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Objective To evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle‐invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC). Patients and methods We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3‐4 or pN+ without neoadjuvant chemotherapy and ypT2‐4 or pN+ treated with neoadjuvant chemotherapy (trial‐eligible group) or others (trial‐ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease‐free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development. Results The median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty‐two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI‐positive status was significantly associated with poor prognosis among patients in the trial‐eligible group. A very high risk (LVI+ or pN+ among the pT3‐4 or ypT2‐4) was significantly associated with poor prognosis. Conclusion A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

PURPOSE To assess the influence of gut microbiome on overactive bladder (OAB) symptoms progression. METHODS This was a 3-year longitudinal study, Hirosaki in Japan. We assessed OAB symptoms and reviewed the medication records of each subject in 2016. We extracted 16S rRNA genes from fecal samples and analyzed gut microbiomes via next-generation sequencing. We evaluated the changes in urinary urgency (UU) and/or urgent urinary incontinence (UUI) from 2016 to 2019. We defined UU/UUI-progression as exacerbation of UU and/or UUI. We compared the clinical backgrounds and microbiota structure between UU/UUI-progression subjects and non-progression (controls). We assessed the impact of gut microbiome on the UU/UUI-progression via multivariate logistic regression analyses. RESULTS Of 669 subjects, 126 were UU/UUI-progression subjects. These subjects had a higher age and prevalence of proton pump inhibitor (PPI) use (14% vs. 5.4%, P = 0.003), irritable bowel syndrome, sleep disturbance, and metabolic syndrome than those without. We found the different microbiota structures between subjects with UU/UUI-progression and those without. A higher relative abundance of genus Streptococcus (harmful bacterial genus for human health) appeared in UU/UUI-progression subjects (3.8% vs. 2.3%, P

Objectives To investigate the eligibility for maintenance immunotherapy and its impact on the prognosis of advanced urothelial carcinoma treated with first‐line chemotherapy, as the selection biases of the eligible population in the JAVELIN Bladder 100 trial remain unclear. Methods We retrospectively evaluated 213 patients (median age, 71 years) with unresectable locally advanced or metastatic urothelial carcinoma treated with platinum‐based first‐line chemotherapy between May 2003 and April 2021. The patients were categorized into the following two groups: progressive disease (PD) within four cycles (trial ineligible group) and non‐PD within four cycles (trial eligible group). The primary outcomes were the estimated proportion of trial eligible patients for maintenance immunotherapy. The secondary outcomes were the comparison of the overall survival in the trial eligible and ineligible groups and the impact of radiologic response at the second cycle on the fourth cycle. Results Among the 213 patients, 81 (38%) were included in the trial eligible group. The trial eligible group had a significantly longer overall survival than the trial ineligible group (P

Background The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA. Methods Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS. Results S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold. Conclusions The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.

Purpose: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. Experimental Design: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. Results: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24–5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60–8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. Conclusions: Detecting low-frequency ctDNA variants with a VAF

Although combination immune checkpoint inhibitor (immuno‐oncology [IO]) therapy is the first‐line treatment for metastatic renal cell carcinoma (mRCC), it mostly causes resistance and tumor regrowth. Therefore, an optimal second‐line therapy is necessary. Such therapy typically comprises vascular endothelial growth factor receptor‐tyrosine kinase inhibitors (VEGFR‐TKIs). This study was aimed at comparing the efficacy of two TKIs—axitinib and sunitinib—in mRCC patients. From January 2008 to October 2018, we registered 703 mRCC patients from 8 Japanese institutes. Of these, 408 patients received axitinib or sunitinib as the first‐line treatment. Thereafter, efficacy and survival rate were compared between the axitinib and sunitinib groups. To reduce the effects of selection bias and potential confounders, propensity score matching analysis was performed. Axitinib and sunitinib were administered in 274 and 134 patients, respectively. More than 25% of the patients received nivolumab sequence therapy. To calculate the propensity scores for each patient, we performed multivariate logistic regression analysis. The objective response rate, progression‐free survival (PFS), cause‐specific survival, and overall survival (OS) were significantly better in the axitinib group than in the sunitinib group. Furthermore, the OS was better in the nivolumab‐treated patients in the axitinib group. Axitinib showed higher efficacy and afforded greater survival benefits than did sunitinib when administered as first‐line therapy in mRCC patients. Thus, from among VEGFR‐TKIs, axitinib might be a possible option for application in the middle of IO drug‐based treatment sequences., Compared to sunitinib, axitinib showed higher efficacy and afforded greater survival benefits as first‐line therapy in patients with metastatic renal cell carcinoma. Axitinib might be better than sunitinib for application in the middle of IO drug‐based treatment sequences.

The aims of this study were to investigate prognosis and validate prognostic models [Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Data Consortium (IMDC), and Japanese metastatic renal cancer (JMRC) models] in the targeted therapy era in Japanese patients with metastatic renal cell carcinoma. We retrospectively analyzed 692 patients who were diagnosed with mRCC from January 2008 to August 2018 in the Michinoku Japan Urological Cancer Study Group database. Nivolumab as sequential therapy was widely used. Other immune checkpoint inhibitors were excluded from this study. The median overall survival (95% confident interval) in all, MSKCC favorable, intermediate, and poor risk patients was 41.0 months (33.9–46.8), not reached (63.5 to not estimable), 46.8 months (37.1–52.9), and 10.4 months (8.9–14.4), respectively. The median overall survival (95% confident interval) in IMDC favorable, intermediate, and poor risk patients was not reached (61.6 to not estimable), 47.4 months (41.4–56.5), and 11.5 (9.9–16.3), respectively. The c-index of the MSKCC, IMDC, and JMRC models calculated at mRCC diagnosis was 0.680, 0.689, and 0.700, respectively. No statistical differences were found in the c-index among the models. While the real-world overall survival in Japanese patients with mRCC in the targeted therapy era improved compared to that previously reported in the cytokine era, there was no clear difference in the survival of poor risk patients between these eras. There were no differences in the superiority among the models.

