Impact of Novel Agents on Patient Characteristics, Treatment Patterns, and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer.

BACKGROUND/AIM: The therapeutic landscape for metastatic castration-resistant prostate cancer (mCRPC) has changed dramatically with the introduction of several novel agents. However, limited data are available to determine whether the introduction of novel agents affected patient characteristics, treatment patterns, and outcomes compared with the period when these agents were not available. The objective of this study was to evaluate the impact of the introduction of novel mCRPC agents on patient characteristics, treatment patterns, and outcomes. PATIENTS AND METHODS: Two cohorts of Japanese patients diagnosed with mCRPC between 2009 and 2014 (Epoch 1) and 2015 and 2019 (Epoch 2) were retrospectively analyzed. RESULTS: A total of 125 treatment-naïve mCRPC patients, consisting of 42 patients in Epoch 1 and 83 patients in Epoch 2, were evaluated. We obtained the following results: (i) a dramatic shift in the first-line treatment from docetaxel to androgen receptor axis-targeted agents (ARATs), (ii) an age range expansion for first-line treatment, and (iii) an overall survival (OS) advantage in Eopch 2 compared to Epoch 1. Multivariate analysis in the overall population showed that Epoch 2 and low prostate-specific antigen (PSA) levels at the start of first-line treatment were independent prognostic factors for OS. CONCLUSION: In real-world mCRPC practice, the introduction of novel agents has improved the prognosis of mCRPC while allowing more patients to receive mCRPC treatment across a broad age range. In addition, low PSA levels at the start of first-line treatment were associated with improved OS, indicating the importance of starting mCRPC treatment while PSA levels are low.

Prognostic Factors of Platinum-Refractory Advanced Urothelial Carcinoma Treated with Pembrolizumab.

INTRODUCTION: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. METHODS: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). RESULTS: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. CONCLUSIONS: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.

Prognosis of Patients Receiving Chemotherapy for Metastatic Upper Tract Urothelial Carcinoma Compared With Metastatic Urinary Bladder Cancer.

BACKGROUND/AIM: The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Patients who underwent platinum-based chemotherapy at the Kindai University Hospital and affiliated hospitals between January 2010 and December 2021 were included in the study. There were 56 patients with mUBC and 73 with mUTUC. Kaplan-Meier curves were used to estimate progression-free (PFS) and overall (OS) survival. Multivariate analyses were performed using Cox proportional hazards model to predict prognostic factors. RESULTS: The median PFS was 4.5 and 4.0 months for the mUBC and mUTUC groups, respectively (p=0.094). The median OS was 17.0 months for both groups (p=0.821). The multivariate analysis showed no prognostic factor for PFS. The multivariate analysis for OS showed that younger age at the initiation of chemotherapy and immune checkpoint inhibitor use after first-line therapy were significantly associated with better OS. CONCLUSION: Platinum-based chemotherapy had a similar effect on patients with mUTUC and mUBC.

Outcome of primary androgen deprivation therapy in super-elderly men with localized high-risk prostate cancer.

The purpose of this study is to provide certain data on clinical outcome of primary androgen deprivation therapy in men over 80 years of age with localized high-risk prostate cancer. This study included 54 Japanese super-elderly men with high-risk prostate cancer treated with primary androgen deprivation therapy between 2005 and 2015. The median overall survival was 9.1 years (95% confidence interval, 8.1-10.1) and no patient died from prostate cancer. Overall, 51.9% of patients experienced any grade of adverse events following androgen deprivation therapy. Associations between clinicopathological factors including comorbidity count at initial diagnosis and overall survival were investigated. On multivariate analysis, only comorbidity count at initial diagnosis [≥2 vs. ≤1; hazard ratio, 5.34 (95% confidence interval, 1.55-18.49); P = 0.003] was an independent risk factor for overall survival. Our findings suggest that comorbidity count at initial diagnosis is robustly prognostic for overall survival. For super-elderly men with localized high-risk prostate cancer, comorbidity count at initial diagnosis should be emphasized when deciding whether primary androgen deprivation therapy is necessary or not.

Clinical features of detrusor underactivity in elderly men without neurological disorders.

OBJECTIVES: To investigate the clinical features of detrusor underactivity (DU) in elderly men without neurological disorders. METHODS: A total of 336 men aged ≥50 years without neurogenic disorders who underwent pressure flow studies and who had DU or bladder outlet obstruction (BOO) were reviewed retrospectively. According to the bladder contractility index (BCI) and the BOO index (BOOI), the subjects were classified into the following three groups: (a) pure DU group, BCI < 100 and BOOI < 40; (b) DU + BOO group, BCI < 100 and BOOI ≥ 40; and (c) pure BOO group, BCI ≥ 100 and BOOI ≥ 40. Subjective and objective parameters were compared among the three groups, and the predictors for pure DU were evaluated by multivariate analysis. RESULTS: Of the 336 patients, 205 who met the study criteria were included in the analysis: 63 (30.7%) with pure DU, 48 (23.4%) with DU + BOO, and 94 (45.9%) with pure BOO. The proportion of the pure DU group increased with increasing age. Prostate volume was the lowest in the pure DU group. Frequency, urgency on the International Prostate Symptom Score (IPSS), and the IPSS storage subscore were the lowest in the pure DU group. Multivariate analysis showed that age (odds ratio [OR] 1.114 [95% CI, 1.032-1.203], P = .005), prostate volume (OR 0.968 [95% CI, 0.949-0.987], P = .001), and urgency (OR 0.623 [95% CI, 0.431-0.900], P = .012) were predictors of pure DU. CONCLUSION: Older age, smaller prostate volume, and less urgency may be clinical features of pure DU.

Forecasting model of activities of the city-level for management of CO2 emissions applicable to various cities.

