Impact of severe acute kidney injury on short-term mortality in urosepsis.

PURPOSE: To evaluate the impact of severe acute kidney injury (AKI) on short-term mortality in patients with urosepsis. METHODS: This prospective cohort study evaluated 207 patients with urosepsis. AKI was diagnosed in accordance with the Kidney Disease Improving Global Outcomes criteria, and severe AKI was defined as stage 2 or 3 AKI. Patients were divided into two groups: patients who developed severe AKI (severe AKI group) and patients who did not (control group). The primary endpoint was all-cause mortality within 30 days. The secondary endpoints were 90-day mortality and in-hospital mortality. The exploratory outcomes were the risk factors for severe AKI development. RESULTS: The median patient age was 79 years. Of the 207 patients, 56 (27%) developed severe AKI. The 30-day mortality rate in the severe AKI group was significantly higher than that in the control group (20% vs. 2.0%, respectively; P < 0.001). In the multivariable analysis, performance status and severe AKI were significantly associated with 30-day mortality. The in-hospital mortality and 90-day mortality rates in the severe AKI group were significantly higher than those in the control group (P < 0.001 and P < 0.001, respectively). In the multivariable analysis, age, urolithiasis-related sepsis, lactate values, and disseminated intravascular coagulation were significantly associated with severe AKI development. CONCLUSIONS: Severe AKI was a common complication in patients with urosepsis and contributed to high short-term mortality rates.

Combination of Muscle Quantity and Quality Is Useful to Assess the Necessity of Surveillance after a 5-Year Cancer-Free Period in Patients Who Undergo Radical Cystectomy: A Multi-Institutional Retrospective Study.

BACKGROUND: Although continuous surveillance after a 5-year cancer-free period in patients with bladder cancer (BC) who undergo radical cystectomy (RC) is recommended, optimal candidates for continuous surveillance remain unclear. Sarcopenia is associated with unfavorable prognosis in various malignancies. We aimed to investigate the impact of low muscle quantity and quality (defined as severe sarcopenia) on prognosis after a 5-year cancer-free period in patients who underwent RC. METHODS: We conducted a multi-institutional retrospective study assessing 166 patients who underwent RC and had five years or more of follow-up periods after a 5-year cancer-free period. Muscle quantity and quality were evaluated using the psoas muscle index (PMI) and intramuscular adipose tissue content (IMAC) using computed tomography images five years after RC. Patients with lower PMI and higher IMAC values than the cut-off values were diagnosed with severe sarcopenia. Univariable analyses were performed to assess the impact of severe sarcopenia on recurrence, adjusting for the competing risk of death using the Fine-Gray competing risk regression model. Moreover, the impact of severe sarcopenia on non-cancer-specific survival was evaluated using univariable and multivariable analyses. RESULTS: The median age and follow-up period after the 5-year cancer-free period were 73 years and 94 months, respectively. Of 166 patients, 32 were diagnosed with severe sarcopenia. The 10-year RFS rate was 94.4%. In the Fine-Gray competing risk regression model, severe sarcopenia did not show a significant higher probability of recurrence, with an adjusted subdistribution hazard ratio of 0.525 (p = 0.540), whereas severe sarcopenia was significantly associated with non-cancer-specific survival (hazard ratio 1.909, p = 0.047). These results indicate that patients with severe sarcopenia might not need continuous surveillance after a 5-year cancer-free period, considering the high non-cancer-specific mortality.

Can Erectile Dysfunction Severity Predict Major Adverse Cardiovascular Events in Men Undergoing Dialysis? A Prospective Cohort Study.

