Hiroshi Yaegashi

Objective: To determine whether response durability refines the clinical interpretation of objective response (OR) to erdafitinib in patients with fibroblast growth factor receptor (FGFR)‐altered metastatic urothelial carcinoma. Patients and Methods: This post hoc exploratory analysis used de‐identified individual participant‐level data from THOR trial Cohort 1 (ClinicalTrials.gov identifier: NCT03390504) The safety population included 247 patients treated with erdafitinib ( n = 135) or chemotherapy ( n = 112). Response–durability phenotypes were defined by integrating best overall response with a 6‐month progression‐free survival threshold: durable OR, durable disease control, non‐durable OR, and limited benefit. Phenotype distributions were compared between treatment arms. Overall survival (OS) was evaluated using Kaplan–Meier and Cox analyses, including 6‐month landmark analyses to reduce guarantee‐time bias. Results: Erdafitinib shifted patients toward more favourable response–durability phenotypes compared with chemotherapy. Limited benefit was less frequent with erdafitinib than with chemotherapy (45.9% vs 75.9%; P < 0.001), whereas OR phenotypes were more common. In erdafitinib‐treated patients, 6‐month landmark OS differed significantly across phenotypes ( P < 0.001). Durable benefit was associated with longer landmark OS than non‐durable benefit (non‐durable vs durable benefit: hazard ratio [HR] 4.09, 95% confidence interval [CI] 2.24–7.49). Among objective responders, non‐durable OR was associated with substantially worse landmark OS than durable OR (HR 8.71, 95% CI 3.30–22.96). Conclusions: In patients with FGFR‐altered metastatic urothelial carcinoma treated with erdafitinib, Response Evaluation Criteria in Solid Tumours (RECIST) OR alone did not fully capture clinically meaningful benefit. Incorporating response durability provided stronger survival stratification and may improve the interpretation of treatment benefit after FGFR‐targeted therapy.

Objectives: To evaluate treatment‐effect heterogeneity associated with local therapy in nonmetastatic advanced prostate cancer and develop a simple hypothesis‐generating framework to estimate the expected absolute survival benefit associated with local therapy. Methods: This multicentre retrospective cohort study included 1198 patients with clinical T3–4N0M0 or cN1M0 prostate cancer from the Kaga Million Uro‐Oncology Network (KAMU‐ON). Multivariable Cox models evaluated the association between local therapy and overall survival. Treatment‐effect heterogeneity was assessed using interaction analyses. Adjusted 5 year overall survival and absolute survival benefit were estimated by g ‐computation. A simple clinical framework based on clinicopathological variables was derived from the subgroup analyses. Results: Local therapy was independently associated with improved overall survival (adjusted hazard ratio 0.32, 95% confidence interval 0.21–0.48; p < 0.001). Significant treatment‐effect heterogeneity was observed according to clinical T stage ( p for interaction = 0.030). The greatest absolute survival benefits were observed in patients with clinical T3b/T4 disease (20.3 percentage points) and Grade Group 4–5 disease (17.2 percentage points). The framework stratified the estimated absolute survival benefit from 0.1 to 19.5 percentage points across score groups ( p for interaction = 0.041; p for trend = 0.023). Conclusions: The survival benefit associated with local therapy varied substantially across patients with nonmetastatic advanced prostate cancer. This hypothesis‐generating framework may provide estimates of expected treatment benefit and support individualized treatment discussions.

Objectives: Low body mass index has been reported as a risk factor for inguinal hernia after robot‐assisted radical prostatectomy, but whether this association reflects reduced fat mass or reduced muscle mass remains unclear. This study aimed to determine which three‐dimensional computed tomography‐derived body composition parameter is associated with postoperative inguinal hernia. Methods: We retrospectively analyzed 280 patients who underwent robot‐assisted radical prostatectomy between February 2016 and January 2024 and had available preoperative non‐contrast computed tomography images. Visceral fat volume, subcutaneous fat volume, and psoas muscle volume were quantified using three‐dimensional analysis. Cox proportional hazards models were used to evaluate factors associated with postoperative inguinal hernia. Results: Inguinal hernia occurred in 23 patients (8%). Patients who developed inguinal hernia had lower BMI, visceral fat volume, and subcutaneous fat volume than those who did not, whereas psoas muscle volume did not differ significantly. In the multivariable visceral fat volume model, greater visceral fat volume was associated with a lower risk of inguinal hernia (HR per 1 000‐cm ³ increase, 0.597; 95% CI, 0.445–0.800; p < 0.001). In a model including both body mass index and visceral fat volume, visceral fat volume remained significant (HR, 0.626; 95% CI, 0.408–0.961; p = 0.032), whereas body mass index did not. Conclusions: Lower visceral fat volume was associated with a higher risk of inguinal hernia after robot‐assisted radical prostatectomy. These findings may provide insight into the body composition factors relevant to the previously reported association between low body mass index and postoperative inguinal hernia.

