Hikaru Mikami

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.

Prostate cancer (PCa) is a clinically heterogeneous disease. Predicting clinically significant PCa with low–intermediate prostate-specific antigen (PSA), which often includes aggressive cancers, is imperative. This study evaluated the predictive accuracy of deep learning analysis using multimodal medical data focused on clinically significant PCa in patients with PSA ≤ 20 ng/mL. Our cohort study included 178 consecutive patients who underwent ultrasound-guided prostate biopsy. Deep learning analyses were applied to predict clinically significant PCa. We generated receiver operating characteristic curves and calculated the corresponding area under the curve (AUC) to assess the prediction. The AUC of the integrated medical data using our multimodal deep learning approach was 0.878 (95% confidence interval [CI]: 0.772–0.984) in all patients without PSA restriction. Despite the reduced predictive ability of PSA when restricted to PSA ≤ 20 ng/mL (n = 122), the AUC was 0.862 (95% CI: 0.723–1.000), complemented by imaging data. In addition, we assessed clinical presentations and images belonging to representative false-negative and false-positive cases. Our multimodal deep learning approach assists physicians in determining treatment strategies by predicting clinically significant PCa in patients with PSA ≤ 20 ng/mL before biopsy, contributing to personalized medical workflows for PCa management.

In patients with high-risk prostate cancer (HRPC) after radical prostatectomy (RP), biochemical recurrence (BCR) increases the risk of distant metastasis. Accordingly, additional prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence (CR) after BCR. The objective of this study was to identify biomarkers in formalin-fixed paraffin-embedded (FFPE) RP samples that are prognostic for CR in patients with HRPC who experience BCR after RP (post-RP BCR). First, we performed a preliminary RNA sequencing analysis to comprehensively profile RNA expression in FFPE RP samples obtained from patients with HRPC who developed CR after post-RP BCR and found that many snRNAs were very abundant in preserved FFPE samples. Subsequently, we used quantitative polymerase chain reaction (qPCR) to compare the expression levels of highly abundant snRNAs in FFPE RP samples from patients with HRPC with and without CR after post-RP BCR (21 CR patients and 46 non-CR patients who had more than 5 years of follow-up after BCR). The qPCR analysis revealed that the expression levels of snRNA RNU1-1/1-2 and RNU4-1 were significantly higher in patients with CR than in patients without CR. These snRNAs were significantly correlated with clinical recurrence-free survival (RFS) in patients with HRPC who experienced post-RP BCR. Furthermore, snRNA RNU1-1/1-2 could serve as an independent prognostic factor for clinical RFS in post-RP BCR of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between CR and non-CR patients. Our findings provide new insights into the involvement of snRNAs in prostate cancer progression.

This study presents the enfortumab vedotin (EV) treatment analysis at our institution. We retrospectively analyzed patients with metastatic urothelial cancer (mUC) treated with EV between January 2021 and October 2023. EV was administered at 1.25 mg/kg on days 1, 8, and 15 in a 28-day cycle. Whole-body computed tomography scans were performed to assess the treatment response. Patient characteristics, treatment histories, response rates, progression-free survival, and adverse events were evaluated. Response rates were determined, and adverse events were recorded. Among the 20 patients, 70% were male and 65% had bladder tumors. Most patients had lung (65%) or lymph node (65%) metastases. The median follow-up was 11.2 months, with 45% of the patients succumbing to the disease. The overall response rate was 55%. The median progression-free and median overall survivals were 10.5 and 12.9 months, respectively. Severe adverse events occurred in 35% of patients. In this real-world study, EV demonstrated promising efficacy and manageable safety profiles in Japanese patients with mUC. The study’s results were consistent with previous clinical trials, although a longer follow-up was required. Our findings support EV use as a treatment option for patients with mUC who exhibit disease progression after platinum-based chemotherapy and immune-checkpoint inhibitor therapy.