PURPOSE: To evaluate the impact of severe erectile dysfunction (ED) on future major adverse cardiovascular events (MACE) in men on dialysis. MATERIALS AND METHODS: This prospective cohort study included 71 men on dialysis. ED was assessed using the Sexual Health Inventory for Men (SHIM). Men were divided into the mild/moderate ED (SHIM score ≥8) and severe ED (SHIM score ≤7) groups. The primary endpoint was MACE-free survival. MACE was a composite of myocardial infarction, cardiovascular death, and stroke. The secondary endpoints were cardiac event-free survival and overall survival (OS). Moreover, the predictive abilities of severe ED for 5-year MACE, 5-year cardiac events, and 5-year overall mortality were evaluated. RESULTS: The median age and follow-up period of the included men were 64 years and 58 months, respectively. The median SHIM score was 4.0; all had a degree of ED, and 64.7% had severe ED. In the background-adjusted multivariable analyses, severe ED was not significantly associated with shorter MACE-free survival (hazard ratio [HR], 1.890; 95% confidence interval [CI], 0.533-6.706; p=0.324), cardiac event-free survival (HR, 2.081; 95% CI, 0.687-6.304; p=0.195), and OS (HR, 0.817; 95% CI, 0.358-1.863; p=0.630). Severe ED did not significantly improve the predictive abilities for 5-year MACE, 5-year cardiac events, and 5-year overall mortality (p=0.110, p=0.101, and p=0.740, respectively). CONCLUSIONS: ED severity was not associated with shorter MACE-free survival, cardiac event-free survival, or OS, and ED severity could not improve the predictive abilities for these outcomes in men undergoing dialysis.

Impact of an optimized surveillance protocol based on the European Association of Urology substratification on surveillance costs in patients with primary high-risk non-muscle-invasive bladder cancer.

OBJECTIVES: The optimal frequency and duration of surveillance in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) remain unclear. The aim of the present study is to develop an optimal surveillance protocol based on the European Association of Urology (EAU) substratification in order to improve surveillance costs after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk NMIBC. MATERIALS AND METHODS: We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. Patients were substratified into the highest-risk and high-risk without highest-risk groups based on the EAU guidelines. An optimized surveillance protocol that enhances cost-effectiveness was then developed using real incidences of recurrence after TURBT. A recurrence detection rate ([number of patients with recurrence / number of patients with surveillance] × 100) of ≥ 1% during a certain period indicated that routine surveillance was necessary in this period. The 10-year total surveillance cost was compared between the EAU guidelines-based protocol and the optimized surveillance protocol developed herein. RESULTS: Among the 428 patients with primary high-risk NMIBC, 97 (23%) were substratified into the highest-risk group. Patients in the highest-risk group had a significantly shorter recurrence-free survival than those in the high-risk without highest-risk group. The optimized surveillance protocol promoted a 40% reduction ($394,990) in the 10-year total surveillance cost compared to the EAU guidelines-based surveillance protocol. CONCLUSION: The optimized surveillance protocol based on the EAU substratification could potentially reduce over investigation during follow-up and improve surveillance costs after TURBT in patients with primary high-risk NMIBC.

Association between Aortic Calcification Burden and the Severity of Erectile Dysfunction in Men Undergoing Dialysis: A Cross-Sectional Study.

PURPOSE: Accelerated atherosclerosis is a major complication in patients with end-stage renal disease and it plays an important role in the pathogenesis of erectile dysfunction (ED). However, the association between aortic calcification burden and the severity of ED remains unclear. The aim of the present study was to investigate this association in men undergoing dialysis. MATERIALS AND METHODS: This cross-sectional study included 71 men undergoing peritoneal dialysis and/or hemodialysis between July 2016 and May 2018 at Mutsu General Hospital. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Aortic calcification index (ACI) was examined as a clinical indicator of abdominal aortic calcification. Multivariable logistic regression analysis was performed to identify the significant factors associated with severe ED. RESULTS: The median age of the study participants was 64 years; all had ED, with 64.8% having severe ED. In the multivariable analyses, a slight association was observed between ankle-brachial index and severe ED (odds ratio [OR], 0.058; p=0.072), whereas ACI was significantly associated with severe ED (OR, 1.022; p=0.022). CONCLUSIONS: Aortic calcification burden was independently associated with severe ED.

Relationships of low-grade systemic inflammation and nutritional status with erectile dysfunction severity in men on dialysis.

