Yuki Endo

Introduction: Sertoli cell tumors are rare testicular sex cord‐stromal tumors, and clinically malignant behavior is uncommon. We report a rapidly progressive metastatic Sertoli cell tumor associated with an APC mutation. Case Presentation: A 27‐year‐old man with familial adenomatous polyposis (FAP) presented with painless right scrotal enlargement. Computed tomography revealed a right testicular tumor and multiple pulmonary nodules suspicious for metastases. Right high inguinal orchiectomy was performed. Histopathological and immunohistochemical findings, including nuclear β‐catenin staining, supported Sertoli cell tumor. Despite bleomycin, etoposide, and cisplatin chemotherapy initially achieving stable disease, metastases progressed after three cycles. Comprehensive genomic profiling identified a pathogenic APC variant likely germline due to his FAP; however, no actionable therapeutic target was identified. Widespread systemic metastases developed. The patient died 11 months post‐orchiectomy. Conclusion: This case highlights the aggressive potential of APC ‐associated Sertoli cell tumors, characterized by metastatic presentation, limited response to chemotherapy, and a rapidly fatal course.

Introduction: Bone marrow carcinomatosis (BMC) is a rare manifestation of metastatic urothelial carcinoma (UC) that may mimic hematologic disease and cause severe cytopenia, diagnostic difficulty, and rapid clinical deterioration. Case Presentation: A 65‐year‐old man presented with back pain, thrombocytopenia, and leukoerythroblastosis. Bone marrow aspiration resulted in a dry tap, but biopsy revealed diffuse carcinoma‐cell infiltration consistent with UC, establishing BMC as the cause of marrow failure. Because of profound marrow dysfunction, reduced‐dose gemcitabine and cisplatin chemotherapy was initiated, leading to hematologic recovery and radiologic improvement. The patient subsequently received standard‐dose chemotherapy and avelumab maintenance and survived for 12.4 months after diagnosis. Conclusion: Histologic confirmation is essential to distinguish UC‐related BMC from primary hematologic disease and may support individualized systemic treatment in carefully selected patients.

Objectives: The Japanese Association for the Surgery of Trauma (JAST) renal trauma classification is widely used in Japan but has not been validated using nationwide multicenter data. This study aimed to assess its clinical validity in blunt renal trauma. Methods: We conducted a retrospective cohort study using 2019–2024 data from the Japan Trauma Data Bank (JTDB), a nationwide multicenter trauma registry. Among 1256 renal trauma patients in the JTDB, we included those with isolated JAST Type 3 blunt renal trauma (severe parenchymal renal trauma) and classified them as Type 3a or 3b. Multivariable logistic regression was used to identify factors associated with operative management (OM). Results: Among 219 patients (Type 3a trauma, n = 136; Type 3b trauma, n = 83), OM was more frequent in Type 3b (14.5% vs. 2.9%, p = 0.002). In multivariable analysis, shock on arrival (odds ratio [OR], 7.96; 95% confidence interval [CI], 2.11–30.08; p = 0.002) and Type 3b trauma (OR, 4.49; 95% CI, 1.35–14.96; p = 0.023) were independently associated with OM. Conclusions: This nationwide multicenter cohort study demonstrated that JAST Type 3b trauma was independently associated with OM in patients with blunt renal trauma. The JAST Type 3 subclassification provides clinically relevant information for predicting the need for OM.

Introduction: The combination of enzalutamide and radium‐223 has demonstrated clinical efficacy in metastatic castration‐resistant prostate cancer; however, real‐world evidence remains limited, particularly with PSA–discordant progression. Case Presentation: A 74‐year‐old man with high‐risk localized prostate cancer was treated with androgen deprivation therapy followed by definitive external beam radiotherapy. Eight months later, the disease progressed radiographically with extensive bone, nodal, and solitary liver metastases, while prostate‐specific antigen levels remained persistently low, consistent with prostate‐specific antigen–discordant progression. Bone turnover markers and disease activity markers were markedly elevated. Combination therapy with enzalutamide and radium‐223 was initiated, and six cycles of radium‐223 were completed. Following treatment, skeletal disease activity and bone turnover markers improved markedly. Apart from grade 3 anemia requiring transfusion, no severe adverse events occurred. Conclusion: This case suggests that enzalutamide combined with radium‐223 may provide clinical benefit in metastatic castration‐resistant prostate cancer with PSA–discordant progression.

