Search

Background: Bladder cancer is the 10th most common cancer globally, with a growing incidence in Japan. Evaluation of molecular, genetic, and cellular biomarkers that predict treatment response and prognosis in patients with metastatic urothelial carcinoma (mUC) may help optimize sequential treatment strategies with chemotherapy and immune checkpoint inhibitors (ICIs). Methods: This multicenter, retrospective cohort study, evaluated programmed death-ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and cancer-immune phenotype as predictive prognostic biomarkers following first-/second-line treatment in Japanese adult patients with mUC. The primary endpoint was prevalence of PD-L1 expression. Secondary endpoints were TMB, overall survival (OS), and progression-free survival (PFS) from initiation of first-line treatment, and exploratory endpoints were cancer-immune phenotype, OS, PFS, and treatment response according to potential biomarker status. Results: Of the 143 patients included (mean age 71.7 years), PD-L1 expression was high in 29.4% of patients. Non-synonymous TMB was high in 33.6% and low in 66.4%. Cancer-immune phenotype was immune-desert in 62.9%, immune-excluded in 30.8%, and inflamed in 6.3%. Median OS and PFS following first-line treatment were 18.2 and 7.4 months, respectively. Overall response to second-line treatment was slightly better with high versus low/negative PD-L1 expression. PD-L1 expression and TMB were non-significant predictors of OS or PFS, whereas immune-excluded phenotype was associated with better OS in comparison with immune-desert phenotype. Conclusion: PD-L1 expression and TMB were non-significant predictors of prognosis after first-line treatment in Japanese patients with mUC, but cancer-immune phenotype may be an important prognostic factor in chemotherapy-ICI sequential treatment strategies. Clinical trial registration number UMIN000037727. [ABSTRACT FROM AUTHOR]

Background: This study is part of the SNPs in Nivolumab PD‐1 inhibitor for RCC (SNiP‐RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. Methods: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression‐free survival (PFS), overall survival (OS), and treatment‐related grade ≥ 3 (serious adverse events [SAEs]). Results: We included 222 patients. The median age was 69 years (interquartile range 62–74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. Conclusion: The SNiP‐RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy. [ABSTRACT FROM AUTHOR]

Background: Anti-PD-1 antibodies are widely used for cancer treatment including advanced renal cell carcinoma (RCC). However, their therapeutic and adverse effects vary among patients. This study aimed to identify genetic markers that predict outcome after nivolumab anti-PD-1 antibody treatment for advanced RCC. Methods: This study was registered on the website of the University Hospital Medical Information Network (protocol ID, UMIN000037739). Patient enrollment was conducted at 23 institutions in Japan between August 19, 2019, and September 30, 2020. Patient follow-up ended on March 31, 2021. Patients were treated with nivolumab for advanced clear cell RCC. A genome-wide association study was performed in the development set, while genotyping of target regions in the validation set was undertaken. Single nucleotide polymorphisms (SNPs) in genes of interest CD274, PDCD1LG2 and PDCD1 were genotyped in the combined set. The primary endpoint was the association of SNPs with objective response following nivolumab treatment. As secondary endpoints, the associations of SNPs with radiographic progression-free survival (rPFS) and treatment-related grade ≥ 3 adverse events (AEs) were evaluated. Results: A genome-wide association study followed by a validation study identified that SNPs in FARP1 (rs643896 and rs685736) were associated with objective response and rPFS but not AEs following nivolumab treatment. Furthermore, SNPs in PDCD1LG2 (rs822339 and rs1411262) were associated with objective response, rPFS, and AEs following nivolumab treatment. Genetic risk category determined according to the number of risk alleles in SNPs (rs643896 in FARP1 and rs4527932 in PDCD1LG2) excellently predicted objective response and rPFS in nivolumab treatment. Conclusion: This study revealed that SNPs in FARP1 and PDCD1LG2 were correlated with outcome in nivolumab treatment. The use of these SNPs may be beneficial in selecting appropriate treatment for individual patients and may contribute to personalized medicine. [ABSTRACT FROM AUTHOR]

Background: Worldwide, prostate cancer (PC) is the second most diagnosed cancer and the fifth leading cause of cancer death in men. Hormonal therapies, commonly used for PC, are associated with a range of treatment-emergent adverse events (TEAEs). The population from Japan seems to be at higher risk of developing TEAEs of skin rash compared to the overall global population. This study was conducted to get a better insight into the incidence, management, and risk factors for skin rash during active treatment for advanced PC in Japan. Methods: A retrospective cohort of PC patients was identified and subsequently categorized, into non-metastatic and metastatic castration-resistant prostate cancer patients (nmCRPC and mCRPC), and metastatic castration-naïve prostate cancer patients (mCNPC). The analysis was based on a dataset from the Medical Data Vision (MDV) database. Descriptive statistics were determined, and a multivariate Cox proportional hazards model was used to the associated risk factors for the onset of rash. Results: Overall, 1,738 nmCRPC patients, 630 mCRPC patients, and 454 mCNPC patients were included in this analysis. The median age was 78 years old and similar across the three cohorts. The skin rash incidence was 19.97% for nmCRPC cohort, 28.89% for mCRPC cohort, and 28.85% for mCNPC cohort. The median duration of skin rash ranged from 29 to 42 days. Statistically significant risk factors for developing skin rash included a history of allergy or hypersensitivity (all cohorts), increased age (nmCRPC and mCRPC), a body mass index (BMI) of < 18.5 (nmCRPC and mCRPC), and a PSA level higher than the median (nmCRPC). Skin rash was commonly managed with systemic and topical corticosteroids which ranged from 41.76% to 67.03% for all cohorts. Antihistamines were infrequently used. Conclusion: This study provides a better understanding of the real-world incidence, onset, duration, management and risk factors of skin rash in patients on active PC treatment in Japan. It was observed that approximately 20–30% of PC patients experience skin rash. Development of skin rash was associated with previous allergy or hypersensitivity, BMI of < 18.5, increased age and higher PSA levels, and was usually treated with corticosteroids. [ABSTRACT FROM AUTHOR]

