A safer method for disinfection of Bacillus Calmette-Guerin-containing urine: a prospective, randomized study.

INTRODUCTION: To examine whether disinfection of Bacillus Calmette-Guerin -containing urine with etaprocohol® (Ethanol 76.9-81.4 vol % and isopropanol as an additive) is safer than disinfection with sodium hypochlorite. METHOD: In prospective research, safety, and efficacy was analyzed in five patients in the etaprocohol® disinfection group and five patients in the sodium hypochlorite disinfection group. The primary endpoint was the temperature change after disinfection and the secondary endpoint was the unpleasantness of the odor caused by disinfection. Additionally, concentration of gas produced was also examined. Sensory tests were taken from staff who performed urine disinfection and the odor generated by disinfection was evaluated. As a safety protocol, post-BCG-treated urine is cultured to verify the negative for Mycobacteria. RESULTS: Mycobacteria was disinfected in all cases. The temperature rise following disinfection was significantly higher in the sodium hypochlorite group. The sensory test outcomes were significantly worse in the group disinfected with sodium hypochlorite. The concentration of gas generated immediately after disinfection in both groups reached the maximum value and declined quickly. CONCLUSIONS: Disinfection of Bacillus Calmette-Guerin -containing urine with etaprocohol® was safer than disinfection with sodium hypochlorite, and an equivalent disinfection effect was achieved.

Early recovery of urinary continence after robot-assisted radical prostatectomy is associated with membranous urethra and neurovascular bundle preservation.

OBJECTIVES: We investigated the correlation between surgical outcomes and postoperative urinary continence recovery in robot-assisted radical prostatectomy (RARP). METHODS: Patients who underwent RARP in our institution (n = 195) were included in this study. Preserved urethral length (PUL) was assessed during the procedure. Other outcomes of the surgical procedure were collected from operative records. Kaplan-Meier analysis with log-rank test was used to compare urinary continence recovery rate with the PUL, sparing of the neurovascular bundle (NVB), and other surgical procedures. Univariate and multivariate analyses were performed using Cox proportional hazards model, and p-values of <0.05 were considered significant. RESULTS: Patients with a PUL ≥26 mm had 10.0%, 24.7%, 36.6%, and 89.0% continence recovery rates at 30, 60, 90, and 365 days after surgery, respectively, while patients with a PUL <26 mm had 0%, 17.8%, 26.1%, and 80.9% recovery rates, respectively. Kaplan-Meier curves showed significantly better postoperative urinary continence recovery at 30 days after RARP in patients with a PUL ≥26 mm than those with a PUL <26 mm (p = 0.0028) and in patients with NVB preservation than those with no NVB preservation (p = 0.014). Urinary continence recovery within 30, 60, and 90 days after surgery was 90.6% for patients with a PUL of ≥26 mm and NVB preservation, while only 82.3% for patients with a PUL of <26 mm or no NVB preservation. CONCLUSION: Our results suggest that a PUL ≥26 mm and NVB preservation after RARP correlate with a significantly higher postoperative rate of recovery of urinary continence.

A feasibility study of provider-level implementation strategies to improve access to colorectal cancer screening for patients with schizophrenia: ACCESS2 (N-EQUITY 2104) trial.

BACKGROUND: People with schizophrenia have a lower colorectal screening rate than the general population. A previous study reported an intervention using case management to encourage colorectal cancer screening for patients with schizophrenia in psychiatric outpatient settings. In this feasibility study, we developed provider-level implementation strategies and evaluated the feasibility of conducting a definitive trial in terms of the penetration of the intervention assessed at the patient level. Additionally, we examined the fidelity of strategies to implement the intervention at the provider level in a routine clinical psychiatric setting. METHODS: This was a multicenter, single-arm feasibility study with medical staff at psychiatric hospitals in Japan. The provider-level implementation strategies developed in this study included three key elements (organizing an implementation team appointed by the facility director, interactive assistance using a clear guide that outlines who in the hospital should do what, and developing accessible educational materials) to overcome major barriers to implementation of the intervention and four additional elements (progress monitoring, joint meetings and information sharing among participating sites, adaptation of encouragement methods to specific contexts, and education of on-site staff), with reference to the elements identified in the Expert Recommendations for Implementing Change (ERIC). The feasibility of the strategies was evaluated by the proportion of patients who were eligible for encouragement (patients with schizophrenia aged 40, 50, or 60) who received encouragement. We set the goal of providing encouragement to at least 40% of eligible patients at each site. RESULTS: Two public and four private psychiatric hospitals in Okayama and Shimane prefectures participated in this study. Regarding fidelity, all elements of the strategies were conducted as planned. Following the procedures in the guide, each team prepared and provided encouragement according to their own facility and region. Penetration, defined as the proportion of eligible patients who received encouragement, ranged from 33.3 to 100%; five of the six facilities achieved the target proportion. CONCLUSIONS: The provider-level implementation strategies to implement encouragement were feasible in terms of penetration of the intervention assessed at the patient level. The results support the feasibility of proceeding with a future definitive trial of these strategies. TRIAL REGISTRATION: jRCT, jRCT1060220026 . Registered on 06/04/2022.