Objective: This study aimed to evaluate the clinical relevance of early relative dose intensity (eRDI) during enfortumab vedotin (EV) monotherapy in patients with metastatic urothelial carcinoma (mUC) based on a Japanese real‐world multicenter cohort. Methods: We retrospectively analyzed 119 patients with mUC who received EV. The temporal trend of total relative dose intensity (tRDI), defined as the cumulative relative dose intensity during treatment, was assessed over the first 5 months. eRDI, calculated as the mean RDI over the initial 3 months, was also evaluated. Survival analyses were performed in 84 patients evaluable beyond the first radiographic assessment, excluding those with early progressive disease (PD). Patients were stratified by eRDI (≥ 80% vs. < 80%), and progression‐free survival (PFS) and overall survival (OS) were compared. Subgroup analyses were conducted according to the presence or absence of adverse event–related dose modification (AE‐related DM). Results: Dose intensity gradually declined during the early treatment phase. The eRDI was not significantly associated with PFS or OS in the PD‐excluded cohort ( n = 84). However, among patients without AE‐related DM ( n = 44), high eRDI was associated with significantly longer PFS (median 11.7 vs. 4.2 months; p = 0.001) and OS (not reached vs. 13.8 months; p = 0.021). No significant association was observed between eRDI and survival in patients with AE‐related DM. Conclusions: Although eRDI was not an overall significant prognostic factor, it showed clinical relevance in patients without AE‐related DM. These findings underscore the importance of preserving eRDI in patients with sufficient tolerability and support individualized dosing strategies for EV therapy.

Background: Avelumab maintenance therapy was approved in Japan in February 2021 for patients with unresectable locally advanced or metastatic urothelial carcinoma (la/mUC) without disease progression after platinum-based chemotherapy (PBC). We report subgroup analyses from the JAVEMACS chart review study of avelumab maintenance therapy in Japan by characteristics of first-line (1L) PBC. Methods: This multicenter, retrospective study collected data from medical charts of patients with la/mUC who received avelumab maintenance after 1L PBC. Protocol-specified subgroups defined by 1L PBC characteristics (PBC regimen, number of PBC cycles, and best overall response to PBC) were analyzed. Results: Between February 2021 and December 2023, 350 patients received avelumab maintenance. Patient characteristics were generally similar across subgroups defined by 1L PBC characteristics. In patients who received 1L gemcitabine + cisplatin ( n = 196) or gemcitabine + carboplatin ( n = 116), median overall survival (OS) was not reached (95% CI, 31.2 months-not estimable [NE]) and 24.3 months (95% CI, 19.5–30.6 months), respectively. In patients who received 1–3 cycles ( n = 68), 4 cycles ( n = 205), 5/6 cycles ( n = 61), or ≥ 7 cycles ( n = 16) of 1L PBC, median OS was 25.0 months (95% CI, 15.2 months-NE), not reached (95% CI, 29.3 months-NE), 31.2 months (95% CI, 18.0 months-NE), and 23.6 months (95% CI, 19.3 months-NE), respectively. In patients with complete response ( n = 32), partial response ( n = 180), or stable disease ( n = 138) as best response to 1L PBC, median OS was not reached (95% CI, 30.6 months-NE), 31.2 months (95% CI, 22.6 months-NE), and 26.5 months (95% CI, 20.2 months-NE), respectively. Across all subgroups, enfortumab vedotin was the most common second-line treatment after discontinuation of avelumab. Conclusions: Results from these descriptive subgroup analyses from JAVEMACS suggest that real-world outcomes with avelumab maintenance therapy are generally consistent regardless of 1L PBC regimen, number of 1L PBC cycles, or best response to 1L PBC. These findings further support the use of avelumab maintenance therapy as a standard of care for patients with la/mUC without disease progression after 1L PBC. Trial registration: NCT06412848.

Background/Objectives: The Vesical Imaging-Reporting and Data System (VI-RADS) provides high diagnostic accuracy for muscle-invasive bladder cancer; however, its prognostic value remains limited. We propose serum cytokeratin 19 fragment (CYFRA 21-1) and tumor contact length (TCL) as complementary prognostic factors. We aimed to construct a composite risk score integrating VI-RADS, CYFRA 21-1, and TCL for prognostic stratification. Methods: We retrospectively analyzed data from 101 patients with bladder cancer (BC) who underwent transurethral resection of bladder tumor (TURBT), magnetic resonance imaging, and postoperative serum CYFRA 21-1 measurement. For each factor, cut-off values were determined using receiver operating characteristic (ROC) analysis; meeting each threshold contributed one point (score range, 0–3). Overall survival (OS) was assessed using Kaplan–Meier and Cox regression analyses. Results: ROC analysis identified cut-offs of VI-RADS ≥ 3 (area under the curve [AUC] 0.779), TCL ≥ 40 mm (AUC 0.817), and CYFRA 21-1 ≥ 2.1 ng/mL (AUC 0.875). Based on these, patients were stratified into low- (0–1, n = 81), intermediate- (2, n = 12), and high-risk (3, n = 8) groups with 3-year OS rates of 95.1%, 75.0%, and 25.0%, respectively (p < 0.001). In univariate Cox regression, all factors significantly predicted poor OS: VI-RADS ≥ 3 (hazard ratio [HR], 6.51; p = 0.015), TCL ≥ 40 mm (HR, 8.36; p < 0.001), and CYFRA 21-1 ≥ 2.1 ng/mL (HR, 14.02; p < 0.001). In multivariate analysis, only CYFRA 21-1 remained independently significant (HR, 11.80; p < 0.001). Conclusions: A composite risk score combining VI-RADS, TCL, and CYFRA 21-1 effectively stratified patients with BC into distinct groups using minimally invasive, peri-TURBT assessments. Prospective multicenter validation is warranted.