Aims To investigate the relationship between urinary urgency (UU) and aponeurotic ptosis (AP) in a health promotion project. Methods This cross-sectional study analyzed 658 women in Aomori, Japan. The presence of UU was evaluated using the Overactive Bladder Symptom Score. The distance from the light reflex on the cornea to the upper eyelid (margin reflex distance-1 [MRD-1]) was measured. AP was defined as MRD-1 of less than 2.0 mm. The daily salt intake amount was estimated using the dietary questionnaire. Daily salt intake was defined as excessive if it was 10 g/day or higher. Independent factors of UU and AP were analyzed via multivariable logistic regression model. Results The number of women with UU and AP was 193 and 65, respectively. Similar background differences were observed in age, cardiovascular disease history, renal function, hypertension, diabetes mellitus, dyslipidemia, and daily salt intake between participants with UU and those with AP. Participants with UU had a higher prevalence of AP (19% vs. 6.2%) than those without. Moreover, more than 50% of the women with AP experienced UU. Multivariable logistic analysis on UU showed that age (≥65 years), diabetes mellitus, daily salt intake (≥10 g/day), and AP (odds ratio, 2.07, p = .014) were independent factors. Multivariable analysis on AP revealed that age (≥65 years), hypertension, daily salt intake (≥10 g/day), and UU were independent factors. Conclusions AP was an independent indicator of UU, in addition to excessive daily salt intake. Women with AP may tend to intake excessive salt and experience UU.

Objectives To assess the clinical benefit of pembrolizumab as second-line therapy for advanced urothelial carcinoma. Methods We retrospectively compared the effects of pembrolizumab with those of conventional chemotherapy on the prognosis of patients with advanced urothelial carcinoma at six hospitals between January 2004 and August 2020. We compared the oncological outcomes between the patients treated with pembrolizumab and those treated with conventional chemotherapy using Kaplan-Meier curve analysis and multivariate Cox regression analysis with the inverse probability of treatment weighting method. Results The numbers of patients in the pembrolizumab and chemotherapy groups were 121 and 67, respectively. Patients in the pembrolizumab group were significantly older (median 72 vs 66 years, P = 0.001), and had poor Eastern Cooperative Oncology Group performance status (median 1 vs 0, P = 0.001). The unadjusted Kaplan-Meier curve analysis showed no significant differences in the median overall survival from the first-line chemotherapy (24.7 months vs 16.3 months, P = 0.159). Inverse probability of treatment weighting-adjusted multivariate Cox proportional hazards analyses showed a significant difference between the pembrolizumab and chemotherapy groups in overall survival (P = 0.003, hazard ratio 0.63). Conclusions Despite the non-negligible age difference between the trial and our clinical practice, our study supports the benefit of second-line pembrolizumab over chemotherapy in real-world practice.

To investigate the prognostic significance of total cell-free DNA (cfDNA) level and androgen receptor amplification (AR-amp) in patients with castration-resistant prostate cancer (CRPC). We retrospectively compared the total cfDNA level and AR-amp in 42 individuals without prostate cancer, 57 patients with localized prostate cancer without androgen-deprivation therapy (ADT), 97 patients with castration-sensitive prostate cancer (CSPC) with ADT, and 97 patients with CRPC. The association of these cfDNA biomarkers on disease status and overall survival was evaluated using Kaplan–Meier analysis and multivariable Cox regression analysis. Finally, a simple risk model was developed including total cfDNA and AR-amp to predict poor prognosis. The median total cfDNA level and AR-amp in patients with CRPC was 387 pg/μL and 1.07 copies, respectively. The total cfDNA levels and AR-amp were significantly higher in the patients with CRPC than in individuals without prostate cancer, patients with localized prostate cancer without ADT, and patients with CSPC with ADT. Total cfDNA-high (> 600 pg/μL) and AR-amp-high (> 1.26 copies) were significantly associated with poor overall survival. Multivariable Cox regression analysis showed cfDNA-high and AR-amp-high were significantly associated with poor overall survival in patients with CRPC. We developed a risk model using cfDNA-high (score 1) and AR-amp-high (score 1). The risk score 1–2 was significantly associated with worse overall survival than score 0. Total cfDNA level and AR-amp are potential biomarkers for poor prognosis in patients with CRPC.

Objective To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilisation and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). Patients and methods We included 289 patients from seven hospitals who underwent radical nephroureterectomy (RNU) for locally advanced UTUC (≥cT3 or cN+) between 2000 and 2020. These patients received RNU alone or two to four courses of NAC with either a cisplatin- or carboplatin-based regimen. We evaluated the temporal changes in NAC use and compared the visceral recurrence-free, cancer-specific, and overall survival rates. The effect of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. Results Of 289 patients, 144 underwent NAC followed by RNU (NAC group) and 145 underwent RNU alone (Control [Ctrl] group). NAC use increased significantly from 19% (2006-2010), 58% (2011-2015), to 79% (2016-2020). Pathological downstaging was significantly higher in the NAC group than in the Ctrl group. The IPTW-adjusted multivariable analyses showed that NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group. Moreover, carboplatin-based NAC significantly improved the oncological outcomes in the NAC group compared with the Ctrl group among patients with chronic kidney disease Stage ≥3. There were no significant differences in oncological outcomes between the cisplatin- and carboplatin-based regimens. Conclusions The use of NAC for high-risk UTUC increased significantly after 2010. Platinum-based short-term NAC followed by immediate RNU may not impede and potentially improves oncological outcomes.

