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.

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.

Relationship of frailty with treatment modality selection in patients with muscle-invasive bladder cancer (FRART-BC study).

BACKGROUND: We aimed to investigate the association of frailty with treatment selection in patients with muscle-invasive bladder cancer (MIBC) as frailty is one of the key factors for modality selection. METHODS: We retrospectively evaluated frailty in 169 patients with MIBC from January 2014 to September 2020 using the Fried phenotype, modified frailty index, and frailty discriminant score. The primary purpose was comparing the frailty between the patients who underwent radical cystectomy (RC) with those who had trimodal therapy (TMT) for bladder preservation. Secondary purposes were comparing the frailty between the groups and the effect of TMT on overall survival adjusting the frailty by multivariate Cox proportional hazards analysis using inverse probability of treatment weighting (IPTW)-adjusted model. RESULTS: Of 169 patients, 96 and 73 were classified into the RC and the TMT groups, respectively. The median age of the TMT group was significantly higher than that of the RC group (80 vs. 69 years). Frailty levels and prevalence in the Fried phenotype, modified frailty index, and frailty discriminant score were significantly higher in the TMT group than those in the RC group. Logistic regression analysis showed that frailty was significantly associated with the TMT selection. Overall survival was significantly shorter in the TMT group by the IPTW-adjusted Cox regression analysis (hazard ratio 2.48, P=0.043). CONCLUSIONS: Frailty was significantly different between the RC and TMT in patients with MIBC and might be one of the key factors for treatment selection.

Prognostic significance of total plasma cell-free DNA level and androgen receptor amplification in castration-resistant prostate cancer.

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

Association between the baseline frailty and quality of life in patients with prostate cancer (FRAQ-PC study).

BACKGROUND: The association between baseline frailty and health-related quality of life (HRQOL) in patients with prostate cancer (PC) remains unknown. METHODS: We retrospectively evaluated the association of pretreatment frailty with HRQOL in 409 patients with PC from February 2017 to April 2020. Frailty and HRQOL were evaluated using the geriatric 8 (G8) screening tool and QLQ-C30 questionnaire, respectively. The primary objective was comparison of G8 and QOL scores between the localized diseases (M0 group) and metastatic castration-sensitive PC (mCSPC group). Secondary objectives were to study the association of G8 and QOL scores in each group and effect of frailty (G8 ≤ 14) on worse QOL. RESULTS: The median age of patients was 70 years. There were 369 (surgery: 196, radiotherapy: 156, androgen deprivation therapy alone: 17) patients in the M0 and 40 patients in the mCSPC groups. There was a significant difference between the M0 and mCSPC groups in the G8 score (14.5 vs. 12.5), functioning QOL (94 vs. 87), global QOL (75 vs. 58), and 100-symptom QOL (94 vs. 85) scores. G8 scores were significantly associated with functioning, global, and 100-symptom QOL scores in both M0 and mCSPC groups. The multivariable logistic regression analyses showed that frailty (G8 ≤ 14) was significantly associated with worse global QOL, functioning QOL, and 100-symptom QOL scores. CONCLUSION: The baseline frailty and HRQOL were significantly different between the localized and metastatic disease. The baseline frailty was significantly associated with worse HRQOL in patients with PC.

Overactive bladder and sleep disturbance have a significant effect on indoor falls: Results from the community health survey in Japan.

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.

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.

Oncologic and patient-reported outcomes after robot-assisted radical prostatectomy in men aged ≥75 years.

OBJECTIVE: The present study aimed to evaluate oncologic outcomes, patient-reported outcomes (PROs), and frailty in older adult patients aged ≥75 years who underwent robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: This retrospective study reviewed the medical records of 752 patients who underwent RARP from July 2011 to May 2020. The PROs were evaluated by Expanded Prostate Cancer Index Composite questionnaire at baseline and 1 year after RARP. Patients were divided into 3 groups according to age at RARP: <70, 70-74, and ≥75 years. Oncologic outcomes and PROs were compared between the ≥75 and 70-74 years groups and between the ≥75 and <70 years groups. RESULTS: Median follow up was 47 months. Of the 752 patients, 469, 216, and 74 were classified into the <70, 70-74, and ≥75 years groups, respectively. No significant differences were observed in the biochemical recurrence-free survival, cancer-specific survival, and overall survival among the groups. No significant differences were observed in the PROs and pad-free rates at baseline and 1 year after RARP among the groups. The full satisfaction (Expanded Prostate Cancer Index Composite score = 100) at 12 months after RARP was significantly higher in the ≥75 years group (27%) than in the <70 years group (15%, P = 0.045). CONCLUSION: The oncologic outcomes and PROs in select patients with prostate cancer aged ≥75 years were feasible and acceptable with RARP.

A Longitudinal Study of Bidirectional Relationships between Sleep Disorder and Frequency of Nocturia: Results from the Iwaki Health Promotion Project.

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

The effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy: A longitudinal analysis (FRARP-QL Study).

OBJECTIVES: We aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP). MATERIALS AND METHODS: We longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP. RESULTS: The median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients' background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening. CONCLUSIONS: Frailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.

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.