The impact of respiratory reactance in oscillometry on survival in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung diseases has recently been reported. Our previous study showed that respiratory reactance (Xrs) measured by oscillometry reflected disease severity and predicted subsequent lung capacity decline in patients with IPF. However, the direct impact of Xrs on survival needs to be determined, and there are currently no reference values in oscillometry to predict prognosis. Therefore, this study aimed to investigate the association between oscillometry measurements, particularly Xrs, and survival in patients with IPF and to determine the cutoff values of Xrs that predict 3-year survival. METHODS: We analyzed the relationship between the measured values of PFT and oscillometry derived from 178 patients with IPF. Univariate and multivariate Cox proportional hazards analyses were performed to investigate the relationships between clinical indices at the time of the first oscillometry and survival. We performed the time-dependent receiver operating characteristic (ROC) curve analysis to set the optimized cutoff values of Xrs for 3-year survival prediction. We examined the discriminating power of cutoff values of Xrs on survival using the Kaplan-Meier method and the log-rank test. RESULTS: Xrs components, especially in the inspiratory phase (In), significantly correlated with the PFT values. In the multivariate analyses, Xrs (all of reactance at 5 Hz [X5], resonant frequency [Fres], and low-frequency reactance area [ALX] in the inspiratory phase) had a significant impact on survival (X5, p = 0.003; Fres, p = 0.016; ALX, p = 0.003) independent of age, sex, and other prognostic factors derived from the univariate analysis. The area under the ROC curve was 0.765, 0.759, and 0.766 for X5 In, Fres In, and ALX In, with cutoff values determined at - 0.98, 10.67, and 5.32, respectively. We found significant differences in survival after dividing patients using each of the cutoff values of Xrs. CONCLUSIONS: In patients with IPF, Xrs measured by oscillometry significantly impacted survival. We also determined the cutoff values of Xrs to discriminate patients with poor prognoses.

Summary of the Clinical Practice Guidelines for Upper Tract Urothelial Carcinoma 2023 by the Japanese Urological Association.

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

Effectiveness and Factors Associated with Response to Golimumab in Japanese Patients with Ulcerative Colitis in Real Clinical Practice: The Phoenix Study.

Introduction: There have been limited reports on the clinical efficacy of golimumab (GLM) in Japanese patients with ulcerative colitis (UC) in real clinical practice. This study aimed to explore the real-life effectiveness and factors associated with response to GLM in Japanese patients with UC. Methods: This observational, retrospective, multicenter study was conducted in hospitals with expertise in inflammatory bowel disease treatment. Sixty-three patients treated with GLM and active UC were included in the analysis. Clinical remission (CR) (partial Mayo (pMayo) score ≤2) in the induction and maintenance phases after GLM treatment and associated factors were evaluated. Results: The proportion of patients achieving CR in the induction and maintenance phases was 41.3% (26/63) and 46.0% (29/63, the last observation carried forward method was used for patients who discontinued treatment for reasons other than inadequate response), respectively. The median pMayo score was 5 (interquartile range (IQR): 4-6) at baseline, 3 (IQR: 1-5) in the induction phase, and 1 (IQR: 0-3) in the maintenance phase. Hemoglobin, platelet, and C-reactive protein levels changed, consistent with the pMayo score. Multivariate logistic analysis revealed that biologic-naive status was an independent factor associated with CR in the induction (p = 0.0200) and maintenance (p = 0.0459) phases, and a disease duration of >60 months until GLM initiation was associated with CR in the induction phase (p = 0.0427). Conclusions: The effectiveness of GLM in daily clinical practice has been confirmed in Japanese patients with active UC. Biologic-naive patients responded more to GLM in the induction and maintenance phases, and patients with disease duration of >60 months until initiation of GLM were more responsive in the induction phase.

Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan: An Observational Analysis.

Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies.

