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Background: We analyzed the relationship between prostate cancer outcomes and pretreatment clinical factors and developed a prognostic nomogram of overall survival (OS) of patients with bone metastasis., Methods: From 1993 to 2011, 463 consecutive patients were treated for bone-metastatic prostate cancer. Data sets from 361 patients were used to develop a nomogram (training data), and data sets of 102 patients were used for validation of the nomogram (validation data). Using the external validation data set, the nomogram was assessed for discriminatory ability, and the predictions were assessed for calibration accuracy by plotting actual survival against predicted risk., Results: Of the 361 patients in the training data set, 205 (56.8%) patients died, 169 (46.8%) deaths of which were due to prostate cancer. The median follow-up period was 55.2 months. In the multivariate analysis, patient age, serum prostate-specific antigen level, clinical T stage, extent of disease on bone scan, and biopsy Gleason sum were independent prognostic factors. We developed a prognostic model comprising these five factors for patients with bone-metastatic prostate cancer. This nomogram can be used to estimate 1-, 3-, and 5-year survival probability. External validation of this model using 102 validation data sets showed reasonable accuracy (concordance index, 0.719)., Conclusion: Our pretreatment prognostic nomogram might be useful for Japanese patients with bone-metastatic prostate cancer.

Background: The ALSYMPCA trial revealed radium‐223 (Ra‐223) to be a life‐prolonging agent for bone metastatic castration‐resistant prostate cancer (CRPC). However, only 2.8% of enrolled patients in that clinical trial were Asian, and no Japanese patients were enrolled. Several retrospective studies have been published concerning Japanese bone metastatic CRPC patients receiving Ra‐223. However, no study has yet reported the correlation between Ra‐223 induction and the survival in Japanese bone metastatic CRPC patients. This study investigated the effect of Ra‐223 as a life‐prolonging agent in a large Japanese healthcare fee database. Methods: A total of around 410 000 prostate cancer patients were extracted from this database, and 25 934 were diagnosed with CRPC. In these patients, the age, date of the CRPC diagnosis, date of Ra‐223 induction, and prognosis were analyzed. Results: A total of 1628 patients received Ra‐223, and 6693 patients were diagnosed with bone metastasis CRPC, with the remaining 17 613 patients diagnosed with CRPC without bone metastasis. The patients who completed six courses of Ra‐223 showed a significantly more favorable overall and cancer‐specific survival than those who received ≤5 courses (p < 0.0001 and p < 0.0001, respectively). For time from CRPC diagnosis date to death, the Ra‐223 induction group showed a significantly more favorable prognosis with regard to both the overall and cancer‐specific survival than the bone metastatic CRPC patients without Ra‐223 (p < 0.0001 and p < 0.0001, respectively). Conclusions: Bone metastatic CRPC patients who received Ra‐223 showed a significantly better prognosis than bone metastatic CPRC patients who did not receive Ra‐223. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to indirectly compare apalutamide and enzalutamide with respect to tolerability and health-related quality of life (HRQoL) among men with non-metastatic castration-resistant prostate cancer (nmCRPC).Methods: Patient-level data from the SPARTAN study [apalutamide + androgen deprivation therapy (ADT) versus placebo + ADT] and aggregate published data from the PROSPER study (enzalutamide + ADT versus placebo + ADT) were used. Anchored matching-adjusted indirect comparison (MAIC) was conducted by weighting patients' baseline characteristics from SPARTAN to match aggregated baseline characteristics in PROSPER. Odds ratios (ORs) of reported adverse events (AEs) and baseline-to-follow-up least squares mean differences in HRQoL [measured with Functional Assessment of Cancer Therapy-Prostate (FACT-P) score] with 95% credible intervals were re-estimated for SPARTAN arms using weighted population and indirectly compared with those in PROSPER through a Bayesian framework. Events of special interest included fatigue, hot flush, nausea, diarrhea, hypertension, falls, dizziness, decreased appetite, arthralgia, asthenia and headache. In addition, any AEs and serious AEs were explored.Results: Of 1207 SPARTAN patients, 1171 were matched to 1401 PROSPER patients. Relative to enzalutamide, apalutamide demonstrated better tolerability as evidenced by the highest probability of reduced occurrence of fatigue [p(OR < 1) = 99.5%], hypertension [p(OR < 1) = 99.2%], decreased appetite [p(OR < 1) = 98.3%], fall [p(OR < 1) = 90.3%], headaches [p(OR < 1) = 86.7%], and nausea [p(OR < 1) = 80.0%]. The probabilities of reduced occurrence of any AEs and SAEs with apalutamide versus enzalutamide were 66.9% and 90.9%, respectively. Relative to enzalutamide, apalutamide treatment was associated with a higher probability of a better HRQoL based on the FACT-P total score [p(diff > 0) = 73.1%]. The probability of a better HRQoL with apalutamide versus enzalutamide was highest for the physical [p(diff > 0) = 97.3%] and functional [p(diff > 0) = 86.7%] wellbeing subscales, and the pain-related subscale [p(diff > 0) = 90.1%].Conclusion: Anchored MAIC suggests that treatment of men with nmCRPC with apalutamide is associated with a higher probability of better tolerability due to fewer AEs and better HRQoL than enzalutamide. [ABSTRACT FROM AUTHOR]

