Sunao Shoji

Functional human humoral immunity remains one of the greatest challenges in humanized mouse research. Although numerous humanized mouse models have been developed, reproducing efficient antigen-specific antibody responses remains difficult. This review proposes a conceptual framework for evaluating humanized mouse models based on the reconstruction of functional humoral immune modules rather than the presence of individual immune cell populations. Functional humoral immunity depends on the coordinated reconstruction of functional modules established through productive cognate interactions between immune cells within spatially organized lymphoid microenvironments. Comparative analyses of representative humanized mouse models demonstrated that these functional modules were only partially reconstructed and differed substantially among currently available models. Moreover, the duration of the humoral immunity window, during which the functional modules required for humoral immunity remain sufficiently coordinated to support productive cognate interactions and effective antigen-specific antibody responses, is limited in current humanized mouse models. Therefore, we propose a spatiotemporal framework for the design, evaluation, and application of next-generation humanized mouse models.

Magnetic resonance imaging (MRI) has become an essential tool for localizing intraprostatic tumors and detecting clinically significant prostate cancer (csPC). However, limitations related to cost, availability, and the presence of MRI-invisible lesions have driven interest in alternative imaging modalities. Transrectal ultrasound (TRUS), routinely performed by urologists, has evolved substantially with the development of advanced ultrasound technologies. Conventional gray-scale TRUS enables real-time assessment of prostate morphology and provides guidance for biopsy; however, its sensitivity for detecting csPC remains limited. Recent advances, including 29-MHz micro-ultrasound, color and power Doppler imaging, contrast-enhanced ultrasound, superb microvascular imaging (SMI), and elastography, have significantly expanded the diagnostic capability of ultrasound. Micro-ultrasound offers high-resolution visualization of ductal architecture and lesion morphology, and it has demonstrated diagnostic performance comparable to multiparametric MRI (mpMRI) in several prospective studies. Doppler-based techniques and SMI enable assessment of tumor-associated vascularity, while elastography provides quantitative assessment of tissue stiffness, which correlates with tumor aggressiveness. The integration of multiple ultrasound modalities, known as multiparametric ultrasound (mpUS), has shown promising diagnostic accuracy for csPC detection. Recent studies suggest that mpUS can identify clinically significant cancers missed by mpMRI and may serve as a complementary or alternative imaging strategy, particularly when MRI is unavailable or impractical.

Editorial Commentary Emerging role of the neurovascular structure-adjacent frozen-section examination technique in robot-assisted radical prostatectomy amidst the diversification of treatment strategies for localized prostate cancer Sunao Shoji

Objective: To evaluate the generalizability of a computer‐aided diagnosis (CADx) system based on the apparent diffusion coefficient (ADC) and wash‐in rate, and trained on a French population to diagnose International Society of Urological Pathology ≥ 2 prostate cancer on multiparametric MRI. Methods: Sixty‐eight consecutive patients who underwent radical prostatectomy at a single Japanese institution were retrospectively included. Pre‐prostatectomy MRIs were reviewed by an experienced radiologist who assigned to suspicious lesions a Prostate Imaging‐Reporting and Data System version 2.1 (PI‐RADSv2.1) score and delineated them. The CADx score was computed from these regions‐of‐interest. Using prostatectomy whole‐mounts as reference, the CADx and PI‐RADSv2.1 scores were compared at the lesion level using areas under the receiver operating characteristic curves (AUC), and sensitivities and specificities obtained with predefined thresholds. Results: In PZ, AUCs were 80% (95% confidence interval [95% CI]: 71–90) for the CADx score and 80% (95% CI: 71–89; p = 0.886) for the PI‐RADSv2.1score; in TZ, AUCs were 79% (95% CI: 66–90) for the CADx score and 93% (95% CI: 82–96; p = 0.051) for the PI‐RADSv2.1 score. The CADx diagnostic thresholds that provided sensitivities of 86%–91% and specificities of 64%–75% in French test cohorts yielded sensitivities of 60% (95% CI: 38–83) in PZ and 42% (95% CI: 20–71) in TZ, with specificities of 95% (95% CI: 86–100) and 92% (95% CI: 73–100), respectively. This shift may be attributed to higher ADC values and lower dynamic contrast‐enhanced temporal resolution in the test cohort. Conclusion: The CADx obtained good overall results in this external cohort. However, predefined diagnostic thresholds provided lower sensitivities and higher specificities than expected.