A multicenter, retrospective observational study investigating baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer treated with primary androgen deprivation therapy.

OBJECTIVE: This multicenter, retrospective, observational study investigated baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer who received primary androgen deprivation therapy, using Japan Study Group of Prostate Cancer registry data. METHODS: Among patients in the Japan Study Group of Prostate Cancer registry, those who initiated primary androgen deprivation therapy and were aged 20 years or older were enrolled in this study. The primary endpoint was time to disease progression, defined as time from primary androgen deprivation therapy initiation to either prostate-specific antigen or clinical progression. Secondary endpoints included prostate-specific antigen progression-free survival, prostate-specific antigen response (90% or greater reduction from baseline) and distribution of second-line treatment. RESULTS: Of the 2494 patients (goserelin, n = 564; leuprorelin, n = 1148; surgical castration, n = 161; degarelix, n = 621), those who received degarelix had higher prostate-specific antigen levels and Gleason scores and were at a more advanced clinical stage than those receiving goserelin or leuprorelin. The median time to disease progression (identical to the prostate-specific antigen progression-free survival result) was not reached for goserelin and leuprorelin, 52.7 months for surgical castration and 54.0 months for degarelix. Although baseline prostate-specific antigen values in the degarelix cohort were higher than those of the leuprorelin or goserelin cohorts, prostate-specific antigen responses were not different among the three cohorts. Regarding second-line treatment, the largest patient group received degarelix followed by leuprorelin (n = 195). CONCLUSIONS: This study clarified patient characteristics and long-term effectiveness of primary androgen deprivation therapy in real-world clinical practice. Japanese urologists appear to select appropriate primary androgen deprivation therapy based on patient background and tumour characteristics, with degarelix largely reserved for higher risk patients.

Perceptions toward issues in cancer care for people with mental illness among psychiatric care providers: A questionnaire study.

OBJECTIVES: To reduce cancer care disparities in people with mental illness, this study aimed to quantify psychiatric care providers' perceptions regarding issues that are insufficiently addressed or difficult to address. METHODS: Psychiatric care providers at 23 psychiatric hospitals in Japan were surveyed using mail questionnaires. Respondents were asked to rate 15 items with four categories related to insufficiencies/difficulties in cancer care for patients with mental illness on a five-point Likert scale. We analyzed the proportion of respondents who answered "insufficient/difficult" for each item. RESULTS: A total of 255 (76.3%) psychiatric care providers responded. For questions related to the skills and attitudes of psychiatric professionals, 48.3%-58.4% of respondents perceived that efforts for supporting cancer screening and treatment were insufficient. For the questions related to collaborations between cancer and psychiatric care providers, 75.3% of respondents perceived that inpatient visits between psychiatric and cancer hospitals were insufficient. For the questions related to in-psychiatric-hospital medical systems, 50.2%-87.2% of respondents perceived that support for screening, diagnosis/treatment, and palliative care for psychiatric inpatients were insufficient/difficult. 41.9%-57.4% of respondents perceived that social services in the community were insufficient. CONCLUSIONS: This study clarified the level of insufficiency/difficulty perceived by psychiatric care providers regarding issues related to cancer care for people with mental illness. Psychiatric care providers are required to have knowledge and skills in cancer screening and treatment. To improve access to cancer prevention, treatment, and palliative care, it may be helpful to establish systems to promote coordination between cancer hospitals and psychiatric hospitals.

Health-related quality of life with enzalutamide versus flutamide in castration-resistant prostate cancer from the AFTERCAB study.

BACKGROUND: Patient-reported outcome (PRO) measures can provide valuable information in evaluating patients' health-related quality of life (HRQoL). Post hoc analysis of the AFTERCAB study was conducted to evaluate the HRQoL benefit of enzalutamide plus androgen deprivation therapy (ADT) compared to flutamide plus ADT for the treatment of patients with castration-resistant prostate cancer (CRPC) in Japan. METHODS: The open-label AFTERCAB study was conducted from November 2016 to March 2020 in Japanese men aged ≥ 20 years with asymptomatic or mildly symptomatic CRPC. Patients received enzalutamide plus ADT or flutamide plus ADT, respectively, as first-line alternative androgen therapy (AAT). HRQoL was analyzed through the Functional Assessment of Cancer Therapy-Prostate, EuroQoL 5-Dimension 5-Level instruments, Brief Pain Inventory-Short Form, and Brief Fatigue Inventory. The longitudinal changes in HRQoL, HRQoL deterioration based on minimally important difference (MID), and time to HRQoL deterioration were evaluated for first-line AAT. RESULTS: Overall, HRQoL between the enzalutamide and flutamide groups was similar during first-line treatment. No statistically significant HRQoL difference in change from baseline to week 61 (least square mean difference; p value) was observed. Furthermore, proportions of pain progression, symptom worsening, and HRQoL deterioration based on MID, were not significantly different between groups. CONCLUSIONS: The results were similar in all subscales of each PRO, demonstrating similar HRQoL deterioration based on MID criteria between the enzalutamide and flutamide groups.

Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association.

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition.

Are there differences in the characteristics of patients who respond to gemcitabine plus cisplatin chemotherapy and those who respond to pembrolizumab therapy for metastatic urothelial carcinoma? Multicenter retrospective study.

OBJECTIVES: To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy. METHODS: We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy. RESULTS: There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004). CONCLUSIONS: Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy.

Issues of cancer care in people with mental disorders as perceived by cancer care providers: A quantitative questionnaire survey.

OBJECTIVES: To reduce cancer care disparities, this study aimed to clarify the difficulties in cancer care for people with mental disorders as perceived by cancer care providers. METHODS: Cancer care providers at 17 designated cancer hospitals in Japan were surveyed using mail questionnaires. Respondents were asked to rate 29 items related to difficulties or insufficiencies in cancer care for patients with mental disorders on a five-point Likert scale. We analyzed the proportion of respondents who answered "difficult/insufficient" in each item. We also calculated the proportions of responders stratified according to the presence of psychiatric support systems within their hospitals. RESULTS: A total of 388 (58.4%) cancer care providers responded. Among the issues related to "difficulties in diagnosing and treating cancer," support for decision-making, assessment of treatment adherence, and assessment of physical symptoms were perceived as most difficult (73.5%-81.5% of respondents). Among the issues related to 'difficulties or insufficiencies in collaboration among multidisciplinary health care providers,' the issue of advance consultation and sharing information with the patient's primary psychiatric care provider was perceived as most difficult (52.2%). Among the issues related to "insufficiencies of in-hospital and community medical systems," education to provide reasonable accommodation was perceived as most insufficient (47.4%). The perceived difficulties of over half of the issues varied significantly between hospitals depending on the level of psychiatric support systems. CONCLUSIONS: This study clarified the difficulties of cancer care in patients with mental disorders as perceived by cancer care providers. Some issues may be resolved by psychiatric liaison teams.

Patients' acceptability and implementation outcomes of a case management approach to encourage participation in colorectal cancer screening for people with schizophrenia: a qualitative secondary analysis of a mixed-method randomised clinical trial.

OBJECTIVES: We examined the efficacy of case management (CM) interventions to encourage participation in colorectal cancer screening for patients with schizophrenia. This study aimed to clarify patients' acceptability of the intervention and the helpful components of the intervention. Simultaneously, the study aimed to determine the acceptability, appropriateness and feasibility of the intervention from the perspective of psychiatric care providers. STUDY DESIGN AND SETTING: This study was a secondary qualitative analysis of a mixed-method randomised controlled trial that evaluated the efficacy of the CM approach to encourage participation in cancer screening for people with schizophrenia. The intervention comprised education and patient navigation for colorectal cancer screening. Interviews were conducted with patients who received the intervention and staff from two psychiatric hospitals in Japan who delivered the intervention. PARTICIPANTS: Of the 172 patients with schizophrenia who participated in the trial, 153 were included. In addition, three out of six providers were included. DATA COLLECTION AND ANALYSIS: Using a structured interview, the case manager asked participants about patient acceptability and the helpful components of the intervention. Content analysis was conducted for the responses obtained, and the number of responses was tabulated by two researchers. For the interviews with the providers, opinions obtained from verbatim transcripts were extracted and summarised. RESULTS: Forty-three of the 56 patients perceived that the intervention was acceptable. For the intervention component, inperson counselling with an explanation of the screening process by psychiatric care providers was most frequently reported by the patients as helpful (48 of the 68 respondents). Psychiatric care providers evaluated the intervention as acceptable, appropriate and easy to understand and administer. However, providing the intervention to all patients simultaneously was considered difficult with the current human resources. CONCLUSIONS: This study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers. TRIAL REGISTRATION NUMBER: UMIN000036017.

A novel ZC4H2 variant in a female with severe respiratory complications.