Introduction: Apalutamide and enzalutamide are next-generation androgen receptor inhibitors that demonstrated efficacy in placebo-controlled studies (SPARTAN for apalutamide; PROSPER for enzalutamide) when used in combination with androgen deprivation therapy (ADT) for treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In the absence of comparative studies between these agents, the present study sought to indirectly compare metastasis-free survival (MFS) and overall survival (OS) in patients with nmCRPC who received these therapies.Methods: Individual patient-level data from SPARTAN (apalutamide plus ADT) and published data from PROSPER (enzalutamide plus ADT) were utilized. An anchored matching-adjusted indirect comparison (MAIC) was conducted by weighting the patients from the SPARTAN study to match baseline characteristics reported for PROSPER. Hazard ratios (HRs) for MFS and OS were re-estimated for SPARTAN using weighted Cox proportional hazards models and indirectly compared with those of PROSPER using a Bayesian network meta-analysis.Results: From the SPARTAN population (N = 1207), a total of 1171 patients were matched to the PROSPER population (N = 1401). The recalculated HRs (95% confidence interval) for apalutamide versus ADT based on the reweighted SPARTAN data to mimic the PROSPER patient population were 0.26 (0.21; 0.33) for MFS and 0.62 (0.41; 0.94) for OS. MAIC-based HRs (95% credible interval) for apalutamide versus enzalutamide were 0.91 (0.68; 1.22) for MFS and 0.77 (0.46; 1.30) for OS. The Bayesian probabilities of apalutamide being more effective than enzalutamide were 73.6% for MFS and 83.5% for OS.Conclusions: MAIC results suggest that nmCRPC patients treated with apalutamide have a higher probability of a more favorable MFS and OS compared with those treated with enzalutamide. [ABSTRACT FROM AUTHOR]