Objectives: This study evaluated and compared the prognostic significance of three different computed tomography (CT)‐based radiological indices of sarcopenia—skeletal muscle index (SMI), psoas muscle index (PMI), and three‐dimensional (3D) psoas muscle volume index (PVI)—in patients with metastatic castration‐sensitive prostate cancer (mCSPC). Methods: We retrospectively reviewed 120 patients diagnosed with mCSPC (2003–2022). Baseline muscle parameters were calculated from diagnostic CT scans. Sarcopenia was defined using the Martin criteria for SMI, and optimal cut‐offs derived from maximally selected rank statistics for PMI (4.08 cm ² /m ² ) and PVI (92 cm ³ /m ² ). Associations of these indices with age, overall survival (OS), and prostate cancer‐specific survival (PCSS) were evaluated. Results: Advancing age was significantly associated with SMI (OR: 1.05, p = 0.036) and PVI‐defined sarcopenia (OR: 1.09, p < 0.001), with a non‐significant trend for PMI (OR: 1.06, p = 0.069). Survival analysis revealed that sarcopenia by all three indices was significantly associated with worse OS (SMI [HR: 1.88, p = 0.032], PMI [HR: 2.19, p = 0.016], and PVI [HR: 2.07, p = 0.013]). In multivariable analyzes, SMI (HR: 1.86, p = 0.042), PMI (HR: 3.73, p < 0.001), and PVI (HR: 2.46, p = 0.006) remained independent risk factors for poorer OS. No significant impacts were observed for PCSS. Conclusions: When using body physique‐adjusted or mathematically optimized thresholds, all three easily and rapidly measurable radiological indices (SMI, PMI, and PVI) may serve as potential, independent prognostic indicators for OS in patients with mCSPC.

Objectives: To evaluate stage‐specific temporal trends in treatment patterns and overall survival (OS) among patients with prostate cancer in a Japanese multicentre cohort. Methods: This multicentre retrospective cohort study used data from the Kaga Million Uro‐Oncology Network (KAMU‐ON) registry. Patients diagnosed with prostate cancer between 2010 and 2024 were categorized as localized, nonmetastatic advanced, or metastatic disease. OS was assessed using Kaplan–Meier analyses and multivariable Cox proportional hazards models adjusted for clinically relevant covariates. Additional analyses with follow‐up administratively restricted at 48 months were performed. Results: A total of 7140 patients with defined disease stage and available survival data were included, comprising 5048 patients with localized disease, 1128 with nonmetastatic advanced disease, and 964 with metastatic disease. Treatment patterns changed substantially across diagnostic eras. Survival improvement appeared most evident in metastatic disease, whereas temporal differences were less apparent in nonmetastatic advanced disease. In multivariable Cox analyses, later diagnostic eras were associated with lower hazards of death in the overall cohort (2014–2017: HR 0.90, 95% CI 0.76–1.08; 2018–2024: HR 0.79, 95% CI 0.64–0.98). Formal interaction testing did not demonstrate statistically significant effect modification according to disease stage ( p = 0.163). Conclusions: Temporal survival trends in prostate cancer appeared to vary across disease stages in this Japanese multicentre cohort. Survival improvement appeared most evident in metastatic disease, whereas changes were less pronounced in nonmetastatic advanced disease. These findings suggest that therapeutic advances may not uniformly translate into survival gains across prostate cancer disease states.

