Real-world effects of novel androgen receptor axis-targeted agents on oncological outcomes in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.

Background: The benefits of novel androgen receptor axis-targeted agents (ARATs) on oncological outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in real-world settings are unclear. Methods: This multi-institutional retrospective study included 178 patients with nmCRPC treated between September 2003 and August 2022. Patients were divided into two groups: those who were treated with any novel ARATs, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate, during any line of nmCRPC treatment (novel ARATs group) and those who were not (control group). Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of novel ARATs on metastasis-free survival (MFS) and overall survival (OS). Results: The median age and follow-up period after nmCRPC diagnosis were 76 years and 37 months, respectively. Of the 178 patients, 122 (69%) were treated with novel ARATs after nmCRPC diagnosis. The MFS and OS in the novel ARATs group were significantly longer than those in the control group (P < 0.001 and P = 0.020, respectively). In multivariable analyses, a prostate-specific antigen doubling time (PSADT) of <3 months and novel ARATs were independently and significantly associated with MFS and OS. The effects of novel ARATs on MFS were consistently observed across subgroups stratified by age (<75 years or ≥75 years), history of radical treatment (no or yes), biopsy Gleason score (<9 or ≥9), clinical stage (≤cT3 and cN0, or cT4 or cN1), and PSADT (≥3 months or <3 months). Conclusion: Novel ARATs were significantly associated with improved oncological outcomes in patients with nmCRPC in a real-world setting, regardless of tumor aggressiveness.

Effect of advanced glycation end products on nocturia or sleep disorders: A longitudinal study.

Objective: This study aimed to investigate the effect of advanced glycation end products (AGEs) on nocturia and sleep disorders in community-dwelling adults. Materials and Methods: This longitudinal study evaluated AGEs level, sleep disorders and nocturia frequency in 447 community-dwelling adults between May 2011 and May 2016. Sleep disorders were evaluated using the Pittsburgh Sleep Quality Index (PSQI) score. Participants were divided into two groups: AGEs-low (≤1.80) and AGEs-high (>1.80). The longitudinal nocturia and PSQI changes for 5 years between the AGEs-low and AGEs-high groups were compared. The effect of baseline oxidative stress on worsening of nocturia or PSQI score 5 years later was evaluated using multivariable logistic regression analyses. Results: There was no significant difference in PSQI score and nocturia frequency between the AGEs-low (n = 223) and AGEs-high (n = 224) groups at baseline. The PSQI score and nocturia frequency increased significantly over 5 years in both groups. However, the PSQI score increased significantly in the AGEs-high group compared with the AGEs-low group, although there was no difference in nocturia. Background-adjusted multivariable analysis showed that the AGE-high was significantly associated with PSQI score worsening, but AGE-high was not significantly associated with nocturia worsening. Conclusions: Oxidative stress may be significantly associated with worsening sleep disorders, although oxidative stress may not significantly worsen nocturia frequency.

Comparison of nivolumab plus ipilimumab with tyrosine kinase inhibitors as first-line therapies for metastatic renal-cell carcinoma: a multicenter retrospective study.

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

Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study.

OBJECTIVES: To investigate the efficacy and safety of first-line nivolumab plus ipilimumab for patients treated with metastatic renal cell carcinoma. METHODS: We retrospectively evaluated 52 metastatic renal cell carcinoma patients who were treated with nivolumab plus ipilimumab between August 2015 and January 2020. Data on patient characteristics, treatment parameters and adverse events were obtained. Oncological outcomes were assessed according to the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model. Furthermore, differences in treatment parameters between patients with objective response (responders) and non-responders were compared. RESULTS: The median age and follow-up periods were 69 years and 8.2 months, respectively. The 1-year progression-free survival and overall survival rates were 55% and 75%, respectively. The objective response rate was 39%, and it was significantly different between the International Metastatic Renal Cell Carcinoma Database Consortium intermediate- and poor-risk groups (52% vs 24%). We observed 36 (69%) any immune-related adverse events, and 19 (37%) severe immune-related adverse events (grades III-V). The International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and higher value of initial C-reactive protein (≥1.0 mg/dL) were significantly associated with non-responders. Patients with two factors (the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group plus C-reactive protein ≥1.0 mg/dL) had a significantly poor overall survival than those with none or a single factor. CONCLUSIONS: In our experience, treatment response to nivolumab plus ipilimumab is comparable with that of the CheckMate 214 clinical trial, but the incidence of treatment-related adverse events is lower. The International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and initial C-reactive protein value might have a prognostic value for poor survival.