Objective: To evaluate the safety and efficacy of using one-surgeon basketing technique by a solo surgeon for stone extraction during flexible ureteroscopy (f-URS) for urolithiasis. Patients and methods: This retrospective study enrolled patients with urinary calculus who underwent f-URS at two institutions in Japan between September 2014 and March 2020. A total of 100 patients were operated by one experienced surgeon using the one-surgeon basketing technique. With this approach, the f-URS apparatus was manipulated with the non-dominant hand and the basket catheter was manipulated with the dominant hand. We retrospectively examined the perioperative results, complications, and stone-free rate [with ‘stone free’ defined as ≤2 mm with kidney–ureter–bladder (KUB) at 1 month after f-URS] to estimate the safety and efficacy for comparison with the results of conventional retrieval basketing technique. Results: Among our study population, the median stone size was 14 mm and median operative time was 74 min. A stone-free status was achieved in 91 patients (91%). The median stone fragmentation time was 15 min and stone retrieval time was 30 min. All included patients were treated using the one-surgeon basketing technique. Complications related to stone retrieval were identified in two patients (2%); the degree of ureteral injury was classified as Clavien–Dindo Grade IIIa. Conclusion: The one-surgeon basketing technique is safe and effective for the extraction of stone fragments during f-URS for urolithiasis. This technique does not require assistance for basketing; therefore, f-URS with active retrieval basketing can be completed by a solo surgeon. Abbreviations: BMI: body mass index; KUB: kidney–ureter–bladder; SFR: stone-free rate; UAS: ureteral access sheath; f-URS: flexible ureteroscopy

Discriminating between urothelial carcinoma (UC), including bladder cancer (BCa) and upper urinary tract UC (UTUC), is often challenging. Thus, the current study evaluated the diagnostic performance of N‐glycosylation signatures of immunoglobulins (Igs) for detecting UC, including BCa and UTUC. N‐glycosylation signatures of Igs from serum samples of the training cohort, including 104 BCa, 68 UTUC, 10 urinary tract infection, and 5 cystitis cases, as well as 62 healthy volunteers, were measured retrospectively using automated capillary‐electrophoresis‐based N‐glycomics. UTUC or BCa scores were then established through discriminant analysis using N‐glycan signatures of Igs. Diagnostic performance was evaluated using the area under receiver operating characteristics curve (AUC) and decision curve analyses (DCA). Our result showed that BCa and UTUC scores for discriminating BCa (AUC: 0.977) and UTUC (AUC: 0.867), respectively, provided significantly better clinical performance compared to urine cytology, gross hematuria, or clinical T1 cases. DCA revealed that adding BCa and UTUC scores to gross hematuria status was the best combination for detecting UC and avoiding the need for more intervention without overlooking UC (risk threshold: 13%–93%). The UC nomogram based on the combination of gross hematuria, UTUC score, and BCa score could detect UC with an AUC of 0.891, indicating significantly better performance compared to gross hematuria status in the validation cohort (251 patients). The limitations of this study include its small sample size and retrospective nature. The UC nomogram based on gross hematuria and N‐glycosylation signatures of Igs can be a promising approach for the diagnosis of UC., We evaluated the diagnostic performance of Bladder cancer (BCa) and upper urinary tract urothelial carcinoma (UTUC) discrimination scores that we developed based on N‐glycosylation signatures of immunoglobulins. The BCa score and UTUC score provided significantly better clinical performance than urine cytology negative or gross hematuria negative or clinical T1 cases.

An amendment to this paper has been published and can be accessed via the original article.

Background The clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naive metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC. Methods We retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients' data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes. Results The median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups. Conclusions No significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC.

Objectives To compare overall survival between patients with metastatic renal cell carcinoma treated by cytoreductive nephrectomy and those not treated by cytoreductive nephrectomy. Methods We retrospectively evaluated 278 patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors between January 2008 and November 2019. Patients were divided into two groups: a cytoreductive nephrectomy group (immediate or deferred cytoreductive nephrectomy) and a group who received systemic tyrosine kinase inhibitor therapies alone without cytoreductive nephrectomy (control group). Overall survival comparisons were made in all patients in the control versus the cytoreductive nephrectomy group, the control versus the immediate cytoreductive nephrectomy group, the control versus the deferred cytoreductive nephrectomy group, and the deferred cytoreductive nephrectomy versus the immediate cytoreductive nephrectomy group. Analyses were weighted using the propensity score-based inverse probability of treatment weighting method to adjust for group imbalances. Results The median (range) age of the patients was 65 (59-73) years. Of the 278 patients, 132 and 146 were in the control group and the cytoreductive nephrectomy (immediate, n = 107 and deferred, n = 39) group, respectively. A significant difference was noted between the control and cytoreductive nephrectomy groups in age, clinical stage, International Metastatic Renal Cell Carcinoma Database Consortium risk factors, and the number of metastatic sites. Inverse probability of treatment weighting-adjusted Cox regression analysis showed a significant difference in overall survival between the control and the cytoreductive nephrectomy groups and between the control and the immediate or deferred cytoreductive nephrectomy groups. However, there was no significant difference in overall survival between the immediate and the deferred cytoreductive nephrectomy groups. Conclusions Our findings suggest that metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy are more likely to have longer overall survival than those who receive tyrosine kinase inhibitor therapy only.