Background: Sarcopenia, systemic inflammation, and malnutrition are established poor prognostic factors in renal cell carcinoma (RCC). This study investigated the utility of a novel preoperative score combining psoas muscle density (PMD)—an imaging-based indicator of muscle quality—and the albumin–bilirubin (ALBI) grade—a blood-based biomarker of liver reserve and systemic nutritional status—for predicting disease-free survival (DFS) and overall survival (OS) in patients undergoing curative surgery for RCC. Methods: This retrospective observational study included 274 patients with non-metastatic RCC treated with radical or partial nephrectomy. Preoperative computed tomography was utilized to measure PMD, defining “low PMD” as a value below the sex-specific median (males: 47.75 Hounsfield Units [HU]; females: 46.25 HU). “Worsened ALBI” was defined as an ALBI grade ≥ 2. Patients were stratified into three risk categories: Score 0 (both normal, n = 122), Score 1 (either abnormal, n = 114), and Score 2 (both abnormal, n = 38). Results: Kaplan–Meier analysis revealed a highly significant, stepwise decline in both DFS and OS as the risk score increased (log–rank p < 0.001 and p = 0.004, respectively). Multivariate Cox regression identified the combined risk score as a robust, independent prognostic factor for DFS (Score 1: HR 1.93, 95% CI 1.11–3.37, p = 0.020; Score 2: HR 3.58, 95% CI 1.82–7.02, p < 0.001). Furthermore, after adjusting for age and comorbidities, the score remained an independent predictor of poor OS (Score 1: HR 2.35, 95% CI 1.08–5.13, p = 0.032; Score 2: HR 3.01, 95% CI 1.16–7.82, p = 0.024). The combined model synergistically enhanced risk stratification accuracy compared to evaluating either factor independently. Conclusions: The concurrent presence of preoperative low PMD and a worsened ALBI grade is a powerful, independent predictor of poor prognosis in localized RCC. Derived solely from routine preoperative imaging and laboratory tests, this straightforward scoring system effectively captures the structural and immunometabolic dimensions of cancer cachexia and host vulnerability. This tool can significantly aid in personalizing postoperative surveillance strategies and identifying high-risk patients who may warrant closer postoperative surveillance or who might be considered as high-risk candidates for adjuvant therapy discussions.

Objectives: Randomized clinical trials have shown that second‐generation androgen receptor signaling inhibitors (ARSIs) improve overall survival (OS) in metastatic castration‐sensitive prostate cancer (mCSPC). In Japan, combined androgen blockade (CAB) has been widely used as conventional hormonal therapy, unlike Western trials in which androgen deprivation therapy (ADT) alone was the primary comparator. Whether this treatment context influences the survival benefit of ARSI‐based therapy in Japanese clinical practice remains uncertain. Methods: We conducted a systematic review and meta‐analysis of studies evaluating ARSI plus ADT versus conventional hormonal therapy (ADT alone or CAB) in Japanese patients with mCSPC. PubMed and Ichushi‐Web were searched through February 2026. Adjusted hazard ratios from multivariable or propensity score–matched analyses were pooled using a random‐effects model. Risk of bias was assessed using ROBINS‐I. Results: Fourteen studies were included. Eleven all‐comer mCSPC cohorts were included in the primary analysis. ARSI‐based therapy was associated with improved OS compared with conventional hormonal therapy (pooled hazard ratio 0.86, 95% confidence interval 0.77–0.96), with no heterogeneity ( I ² = 0%). The prediction interval was 0.76 to 0.98. Sensitivity and subgroup analyses, including CAB‐based comparator cohorts, showed consistent results. Conclusions: ARSI‐based therapy was associated with a modest but consistent improvement in OS in Japanese mCSPC. The attenuated effect size compared with randomized trials may reflect multiple factors, including differences in baseline treatment strategies, subsequent therapies, healthcare systems, and study design. These findings highlight the importance of treatment context when interpreting randomized trial evidence. Trial Registration: This systematic review and meta‐analysis was conducted in accordance with the PRISMA 2020 statement and was registered in PROSPERO (registration number: CRD420261380244)