Purpose: We compared the real-world efficacy and medical costs for treatment with upfront docetaxel (DOC) and abiraterone acetate (ABI) up to progression-free survival 2 (PFS2) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Methods: This multicenter retrospective study included 340 patients with mHSPC treated with either upfront DOC or upfront ABI between October 2015 and December 2021. We compared PFS2 and medical costs between the two treatment groups. PFS2 was defined as the time from first-line therapy to progression on second-line therapy. Medical costs were estimated using the National Health Insurance drug prices in 2022 in Japan. Results: The upfront DOC and ABI groups included 107 and 233 patients, respectively. The incidence of metastatic castration-resistant PC progression was significantly higher in the upfront DOC group compared with the incidence in the upfront ABI group. However, no significant differences in PFS2 were observed between the two treatment groups. Monthly medical costs per patient were significantly higher in the upfront ABI group ($3453) compared with the costs in the upfront DOC group ($1239, P < 0.001). The cost differences were significantly influenced by differences in the length of androgen deprivation therapy monotherapy (DOC group, 13.4 months vs. ABI group, 0.0 months). Conclusions: We observed a significant cost benefit in the upfront DOC group in Japanese real-world practice, while the PFS2 rates were similar between the groups. Upfront DOC was a more cost-effective option for men with mHSPC who were eligible for toxic chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: Robot‐assisted partial nephrectomy is widely performed for small renal masses, achieving excellent perioperative and intermediate oncological outcomes. However, long‐term oncological, functional, and quality of life outcomes after robot‐assisted partial nephrectomy remain unclear. In this study, we aimed to evaluate quality of life at 1 year and oncological and functional outcomes of robot‐assisted partial nephrectomy after a minimum follow‐up of 5 years. Methods: Personal, perioperative, postoperative, functional, oncological, and quality of life data were evaluated. The EQ‐5D‐5L tool, which incorporates health profiles and a EuroQol Visual Analog Scale, was used to assess quality of life preoperatively and 365 days postoperatively. Regarding oncological and functional outcomes, overall survival, recurrence‐free survival, and changes in estimated glomerular filtration rate were calculated. Results: There were few changes in levels between the two time points for all EQ‐5D dimensions. The mean change in EQ‐5D‐5L was 0.020 (95% confidence interval 0.006–0.033, P = 0.006), and in EuroQol Visual Analog Scale score 4.60 (95% confidence interval 2.17–7.02, P = 0.0003). Overall and recurrence‐free survival 5 years after robot‐assisted partial nephrectomy were 97.9% and 92.8%, respectively. After an early postoperative decrease, the estimated glomerular filtration rate remained stable over time. Conclusions: Robot‐assisted partial nephrectomy in patients with a T1 renal tumor is safe, feasible, and effective from the perspective of quality of life and survival, even after 5 years. When making treatment decisions, perioperative and quality of life outcomes should be considered together with long‐term oncological outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To explore associations between the gut microbiome and overactive bladder (OAB) with daily urinary urgency among individuals reporting this diagnosis within a single community. Methods: 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. Results: Individuals reporting OAB with daily urinary urgency demonstrated a lower bacterial diversity between individuals (Bray–Curtis distance 0.48 vs. 0.53, P < 0.001); the results cluster differently in the non-OAB groups. The relative abundance of genus Bifidobacterium was significantly lower among those reporting daily urgency (2.41% vs. 4.23%, P = 0.014). By contrast, the relative abundance of genus Faecalibacterium (9.25% vs. 6.26%, P = 0.006) was significantly higher in this group. Conclusion: We observed significant differences in gut microbial contents and specific bacterial genera in association with OAB with daily urgency. Further study will be necessary to assess causal relationships between the gut microbiome and OAB. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between serum serotonin (5-HT) levels and overactive bladder (OAB) in a community-dwelling population. Methods: 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. Results: 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 < 0.001). Multivariable analysis showed that age (odds ratio [OR]; 1.06, 95% confidence interval [CI]; 1.04–1.08, P < 0.001) and log serum 5-HT level (OR; 0.25, 95% CI; 0.10–0.68, P = 0.006) were independently associated with OAB. Conclusions: Lower serum 5-HT levels could independently be associated with the presence of OAB. Further study is necessary to elucidate a possible causal relationship between serum 5-HT levels and OAB. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Aims: To investigate the longitudinal association of microalbuminuria with overactive bladder (OAB). Methods: This longitudinal study investigated 561 participants of the Iwaki Health Promotion Project in both 2015 and 2019 in Japan. Microalbuminuria and OAB symptoms were assessed using the urine albuminuria creatinine ratio (ACR) and the overactive bladder symptom score (OABSS), respectively. Urine ACR was defined as high if ≥9.3 mg/gCr. Differences in OABSS between 2015 and 2019 were evaluated as ∆OABSS. Participants were divided into two groups according to ΔOABSS: high (ΔOABSS > 1) and control (≤1). We used baseline data acquired in 2015, such as urine ACR, the Pittsburgh Sleep Quality Index (PSQI), and arterial stiffness expressed by brachial‐ankle pulse wave velocity (baPWV). Predictive factors of a ΔOABSS > 1 were assessed by multivariable logistic regression analysis. Results: This study included 332 women and 229 men. Of those, 86 (34 males and 52 females) were classified into the ΔOABSS > 1 group. There were significant group differences in age, renal function, and hemoglobin A1c. Participants in the ΔOABSS > 1 had a higher prevalence of PSQI > 5, baPWV ≥ 1400 seconds/cm, and urine ACR ≥ 9.3 mg/gCr (49% vs 20%, P =.001) than those in the control group. Multivariable analysis revealed that PSQI > 5 (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.15‐4.60; P =.002) and urine ACR ≥ 9.3 mg/gCr (OR, 1.93; 95% CI, 1.15‐3.23; P =.013) were independent risk factors for ΔOABSS > 1. Conclusions: Microalbuminuria may be an independent risk indicator for OAB symptom exacerbation. [ABSTRACT FROM AUTHOR]

Purpose: Clinical outcomes of patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC) and initially treated with androgen deprivation therapy (ADT) were evaluated. Methods: The medical records of 605 consecutive mHNPC patients with initial ADT or combined androgen blockade (CAB) at nine study centers between 2008 and 2016 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free and overall survival (OS) were estimated by the Kaplan–Meier method. The association of pretreatment risk factors with CRPC-free survival and OS was evaluated by Cox proportional hazard models and differences in survival were classified by the number of risk factors. Results: Median follow-up was 2.95 years, median CRPC-free survival was 21.9 months and median OS was 5.37 years. Multivariable analysis found that four risk factors, a Gleason score ≥ 9, lymph node metastasis, an extent of disease score ≥ 2, and serum LDH of > 220 IU were independently associated with both CRPC-free survival and OS. Median CRPC-free survival of low-risk patients with no or one factor was 86.5 months, 17.9 months in intermediate-risk patients with two or three factors, and 11.0 months in high-risk patients with four factors. Median OS was 4.72 years in intermediate- and 2.44 years in high-risk patients. It was not reached in low-risk patients. Conclusion: In this series, CRPC-free and OS of a subset of mHNPC patients in Japan who were treated with ADT or CAB had better CRPC-free and overall survivals in Japan. Risk-adapted treatment based on the presence of novel prognostic factors may be beneficial for selected mHNPC patients. [ABSTRACT FROM AUTHOR]