BACKGROUND: Low-grade systemic inflammation and malnutrition are frequently observed in patients on dialysis and contribute to the development of endothelial dysfunction; however, the role of these conditions in erectile dysfunction (ED) severity remains to be elucidated. OBJECTIVES: To investigate the relationships of low-grade systemic inflammation and nutritional status with ED severity in men on dialysis. MATERIALS AND METHODS: The present study included 71 men on dialysis. The sexual health inventory for men (SHIM) was used to assess ED. Men were classified as the mild/moderate (SHIM score ≥ 8) and severe ED (SHIM score ≤ 7) groups. C-reactive protein/albumin ratio (CAR) and Geriatric Nutritional Risk Index (GNRI) were used to evaluate low-grade systemic inflammation and nutritional status, respectively. We performed multivariate analysis to assess the relationships of CAR and GNRI with severe ED. RESULTS: The median age of the included men was 64 years old. All men had any degree of ED with 65% having severe ED. In the univariate analyses, a significant association was observed between elevated CAR (≥0.09) and severe ED (odds ratio [OR]: 4.038, p = 0.025), whereas no significant association was observed between lower GNRI (<92) and severe ED (OR: 2.357, p = 0.109). In the multivariate analysis, an association between elevated CAR and severe ED was still significant (OR: 5.985, p = 0.010). DISCUSSION AND CONCLUSION: Low-grade systemic inflammation was significantly associated with ED severity, whereas lower GNRI was not. These results may be helpful for further research to identify the optimal treatment for men suffering from severe ED.

Association of oxidative stress with erectile dysfunction in community-dwelling men and men on dialysis.

OBJECTIVES: To investigate the association between oxidative stress and erectile dysfunction (ED) in community-dwelling men and men on dialysis. METHODS: This cross-sectional study included 398 community-dwelling men and 42 men on dialysis. Oxidative stress was assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG). Univariable and multivariable logistic regression analyses were performed to evaluate the association between oxidative stress and ED. RESULTS: Spearman's rank correlation test showed no significant correlation between urine 8-OHdG levels and the 5-Item International Index of Erectile Function scores in community-dwelling men (ρ = -0.005, p = 0.917) and between plasma 8-OHdG levels and the Sexual Health Inventory for Men scores in men on dialysis (ρ = 0.166, p = 0.295). In community-dwelling men, univariable and multivariable analyses revealed that urine 8-OHdG level was not significantly associated with ED (odds ratio [OR]: 1.005, 95% confidence interval [CI]: 0.884-1.144, p = 0.934; OR: 0.930, 95% CI: 0.798-1.084, p = 0.353; respectively). In men on dialysis, univariable analyses revealed that plasma 8-OHdG level was not significantly associated with severe ED (OR: 0.967, 95% CI: 0.876-1.066, p = 0.498). CONCLUSIONS: Oxidative stress was not significantly associated with ED prevalence and severity in community-dwelling men and men on dialysis.

Risk score-based substratification improves surveillance costs after transurethral resection of bladder tumor in patients with primary high-risk non-muscle-invasive bladder cancer.

High-risk non-muscle-invasive bladder cancer (NMIBC) has a heterogeneity and intensive surveillances after transurethral resection of bladder tumor (TURBT) are major factors of increased costs. Therefore, we aimed to develop optimized surveillance protocols based on the risk score-based substratifications to improve surveillance costs. We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT. Patients were substratified into intra-lower, intra-intermediate, and intra-higher groups or UUT-lower, UUT-intermediate, and UUT-higher groups by summing each of the independent risk factors of intravesical and UUT recurrences, respectively. The optimized surveillance protocols that enhance cost-effectiveness were then developed using real incidences of recurrence after TURBT. The 10-year total surveillance costs were compared between the European Association of Urology (EAU) guidelines-based and optimized surveillance protocols. The Kaplan-Meier curves of intravesical and UUT recurrence-free survivals were clearly separated among the substratified groups. The optimized surveillance protocols promoted a 43% reduction ($487,599) in the 10-year total surveillance cost compared to the EAU guidelines-based surveillance protocol. These results suggest that the optimized surveillance protocols based on risk score-based substratifications could potentially reduce over investigation and improve surveillance costs after TURBT in patients with primary high-risk NMIBC.

Single immediate instillation of chemotherapy is associated with decreased recurrence and progression in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.