Reliable early biomarkers of immune checkpoint inhibitor (ICI) efficacy remain limited in urothelial carcinoma (UC) and renal cell carcinoma (RCC). Because ICIs reshape tumor-reactive T-cell populations, early peripheral T-cell receptor (TCR) repertoire changes may provide treatment-informed prognostic information. We analyzed peripheral blood samples from 70 patients with UC or RCC treated with anti–PD-1/PD-L1 therapy, collected at baseline and 3–4 weeks after treatment initiation. TCRα and TCRβ repertoires were profiled using adaptor-ligation PCR and deep sequencing. Repertoire diversity was quantified using the Shannon index, and changes from baseline were calculated. Associations with progression-free survival, cancer-specific survival, and overall survival were assessed using Cox regression and Kaplan–Meier analyses. Pretreatment TCR diversity did not stratify clinical outcomes. In contrast, higher posttreatment TCRα diversity was associated with improved cancer-specific and overall survival, while increased TCRα diversity from baseline further stratified overall survival. A four-quadrant classification integrating posttreatment TCRα diversity and its early change showed clear separation of overall survival curves, with patients in the High–High group having the most favorable prognosis. TCRβ-based metrics showed weaker but directionally similar associations. These findings suggest that early on-treatment remodeling of the peripheral TCRα repertoire, particularly higher posttreatment diversity and greater increases from baseline, may serve as a minimally invasive biomarker for long-term survival in patients receiving ICI therapy.

Objectives: To elucidate the urethral closure mechanism during abdominal pressure in men, we investigated changes in pelvic anatomy during abdominal pressure using dynamic Magnetic Resonance Imaging (MRI). Methods: This study retrospectively analyzed data from 145 patients scheduled for robot‐assisted radical prostatectomy at Kanazawa University Hospital from 2016 to 2022. Preoperative dynamic MRI was used to take measurements at several anatomical points to assess changes in pelvic anatomy during abdominal pressure. Results: Dynamic MRI measurements during abdominal pressure revealed that the prostate apex rotates anteriorly at an average of 5.6°, and the internal urethral orifice shifts dorsally. Additionally, the prostate apex moves 1.2 mm toward the pubic bone. Conversely, the distal end of the membranous urethra shifts 0.9 mm dorsally during abdominal pressure. Consequently, a misalignment between the prostate apex and the membranous urethra is observed, resulting in the closure of the anterior–posterior direction of the proximal membranous urethra that may contribute to urethral closure during abdominal pressure. Conclusion: These results may suggest that prostate rotation during abdominal pressure creates a step‐like displacement at the proximal membranous urethra, which could contribute to urethral closure in men with an intact prostate. Dynamic MRI provides anatomical evidence supporting a complementary role of prostate motion in this mechanism. Clinical Trial Registration: Not applicable. This study was conducted prospectively with written informed consent and institutional ethical approval; however, it was not designed as a clinical trial because it was a non‐interventional observational study in which a specialized MRI protocol was added to standard clinical imaging without any therapeutic intervention or treatment allocation.

Objectives: To evaluate the diagnostic performance of the Prostate Health Index (phi) in detecting clinically significant prostate cancer (csPC) among men within the PSA gray zone (2.01–10.00 ng/mL), compared with total PSA and the free‐to‐total PSA ratio (F/T ratio), using a population‐based screening database in Kanazawa city, Japan. Methods: Between 2019 and 2023 (excluding 2022), 14 840 men participated in a biennial population‐based prostate cancer screening program in Kanazawa city, Japan. Among them, 2776 men with PSA levels of 2.01–10.00 ng/mL were identified, and 571 men who underwent prostate biopsy were included in the final analysis. The diagnostic accuracy for detecting csPC was compared among PSA, the F/T ratio, and phi using receiver operating characteristic (ROC) and decision curve analyses (DCA). Results: The area under the ROC curve (AUC) for detecting csPC was 0.691 for PSA, 0.673 for F/T ratio, and 0.761 for phi. The AUC for phi was significantly higher than that for F/T ratio ( p < 0.05). The DCA demonstrated that phi provided the greatest net benefit across threshold probabilities between 0.2 and 0.6, indicating improved clinical utility for csPC detection in the gray zone. Conclusions: In population‐based screening, adding phi to PSA and F/T ratio improved discrimination for csPC and may reduce unnecessary referrals and improve screening efficiency among men in the PSA gray zone.