Focal therapy is a minimally invasive alternative treatment for localized prostate cancer (PC) aiming to achieve oncological control while preserving urinary and sexual functions. High‐intensity focused ultrasound (HIFU) and high‐intensity directional ultrasound (HIDU) enable precise prostate ablation guided by real‐time transrectal ultrasound or magnetic resonance imaging (MRI) fusion imaging. This review evaluates the current status and prospects of ultrasound technology in the treatment of PC. HIFU provides precise tumor ablation with minimal damage to the surrounding tissues, whereas HIDU allows MRI‐guided transurethral treatment with real‐time thermometry. Clinical studies have reported favorable biochemical recurrence‐free survival and functional outcomes. In Japan, a multi‐institutional prospective study on focal therapy using HIFU has been approved as an advanced medical technology by the Minister of Health, Labor, and Welfare. This study compared the oncological and functional outcomes of HIFU‐based focal therapy and radical prostatectomy in pair‐matched patients to evaluate the effectiveness of HIFU in treating localized PC. HIFU induces immunogenic cell death, releases tumor‐associated antigens, and reduces immunosuppressive cells. Low‐intensity focused ultrasound enhances tumor immunogenicity by promoting heat shock protein expression and CD8 ⁺ T cell activation. In conclusion, HIFU and HIDU offer effective focal therapy options for localized PC, and the immunomodulatory properties of HIFU and low‐intensity focused ultrasound may benefit advanced PC treatment. Future studies should optimize patient selection by developing advanced imaging technologies and predictive models capable of visualizing MRI‐invisible lesions and accurately detecting micro‐metastatic disease. Moreover, evaluating long‐term outcomes and exploring their combination with immunotherapy to enhance oncological efficacy will be essential.

Objectives: To test the feasibility of combining percentage prostate‐specific antigen (PSA) reduction and multiparametric magnetic resonance imaging (mpMRI) to determine the clinical scenario in which follow‐up biopsy could be avoided after focal therapy (FT) with high‐intensity focused ultrasound (HIFU) for prostate cancer.Methods: We reviewed 90 men treated with FT. Percentage PSA reduction was calculated by PSA nadir within postoperative 6 months. mpMRI was arranged at postoperative 6 months, followed by routine biopsy. Logistic regression analyses were performed to identify predictors for clinically significant prostate cancer (csPC) on follow‐up biopsy. Receiver operating characteristic curve analysis was done to assess the area under the curve (AUC). The diagnostic performance of percentage PSA reduction and mpMRI to predict csPC was also calculated.Results: Eight patients had csPC recurrence. Percentage PSA reduction and Prostate Imaging–Reporting and Data System (PI‐RADS) ≥ 3 at postoperative 6 months were predictors for csPC (p = 0.033 and p = 0.02, respectively). The AUC of mpMRI, percentage PSA reduction, and their combination were 0.95, 0.816, and 0.982, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSA reduction < 70% and PI‐RADS ≥ 3 to predict csPC were 87.5%, 69.5%, 21.9%, 98.3%, and 87.5%, 96.3%, 70%, 98.8%, respectively. Using the criteria of PSA reduction < 70% or PI‐RADS ≥ 3 to determine biopsy candidates could avoid 60% of biopsies, without missing csPC.Conclusion: For patients whose PSA reduction > 70% and PI‐RADS < 3, we suggested avoiding routine biopsy at 6 months after FT with HIFU.

Background To evaluate clinical outcomes of focal therapy using high-intensity focused ultrasound (HIFU) with intraoperative prostate compression for patients with localized prostate cancer (PC). Methods Patients were included if they had prostate specific antigen levels of ≤20 ng/mL and clinically significant PC (CSPC) within the left or right half, or upper or lower half of the prostate. CSPC was detected using magnetic resonance imaging-transrectal ultrasound fusion image-guided target biopsy and a 12-core systematic biopsy. Focal therapy using HIFU with intraoperative prostate compression was administered to lesions visible on the magnetic resonance imaging. Biochemical failure was defined by the Phoenix ASTRO definition. Pathological failure was defined as having CSPC in the biopsy at the time of biochemical failure. Results The patients (n = 240; median age, 69 years old; median prostate specific antigen level, 6.42 ng/mL) were divided according to the D’Amico risk classification into: ‘low’ (n = 51), ‘intermediate’ (n = 107), and ‘high’ (n = 82) groups. The biochemical and the pathological disease-free survival rates after a single treatment for the low-, intermediate-, and high-risk groups were 93.7% and 92.2%, 88.5% and 91.6%, and 84.8% and 86.6%, respectively. The radical or systematic treatment-free survival rates were 96.1%, 94.4%, and 95.1%, respectively. Median follow-up period was 48 months (range 24–84). The urinary and sexual function at 1 month post-treatment had deteriorated but returned to preoperative levels at 3 or 6 months after treatment. Conclusions Focal therapy using HIFU with intraoperative prostate compression would improve medium-term oncological outcomes without the risk of functional deterioration.