INTRODUCTION: An X-linked ZC4H2 variant is associated with a variety of phenotypes that have abnormalities related to external malformation and neurodevelopment. There have been no reports on severe respiratory dysfunction resulting in surgical treatments not being possible due to the deformity resulting from in this disease. Here we report a female with arthrogryposis multiplex congenita with a severe respiratory complication. CASE: A two-year-old girl had arthrogryposis multiplex congenita at delivery and subsequently had hypotonia and feeding difficulty. A novel ZC4H2 frameshift variant was identified by whole-exome sequencing in her genome. At eight months, she had recurrent aspiration pneumonia. A tracheostomy and gastrostomy were required; however, surgical intervention was not possible because of her short neck and complicated airway. CONCLUSION: We compared this case with previous reports. The truncation group had more described phenotypes than the non-truncation group. The patient had the most severe respiratory dysfunction in truncating variant.

Late recurrence in patients with non-muscle-invasive bladder cancer after 5-year cancer-free periods.

OBJECTIVES: There is no consensus about the follow-up schedule after 5-year cancer-free periods. In this study, we aimed to elucidate the risk factors for the recurrence in patients with non-muscle-invasive bladder cancer who remained cancer free for more than 5 years. METHODS: Data from six Japanese institutions were retrospectively reviewed. Among the patients with non-muscle-invasive bladder cancer who were treated with transurethral resection of bladder tumor between 1990 and 2013, those who had no recurrence for more than 5 years were included in this study. The Kaplan-Meier method and Cox hazards model were used to estimate recurrence-free survival and to determine the pathologic and clinical factors affecting late recurrence. RESULTS: In total, 434 patients were enrolled in this study. Of these patients, 55 patients (12.7%) experienced late recurrence. The median follow-up time was 8.9 years (interquartile range 6.9-11.3 years). Prior history of bladder cancer before the most recent transurethral resection was a significant predictor for late recurrence (hazard ratio 1.99 [95% confidence interval 1.13-3.47], P = 0.019), although other clinical factors including tumor grade, pathologic stage, tumor multiplicity, and current risk classification systems were not associated with late recurrence. CONCLUSIONS: Late recurrence after a long tumor-free period is not rare and it was not predicted by current risk classification systems. Only prior history of bladder cancer was a significant predictor for late recurrence in this study.

Enzalutamide + androgen deprivation therapy (ADT) versus flutamide + ADT in Japanese men with castration-resistant prostate cancer: AFTERCAB study.

Objectives: The objective of the study is to compare the efficacy and safety of alternative androgen therapy (AAT) with enzalutamide + androgen deprivation therapy (ADT) and flutamide + ADT in the treatment of Japanese men with metastatic or nonmetastatic castration-resistant prostate cancer (CRPC) who progressed despite combined androgen blockade (CAB) with bicalutamide + ADT. AAT treatment sequence was also investigated. Materials and methods: The open-label, Phase 4 AFTERCAB study (NCT02918968) was conducted from November 2016 to March 2020 in Japanese men aged ≥20 years with asymptomatic or mildly symptomatic CRPC. Patients were initially randomized to enzalutamide (160 mg/day) + ADT (enzalutamide first) or flutamide (375mg/day [125mg three times daily]) + ADT (flutamide first) as first-line therapy. Following prostate-specific antigen (PSA) progression, other disease progression, or discontinuation of first-line therapy due to an adverse event (AE), patients switched to the other treatment as second-line therapy. The primary endpoint was time to PSA progression with first-line therapy (TTPP1). Secondary endpoints included TTPP2 (TTPP1 + time to PSA progression with second-line therapy). AEs were monitored to assess safety. Results: Overall, 206 men were randomized (enzalutamide first, n = 102; flutamide first, n = 104) and stratified by study site and disease stage; 133 patients transitioned to second-line therapy (enzalutamide first, n = 48; flutamide first, n = 85). TTPP1 was significantly improved with enzalutamide first versus flutamide first (median 21.4 months vs. 5.8 months; hazard ratio [HR] 0.42; 95% confidence interval [CI] [0.29, 0.61]). TTPP2 was numerically improved with enzalutamide first versus flutamide first (median not reached vs. 21.2 months; HR 0.76; 95% CI [0.48, 1.19]). Both treatments were generally well tolerated, with AEs consistent with their known safety profiles. Conclusion: First-line AAT with enzalutamide + ADT provided a significant improvement in time to PSA progression versus flutamide + ADT. Enzalutamide + ADT may therefore be the preferred first-line AAT option in Japanese men with metastatic or nonmetastatic CRPC who progress despite CAB with bicalutamide + ADT.