Introduction. Nearly 80% of advanced prostate cancer patients respond to initial androgen deprivation therapy (ADT). However, ADT does not prevent the progression of prostate cancer over the long term, and the disease eventually progresses to castration-resistant prostate cancer (CRPC). Prior to the development of enzalutamide (ENZ) and abiraterone acetate, docetaxel was the only established treatment with life-prolongation for CRPC. ENZ is a second-generation anti-androgen receptor drug that has contributed to improving the prognosis of CRPC. Several studies have reported factors predicting the efficacy of ENZ; however, there are no confirmed biomarkers. The neutrophil-to-lymphocyte ratio (NLR) is an easily calculated biomarker that is associated with the prognosis of several solid malignancies. However, there were few studies investigated NLR for ENZ in patients with mCRPC. We examined the usefulness of the NLR as a predictive tool for ENZ. Methods. We retrospectively examined a total of 106 CRPC patients who were treated with ENZ until September 2016 in Yokohama City University Hospital, Yokohama City University Medical Center, and National Cancer Center Hospital East. ENZ was routinely started as a dose of 160 mg per day; the dosage was reduced in some patients due to side effects. Drug holiday for 1-2 weeks or dose reduction to 80-120mg was done and no patients discontinued ENZ treatment due to adverse effects. ENZ was stopped when cancer progression was detected based on PSA elevation, radiographic findings, and deterioration of the patient's performance status. The cut-off NLRs for overall survival (OS) and cancer-specific survival (CSS) were determined based on the receiver-operator curves. Kaplan-Meier curves were used to analyze the factors associated with OS or CSS and a log-rank test was performed. A multivariate analysis was also performed to analyze the factors associated with the prognosis. Results. We retrospectively reviewed 106 consecutive CRPC patients who were both treated with ENZ and were able to be counted before ENZ NLR. Cut-off point was 2.14 for both OS and CSS by receiver operator characteristic curve. The patients were then divided into the higher NLR group (≥2.14) and lower NLR group (<2.14). Multivariate analysis showed that NLR and predocetaxel chemotherapy were independent risk factors for both overall and cancer-specific survival. Conclusions. The NLR might be a useful biomarker for predicting the prognosis of mCRPC patients who are treated with ENZ. [ABSTRACT FROM AUTHOR]

Background: A computer-assisted diagnostic system for analyzing bone scans (BONENAVI) calculates the automated bone scan index (aBSI). Here we evaluated the aBSI as a prognostic imaging biomarker for men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel.Methods: We retrospectively analyzed 48 patients who received cabazitaxel for mCRPC and evaluated the ability of the aBSI to predict overall survival (OS). The Cox proportional hazards model was used to investigate the associations between baseline aBSI at cabazitaxel treatment and OS with the clinical variables as follows: age, number of cycles of docetaxel, serum prostate-specific antigen, hemoglobin (Hb), lactate dehydrogenase (LDH), and alkaline phosphatase. We determined the C-index to evaluate the discriminatory ability of our models when we included or excluded the aBSI from the analyses.Results: The median OS after cabazitaxel treatment was 10.0 months, and patients with aBSI ≤1% achieved significantly longer OS compared with patients with aBSI ≥1%. Multivariate analysis showed that age, Hb, LDH, and aBSI were independent prognostic factors of OS. Adding aBSI to the base model increased the C-index from 0.78 to 0.80.Conclusions: The aBSI may serve as a useful imaging biomarker for predicting OS among men with mCRPC treated with cabazitaxel. Prospective studies are required to establish the value of aBSI as prognostic imaging biomarker. [ABSTRACT FROM AUTHOR]

Introduction and Objectives. An elevated neutrophil-to-lymphocyte ratio (NLR) has been suggested to be associated with a poor prognosis in several cancers. We evaluated the utility of an elevated NLR as a biomarker to predict the prognosis of metastatic castration-resistant prostate cancer (mCRPC) patients treated with cabazitaxel (CBZ). Methods. We analyzed 47 patients who received CBZ chemotherapy for mCRPC in our institutions. The NLR was calculated using the neutrophil and lymphocyte counts before CBZ chemotherapy. We determined the NLR cut-off value based on the sensitivity and specificity levels derived from area under the receiver operator characteristic curves for death. A multivariate analysis was performed to investigate the association between the NLR and the prognosis. Results. The median overall survival (OS) after CBZ was 10.0 months (range: 6.3–13.2). The median OS was shorter in patients with a high NLR (≥3.83) than in those with a low NLR (<3.83) (5.8 versus 13.2 months, p=0.018). In the multivariate analysis, the NLR, patient age, and lymph node (LN) metastasis were independent predictors of the OS (hazard ratio 3.01, p=0.030; hazard ratio 3.10, p=0.029; hazard ratio 12.38, p=0.001, resp.). Conclusions. NLR might be a useful prognostic biomarker in mCRPC patients treated with CBZ. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-to-lymphocyte ratio (NLR) is reported as a biomarker for some solid malignant diseases. Thus far, however, no reports of the relationship between the NLR and adrenal tumors have been published. We analyzed the utility of the preoperative NLR as a biomarker for predicting the prognosis or diagnosis of malignant disease.Methods: A total of 59 patients with adrenal tumors (13 cases of malignant disease and 46 with benign disease) were analyzed in this study from February 2004 to June 2015 at our institute. The NLR was obtained just before adrenalectomy. The diagnosis of adrenal tumor was confirmed by a pathological examination of surgical specimens.Results: The NLR in malignant adrenal tumor specimens was significantly higher than in non-malignant specimens (p = 0.028). Adrenocortical carcinoma (ACC) showed the highest NLR among all adrenal tumors. In ACC, the higher NLR group (NLR ≥ 5) showed a significantly poorer overall survival than the lower NLR group (NLR < 5) (p = 0.032).Conclusions: In adrenal tumors, a higher NLR indicates a higher incidence of malignancy. The NLR might be a new biomarker for predicting the prognosis of adrenal tumor patients. [ABSTRACT FROM AUTHOR]