Objectives: To carry out a comparison of upper urinary tract urothelial carcinoma characteristics and behavior between patients in Taiwan and Japan. Methods: A Taiwan urinary tract urothelial carcinoma cohort was obtained from Kaohsiung Chang Gung Memorial Hospital, and a Japan urinary tract urothelial carcinoma cohort from Hirosaki University Hospital. The inclusion criteria were urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy. Those who received perioperative chemotherapy were excluded. Finally, 765 patients in the Taiwan cohort and 325 in the Japan cohort were analyzed. The end‐point of this study was to study the natural course of urinary tract urothelial carcinoma within 5 years between these two groups. Results: The main finding was that urinary tract urothelial carcinoma patients in Taiwan were younger (P < 0.001), more were women (P < 0.001), with low‐stage disease (P < 0.001), with more chronic kidney disease (P < 0.001), with less smoking history (P < 0.001), with more bladder cancer history (P = 0.002), with more multifocal (P < 0.001) and less high‐grade disease (P = 0.015), as well as less lymphovascular invasion (P < 0.001) and more squamous differentiation (P < 0.001). However, the multivariate Cox regression analysis showed no racial difference in oncologic outcome, such as intravesical recurrence, systemic recurrence or cancer‐specific death in primary and propensity‐matched cohorts. Bladder cancer history was found to be the most important factor predicting intravesical recurrences, whereas stage was strongly associated with systemic recurrence and cancer specific mortality. Conclusions: The clinical characteristics of urinary tract urothelial carcinoma in Taiwan are significantly different from those of urinary tract urothelial carcinoma in Japan. However, there is no racial difference in stage‐specific oncologic outcome after standard nephroureterectomy. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone‐naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). Methods: At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer‐specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results: During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5‐year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5‐year net CSS and OS survival gradually increased for all the patients. In patients given a 5‐year survivorship, the conditional 5‐year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) ≥2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions: The conditional 5‐year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient's risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5‐year follow‐up. Conditional net survival can play a role in clinical decision‐making, providing intriguing information for cancer survivors. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between the Geriatric Nutritional Risk Index (GNRI) and prognosis of patients with metastatic hormone-naïve prostate cancer (mHNPC) and to design the optimal risk score predicting for prognosis. Methods: We retrospectively reviewed data from the Michinoku Japan Urological Cancer Study Group database, containing information about 656 patients with mHNPC who initially received androgen-deprivation therapy between 2005 and 2017. The baseline GNRI was calculated using serum albumin level and body mass index. Poor nutrition was defined as GNRI < 92.0. The impact of GNRI, CHAARTED criteria, and laboratory parameters on oncological outcomes was investigated using the multivariable Cox regression models. We developed the risk comprising GNRI and laboratory parameters and compared its prognostic performance with the CHAARTED criteria using the receiver operating characteristic curve with the DeLong method. Results: Of 339 patients with sufficient data, 66 (19%) were diagnosed with poor nutrition. Multivariate analyses showed that GNRI < 92.0 was an independent prognostic factor of cancer-specific survival [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.04–2.98, P = 0.035] and overall survival (HR 1.80; 95% CI 1.13–2.89, P = 0.013), in addition to hemoglobin (Hb) and lactic dehydrogenase (LDH) levels. We designed the risk score comprising GNRI < 92.0, Hb < 13.0 g/dL, and LDH > 222 IU/L. The predictive value of the risk score was significantly superior to that of the CHAARTED criteria. Conclusions: Poor nutrition may predict mortality in patients with mHNPC. Risk factors, such as nutritional status and laboratory parameters, may be useful in decision-making regarding aggressive treatments for patients with mHNPC. [ABSTRACT FROM AUTHOR]

Background: The impact of distance between donor and recipient hospitals on outcomes in cadaveric kidney transplantations is unknown. We investigated the association between inter-hospital distance and outcomes in cadaveric kidney transplantations in Japan. Methods: We retrospectively analyzed 363 cadaveric kidney transplantations between 2002 and 2017 in Japan. Inter-hospital distance, graft transport time, total ischemic time (TIT), and graft survival were compared between our hospital and national transplantation cohort in Japan. Estimated glomerular filtration rate (eGFR) 1 month and 1 year after transplantation was compared between cadaveric and living-donor kidney transplantations in our hospitals. Additionally, inter-hospital distances among the seven geographical regions in Japan were assessed. Results: There were 12 and 351 cadaveric kidney transplantations at our hospital and in Japan, respectively. Mean inter-hospital distance at our hospital (217 ± 121 km) was significantly longer than that of the national cohort (53 ± 80 km; P < 0.001). Mean TIT and graft survival for our hospital and national cohort were 539 ± 200 min and 91% and 491 ± 193 min and 81%, respectively. Mean eGFRs 1 year after cadaveric and living-donor transplantations at our hospitals were comparable (47 ± 16 vs. 47 ± 15 mL/min/1.73 m2). The comparison among seven regions in Japan indicated a regional difference in inter-hospital distance with an association between area (km2) and inter-hospital distance (km). Conclusions: Despite the longer inter-hospital distance at our hospital, TIT and transplant outcomes were acceptable in our cases. In addition, geographical inequity in graft allocation in Japan was suggested. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population. Materials and Methods: The cross‐sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses. Results: This study included 431 men and 682 women. AGEs and 8‐OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8‐OHdG levels. Conclusions: We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia. [ABSTRACT FROM AUTHOR]

Objectives To determine the characteristics of testicular germ cell tumors in older patients. Methods A testicular cancer survey was carried out by the Japanese Urological Association in 2011 to register the testicular cancers diagnosed in 2005 and 2008. The survey included age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, treatment and clinical outcomes. These factors were compared between patients aged ≥50 years and those aged <50 years at diagnosis. Results Of the 1119 cases of primary testicular germ cell tumors, 123 (11.0%) were diagnosed at age ≥50 years. Compared with patients aged <50 years, germ cell tumors in older patients were more frequently seminomas (74.8% vs 61.4%, P = 0.004) and clinical stage I at diagnosis (79.5% vs 70.7%, P = 0.041). Metastatic germ cell tumors in patients aged ≥50 years were more frequently classified into the good prognosis group according to the International Germ Cell Consensus Classification compared with those in younger patients (84.0% vs 53.8%, P = 0.003). Nevertheless, cancer-specific survival of patients aged ≥50 years was not superior to that of younger patients (4-year survival rates; 93.7% vs 97.8%). Conclusions Testicular germ cell tumors in patients aged ≥50 years are more commonly seminomas, and tend to be diagnosed at earlier stages compared with younger patients; however, the prognosis of older patients is not favorable compared with that of younger patients. [ABSTRACT FROM AUTHOR]

The Japanese Urological Association revised the clinical practice guidelines for bladder cancer in April 2015. This was the first update carried out in the 6 years since the development of the initial clinical practice guidelines for bladder cancer in 2009. The descriptive content was revised, and additions were made with a focus on new-found evidence and advances in the latest medical practices, and on the basis of the increasingly aging population observed in the underlying social context in Japan. An algorithm for the treatment of bladder cancer has been presented as a new trial. In the present article, we will introduce the essential contents and clinical questions that address the present revisions. [ABSTRACT FROM AUTHOR]