Background: Current guidelines lack recommendations for serum tumor markers in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). This study assessed the potential of the postoperative serum C-terminus of cytokeratin 19 (CYFRA21-1, CYFRA) level, hereafter referred to as poCY, as a predictor of early progression in patients treated with RNU. Methods: Overall, 117 patients were categorized into the high group (HG) or low group (LG) based on a poCY cutoff level of 3.5 ng/mL after excluding those who did not meet the inclusion criteria. Kaplan-Meier curves and log-rank tests were used to measure cancer-specific survival (CSS) and progression-free survival (PFS) rates. Multivariate analysis was performed using the Cox proportional hazards model. Results: During a median follow-up of 34 months, the 5-year CSS and PFS rates were 79% and 66%, respectively. The HG had a significantly worse CSS and 2-year PFS than the LG. Multivariate analyses identified poCY and lymph node involvement (LNI) as independent prognostic factors. Regarding the 2-year PFS, poCY, LNI, and resection margin status (RM) emerged as independent prognostic factors. Conclusions: poCY, LNI, and RM predicted early progression following RNU in patients with UTUC. Patients with elevated poCY may benefit from adjuvant chemotherapy, irrespective of their pathological findings.

We investigated the clinical significance of positive surgical margins (PSMs) in index tumors following radical prostatectomy (RP), with particular attention to the tumor’s zonal origin. Among 1148 patients with localized prostate cancer who underwent RPs, 973 were included after excluding those who received perioperative therapy or had incomplete data. Index tumors were categorized by zonal origin: transition zone, peripheral zone, or central zone (CZ). Overall, PSMs were observed in 26.4% of index tumors. Although CZ index tumors were relatively uncommon (6.5%), they exhibited the highest PSM rate (42.9%) and showed the most aggressive pathological features. The 5-year biochemical recurrence (BCR)-free survival rate was significantly lower in patients with PSMs in index tumors than in those with negative surgical margins (45.6% vs. 86.8%, p < 0.0001). Notably, patients with PSMs in CZ index tumors had the worst outcomes, with a 5-year BCR-free survival rate of 22.0%. Multivariate analysis identified PSMs in index tumors as an independent predictor of BCR (HR: 3.4; 95% CI: 2.5–4.5), with a similar trend observed in early recurrence. These findings highlight the prognostic significance of PSMs in index tumors during RP, especially in CZ tumors, and emphasize the importance of securing local control in these cases.

The Vesical Imaging Reporting and Data System (VI-RADS) is used to detect muscle-invasive bladder cancer, with emerging prognostic implications. Integrating imaging parameters with molecular biomarkers may improve risk stratification in bladder cancer. This study evaluated whether combining VI-RADS scores with serum cytokeratin fragment 19 (CYFRA 21-1) levels—a clinically relevant biomarker for bladder cancer—could improve overall survival (OS) prediction. We retrospectively analyzed 134 patients who underwent transurethral resection of bladder tumors, magnetic resonance imaging, and postoperative serum CYFRA 21-1 measurements. In total, 15 cancer-specific deaths were observed during follow-up. Receiver operating characteristic curve analysis identified optimal prognostic cut-off values: VI-RADS score ≥ 4 and CYFRA 21-1 level ≥ 1.8 ng/mL. The 1-, 2-, and 3-year OS in patients with both high VI-RADS scores and CYFRA 21-1 levels were 42.9%, 16.7%, and 8.3%, respectively, significantly lower than those in other groups (p < 0.001, 0.002, and 0.003, respectively). Multivariate Cox proportional hazards analysis demonstrated that such patients had the poorest OS (hazard ratio: 7.51; p = 0.002). This suggests that combining VI-RADS and CYFRA 21-1 improves prognostic accuracy in bladder cancer, demonstrating potential clinical utility by informing individualized treatment strategies; however, limitations include the retrospective study design and absence of external validation.