tumor immunity, and response to immune checkpoint inhibitors (ICIs), but its role in genitourinary cancers remains less clearly defined than in melanoma or colorectal cancer. In this review, we summarize evidence that microbiome‐related pathways influence urothelial carcinoma (UC) and renal cell carcinoma (RCC) across the continuum from tumor initiation to immunotherapy outcome. We highlight recent preclinical studies showing that gut microbial environments can causally modify urothelial carcinogenesis through carcinogen metabolism, inflammatory priming, and diet‐microbiome interactions in N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine‐based mouse models, including a newly established upper tract urothelial carcinoma mouse model, as well as emerging clinical data indicating that circulating extracellular vesicle (EV)‐associated bacterial DNA is associated with tumor immune phenotypes and ICI outcomes in UC and RCC. Because blood is a low‐biomass matrix, we use the term “circulating microbial signals” rather than “blood microbiome” and emphasize the need for contamination‐aware analysis, careful EV characterization, and external validation. Current evidence supports a framework in which microbiome‐related signals connect intestinal ecology, systemic immune tone, tumor immune contexture, and treatment response, while indicating that circulating EV‐associated bacterial DNA remains an exploratory biomarker platform.