Objectives To explore predictive factors of disease recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial cancer. Methods A multi-institutional national database promoted by the Japanese Urological Association including 293 institutions and 1172 patients was used for the present study. Patient with non-metastatic upper urinary tract urothelial cancer who underwent primary radical nephroureterectomy with curative intent were analyzed. Univariate analysis using the Kaplan-Meier method and multivariate Cox regression models with stepwise selection was used to evaluate time to recurrence after surgery. Results The median duration of follow up was 55.8 months, and disease recurred in 325 (27.7%) patients at a median of 11.4 months after radical nephroureterectomy. According to a Cox proportional hazards model, the Union International Contre le Cancer 2002 pathological stage of the primary tumor, lymph node status, presence of lymphatic and/or vascular invasion, infiltrative growth pattern, and age were independent predictors ( P < 0.05) of recurrence-free survival. Conclusions Despite several limitations, our analysis suggests that pathological tumor stage, lymph node status, lymphovascular invasion, infiltrative growth pattern and age represent important prognostic variables after radical nephroureterectomy in Japanese patients with upper urinary tract urothelial cancer. This information could be potentially used to select patients for adjuvant systemic therapy. [ABSTRACT FROM AUTHOR]

Objectives To examine the influence of smoking history on the diagnosis and other tumor characteristics of upper tract urothelial carcinoma in Japan. Methods A total of 1509 patients with upper tract urothelial carcinoma who were diagnosed in 2005 from 348 Japanese institutions were registered using the multi-institutional national database of the Japanese Urological Association and included in this analysis. Clinical data of the patients were collected in 2011. The associations between the patients' self-reported smoking history and their age at the diagnosis of upper tract urothelial carcinoma, sex, pathological T stage and tumor grade were analyzed. Results The mean age at the diagnosis of upper tract urothelial carcinoma was approximately 5 years earlier for the 238 current smokers than for the 618 current non-smokers ( P < 0.0001). Similar associations between smoking and the early diagnosis of upper tract urothelial carcinoma were shown in the sex subgroups and in subgroups stratified by pathological T stages. Among the current smokers, the age at diagnosis for the smoking ≥ 20 cigarettes per day group was 6.5 years lower than that of the < 20 cigarettes per day group, which was significantly different ( P < 0.0001). Conclusion Current smoking is a significant risk factor for the earlier diagnosis of upper tract urothelial carcinoma. The finding is important from the perspective of both healthcare and medical economies. [ABSTRACT FROM AUTHOR]

Objectives To describe the clinical and pathological characteristics and the outcomes of renal pelvic and ureteral cancer patients diagnosed in 2005 in Japan. Methods In 2011, data were collected from renal pelvic and ureteral cancer patients diagnosed in 2005. A total of 1509 registered patients from 348 institutions were analyzed. Epidemiology and survival were analyzed based on each cancer location and on cancer multiplicity. Results The 5-year overall survival of the 1509 patients was estimated at 0.64. Open surgery was carried out in 409 renal pelvic cancer cases (66.9%) and 315 ureteral cancer cases (63.0%). The retroperitoneal approach was common, and lymph node dissection was carried out in approximately one-third of open surgery cases and one-fifth of laparoscopic cases. Approximately 60% of the operated unilateral renal pelvic or ureteral cancer was diagnosed as invasive, and just 14.6% was diagnosed as stage pTa. Distribution of the estimated worst tumor grade was significantly different for renal pelvic cancer and ureteral cancer. Conclusions This article presents the first large population report of survival data in Japanese renal pelvic and ureteral cancer patients. In comparison with the Japanese bladder cancer database report in 1999-2001 from the Cancer Registration Committee of the Japanese Urological Association, the pathological characteristics of renal pelvic and ureteral cancer were diagnosed as aggressive. [ABSTRACT FROM AUTHOR]

Regional and facility disparities in androgen deprivation therapy for prostate cancer from a multi-institutional Japan-wide database. Despite several limitations, this study is the first to compare the prognostic impact of regional differences and facility type in patients with prostate cancer treated with primary androgen deprivation therapy. Shiota I et al i .2 investigated the oncological outcomes of patients treated with primary androgen deprivation therapy in urban compared with rural areas, and academic centers compared with non-academic hospitals/clinics using a Japanese multi-institutional registry, established by the Japan Study Group of Prostate Cancer (J-CaP; I n i = 19 162). [Extracted from the article]

Background Management of renal cell carcinoma (RCC) with tumor thrombus extending to the renal vein and inferior vena cava (IVC) is challenging. The aim of this study was to evaluate the benefit of surgical management in such patients. Methods From February 1995 to February 2013, 520 patients were treated for RCC at Hirosaki University Hospital, Hirosaki, Japan. The RCC patients with tumor thrombus extending to the renal vein (n = 42) and IVC (n = 43) were included in this study. The records of these 85 patients were retrospectively reviewed to assess the relevant clinical and pathological variables and survival. Prognostic factors were identified by multivariate analysis. The benefit of surgical management was evaluated using propensity score matching to compare overall survival between patients who received surgical management and those who did not. Results RCC was confirmed by pathological examination of surgical or biopsy specimens in 74 of the 85 patients (87%). Sixty-five patients (76%) received surgical management (radical nephrectomy with thrombectomy). Distant metastasis was identified in 45 patients (53%). The proportion of patients with tumor thrombus level 0 (renal vein only), I, II, III, and IV was 49%, 13%, 18%, 14%, and 5%, respectively. The estimated 5-year overall survival rate was 70% in patients with thrombus extending to the renal vein and 23% in patients with thrombus extending to the IVC. Multivariate analysis identified thrombus extending to the IVC, presence of distant metastasis, surgical management, serum albumin concentration, serum choline esterase concentration, neutrophil-lymphocyte ratio, and Carlson comorbidity index as independent prognostic factors. In propensity score-matched patients, overall survival was significantly longer in those who received surgical management than those who did not. Conclusions Surgical management may improve the prognosis of RCC patients with thrombus extending to the renal vein and IVC. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify risk factors for erectile dysfunction (ED) in healthy men. A comprehensive risk factor investigation was carried out in a Japanese community. The subjects were 280 healthy male volunteers with an average age of 56 years (range: 20–83 years) who participated in the Iwaki Health Promotion Project in 2006. They were residents of Iwaki district, Hirosaki City, in northern Japan. The participants completed the five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (I-PSS) surveys at the site of examination. We measured blood pressure and brachial-ankle pulse wave velocity (baPWV). We also measured risk factors for metabolic syndrome and sex hormones. We compared these risk factors with the IIEF-5 scores. Ninety-five participants (34%) scored 11 points or fewer on the IIEF-5 survey (severe/moderate ED), 154 (55%) scored 12–21 points (mild ED) and 31 (11%) scored 22 points or more (no ED). The prevalence of ED in the Japanese rural community was 89% (249/280). The severe/moderate ED group had significantly higher total I-PSS scores ( p = 0.001), baPWV values ( p < 0.001) and systolic blood pressure ( p < 0.001) than the mild/no ED group. The same group had significantly lower free testosterone ( p < 0.001) and dehydroepiandrosterone sulphate ( p < 0.001) than the mild/no ED group. Logistic regression analysis revealed significant differences in baPWV ( p = 0.003), total I-PSS ( p = 0.015) and free testosterone ( p = 0.003). Lower urinary tract symptoms, baPWV and free testosterone are independent risk factors for ED in healthy Japanese men. [ABSTRACT FROM AUTHOR]