CO2 reduction has become one of the most critical issues globally, and considering sustainable development, many countries are implementing and reviewing CO2 reduction policies. To examine the effect of the CO2 reduction policies, a forecasting model that considers the relationship between variables such as population, building area, industries, vehicle use, and the environment is required. Moreover, this model should also be applicable to various cities to support effective policymaking. In this study, we develop a model that can predict CO2 emissions from the relationship between the variables using System Dynamics, a method to model cities to represent one system composed of various variables. To expand the applicability of the model to various cities in Japan, the proposed model assigns statistical data as input data that can be obtained in any city and standardizes the system structure and variables of the model. In this study, we selected three cities, namely Fukuoka, Kashiwa, and Kumano, which had different populations and industrial characteristics. The calculation accuracy error of CO2 emissions for the three cities was found to be less than 6%. In addition, through the parameter study, it was confirmed that the proposed model can be used to examine the sectors that require CO2 reduction policies, along with the optimal application period. This study aims to provide an effective model that can help in CO2 forecasting and thus in environmental and sustainable development policymaking. Our approach to the CO2 forecasting model facilitates calculating effective CO2 reductions in various cities.

Comparison of the Safety and Efficacy of Photoselective Vaporization of the Prostate (PVP) and Transurethral Enucleation with a Bipolar System (TUEB): A Single-Center Retrospective Study.

PURPOSE: The aim of this study was to compare the safety and efficacy of photoselective vaporization of the prostate (PVP) and transurethral enucleation with a bipolar system (TUEB). PATIENTS AND METHODS: Patients who underwent PVP or TUEB surgery for lower urinary tract symptoms due to bladder outlet obstruction at our institution from September 2015 to May 2019 were retrospectively reviewed. A total of 83 patients (PVP: n=45, TUEB: n=38) who were available for follow-up at least 12 months after surgery were included. Preoperative characteristics, perioperative parameters, and postoperative outcomes-such as International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), and complications-at 3, 6, and 12 months after surgery were compared between the two groups. RESULTS: Although differences in age, IPSS, and QoL were not significant, a significantly greater prostate volume, lower Qmax, and greater PVR were noted in the TUEB group. In perioperative parameters, a significantly shorter operation time, less change in serum hemoglobin, fewer days of catheterization, and shorter length of stay were observed in the PVP group. As for postoperative outcomes, the IPSS storage subscore and PVR were significantly improved in the TUEB group. As complications, stress urinary incontinence was more frequently observed in the TUEB group, and urethral stricture was more common in the PVP group. CONCLUSION: The present data suggest that PVP and TUEB are efficient and safe surgical treatment options. Management of patients undergoing PVP in the perioperative period appears easy. Improvements of subjective and objective parameters were superior after TUEB than after PVP.

Daily salt intake is associated with leg edema and nocturnal urinary volume in elderly men.

AIMS: There is accumulating evidence that excessive salt intake contributes to nocturnal polyuria. We aimed to investigate the relationship between salt intake, leg edema, and nocturnal urine volume (NUV) to assess the etiology of nocturnal polyuria. METHODS: A total of 56 men aged ≥60 years who were hospitalized for benign prostatic hyperplasia or with suspected prostatic cancer were enrolled. Urine frequency-volume charts of the patients were maintained, and they underwent bioelectrical impedance analysis twice daily (at 5:00 pm and 6:00 am) and examination of blood (brain natriuretic peptide levels) and urine (sodium and creatinine levels and osmotic pressure) samples once daily (at 6:00 am). Free-water clearance, solute clearance, and sodium clearance at night were measured, and daily salt intake was estimated. RESULTS: The data of 52 patients were analyzed. Daily salt intake positively correlated with leg edema at 5:00 pm, differences in leg extracellular fluid levels between 5:00 pm and 6:00 am, and NUV, but not with diurnal urine volume. Partial correlation coefficients showed that salt intake was a factor of the correlation between NUV and change in extracellular volume in the legs between 5:00 pm and 6:00 am. A multivariate logistic model showed that sleep duration and sodium clearance were independent predictive factors for nocturnal polyuria. CONCLUSIONS: Sodium intake correlates with diurnal leg edema and NUV in elderly men. These results provide evidence supporting sodium restriction as an effective treatment for nocturnal polyuria.

Serious Hypokalemia Associated with Abiraterone Acetate in Patients with Castration-Resistant Prostate Cancer.

INTRODUCTION: The treatment strategy for castration-resistant prostate cancer (CRPC) has changed with the approval of several new agents. In 2011, abiraterone acetate was approved for the treatment of metastatic CRPC; however abiraterone is known to cause mineralocorticoid excess syndrome characterized by hypokalemia, fluid retention, and hypertension. We experienced two cases of grade 4 hypokalemia associated with abiraterone treatment. CASE PRESENTATION: Case 1: a 71-year-old male with metastatic CRPC presented with convulsive seizures two weeks after receiving abiraterone plus prednisone. The serum potassium level was 2.1mEq/l. We determined that convulsive seizure was caused by hypokalemia associated with abiraterone. Case 2: a 68-year-old male with metastatic CRPC presented with severe lethargy one month after receiving abiraterone plus prednisone. The serum potassium level was 1.7mEq/l and we concluded that severe lethargy was caused by hypokalemia associated with abiraterone. They were treated with potassium supplementation and increased prednisone following withdrawal of abiraterone. DISCUSSION: The two patients had been on glucocorticoid therapy before abiraterone therapy. Prolonged administration of exogenous glucocorticoid can lead adrenocortical insufficiency and consequently reduce endogenous glucocorticoid production. This situation may increase the risk of abiraterone-induced mineralocorticoid excess. To reduce the risk of abiraterone-induced hypokalemia, evaluation of adrenocortical insufficiency is required.