OBJECTIVES: To investigate whether a single intravesical instillation of chemotherapy is associated with improved oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy. METHODS: This multi-institutional retrospective study included 205 patients with high-risk non-muscle-invasive bladder cancer who received adjuvant induction bacillus Calmette-Guérin therapy. Patients were divided into two groups: those who received the combined therapy of a single instillation of chemotherapy plus subsequent adjuvant induction bacillus Calmette-Guérin therapy (combined therapy group), and those who received adjuvant induction bacillus Calmette-Guérin therapy alone (bacillus Calmette-Guérin monotherapy group). Multivariable analyses using the inverse probability of treatment weighting method and Fine-Gray competing risk regression models were performed to evaluate the impact of a single instillation of chemotherapy on intravesical recurrence-free survival and muscle-invasive bladder cancer-free survival. RESULTS: Among the 205 patients, 130 (63%) and 75 (37%) were classified as the combined therapy and bacillus Calmette-Guérin monotherapy groups, respectively. Multivariable analyses using the inverse probability of treatment weighting method showed that a single instillation of chemotherapy was significantly associated with longer intravesical recurrence-free survival (hazard ratio 0.279; P < 0.001) and muscle-invasive bladder cancer-free survival (hazard ratio 0.078; P < 0.001). Fine-Gray competing risk regression model revealed that a single instillation of chemotherapy was associated with a significantly lower probability of intravesical recurrence and muscle-invasive bladder cancer progression, with an adjusted subdistribution hazard ratio of 0.477 (P = 0.008) and 0.261 (P = 0.043), respectively. CONCLUSION: A single intravesical instillation of chemotherapy may be a potential treatment option in patients with high-risk non-muscle-invasive bladder cancer who receive adjuvant induction bacillus Calmette-Guérin therapy.

Associations of impaired grip strength and gait function with the severity of erectile dysfunction in men undergoing dialysis: a cross-sectional study.

OBJECTIVE: To investigate the associations of impaired muscle strength and gait function with the severity of erectile dysfunction (ED) in men undergoing dialysis. METHODS: This cross-sectional study included 63 men undergoing dialysis. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Correlations between variables were analyzed using Spearman's rank correlation coefficient. Multivariable logistic regression analyses were performed to evaluate the impact of impaired grip strength and gait function on the severity of ED. RESULTS: The median age of the study participants was 62 years; all had ED, with 67% having severe ED. Spearman's rank correlation test demonstrated significant negative and positive correlations between gait function and SHIM score (ρ = -0.257, p = 0.042) and between grip strength and SHIM score (ρ = 0.305, p = 0.015), respectively. In the multivariable analyses, impaired grip strength was significantly associated with severe ED (odds ratio [OR]: 4.965, p = 0.017), whereas gait function was not (OR: 3.147, p = 0.064). CONCLUSION: Impaired muscle strength was significantly associated with severe ED, whereas impaired gait function had a marginal effect on this erectile condition.

Necdin: A purposive integrator of molecular interaction networks for mammalian neuron vitality.

Necdin was originally found in 1991 as a hypothetical protein encoded by a neural differentiation-specific gene transcript in murine embryonal carcinoma cells. Virtually all postmitotic neurons and their precursor cells express the necdin gene (Ndn) during neuronal development. Necdin mRNA is expressed only from the paternal allele through genomic imprinting, a placental mammal-specific epigenetic mechanism. Necdin and its homologous MAGE (melanoma antigen) family, which have evolved presumedly from a subcomplex component of the SMC5/6 complex, are expressed exclusively in placental mammals. Paternal Ndn-mutated mice totally lack necdin expression and exhibit various types of neuronal abnormalities throughout the nervous system. Ndn-null neurons are vulnerable to detrimental stresses such as DNA damage. Necdin also suppresses both proliferation and apoptosis of neural stem/progenitor cells. Functional analyses using Ndn-manipulated cells reveal that necdin consistently exerts antimitotic, anti-apoptotic and prosurvival effects. Necdin interacts directly with a number of regulatory proteins including E2F1, p53, neurotrophin receptors, Sirt1 and PGC-1α, which serve as major hubs of protein-protein interaction networks for mitosis, apoptosis, differentiation, neuroprotection and energy homeostasis. This review focuses on necdin as a pleiotropic protein that integrates molecular interaction networks to promote neuronal vitality in modern placental mammals.

Impact of symptomatic recurrence on oncological outcomes in patients with primary high-risk non-muscle-invasive bladder cancer.