Introduction: To determine the impact of cauda equina symptoms on male lower urinary tract function, we investigated the related risk factors in healthy Japanese men. Methods: Subjects included 345 healthy males (average age 56 years; range 26–83) who participated in the Iwaki Health Promotion Project in 2006. They were residents of Iwaki district, Hirosaki City, northern Japan. Using a self-administered, self-reported questionnaire for lumbar spinal stenosis and International Prostate Symptom Score (IPSS), we investigated the prevalence of cauda equina symptoms. We also measured body mass index; blood pressure; and triglyceride, cholesterol, glucohemoglobin, and prostate-specific antigen levels. Results: Nineteen participants (5.5%) were positive for cauda equina symptoms; 270 participants (78.3%) scored 0–7 points on the total IPSS survey, 65 (18.8%) scored 8–19, and 10 (2.9%) scored 20–35. The total IPSS, and storage and voiding symptom scores of participants negative for cauda equina symptoms were significantly lower than those who were positive. Multiple logistic regression analysis revealed that age and cauda equina symptoms were independent significant risk factors for total IPSS and storage symptoms. Conclusions: Cauda equina symptoms are closely related to lower urinary tract symptoms in healthy Japanese men. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Minimally invasive radical cystectomy for patients with muscle-invasive bladder cancer is one of the standard therapies.[1], [2], [3] However, the benefit of laparoscopic intracorporeal ileal conduit urinary diversion (ICUD-IC) remains unclear in comparison with extracorporeal ileal conduit urinary diversion. Kanno I et al i . compared the perioperative and oncological outcomes of pure laparoscopic ICUD-IC with extracorporeal ileal conduit urinary diversion after laparoscopic radical cystectomy for muscle-invasive bladder cancer.[4] Of 455 patients, they used matched pairs (72 I vs i 72), and they concluded that the laparoscopic ICUD-IC is safe, feasible with faster postoperative bowel recovery, decreased wound-related complication rates, and comparable postoperative complication rates and oncological outcomes compared with extracorporeal ileal conduit urinary diversion. As the authors stated, the substantial disadvantage of pure laparoscopy is the difficulty in the limited working field, especially in the ureteroenteric anastomosis.[5] In this regard, the majority of urologists agree with the benefit of robotic surgery for ICUD-IC. [Extracted from the article]

CHAARTED-HVD was defined as the presence of visceral metastases and/or four more bone metastases with at least one outside of the vertebral column and pelvis.[2] CRPC-FS and OS were compared using Kaplan-Meier with the log-rank test and uni-/multivariate Cox regression analyses. Similar to the present study, a retrospective study reported the utility of the CHAARTED criteria in Japanese mHNPC patients.[4] However, the presence of visceral metastasis was not significantly associated with prognosis in the present study. Impact of the site of metastases on survival in patients with metastatic prostate cancer. [Extracted from the article]

Accurate clinical staging of patients with upper urinary tract urothelial carcinoma (UTUC) is essential for the selection of optimal treatment.1 However, the detection of clinical T stage before radical nephroureterectomy is challenging in the setting of the currently available imaging modalities.2 Shiga I et al i .3 investigated discrepancies between clinical and pathological T stages in patients with nonmetastatic UTUC (cT1-4N0M0) treated with radical nephroureterectomy alone in 6831 patients. This study had two important findings: (i) approximately 30% of UTUC patients had upstaging, and (ii) there was a higher rate of accurate cT3 staging, but a lower rate of accurate cT2 staging in UTUC. The authors showed that UTUC patients with cT3 disease had a higher accurate staging rate (83.1% in ureteral and 80.2% in renal pelvis cancers) compared to those with cT2 disease (48.5% in ureteral and 33.3% in renal pelvis cancers). [Extracted from the article]

Objective To understand the current practice pattern of active surveillance using a nationwide survey among Japanese urologists. Methods A new questionnaire about active surveillance was developed and mailed to 863 training institutes in January 2014. The questionnaire included indications for active surveillance, percentage of active surveillance for localized prostate cancer, problems with active surveillance, which protocol was used, timing of first repeat biopsy, use of prostate-specific antigen or doubling time and use of magnetic resonance imaging. Results A total of 2133 Japanese urologists in the 632 training institutes answered the questionnaire. The median age was 42 years (26-84 years). Of the responders, 26.9% had no use of active surveillance for localized prostate cancer. The Prostate Cancer Research International: Active Surveillance criteria were most frequently used (29.7%), followed by a low-risk group without a definitive follow-up protocol (29.4%). Regarding repeat biopsy, 40.6% carried it out at 1 year after active surveillance initiation, but 24.1% did not usually carry it out and 31.8% carried it out only when they considered it necessary. Magnetic resonance imaging was used routinely in 22.2% and as required in 67.6%. Re-biopsy or magnetic resonance imaging was less carried out in general hospitals than in universities. The percentage of no usual repeat biopsy was significantly higher in urologists who had more than 10 years of experience. Repeat biopsies (60.3%), inadequate inclusion criteria (49.9%), psychological burden for patients (43.7%), unexpected progression (41.1%) and unknown long-term outcomes (40.6%) were considered the major problems of active surveillance in the responders. Conclusions The practice pattern of active surveillance varies widely among Japanese urologists. It is necessary to gain a correct understanding of active surveillance. [ABSTRACT FROM AUTHOR]

Because of the serious donor shortage in Japan, there is an increasing need for ABO blood type–incompatible kidney transplantation (ABOi-KT) in living-related donor kidney transplantation. We evaluated the outcomes of ABOi-KT performed at our hospitals using a contemporary immunosuppression strategy with low-dose rituximab. Between June 2006 and April 2019, 107 patients underwent living-related donor kidney transplantation at our hospitals. The patients were divided into ABO-compatible (ABOc) and ABOi groups. The basic immunosuppression regimen differed between the 2 groups in the use of low-dose rituximab and therapeutic apheresis in the ABOi group. We compared graft survival, patient survival, rejection, viral infection, and posttransplant renal function between the 2 groups. Of 107 recipients, 37 (35%) underwent ABOi-KT. The 5-year graft survival rates in the ABOc and ABOi group were 91% and 100%, respectively. The Kaplan-Meier analyses showed no difference in graft survival (P =.168) or patient survival (P =.873) between the groups. Biopsy-proven rejection in the ABOc and ABOi groups was observed in 13 (19%) and 7 (19%) patients, respectively (P =. 965), and viral infection was observed in 21 (30%) and 10 (27%) patients (P =. 747), respectively. Renal function by estimated glomerular filtration rate from 1 week to 5 years after transplantation was similar in both groups. The outcomes of ABOi-KT with low-dose rituximab were comparable with those of ABOc-KT at our hospitals. ABOi-KT with proper immunosuppression may be an option to help resolve the severe donor shortage in Japan. • We retrospectively evaluated outcomes of ABO blood type–incompatible living-related donor kidney transplantation (ABOi-KT) under a contemporary immunosuppression strategy with low-dose rituximab. • There were no differences in graft survival, patient survival, rejection, viral infection, or posttransplantation renal function between ABOi-KT and ABO-compatible living kidney transplantation (ABOc-KT). • ABOi-KT has the potential to have similar efficacy and safety to ABOc-KT depending on the desensitization strategy. [ABSTRACT FROM AUTHOR]