Introduction: The causal relationship between sleep disorder and frequency of nocturia remains unclear. Methods: We longitudinally evaluated sleep disorder and frequency of nocturia in 547 community-dwelling adults between baseline and 5-year follow-up. We included participants ≥50 years old who have no sleep disorder (the Pittsburgh Sleep Quality Index [PSQI] ≥ 5) nor nocturia (≥1). For 5 years, we evaluated the temporal changes in sleep disorder and nocturia and the bidirectional relationships between sleep disorder and nocturia. Results: Of the 547 participants, we included 268 adults with a median age of 61 years in this study. Median PSQI and nocturia were significantly increased for 5 years from 2 to 3 and from 1 to 2, respectively. New onset of sleep disorder (PSQI > 5) and nocturia >1 was observed in 42 (16%) and 137 (51%) participants, respectively. The cross-lagged panel analysis showed that the path coefficient from PSQI to nocturia (β = 0.22, p = 0.031) was significantly higher than that from nocturia to PSQI (β = 0.02, p = 0.941). Conclusions: Our longitudinal study showed the effect of sleep disorder on nocturia was significant, although nocturia may not significantly worsen sleep disorder in community-dwelling adults.

This study compared real-world outcomes of metastatic renal-cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors or nivolumab plus ipilimumab. Using the International mRCC Database Consortium (IMDC), we retrospectively evaluated intermediate- and poor-risk mRCC patients who were treated with nivolumab plus ipilimumab (Nivo-Ipi), tyrosine kinase inhibitors (TKIs) as the first-line therapy between August 2015 and January 2020. We compared oncological outcomes between the Nivo-Ipi group and TKIs group using multivariate logistic regression analysis with the inverse probability of treatment weighting (IPTW) method. In this study 278 patients were included. There were 52 and 226 patients in the Nivo-Ipi and TKIs groups (sunitinib 97, axitinib 118, sorafenib 9, pazopanib 2), respectively. The median age in the Nivo-Ipi and TKIs groups were 69 and 67 years, respectively. There was no significant difference in age, performance status, history of nephrectomy, and the IMDC risk group distribution between the groups. The objective response rate was significantly higher in the Nivo-Ipi group (38%) than in the TKIs group (23%, P = 0.018). The IPTW-adjusted Cox regression analysis showed that a significantly longer progression-free survival (hazard ratio 0.60, P = 0.039) and overall survival (hazard ratio 0.51, P = 0.037) rates in the Nivo-Ipi group than those in the TKIs group. The oncological outcomes of patients receiving the first-line therapy of nivolumab plus ipilimumab in real-world practice were significantly improved in comparison with first-line TKIs therapy.

Objective To determine the safety and efficacy of the one-surgeon basketing technique for stone extraction during flexible ureteroscopy when carried out by novice surgeons under instructor guidance. Methods We retrospectively compared perioperative results, complications and the "stone-free" rate (defined as ≤2 mm fragments on kidney-ureter-bladder imaging 1 month after flexible ureteroscopy) between experienced (group A, n = 50) and novice (group B, n = 50) surgeons using the one-surgeon basketing technique. Results Baseline patients' characteristics were similar between the two groups. There were no significant differences between groups A and B in operative time (mean 76 min vs 85 min, P = 0.46), stone-free rate (98% vs 92%, P = 0.36), postoperative fever events (4% vs 4%, P = 1.00) and postoperative hospital stay (24 h vs 24 h, P = 1.00). Clavien-Dindo grade IIIa complications (ureter injury) were only observed in two cases (4%) in group B. Conclusions The one-surgeon basketing technique for the extraction of stone fragments during flexible ureteroscopy might be safely and effectively carried out by surgeons with no prior experience under proper guidance.

Introduction Cell-free DNA is suggested as a prognostic biomarker in metastatic castration-resistant prostate cancer. However, it remains unknown which parameter of cell-free DNA is correlated with the progression and prognosis of metastatic castration-resistant prostate cancer. Case presentation A 75-year-old man with newly diagnosed prostate cancer (serum prostate-specific antigen 4891 ng/mL, Gleason score 4 + 5 = 9, cT3bN1M1) was referred to our department. He first received sequential hormonal therapies and was consequently diagnosed metastatic castration-resistant prostate cancer 64 months after initial treatment. He underwent serial examinations of plasma cell-free DNA, including concentration, androgen receptor amplification, TP53 point mutation, and PTEN loss. Only the cell-free DNA concentration increased along with disease progression and declined after the administration of abiraterone and enzalutamide. Conclusion This case presented that cell-free DNA concentration was possibly correlated with response to castration-resistant prostate cancer treatment and disease progression. Cell-free DNA concentration was proposed as a potential prognostic biomarker of metastatic castration-resistant prostate cancer.