OBJECTIVES: To evaluate the impact of symptomatic recurrence on oncological outcomes in patients with primary high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. Of the 428 patients, 140 had experienced recurrence at any site and were divided into 2 groups: patients who had experienced recurrence detected by the surveillance (asymptomatic group) and patients who had experienced recurrence detected by a symptom-driven investigation (symptomatic group). Background-adjusted multivariable analyses with the inverse probability of treatment weighting method were performed to evaluate the impact of symptomatic recurrence on cancer-specific survival and overall survival after first recurrence in patients who had experienced recurrence. Moreover, multivariable analysis was performed to identify predictive factors of symptomatic recurrence in the entire cohort. RESULTS: Median age and follow-up periods were 72 (interquartile range [IQR] 64-79) years and 55 (IQR 29-96) months, respectively. Of the 140 patients who experienced recurrence, 106 (76%) were diagnosed by the surveillance (asymptomatic group) and 34 (24%) were diagnosed by a symptom-driven investigation (symptomatic group). In the background-adjusted multivariable analyses with the inverse probability of treatment weighting model, symptomatic recurrence was significantly associated with shorter cancer-specific survival along with shorter overall survival after first recurrence. In the multivariable analysis, only tumor grade was selected as a significant predictive factor of symptomatic recurrence after TURBT. CONCLUSIONS: Symptomatic recurrence was significantly associated with poor oncological outcomes in patients with primary high-risk NMIBC. Patients with grade 3 tumors may require more intensive surveillance after TURBT.

Effect of frailty and comorbidity on surgical contraindication in patients with localized prostate cancer (FRART-PC Study).

OBJECTIVES: To determine how frailty and comorbidities affect surgical contraindication in patients with localized prostate cancer (CaP). MATERIALS AND METHODS: We evaluated the effects of frailty in 479 patients with localized CaP who were treated with robot-assisted radical prostatectomy (RARP), or radiotherapy (RT) eligible for surgery (RT-nonfrail), or those with RT ineligible for surgery due to frailty or comorbidity (RT-frail) from February 2017 to April 2020. We retrospectively compared the geriatric 8 screening (G8) scores between patients with surgical indications (RARP and RT-nonfrail groups) and those with surgical contraindications (RT-frail group). The effect of G8 score in the RT-frail groups was investigated using multivariate logistic regression analysis. We developed and validated a nomogram for surgical contraindication in patients with localized CaP. RESULTS: The median age of patients was 70 years. There were 256, 60, and 163 patients in the RARP, RT-nonfrail, and RT-frail, respectively. The G8 score in the RARP and RT-nonfrail groups was significantly higher than in the RT-frail group (15 vs. 14, respectively, P < 0.001). Age, comorbidities (cerebrocardiovascular disease or chronic respiratory disease), and G8 score were significantly associated with the RT-frail group. The nomogram showed that the area under the curve was 0.872 and 0.923 in the training and validation sets, respectively. The cutoff for surgical contraindication was >39.5%. CONCLUSIONS: The G8 score and comorbidities have a significant effect on surgical contraindication in patients with localized CaP.

Intraoperative upper urinary tract cytology examination is a risk factor of upper urinary tract recurrence in patients with non-muscle-invasive bladder cancer.

OBJECTIVES: To evaluate the impact of intraoperative upper urinary tract (UUT) cytology examination in patients with non-muscle-invasive bladder cancer (NMIBC) who had undergone transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively evaluated 414 patients with NMIBC who had undergone transurethral resection of bladder tumor between November 1993 and April 2019. Patients with simultaneous UUT urothelial carcinoma (UC) detected via computed tomography were excluded. Patients were divided into 2 groups: those who had undergone intraoperative bilateral UUT cytology examination via retrograde catheterization (study group) and those who had not (control group). We evaluated the utility of intraoperative UUT cytology examination, comparing surgical outcomes and perioperative complications between the 2 groups. In addition, we evaluated the impact of UUT cytology examination on UUT recurrence using background-adjusted multivariate analysis. RESULTS: We obtained 292 UUT urine samples from 146 patients with a median age of 72 years. Of 292 UUT urine samples, 11 (3.7%) were positive and 3 were finally diagnosed as UUT UC. Positive predictive value and false positive rate were 18% and 3.1%, respectively. Operative time for the study group was significantly longer than for the control group. Rate of perioperative complications were not significantly different between the 2 groups. However, in background-adjusted multivariate analysis, intraoperative UUT cytology examination was associated with significantly shorter UUT recurrence-free survival. CONCLUSION: Intraoperative UUT cytology examination may not be recommended as a result of low positive predictive value due to contamination and UUT recurrence risk in patients with NMIBC.

Impact of chronic kidney disease on oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who underwent adjuvant bacillus Calmette-Guérin therapy.