Although physical activity is associated with a decreased risk of erectile dysfunction (ED), the association of ED with physical function remains unclear. To investigate the relationship between gait function and ED in a community-dwelling population. This cross-sectional study analyzed 324 men who participated in the Iwaki Health Promotion Project in 2015 in Hirosaki, Japan. ED was assessed with the 5-Item International Index of Erectile Function (IIEF-5). The participants were divided into 2 groups: low IIEF-5 score (≤16) and high IIEF-5 score (>16). We evaluated physical function, including gait function and grip strength. Gait function was evaluated by 10-meter gait speed and 2-step score (the ratio of the maximum length of 2 strides to height). We assessed daily physical activity, comorbidities, mental status, and laboratory data. The association between physical function and a low IIEF-5 score was analyzed by multivariate logistic regression analysis. The main outcome measure was to assess whether gait function was an independent indicator for erectile dysfunction. Of 324 men, 154 (48%) had a low IIEF-5 score. Grip strength, 2-step score, and 10-meter gait speed in the low IIEF-5 group were significantly inferior to those in the high IIEF-5 group. Multivariate analysis showed that the 2-step score (odds ratio = 0.08), age, and total testosterone were independently associated with a low IIEF-5. This study may motivate clinicians to investigate predictive values of physical function for ED. The strength of this study was the use of simple, objective, and feasible tests for gait function to assess its association with ED. The limitations of this study were selection bias, regional bias, and nature of the cross-sectional study. Of the gait functional tests, not the 10-meter gait speed but 2-step score was an independent indicator for the presence of ED. Okamoto T, Hatakeyama S, Imai A, et al. The Relationship Between Gait Function and Erectile Dysfunction: Results from a Community-Based Cross-Sectional Study in Japan. J Sex Med 2019; 16:1922–1929. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that the prostate-specific antigen (PSA) gene polymorphisms may be associated with the risk of prostate cancer in Caucasian populations. To verify the association, we examined the PSA polymorphisms at positions −158 and −252 in 300 prostate cancer cases, 216 benign prostatic hyperplasia (BPH) cases, and 266 controls by the PCR-restriction fragment length polymorphism analysis. Regarding the PSA polymorphism at position −158, the A allele was less common in the Japanese population (A 0.22, G 0.78) than that in other ethnic populations (A 0.37–0.52, G 0.48–0.63). No significant associations were found between the polymorphism and the risks of prostate cancer (P=0.530) and BPH (P=0.740) and between the polymorphism and the serum PSA level (P=0.626). As for the polymorphism at position −252, no significant results were also found. In conclusion, the PSA polymorphisms may not be associated with the risk of prostate cancer development and its disease progression and the risk of BPH in Japanese men, and may also be not related to the serum PSA level in Japanese men with prostate cancer. [Copyright &y& Elsevier]

Purpose: We assessed the association between oral frailty risk and LUTS among middle-aged and older adults in a community-dwelling population., Methods: This cross-sectional study was conducted among 586 subjects aged ≥ 40 years who participated in the Iwaki Health Promotion Project in Hirosaki, Japan. We used the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS) to assess LUTS. LUTS was defined as an IPSS score of 8 or higher or meeting diagnostic criteria for OAB. Oral frailty risk was defined as experiencing two or more of the following: decreased chewing ability, decreased biting force, and dry mouth sensation. Physical performance (10-m gait speed and grip strength) was used for analysis. The association between oral frailty risk and LUTS was examined using multivariate logistic regression analyses., Results: The study included 218 men and 370 women, of whom 140 had LUTS. The mean age of this cohort was 59 years. Significant differences were observed between the LUTS and non-LUTS groups, including age, hypertension, history of CVD, depressive status, sleep disturbance, and 10 m gait speed. The prevalence of oral frailty risk was significantly higher in the LUTS group than in the non-LUTS group (26% vs. 11%, P < 0.001). Multivariate analysis revealed that age, male gender, and oral frailty risk (odds ratio: 2.67, 95% confidence interval: 1.57-4.51, P < 0.001) were independent factors for LUTS. Moreover, oral frailty risk was an independent factor in both participants aged < 65 years and participants aged ≥ 65 years., Conclusions: Oral frailty was independently associated with LUTS., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This article is an English translation of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma (2nd edition) published in June 2023. The Japanese Urological Association's (JUA) Guidelines Committee on Upper Tract Urothelial Carcinoma (UTUC) created a 2023 update guideline to support clinicians' current evidence-based management of UTUC and to incorporate its recommendations into clinical practice. The new guideline adhered as closely as possible to the Minds Manual for Guideline Development 2020 ver. 3.0. Findings related to epidemiological, pathological, diagnosis, treatment, and follow-up were reviewed. In addition, seven clinical questions (CQs) were set to determine the grade of recommendation and level of evidence. Preconceptions and biases were removed from the preparation process, the overall evidence was evaluated appropriately, and recommendations were made after fully considering the balance between benefits and harms. Although the evidence is still insufficient to be taken up as a CQ, the latest important information is described in seven columns, and clinical issues that should be resolved in the future related to the CQ are described as recommendations for tomorrow. We hope that these guidelines will help medical professionals, patients, and their families involved in the treatment of UTUC in their decision-making, and hope that a critical review of these guidelines will lead to further refinements in the next edition., (© 2023 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Objectives: To investigate the efficacy of pharmacotherapy for metastatic non-clear cell renal cell carcinoma (nccRCC) in Japanese population., Methods: In this retrospective analysis, we compared the time to treatment failure (TTF) for molecular-targeted agents as first-line therapy, or nivolumab therapy as sequential therapy between ccRCC and nccRCC using the data of Japanese metastatic RCC patients registered in the Michinoku Japan Urological Cancer Study Group database., Results: In total, 511 cases of ccRCC and 77 cases of nccRCC were treated with pharmacotherapy. After excluding the patients who received cytokine therapy, chemotherapy, or others, there were 391 ccRCC patients and 60 nccRCC patients who were treated with tyrosine kinase inhibitors (TKIs), and 7 ccRCC patients and 7 nccRCC patients who were treated with mammalian-target of rapamycin inhibitors (mTORIs). In addition, 132 ccRCC patients and 16 nccRCC patients received nivolumab. There was no significant difference in IMDC risk classification before first-line therapy between ccRCC and nccRCC groups, or in each subgroup within the nccRCC group. TTF for TKIs (161 days, 95% CI: 75-212 days) and mTORIs (21 days, 95% CI: 9-31 days) didn't differ significantly between nccRCC and ccRCC groups (205 days, 95% CI: 174-243 days and 33 days, 95% CI: 8-113 days, respectively). TTF for TKIs was significantly longer than that for mTORIs in nccRCC group (p<0.01). There was no significant difference in TTF between the different TKIs in nccRCC group. In addition, no significant difference in TTF for nivolumab was seen between ccRCC and nccRCC groups., Conclusions: The results showed that the efficacy of molecular-targeted agents as first-line therapy was similar oncological outcomes between metastatic nccRCC and ccRCC in Japanese patients. TKIs may be more effective than mTORIs in metastatic nccRCC patients. Nivolumab administration might also be as effective in nccRCC patients as in ccRCC patients in Japanese population., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The Modified International Metastatic Renal Cell Carcinoma Dataset Consortium model (mIMDC) is a preoperative prognostic model for pT3cN0M0 renal cell carcinoma (RCC). This study aimed to validate the mIMDC and to construct a new model in a localized and locally advanced RCC (LLRCC)., Methods: A database was established (the Michinoku Japan Urological Cancer Study Group database) consisting of 79 patients who were clinically diagnosed with LLRCC (cT3b/c/4NanyM0) and underwent radical nephrectomy from December 2007 to May 2018. Using univariable and multivariable analyses, we retrospectively analyzed disease-free survival (DFS) and overall survival (OS) in this database, constructed a new prognostic model according to these results, and estimated the model fit using c-index on the new and mIMDC models., Results: Independent poorer prognostic factors for both DFS and OS include the following: ≥ 1 Eastern Cooperative Oncology Group performance status, 2.0 mg/dL C-reactive protein, and > upper normal limit of white blood cell count. The median DFS in the favorable (no factor), intermediate (one factor), and poor-risk group (two or three factors) was 76.1, 14.3, and 4.0 months, respectively (P < 0.001). The 3-year OS in the favorable, intermediate, and poor-risk group were 92%, 44%, and 0%, respectively (P < 0.001). The c-indices of the new and mIMDC models were 0.67 and 0.60 for DFS (P = 0.060) and 0.74 and 0.63 for OS (P = 0.012), respectively., Conclusion: The new preoperative prognostic model in LLRCC can be used in patient care and clinical trials., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