Kidney transplantation from marginal donors is an important solution for organ shortage problems. In this study, we evaluated the safety and effectiveness of living kidney transplantation from marginal donors at our hospitals.Between June 2006 and April 2019, 107 patients underwent living kidney transplantation at our hospitals. Marginal donors were defined as those with 1. age70 years, 2. hypertension, 3. creatinine clearance 80 mL/min, 4. body mass index30 kg/mThirty-one (29%) donors were defined as marginal. The primary reason for being defined as marginal was hypertension (74%). The mean age of the marginal donors (62 ± 10 years) was higher than that of standard donors (52 ± 12 years, P .001). The estimated glomerular filtration rate (eGFR) before and after transplantation was lower in the marginal group, whereas the decline ratio of eGFR was not different between the marginal and standard donors. Five-year graft survival of transplantations from marginal donors (89%) was not significantly inferior to that from standard donors (95%). Meanwhile, recipient eGFR was lower in transplantation from marginal donors than standard donors from 1 month through 5 years after transplantation.No significant differences were observed between the groups regarding the decline ratios of donor eGFR and graft survival. Thus, transplantation from marginal donors may be a feasible solution for donor shortage problems.

Objectives Despite just a 4-year interval from the last version (2015) of the Clinical Practice Guidelines for Bladder Cancer, several dramatic paradigm shifts have occurred in the latest clinical practice regarding both the diagnosis and treatment of bladder cancer. Herein, we updated the 2019 version of the Clinical Practice Guidelines for Bladder Cancer under the instruction of the Japanese Urological Association. Methods We previously reported in a revision working position paper for Clinical Practice Guidelines for Bladder Cancer 2019 edition and described the methods of revision detail. Results The major points of change in the 2019 version are presented and explanations are given as follows: (i) introduction of the new reference assessment system; (ii) modification of the risk classification for non-muscle-invasive bladder cancer; (iii) addition of clinical questions for the new tumor-visible techniques in non-muscle-invasive bladder cancer; (iv) inclusion of minimally invasive surgeries for muscle-invasive bladder cancer and immune checkpoint inhibitors for locally advanced/metastatic muscle-invasive bladder cancer; (v) overview chapter of the histological variant of urothelial cancer and rare cancers of the bladder; and (vi) recommendation of follow up in non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Conclusions Guidelines should be updated based on the current evidence and updates carried out without delay. The hope is that this guidelines will be assessed by many urologists and will be the cornerstone for the next revision.

To evaluate the association between the score of the Geriatric 8 screening tool and treatment by disease stages in patients with prostate cancer.Between January 2017 and June 2019, we prospectively evaluated the Geriatric 8 in 540 prostate cancer patients who were treated with robot-assisted radical prostatectomy, radiotherapy, androgen deprivation therapy alone and standard of care for metastatic hormone-naïve prostate cancer or castration-resistant prostate cancer. The primary purpose was the association between frailty (Geriatric 8 ≤14) and robot-assisted radical prostatectomy, radiotherapy, androgen deprivation therapy alone, and metastatic diseases. Secondary purposes included a comparison of the Geriatric 8 scores among the disease status and the influence of Geriatric 8 score on overall survival.The median age was 75 years. Geriatric 8 scores ≤14 were seen in 36% of robot-assisted radical prostatectomy (n = 78/214), 57% of radiotherapy (n = 119/209), 91% of androgen deprivation therapy alone (n = 19/21) and 70% of metastatic diseases (n = 67/96). The median Geriatric 8 score in patients treated with robot-assisted radical prostatectomy, radiotherapy, androgen deprivation therapy alone and metastatic diseases was 15.0, 14.0, 12.0 and 12.8, respectively. The median Geriatric 8 score was significantly higher in the metastatic disease than that in localized disease (14.5 vs 12.8, respectively). Robot-assisted radical prostatectomy patients had a significantly higher Geriatric 8 score than radiotherapy patients, with the cut-off value of14.5. The overall survival was significantly different between Geriatric 8 scores ≤13 and13 in metastatic hormone-naïve prostate cancer patients, and between Geriatric 8 scores ≤12 and12 in castration-resistant prostate cancer patients.The Geriatric 8 score is significantly associated with treatment by disease stages in patients with prostate cancer.

Objectives To evaluate the effect of overactive bladder (OAB) and frailty on indoor fall events in community-dwelling adults aged 50 or older. Methods We conducted a cross-sectional study involving 723 adults between 2016 and 2017 in Hirosaki, Japan. OAB symptoms and sleep disturbance were assessed using the Overactive Bladder Symptom Score (OABSS) and the Pittsburgh Sleep Quality Index (PSQI). Indoor fall events (falls or near-falls) within 1 year were evaluated. Frailty was evaluated by the frailty discriminant score. We investigated the association of OAB symptoms with sleep disturbance, frailty, and indoor fall events. Multivariate logistic regression analysis was performed to investigate the effect of OAB symptoms on fall events controlling for confounding factors such as age, gender, comorbidity, frailty, and sleep disturbance. Results The median age was 64. We observed OABSS ≥6 in 98 participants (14%), nocturia ≥2 in 445 (62%), urgency score ≥3 in 80 (11%), urge incontinence score ≥3 in 36 (5.0%), PSQI ≥6 in 153 (21%), frailty in 169 (23%), and indoor fall events in 251 (35%). Older age, diabetes, OABSS, nocturia, urgency, urge incontinence, and the PSQI were significantly associated with indoor fall events. Multivariate logistic regression analyses showed that OAB symptoms and sleep disturbance were significantly associated with fall events. Conclusions The effect of OAB symptoms and sleep disturbance on indoor fall events was significant. The causal relationship between OAB and falls needs further study.