OBJECTIVES: To investigate the impact of chronic kidney disease (CKD) on oncological outcomes in patients with high-risk non-muscle invasive bladder cancer (NMIBC) who underwent adjuvant induction bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We conducted a multi-institutional retrospective study assessing 209 patients with high-risk NMIBC who underwent TURBT and subsequent adjuvant induction BCG therapy from December 1998 to April 2019. Patients were divided into 2 groups: those with preoperative estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 (non-CKD group), and those with eGFR < 60 ml/min/1.73 m2 (CKD group). Primary endpoints were intravesical recurrence-free survival (RFS) and muscle-invasive bladder cancer (MIBC)-free survival. Background-adjusted multivariate analyses with the inverse probability of treatment weighting (IPTW) method using the propensity score were performed to evaluate the impact of CKD on intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. Moreover, multivariable analyses were performed to assess the impact of CKD on intravesical recurrence and MIBC progression, adjusting for the competing risk of death using the Fine-Gray competing risk regression model. RESULTS: Median age and follow-up period after TURBT were 72 years and 45 months, respectively. Of 209 patients, 71 (34%) were diagnosed with CKD before TURBT. Background-adjusted multivariate analyses with the IPTW method indicated that CKD was significantly associated with shorter intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. In the Fine-Gray competing risk regression model, CKD showed significantly higher probabilities of intravesical recurrence and MIBC progression, with an adjusted subdistribution hazard ratio of 1.886 (95% confidence interval 1.069-3.330, P = 0.028) and 3.740 (95% confidence interval 1.060-13.20, P = 0.040), respectively. CONCLUSIONS: CKD presents a risk factor of poor oncological outcomes in patients with high-risk NMIBC who underwent adjuvant induction BCG therapy after TURBT.

Geriatric 8 screening of frailty in patients with prostate cancer.

OBJECTIVES: To evaluate the association between the score of the Geriatric 8 screening tool and treatment by disease stages in patients with prostate cancer. METHODS: 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. RESULTS: 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 of <14.5. The overall survival was significantly different between Geriatric 8 scores ≤13 and >13 in metastatic hormone-naïve prostate cancer patients, and between Geriatric 8 scores ≤12 and >12 in castration-resistant prostate cancer patients. CONCLUSION: The Geriatric 8 score is significantly associated with treatment by disease stages in patients with prostate cancer.

Impact of substratification on predicting oncological outcomes in patients with primary high-risk non-muscle-invasive bladder cancer who underwent transurethral resection of bladder tumor.

OBJECTIVES: To validate the substratification of high-risk in the European Association of Urology (EAU) guidelines and to develop the simplified substratification to improve usefulness and predictive accuracy on oncological outcomes in patients with primary high-risk nonmuscle-invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. First, the efficacy of the EAU highest-risk on intravesical recurrence-free survival (RFS) and muscle-invasive bladder cancer (MIBC)-free survival was evaluated with univariate analyses. Second, we developed our simplified substratification based on multivariate analysis for intravesical RFS (lower- and higher-risk). We compared predictive accuracy on oncological outcomes using the receiver operating characteristic curve between the EAU and the simplified substratifications. RESULTS: Median age and median follow-up periods were 72 years and 51 months, respectively. The EAU highest-risk was not associated with shorter intravesical RFS and MIBC-free survival (P = 0.054 and P = 0.350, respectively). In multivariate analysis, tumor size, grade 3, and chronic kidney disease were significantly associated with shorter intravesical RFS, and we developed the simplified substratification including those 3 factors. Of 428 patients, 89 (21%) were substratified into the simplified higher-risk. The predictive accuracy of the simplified substratification on intravesical recurrence, MIBC and metastasis progression, and cancer-specific mortality was significantly superior to the EAU substratification. CONCLUSION: Our simplified substratification might contribute to improving predictive accuracy on intravesical recurrence, MIBC and metastasis progression, and cancer-specific mortality in patients with primary high-risk NMIBC who underwent TURBT.

Frailty is significantly associated with the type of urinary diversion in patients with muscle-invasive bladder cancer.