We aimed to evaluate the seroprevalence and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of antibody titers. The antibody titer against the receptor-binding domain of SARS-CoV-2 spike (S) protein was determined. We compared seroprevalence rates (immunoglobulin G [IgG] level of ≥ 0.8 or ≥ 15 U/mL) between the healthy controls and KT recipients and identified factors associated with impaired humoral response. The seroprevalence rate of the healthy controls and KT recipients was 98% and 22%, respectively. Univariate logistic regression analysis revealed that age > 53 years, rituximab use, mycophenolate mofetil use, and KT vintage < 7 years were negatively associated with the rate of anti-SARS-CoV-2 S IgG ≥ 15 U/mL in KT recipients. ABO blood type incompatible KT was not significantly associated with seroprevalence. Humoral response after the second BNT162b2 mRNA vaccine was greatly hindered by immunosuppression therapy in KT recipients. Older age, rituximab use, mycophenolate mofetil use, and KT vintage may play key roles in seroconversion., (© 2022. The Author(s).)

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 < 0.001). Multivariate analysis revealed that age ≥ 65 years, current smoking, sleep disturbance, metabolic syndrome, and genus Streptococcus (Odds ratio: 1.05, P = 0.029) were independent risk factors for UU/UUI-progression. PPI use turned to be a significant risk factor on a multivariate analysis without including genus Streptococcus., Conclusions: Gut microbiome might be associated with a risk for OAB symptoms progression. PPI use might cause gut dysbiosis and increase this risk., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (© 2021. Japan Society of Clinical Oncology.)

We conducted a risk-adapted upfront docetaxel (DOC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Here, we reported an interim analysis of the study. The study enrolled 68 patients with newly diagnosed mHSPC between 2016 and 2018. According to the presence of visceral metastasis, an EOD score ≥ 3, or prostate-specific antigen (PSA) level at 3 months of ≥ 1 ng/mL, patients were divided into low- and high-risk groups. Patients were treated with androgen deprivation therapy (ADT) with or without bicalutamide; those in the high-risk group received upfront treatment involving six cycles of DOC (70 mg/m 2 ). Short-term treatment effect, adverse events, and quality of life (QOL) were evaluated. Fifty (73.5%) were classified in the high-risk group, and 46 (67%) received upfront ADT + DOC. In the ADT + DOC group, 43.5% (20/46) patients achieved a PSA level ≤ 0.2 ng/mL. PSA nadir and time to PSA nadir were 0.291 ng/mL and 288 days, respectively. In the ADT + DOC group, 76.1% (35/42) patients had adverse events (AEs) of grade ≥ 3. During a median follow-up of 18.5 months, 36.4% (8/22) patients in the ADT group and 43.5% (20/46) in the ADT + DOC group had CRPC. Two QOL scores including the physical status and appetite loss at 6 months significantly worsened in the ADT + DOC group but was resolved by 12 months. Upfront DOC achieved high PSA responses without long-term QOL deterioration. However, the short-term outcomes were limited. Longer follow-up is needed to determine the survival advantage.

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., (© 2020 The Japanese Urological Association.)

Purpose: We investigated the gut microbiome in subjects with erectile dysfunction (ED) in a community-based population., Methods: 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., Results: 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., Conclusion: 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.

The Clinical Practice Guidelines for Bladder Cancer edited by the Japanese Urological Association were first published in 2009 and a revised edition was released in 2015. Four years has passed since the 2015 edition, and the clinical practice environment surrounding bladder cancer has drastically changed during that time. The main changes include: (i) insurance coverage of a new diagnostic method for non-muscle-invasive bladder cancer; (ii) insurance coverage of an immune checkpoint inhibitor in advanced and metastatic bladder cancer; and (iii) advances in robot-assisted radical cystectomy as a minimally invasive treatment for muscle-invasive bladder cancer. A paradigm shift in bladder cancer diagnosis and treatment is occurring day by day. Therefore, in this 2019 edition, while dealing with the above changes, we carefully selected clinical questions with clear evidence and included other clinically important points in the general statement. We also added a new chapter on rare cancers of the urinary tract. As a new method for the evaluation of study evidence level, we introduce "The Grading of Recommendations Assessment, Development and Evaluation" system modified to Japanese by the Medical Information Network Distribution Service., (© 2020 The Japanese Urological Association.)