To explore associations between the gut microbiome and overactive bladder (OAB) with daily urinary urgency among individuals reporting this diagnosis within a single community. This cross-sectional study surveyed 1113 individuals who participated in the Iwaki Health Promotion Project in Japan. OAB was defined as urinary urgency at least once per week and an Overactive Bladder Symptom Score (OABSS) of ≥ 3. OAB with urinary urgency at least once a day was defined as daily urgency. The gut microbiomes were assessed by next-generation sequencing of 16S rRNA genes extracted from fecal samples. The participants were divided into two groups: OAB-daily urgency and non-OAB. Cases were selected for inclusion on the basis of 1:1 propensity score matching; we assigned 58 individuals to each group (23 men and 35 women) for our analysis. Individuals reporting OAB with daily urinary urgency demonstrated a lower bacterial diversity between individuals (Bray–Curtis distance 0.48 vs. 0.53, P

OBJECTIVES To evaluate the association of tumor burden with the prognosis in real-world patients with metastatic castration-sensitive prostate cancer and to investigate the eligibility for upfront intensification therapy. METHODS We retrospectively evaluated 679 patients with metastatic castration-sensitive prostate cancer who were initially treated with conventional androgen deprivation therapy between August 2001 and November 2018. The primary purpose was to investigate the eligibility for upfront intensification therapy based on the progression of metastatic castration-resistant prostate cancer. The secondary purpose included the comparison of the metastatic castration-resistant prostate cancer progression rate, metastatic castration-resistant prostate cancer-free survival and overall survival after castration-resistance in CHAARTED low- or high-volume disease patients. RESULTS The number of patients with metastatic castration-resistant prostate cancer progression was 119 (52%) and 319 (71%) in the low- and high-volume disease groups, respectively. The metastatic castration-resistant prostate cancer progression rate (P

Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab’s efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years. From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and

Introduction We aimed to evaluate the treatment sequence for patients with metastatic castration-resistant prostate cancer (mCRPC) in real-world practice and compare overall survival in each sequential therapy. Patients and Methods We retrospectively evaluated 146 patients with mCRPC who were initially treated with androgen deprivation therapy as metastatic hormone-naive prostate cancer in 14 hospitals between January 2010 and March 2019. The agents for the sequential therapy included new androgen receptor-targeted agents (ART: abiraterone acetate or enzalutamide), docetaxel, and/or cabazitaxel. We evaluated the treatment sequence for mCRPC and the effect of sequence patterns on overall survival. Results The median age was 71 years. A total of 35 patients received ART-ART, 33 received ART-docetaxel, 68 received docetaxel-ART, and 10 received docetaxel-cabazitaxel sequences. The most prescribed treatment sequence was docetaxel-ART (47%), followed by ART-ART (24%). Overall survival calculated from the initial diagnosis reached 83, 57, 79, and 37 months in the ART-ART, ART-docetaxel, docetaxel-ART, and docetaxel-cabazitaxel, respectively. Multivariate Cox regression analyses showed no significant difference in overall survival between the first-line ART (n = 68) and first-line docetaxel (n = 78) therapies (hazard ratio [HR], 0.84; P = .530), between the ART-ART (n = 35) and docetaxel-mixed (n = 111) sequences (HR, 0.82; P = .650), and between the first-line abiraterone (n = 32) and first-line enzalutamide (n = 36) sequences (HR, 1.58; P = .384). Conclusion The most prescribed treatment sequence was docetaxel followed by ART. No significant difference was observed in overall survival among the treatment sequences in real-world practice.

Although a shortage in organ donation is a critical problem in Japan, understanding of and attitude toward organ transplantation in medical students have not been sufficiently reported. Between 2013 and 2018, we surveyed 702 medical students in the fifth-year clinical training in our urology department. The survey concerned (1) knowledge of Japanese transplantation law, which was amended in 2010, and (2) whether the respondents had an organ donor card and had agreed to be a brain-dead donor or a living donor in kidney transplantation with specific reasons for their choices. All 702 students answered the survey. Of 657 students who provided valid answers to the first section, 402 (61%) recognized the amendment to the Japanese transplantation law, and only 11 (1.7%) fully understood its contents. Of 702 students, 194 (28%) had a donor card, 384 (55%) agreed to be a brain-dead donor, and 529 (75%) agreed to be a living donor in kidney transplantation. As the specific reasons for their choices, only a few medical students wrote reasons based on their medical standpoint, and more students wrote emotional reasons. The understanding of and attitude toward organ transplantation were not remarkably high in the fifth-year medical students in Japan. To solve the donor shortage problem, education about organ transplantation may need to be more effective.

We investigated the gut microbiome in subjects with erectile dysfunction (ED) in a community-based population. This cross-sectional study surveyed comprehensive health status in 408 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. The gut microbiome was assessed by tag sequencing of the 16S rRNA gene, which we extracted from fecal samples. Erectile function was evaluated with the five-item International Index of Erectile Function (IIEF-5), and the men were divided into two groups: low-IIEF-5 (≤ 16) and high-IIEF-5 (> 16). Of those, we selected age-adjusted 192 men (96 each) for analysis. We investigated the association of gut microbiome with IIEF-5 between the two groups. Median age was 50 years. No significant difference was seen in the history of hypertension, DM, CKD, and CVD between the low-IIEF-5 and high-IIEF-5 groups. However, the relative abundance of Alistipes (related with anti-inflammation) and Clostoridium XVIII (related with bowel movement) was significantly different between the two groups. Multivariate logistic analysis demonstrated that the relative abundance of Clostridium XVIII (OR, 2.06; 95% CI, 1.20–3.55, P = 0.009) and Alistipes (OR, 0.81; 95% CI, 0.66–0.99, P = 0.040) and, with an IPSS ≥ 8, were independent factors for low IIEF-5. We observed significant association between the low-IIEF-5 and high-IIEF-5 groups in Alistipes and Clostoridium XVIII. Further study is necessary to access the causal relationship between the gut microbiome and ED.