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.

Sleep Disturbance Has a Higher Impact on General and Mental Quality of Life Reduction than Nocturia: Results from the Community Health Survey in Japan.

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.

The relationship between poor nutritional status and progression of aortic calcification in patients on maintenance hemodialysis.

BACKGROUND: Although aortic calcification has a significant negative impact on prognosis in patients on hemodialysis (HD), risk factors for aortic calcification progression remain unclear. The aim of this study was to investigate the relationship between malnutrition and aortic calcification progression in patients on HD. METHODS: Between April 2015 and October 2016, we treated 232 patients on HD. Of those, we retrospectively evaluated data from 184 patients who had had regular blood tests and computed tomography (CT) scans. The abdominal aortic calcification index (ACI) was quantitatively measured by abdominal CT. Nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI). A normalized treatment ratio of functional urea clearance was evaluated by Kt/V. The difference in ACI values between 2015 and 2016 was evaluated as a ΔACI, and patients were stratified into two groups according to ΔACI value: high (≥75th percentile, ΔACI-high group) and low (<75th percentile, ΔACI-low group). Variables such as age, sex, comorbidities, dialysis vintage, serum data, and GNRI were compared between ΔACI-high and ΔACI-low patients. Factors independently associated with a higher ΔACI progression (ΔACI ≥75th percentile) were determined using multivariate logistic analysis. RESULTS: Median values of ACIs in 2015 and 2016 were 40.8 and 44.6%, respectively. Of 184 patients, 125 (68%) patients experienced ACI progression for 1 year. The median ΔACI and 75th percentile of ΔACI were 2.5% and 5.8%, respectively. The number of patients in the ΔACI-low and ΔACI-high groups were 128 (70%) and 56 (30%), respectively. There were significant differences in sex, presence of diabetic nephropathy, HD vintage, serum albumin, serum phosphate, C-reactive protein, intact parathyroid hormone, Kt/V, and GNRI. Multivariate logistic regression analysis revealed that independent factors associated with a higher ΔACI progression were male sex, serum phosphate levels, HD vintage, and GNRI of < 90. CONCLUSIONS: Our results suggest that poor nutritional status is an independent risk factor for the progression of aortic calcification. Nutrition management may have the potential to improve progression of aortic calcification in patients on HD. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000028050 .

Detecting asymptomatic recurrence after radical nephroureterectomy contributes to better prognosis in patients with upper urinary tract urothelial carcinoma.

BACKGROUND: The prognostic benefit of regular follow-up to detect asymptomatic recurrence after radical nephroureterectomy (RNU) remains unclear. We aimed to assess whether regular follow-up to detect asymptomatic recurrence after RNU improves patient survival. MATERIALS AND METHODS: We retrospectively analysed 415 patients who underwent RNU for upper tract urothelial carcinoma at four hospitals between January 1995 and February 2017. All patients had regular follow-up examinations after RNU including urine cytology, blood biochemical tests, and computed tomography. We investigated the first site and date of tumor recurrence. Overall survivals of patients who developed recurrence, stratified by mode of recurrence (asymptomatic vs. symptomatic group), were estimated using the Kaplan-Meier method with the log-rank test. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of the mode of recurrence on survival. RESULTS: Of the 415 patients, 108 (26%) experienced disease recurrences after RNU. Of these, 62 (57%) were asymptomatic and 46 (43%) were symptomatic at the time of diagnosis. The most common recurrence site and symptom were lymph nodes and pain, respectively. Overall survival after RNU and time from recurrence to death in the asymptomatic group were significantly longer than that in the symptomatic group. Multivariate Cox regression analysis showed that symptomatic recurrence was an independent risk factor for overall survival after RNU and survival from recurrence to death. CONCLUSIONS: Routine oncological follow-up for detection of asymptomatic recurrence contributes to a better prognosis after RNU.

Oncologic outcomes for open and laparoscopic radical nephroureterectomy in patients with upper tract urothelial carcinoma.