OBJECTIVES: To investigate the effect of frailty on the type of urinary diversion after radical cystectomy in patients with muscle-invasive bladder cancer. METHODS: Between January 2014 and January 2020, we prospectively evaluated frailty in 88 patients with localized muscle-invasive bladder cancer, who had received radical cystectomy and urinary diversion. The selection of the type of urinary diversion was determined by the operating surgeon based on performance status, comorbidities, tumor status and the patient's preference. The frailty evaluation included the Fried phenotype criteria, the modified frailty index and the frailty discriminant score. We investigated the association between frailty and type of urinary diversion, the effect of frailty on postoperative complications and the effect of frailty on overall survival. RESULTS: The median age of the selected participants was 68 years. The number of patients with an orthotopic neobladder and any postoperative complications was 54 (61%) and 46 (52%), respectively. Of the frailty assessment tools that were used, Fried phenotype criteria and frailty discriminant score were significantly associated with the selection of non-orthotopic neobladder urinary diversion. Occurrences of postoperative complications in participants were significantly associated with modified frailty index, but not with Fried phenotype criteria and frailty discriminant score. Multivariate Cox regression analysis showed that a higher frailty discriminant score was significantly associated with poor overall survival, whereas higher Fried phenotype criteria and modified frailty index were not. CONCLUSION: Frailty is significantly associated with the type of urinary diversion, and it should be considered for the selection of urinary diversion in muscle-invasive bladder cancer patients undergoing radical cystectomy.

Safety and efficacy of intensive instillation of low-dose pirarubicin vs. bacillus Calmette-Guérin in patients with high-risk non-muscle-invasive bladder cancer.

OBJECTIVES: To evaluate the safety and efficacy of intensive intravesical instillation of low-dose pirarubicin (THP) for 6 times vs. bacillus Calmette-Guérin (BCG) without maintenance therapy after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively evaluated 370 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. The patients were divided into 2 groups: patients treated with intravesical instillation of BCG without maintenance therapy (BCG group) and intensive intravesical instillation of low-dose (20 mg) THP for 6 times within 10 days after TURBT (THP group). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Background-adjusted multivariate analyses were performed to evaluate the effect of intensive intravesical instillation of low-dose THP on oncological outcomes, including intravesical recurrence-free survival (RFS), upper urinary tract RFS, muscle-invasive bladder cancer-free survival, metastasis-free survival, cancer-specific survival, and overall survival. RESULTS: Of the 370 patients with primary high-risk NMIBC, 180 (49%) and 190 (51%) were stratified into the BCG and THP groups, respectively. The incidence rate of adverse events of any grade in the BCG group was significantly higher than that in the THP group (P < 0.001). In the background-adjusted multivariate analyses, no significant differences were observed in oncological outcomes between the BCG and THP groups. CONCLUSIONS: Intensive intravesical instillation of low-dose THP for 6 times may be one of the treatment options in view of safety and efficacy after TURBT in patients with primary high-risk NMIBC.

Safety and Feasibility of Radiation Therapy to the Primary Tumor in Patients With Metastatic Castration-resistant Prostate Cancer.

INTRODUCTION: The objective of this study was to evaluate the safety and feasibility of radiation therapy (RT) to the primary tumor in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This retrospective study included 105 patients with mCRPC who were treated between April 2004 and May 2019. We divided the patients into 2 groups: patients treated with RT to the primary tumor after they developed CRPC (RT group) and without (non-RT group). The primary purpose was safety assessed using the Common Terminology Criteria for Adverse Events. The secondary purpose included prostate-specific antigen (PSA) response, cancer-specific survival (CSS), and overall survival (OS). Background-adjusted multivariate analyses, with the inverse probability of treatment weighting (IPTW) method, were performed to evaluate impact of RT on CSS and OS. RESULTS: The median age at CRPC diagnosis was 75 years, and the median follow-up period after CRPC diagnosis was 21 months. The adverse events rates related to RT in any grade and grade ≥ 3 were 55% and 23%, respectively. Nine (29%) patients achieved ≥ 30% PSA decline with RT. In multivariate analyses with the IPTW method, the CSS and OS in the RT group were significantly longer than those in the non-RT group. In subgroup analyses with the IPTW method, RT was significantly associated with improved OS in patients aged ≥ 75 years and patients with initial PSA ≥ 500 ng/mL, cT4, Gleason score ≥ 8, and high-volume metastatic burden. CONCLUSIONS: RT to the primary tumor is safe and feasible, and it has potential benefits on oncologic outcomes in patients with mCRPC.