To investigate the association between serum serotonin (5-HT) levels and overactive bladder (OAB) in a community-dwelling population. This cross-sectional study analyzed 1024 subjects who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. OAB was assessed using the Overactive Bladder Symptom Score (OABSS). OAB was defined as an occurrence of urinary urgency at least once a week and an OABSS of ≥ 3. We assessed serum 5-HT levels, laboratory data, and comorbidities of each participants. Participants’ mental health status was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale. The association of serum 5-HT levels and OAB was analyzed by multivariable logistic regression analysis. This study included 394 men and 630 women. Of those, 118 (44 male and 74 female) were OAB sufferers. There were significant group differences in age, history of cardiovascular disease, chronic kidney disease, hypertension, diabetes mellitus, and CES-D score. Participants’ serum 5-HT levels in the OAB group were significantly lower than those in the non-OAB group (100 vs. 127 ng/mL, P

A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naïve patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (n = 25) or placebo with docetaxel and dexamethasone (n = 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%; P = 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (P = 0.018) and CTL (P = 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with ≥ 26% lymphocytes or PSA levels of

Objectives To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real‐world practice in Asia using the United in Fight against prOstate cancer (UFO) registry. Patients and Methods We established a multi‐national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high‐risk localised prostate cancer (HRL), non‐metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed‐up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient‐reported quality of life was prospectively assessed using the European Quality of Life‐five Dimensions, five Levels (EQ‐5D‐5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017. Results Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co‐morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of

OBJECTIVE To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P

This study aimed to determine the prognostic factors associated with biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with pathological T2 (pT2) prostate cancer (PCa) and negative resection margin (RM) status at a single institution. In this retrospective study, we examined 386 patients who were diagnosed with pT2 PCa with negative RM after RP. The length of the tumor was provided for each biopsy core and the overall percentage of PCa was calculated by a pathologist at our institution. We estimated the BCR-free survival (BRFS) in these patients. Univariate and multivariate analyses were performed using the Cox proportional hazard model to determine the risk factors of BCR. The median age of the participants was 68 years, and their initial prostate-specific antigen level was 6.55 ng/mL. The median follow-up period was 85.7 months. The 5-year BRFS rate of the participants was 89.0%. The 5-year BRFS rates were 89.8% in patients with a biopsy Gleason score of 6, 90.4% in those with 7, and 64.1% in those with ≥8 (P = 0.007). The BRFS rate was 93.3% in patients who had a biopsy positive core ≤20% and 82.0% in those who had ≥21% (P = 0.001). Based on the multivariate analysis, the proportion of biopsy positive core was significantly associated with BCR. The proportion of biopsy positive core may predict preoperative covariates in patients with pT2 PCa and negative RM status after RP.

Radical prostatectomy (RP) is relatively better oncological outcomes in patients with prostate cancer (PCa). However, the incidence of castration-resistant PCa (CRPC) and PCa-specific mortality in patients with biochemical recurrence (BCR) after RP remains unclear. The aim of this study was to evaluate the cancer-specific survival (CSS) in patients with CRPC after RP, in particular those who had metastases or not. We retrospectively reviewed the data of 1582 consecutive patients who underwent RP between July 1996 and January 2019. The enrolled patients had histologically confirmed stage T1a–T3b PCa without lymph node involvement or distant metastasis. The endpoints were oncological outcomes, including CSS and BCR, in patients with PCa with or without metastases at the time of diagnosis with CRPC. A total of 1474 patients were enrolled in this study. By the end of the follow-up period, 352 patients (24.6%) in the enrolled patients had BCR after RP. A total of 42 patients (2.9%) developed CRPC and 18 (1.3%) had died of PCa. With regard to metastasis in patients who diagnosed CRPC, the 5-year CSS rate was 100% for nonmetastatic CRPC (nmCRPC) patients and 53.8% for metastatic CRPC (mCRPC) patients after RP. The 5-year CSS rate was 100% for nmCRPC patients and 27.1% for mCRPC patients after the diagnosis with CRPC. CRPC is one of the lethal causes with PCa death. However, nmCRPC may achieve relatively good prognosis in patients with PCa after RP.