The impact of microalbuminuria on overactive bladders: Results from a community-based four-year longitudinal study in Japan.

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.

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.

Outcome of ABO Blood Type-Incompatible Living-Related Donor Kidney Transplantation Under a Contemporary Immunosuppression Strategy in Japan.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Living Kidney Transplantation From Marginal Donors Presents Feasible Donor Renal Function Despite Inferior Recipient Renal Function.

INTRODUCTION: Kidney transplantation from marginal donors is an important solution for organ shortage problems. In this study, we evaluated the safety and effectiveness of living kidney transplantation from marginal donors at our hospitals. METHODS: Between June 2006 and April 2019, 107 patients underwent living kidney transplantation at our hospitals. Marginal donors were defined as those with 1. age >70 years, 2. hypertension, 3. creatinine clearance <80 mL/min, 4. body mass index >30 kg/m2, or 5. hemoglobin A1c >6.2%. We retrospectively compared renal function and its chronological changes between marginal and standard donors. We also compared graft survival and recipient renal function between the groups. RESULTS: Thirty-one (29%) donors were defined as marginal. The primary reason for being defined as marginal was hypertension (74%). The mean age of the marginal donors (62 ± 10 years) was higher than that of standard donors (52 ± 12 years, P < .001). The estimated glomerular filtration rate (eGFR) before and after transplantation was lower in the marginal group, whereas the decline ratio of eGFR was not different between the marginal and standard donors. Five-year graft survival of transplantations from marginal donors (89%) was not significantly inferior to that from standard donors (95%). Meanwhile, recipient eGFR was lower in transplantation from marginal donors than standard donors from 1 month through 5 years after transplantation. CONCLUSIONS: No significant differences were observed between the groups regarding the decline ratios of donor eGFR and graft survival. Thus, transplantation from marginal donors may be a feasible solution for donor shortage problems.

Association of tumor burden with the eligibility of upfront intensification therapy in metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

OBJECTIVES: To evaluate the association of tumor burden with the prognosis in real-world patients with metastatic castration-sensitive prostate cancer and to investigate the eligibility for upfront intensification therapy. METHODS: We retrospectively evaluated 679 patients with metastatic castration-sensitive prostate cancer who were initially treated with conventional androgen deprivation therapy between August 2001 and November 2018. The primary purpose was to investigate the eligibility for upfront intensification therapy based on the progression of metastatic castration-resistant prostate cancer. The secondary purpose included the comparison of the metastatic castration-resistant prostate cancer progression rate, metastatic castration-resistant prostate cancer-free survival and overall survival after castration-resistance in CHAARTED low- or high-volume disease patients. RESULTS: The number of patients with metastatic castration-resistant prostate cancer progression was 119 (52%) and 319 (71%) in the low- and high-volume disease groups, respectively. The metastatic castration-resistant prostate cancer progression rate (P < 0.001) and castration-resistant prostate cancer-free survival (P < 0.001) were significantly different between the low- and high-volume disease groups, but no difference was found for overall survival after castration resistance (P = 0.363). Multivariate Cox regression analysis showed no significant association between tumor burden and overall survival after castration resistance (P = 0.522; hazard ratio 1.14). CONCLUSIONS: The progression rate in metastatic castration-resistant prostate cancer patients with the low-volume disease under conventional androgen deprivation therapy is approximately 50%. Upfront intensification therapy might be beneficial for approximately half of patients with low-volume disease. A novel maker to predict the castration-resistant status is required to select optimal patients for upfront intensification therapy.

Survey on attitudes toward brain-dead and living donor transplantation in medical students: a cross-sectional study in Japan.

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.

STone Episode Prediction: Development and validation of the prediction nomogram for urolithiasis.

OBJECTIVES: To develop and validate a nomogram predicting the occurrence of a stone episode, given the lack of such predicting risk tools for urolithiasis. METHODS: We retrospectively analyzed 1305 patients with urolithiasis and 2800 community-dwelling individuals who underwent a comprehensive health survey. The STone Episode Prediction nomogram was created based on data from the medical records of 600 patients with urolithiasis and 1300 controls, and was validated using a different population of 705 patients with urolithiasis and 1500 controls. Logistic regression analysis was used to construct a model to predict the potential candidate for a stone episode. The predictive ability of the model was evaluated using the results of the area under the receiver operating characteristics curve (area under the curve). RESULTS: Age, sex, diabetes mellitus, renal function, serum albumin, and serum uric acid were found to be significantly associated with urolithiasis in the training set and were included in the STone Episode Prediction nomogram. The optimal cut-off value for the probability of a stone episode using the nomogram was >28% with a sensitivity of 79%, a specificity of 76%, and area under the curve of 0.860. In the validation test, area under the curve for the detection of urolithiasis was 0.815 with a sensitivity of 81% and specificity of 63%. CONCLUSIONS: Herein, we developed and validated the STone Episode Prediction nomogram that can predict a potential candidate for an episode of urolithiasis. This nomogram might be beneficial for the first step in stone screening in individuals with lifestyle-related diseases.

Utility of plasma cell-free DNA in metastatic castration-resistant prostate cancer.

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