Objectives: To evaluate the relationship between frailty and lower urinary tract symptoms (LUTS), the association of frailty and LUTS remains unclear., Methods: This cross-sectional study investigated LUTS and frailty in 710 individuals (249 men and 461 women, aged ≥60 years) who participated in the Iwaki Health Promotion Project between 2014 and 2015 in Hirosaki, Japan. Parameters of frailty were compared for individuals with mild and moderate to severe symptoms of LUTS. The International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) were used to evaluate LUTS. Frailty was evaluated by the frailty phenotype (FP), modified frailty index (mFI), and frailty discriminant score (FDS). The influence of frailty on LUTS was investigated by multivariate logistic regression analyses., Results: Frailty parameters of age, renal function, and lower physical activity were significantly associated with severity of IPSS and OABSS. FP and mFI were significantly associated with severity of OABSS and IPSS, respectively. The FDS was significantly associated with severity of IPSS and OABSS. FP, mFI, and FDS were significantly associated with severity of nocturia. Multivariate logistic regression analyses revealed that FDS was independently associated with the severity of IPSS, OABSS, and nocturia, whereas FP and mFI were significantly associated with the severity of nocturia alone., Conclusions: Individuals with LUTS are potentially frailer than those without LUTS. Although the influence of frailty on LUTS is different depending on the measurement tool, attention for frailty is necessary for subjects with LUTS., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: To evaluate whether serum N-glycan profile can be used as a diagnostic marker of graft rejection after living-donor kidney transplants (KT)., Methods: We retrospectively examined 174 KT recipients at five medical centers. N-Glycan levels were analyzed in postoperative serum samples using glycoblotting combined with mass spectrometry. We developed an integrated score to predict graft rejection based on a combination of age, gender, immunological risk factors, and serum N-glycan levels at post-KT day D1 and D7. Rejection-free survival rates stratified by the sum of integrated scores (D1 + D7) were evaluated using Kaplan-Meier curves., Results: Of 174, 52 showed graft rejection (Rejection-pos. group) and 122 recipients did not show graft rejection (Rejection-neg. group). The integrated scores were significantly higher in the Rejection-pos. group than those of the Rejection-neg. group. Area-under-curve (AUC) value of integrated scores at post-KT D1, and D7 were 0.84 and 0.84, respectively. The sum of integrated scores (D1 + D7) ≥ 0.50 identified graft rejection with 81% sensitivity and 80% specificity; with an AUC value of 0.87. Recipients with higher sum of integrated scores (D1 + D7 ≥ 0.5) had significantly shorter rejection-free survival than those with lower scores., Conclusion: Evaluation of serum N-glycosylation profiles can identify recipients who are prone to rejection.

Purpose: We investigated the impact of previous, simultaneous or subsequent bladder cancer on the clinical outcomes of upper urinary tract urothelial carcinoma., Materials and Methods: We retrospectively collected data on 2,668 patients who underwent radical nephroureterectomy of nonmetastatic upper urinary tract urothelial carcinoma in 1995 to 2009. We evaluated the impact of bladder cancer on overall mortality and the factors predictive of subsequent bladder cancer., Results: A total of 631 patients (23.7%) had previous or simultaneous bladder cancer. Patients with previous or simultaneous bladder cancer had significantly shorter overall survival than patients without previous or simultaneous bladder cancer (HR 1.29, 95% CI 1.09-1.53, p=0.0026). Of the 2,037 patients without previous or simultaneous bladder cancer 683 (33.5%) subsequently had bladder cancer after radical nephroureterectomy. Of patients with pT0-2 disease those with subsequent bladder cancer had significantly shorter overall survival than patients without subsequent bladder cancer (HR 1.81, 95% CI 1.23-2.67, p=0.0025). In patients with pT3-4 disease subsequent bladder cancer was not associated with worse overall survival. On multivariable analyses independent predictors of subsequent bladder cancer were gender, preoperative urine cytology and clinical node status in the preoperative setting, and gender, adjuvant chemotherapy and pathological node status in the postoperative setting., Conclusions: Bladder cancer was significantly associated with worse clinical outcomes after radical nephroureterectomy of upper urinary tract urothelial carcinoma. Preventing subsequent bladder cancer in patients with pT0-2 upper urinary tract urothelial carcinoma may lead to better prognosis in those who undergo radical nephroureterectomy.

Background: Nocturia has been reported to be associated with sleep disturbance. However, whether nocturia or sleep disturbance has a more negative influence on the quality of life (QOL) of individuals remains unclear., Objective: To compare the impact of nocturia and sleep disturbance on QOL., Design, Setting, and Participants: This was a cross-sectional study including 3992 adults who participated in the Iwaki Health Promotion Project between 2011 and 2015 in Hirosaki, Japan., Outcome Measurements and Statistical Analysis: Sleep disturbance and nocturia were assessed in all participants using the Pittsburgh Sleep Quality Index (PSQI), international prostate symptom score for men, and overactive bladder symptom score for women. Sleep disturbance was defined as a PSQI score of ≥6. QOL was measured using the Short Form-36 questionnaire. Impacts of nocturia and sleep disturbance on QOL reduction (>30%) were investigated using logistic regression analyses., Results and Limitation: Of the 3992 participants, sleep disturbance was observed in 632 (16%). The frequency of nocturia was significantly associated with PSQI scores. Of QOL domains, both sleep disturbance and nocturia were significantly associated with decreases in the physical component summary score (physical QOL). However, nocturia was not associated with general health (general QOL) and mental component summary (mental QOL) scores. Multivariate logistic regression analysis showed that nocturia was not associated with a >30% reduction in general and mental QOL, whereas sleep disturbance was significantly associated with general, physical, and mental QOL reduction. As this was a cross-sectional study, the causality of nocturia and sleep disturbance could not be assessed., Conclusions: Nocturia and sleep disturbance affect QOL domains differently. Sleep disturbance has a higher impact on general and mental QOL reduction than nocturia., Patient Summary: We compared the impact of nocturia and sleep disturbance on quality of life (QOL). Nocturia was not associated with general and mental QOL reduction, whereas sleep disturbance was associated with general, physical, and mental QOL reduction., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate the effect of pretreatment C-reactive protein/albumin ratio and modified Glasgow prognostic score on the prognosis in patients with metastatic renal cell carcinoma., Methods: A retrospective study was carried out in 176 patients with metastatic renal cell carcinoma who received first-line tyrosine kinase inhibitors. The effect of adding inflammatory prognostic scores to the International Metastatic Renal Cell Carcinoma Database Consortium model (International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio and International Metastatic Renal Cell Carcinoma Database Consortium-Glasgow prognostic score models) on overall survival was evaluated using receiver operating characteristic curves. The prognostic value of inflammatory prognostic scores (C-reactive protein/albumin ratio-modified Glasgow prognostic score) was tested using the Kaplan-Meier method and Cox proportional regression models., Results: Patients were stratified into two groups using the cut-off value of 0.05: C-reactive protein/albumin ratio-low (<0.05) and C-reactive protein/albumin ratio-high (≥0.05). The area under the curve was significantly higher in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model (0.720) than that of the International Metastatic Renal Cell Carcinoma Database Consortium model (0.689) and the International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score model (0.703). Significant differences were observed in overall survival stratified by the number of risk factors in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio risk model between one or two and three or four factors (P < 0.001), and three or four and five or more factors (P = 0.001). For the patients in the International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk group, overall survival was significantly different between the C-reactive protein/albumin ratio-low and -high groups (P = 0.001), whereas it was not significantly different between the patients with one and two International Metastatic Renal Cell Carcinoma Database Consortium risk factors (P = 0.106)., Conclusion: The C-reactive protein/albumin ratio is a simple and independent predictor of overall survival in patients with metastatic renal cell carcinoma. The predictive activity was significantly improved in the International Metastatic Renal Cell Carcinoma Database Consortium-C-reactive protein/albumin ratio model compared with the International Metastatic Renal Cell Carcinoma Database Consortium/International Metastatic Renal Cell Carcinoma Database Consortium-modified Glasgow prognostic score models., (© 2019 The Japanese Urological Association.)