Background Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonistplus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial.Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m 2 (60 mg/m 2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues.Findings Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7.4 months (IQR 3.5-13.9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4.1 months [95% CI 3.3-4.8] vs 2.8 months [2.6-2.9]; HR 0.696 [95% CI 0.573-0.845]; p=0.0002). Median overall survival was 9.4 months (95% CI 7.9-11.4) in the ramucirumab group versus 7.9 months (7.0-9.3) in the placebo group (stratified HR 0.887 [95% CI 0.724-1.086]; p=0.25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group.Interpretation Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

BACKGROUND: Altered prostate-specific antigen (PSA) glycosylation patterns can be useful biomarkers in detecting high-grade prostate cancer (HGPC). The microfluidic immunoassay system can analyse α2,3-linked sialylated PSA (α2,3-Sia-PSA) and α1,6-linked fucosylated PSA (α1,6-Fuc-PSA) using different lectins, Mackkia amurensis agglutinin and Pholiota squarrosa lectin, respectively. Here, we investigated the diagnostic value of simultaneous analysis of α2,3-Sia-PSA and α1,6-Fuc-PSA for the detection of HGPC. METHODS: Men with serum PSA levels of 4–20 ng/mL who underwent prostate biopsy were included. The model to predict HGPC (Gleason grade ≥2) was constructed by multivariate logistic regression analysis, in combination with α2,3-Sia-PSA and α1,6-Fuc-PSA (SF index). RESULTS: In the development cohort (n = 150), the SF index showed good discrimination for HGPC (area under the receiver-operating curve (AUC) 0.842; 95% confidence interval (CI) 0.782–0.903), compared to the single PSA test (AUC 0.632, 95% CI 0.543–0.721), α2,3-Sia-PSA (AUC 0.711, 95% CI 0.629–0.793) and α1,6-Fuc-PSA (AUC 0.738, 95% CI 0.657–0.819). Decision-curve analysis showed the superior benefit of the SF index. In the validation cohort (n = 57), the SF index showed good discrimination for HGPC (AUC 0.769, 95% CI 0.643–0.895). CONCLUSIONS: The SF index could differentiate HGPC, providing useful information for decision making for prostate biopsy in men with abnormal PSA levels.

Objective To evaluate the effects of the concomitant use of proton pump inhibitors (PPIs) and/or antibiotics (Abs) on oncological outcomes in patients with advanced urothelial carcinoma. Patients and methods We retrospectively evaluated 155 patients with advanced urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs) between August 2015 and April 2021. The concomitant use of PPI or Abs was defined as any PPI or Abs administered within 30 days before ICI initiation and during ICI therapy. The primary outcomes were the effect of PPI and/or Abs use on the objective response rate (ORR) and immune‐related adverse events (irAEs). The secondary outcomes were the effects of PPI and/or Abs use on progression‐free survival (PFS) and overall survival (OS) after ICI therapy analyzed using the inverse probability of treatment weighting‐adjusted Cox regression analysis. Results Of the 155 patients enrolled in the study, 99 (64%) were PPI users and 56 (36%) Abs users. PPI users were associated with a significantly poorer ORR than non‐PPI users (41% vs. 20%, respectively), whereas Abs use was not significantly associated with changes in ORR. The rate of irAEs was not significantly associated with the use of PPIs or Abs. Multivariate inverse probability of treatment weighting‐adjusted Cox regression analysis revealed significantly poorer PFS and OS in PPI users than in non‐PPI users, whereas Abs use was not associated with poorer outcomes. Conclusion The concomitant use of PPI may adversely affect oncological outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with ICI therapy.

The evaluation of surgical damage is challenging because of the lack of specific biomarkers. Total cell-free DNA (cfDNA) levels have been reported to increase with external trauma and may be a biomarker for tissue damage. To investigate the utility of perioperative total cfDNA levels in evaluating surgical damage in urological surgeries. This multicenter, prospective, observational study included 196 patients scheduled for urological surgeries between September 2020 and July 2021. The primary outcome was the change in total cfDNA levels before and after urological surgery. The secondary outcome was the effect of surgical type on total cfDNA ratio before and after urological surgery. The postoperative median total cfDNA level of the 196 patients was significantly increased 2.5-fold compared to the preoperative level (185.2 ng/mL vs. 406.7 ng/mL, P

INTRODUCTION AND OBJECTIVE:Osteopontin (OPN) is one of the most important components in the calcium stone matrix. However, the detailed mechanism of OPN-related urinary stone formation remains unkn...

INTRODUCTION AND OBJECTIVE:Although exact etiologies of overactive bladder (OAB) remains unclear, one of the believed theories to describe the disease process involves ischemia, vascular damage, an...

INTRODUCTION AND OBJECTIVE:Discriminating between urothelial carcinoma (UC) including bladder cancer (BCa) and upper urinary tract UC (UTUC) is often challenging.METHODS:We evaluated the diagnostic...

INTRODUCTION AND OBJECTIVE:Nivolumab, a novel anti-programmed cell death protein 1 (PD-1) antibody, is a standard therapy for patients with metastatic renal cell carcinoma (mRCC) that is used in co...

INTRODUCTION AND OBJECTIVE:There is limited evidence in the available literature regarding the association between nutritional status and urolithiasis. We investigated whether nutritional status is...

INTRODUCTION AND OBJECTIVE:To evaluate temporal trends in neoadjuvant chemotherapy (NAC) utilization and outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC).METHODS:W...

INTRODUCTION AND OBJECTIVE:Selection of patients for cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) is challenging. We evaluated the utility of the scoring system of Regis...

INTRODUCTION AND OBJECTIVE:The treatment strategy for patients with de novo metastatic prostate cancer (mPCa) has changed in recent years. Thus, an accurate assessment of the prognosis is critical....

INTRODUCTION AND OBJECTIVE:Overactive bladder (OAB) is part of lower urinary tract symptoms (LUTS) and prevalent among middle-aged and older individuals. Specific alterations of the microbiome (dys...

INTRODUCTION AND OBJECTIVE:To investigate the prognostic significance of total cell-free DNA (cfDNA) and androgen receptor amplification (AR -amp) in patients with castration-resistant prostate can...