BACKGROUND: Oncologic benefits of laparoscopic radical nephroureterectomy (LNU) are unclear. We aimed to evaluate the impact of surgical approach for radical nephroureterectomy on oncologic outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC). METHODS: Of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017, we retrospectively investigated oncological outcomes in 229 with locally advanced UTUC (stages cT3-4 and/or cN+). The surgical approach was classified as open nephroureterectomy (ONU) or LNU, and oncologic outcomes, including intravesical recurrence-free survival (RFS), visceral RFS, cancer-specific survival (CSS), and overall survival (OS), were compared between the groups. The inverse probability of treatment weighting (IPTW)-adjusted Cox-regression analyses was performed to evaluate the impact of LNU on the prognosis. RESULTS: Of the 229 patients, 48 (21%) underwent LNU. There were significant differences in patient backgrounds, including preoperative renal function, lymph-node involvement, lymphovascular invasion, and surgical margins, between the groups. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS were significantly inferior in the ONU group than in the LNU group. However, in the IPTW-adjusted Cox-regression analysis, no significant differences were observed in intravesical RFS (hazard ratio [HR], 0.65; P = 0.476), visceral RFS (HR, 0.46; P = 0.109), CSS (HR, 0.48; P = 0.233), and OS (HR, 0.40; P = 0.147). CONCLUSION: Surgical approaches were not independently associated with prognosis in patients with locally advanced UTUC.

Opacity of big toenail predicts poor prognosis in patients with end-stage renal disease on hemodialysis.

BACKGROUND: The impact of nail abnormalities on prognosis in hemodialysis patients is unknown. This study investigated whether toenail opacity as a readout of nail abnormalities predicted prognosis in hemodialysis patients. METHODS: In this observational study, 494 eligible hemodialysis patients who received hemodialysis at Oyokyo Kidney Research Institute between September 2010 and December 2015 were included. The presence of nail abnormalities was objectively evaluated by big toenail opacity ratio measurement. Primary endpoint was overall survival, and secondary endpoints were lower limb amputation and determination of risk factors for poor prognosis among patient demographics, comorbidities, blood tests, and big toenail opacity. Overall survival and lower limb survival were evaluated using the Kaplan-Meier method with log-rank test. Multivariate Cox regression analyses assessed predictors for poor prognosis. RESULTS: Big toenail opacity was found in 259 (52%) patients. Patients with big toenail opacity were significantly older, had shorter duration of dialysis, higher prevalence rates of diabetes mellitus (DM), cardiovascular disease (CVD), and higher mortality rates than those without opacity. Presence of big toenail opacity predicted poor prognosis for both overall and lower limb survival. Multivariate Cox regression analyses revealed serum albumin, the presence of DM and big toenail opacity were independent risk factors for both poor overall and lower limb survivals. CONCLUSION: The prevalence of big toenail opacity was high in hemodialysis patients. Despite the short observation period, our findings indicated that big toenail opacity had significant predictive power for poor overall and lower limb survival.

Preoperative chronic kidney disease predicts poor oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma.

OBJECTIVE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes in patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy. METHODS: A total of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017 were retrospectively examined. Oncological outcomes, including intravesical recurrence-free, visceral recurrence-free, cancer-specific, and overall survival rates (intravesical RFS, visceral RFS, CSS, and OS, respectively) stratified by preoperative CKD status (CKD vs. non-CKD) were investigated. Cox proportional hazards regression analysis was performed using inverse probability of treatment weighting (IPTW) to evaluate the impact of preoperative CKD on prognosis and a prognostic factor-based risk stratification nomogram was developed. RESULTS: Of the 426 patients, 250 (59%) were diagnosed with CKD before radical nephroureterectomy. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS after radical nephroureterectomy were significantly shorter in the CKD group than in the non-CKD group. Background-adjusted IPTW analysis demonstrated that preoperative CKD was significantly associated with poor visceral RFS, CSS, and OS after radical nephroureterectomy. Intravesical RFS was not significantly associated with preoperative CKD. The nomogram for predicting 5-year visceral RFS and CSS probability demonstrated a significant correlation with actual visceral RFS and CSS (c-index = 0.85 and 0.83, respectively). CONCLUSIONS: Upper tract urothelial carcinoma patients with preoperative CKD had a significantly lower survival probability than those without CKD.