Introduction. Gemcitabine and cisplatin (GC) is a gold-standard first-line systemic chemotherapy for advanced urothelial carcinoma (UC). However, it may cause severe adverse effects such as renal toxicity, gastrointestinal toxicity, and neurotoxicity. Sarcopenia is the age-related loss of skeletal muscle mass. A correlation between sarcopenia and the oncological prognosis has been reported. In UC, several studies have noted that patients with sarcopenia had a greater incidence of complications and worse survival after radical cystectomy or chemotherapy. Our institute introduced gemcitabine and nedaplatin (GN) for UC patients with renal failure. We investigated whether the presence of sarcopenia predicted the prognosis of patients with advanced UC who were treated by GN chemotherapy. Methods. A total of 27 patients (male, n=21; female, n=6) received GN therapy for metastatic UC from 2005 to 2016. The institutional review board of Yokohama City University Hospital approved this study. The psoas muscle index (PMI, cm2/m2) was calculated using this formula: right psoas muscle area (cm2)/the square of the body height (m2). The overall survival (OS) of the high PMI group (male: ≥2.49, female: ≥2.07) and low PMI group (male: <2.49, female: <2.07) was compared. Results. Kaplan-Meier survival curves and a log-rank test revealed that the high PMI group had significantly better OS than the low PMI group (p=0.015). The mean survival of the high and low PMI groups was 561 days and 223 days, respectively. Conclusions. In the present study, we revealed that sarcopenia (a low psoas muscle volume) might be a predictive factor for poorer overall survival in patients with advanced urothelial carcinoma who are undergoing GN chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction and Objectives. Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a simple marker of the systemic inflammatory response in critical care patients. We previously assessed the utility of NLR as a biomarker to predict tumor recurrence and cancer death in bladder cancer patients who underwent radical cystectomy. In this study, we evaluated the prognostic impact of NLR in bladder cancer patients who received gemcitabine and nedaplatin (GN) chemotherapy. Methods. A total of 23 patients who received GN chemotherapy for advanced bladder cancer were enrolled in this study. The cut-off point of NLR according to the sensitivity and specificity levels was derived from the area under receiver operator characteristics (AUROC) curve plotted for disease progression or overall mortality. Results. The NLR cut-off point was determined as 4.14 for both tumor progression and overall mortality. Median progression-free survival (PFS)/overall survival (OS) in the higher NLR group (NLR ≥ 4.14) and lower NLR group (NLR < 4.14) were 194/468 days versus 73/237 days, respectively. Kaplan-Meier analysis showed that higher NLR significantly correlated with poorer PFS (p=0.011) and OS (p=0.045). Conclusions. NLR may serve as a new biomarker to predict responses to GN-based chemotherapy in advanced bladder cancer patients and/or their prognosis. [ABSTRACT FROM AUTHOR]

Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p=0.834), pathological T stage (p=0.082), lymph node metastasis (p=0.062), or resection margin status (p=0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy. [ABSTRACT FROM AUTHOR]

We examined the significance of a pathologic ‘fused gland’ according to the WHO-Mostofi classification for predicting prognosis in hormonally treated prostate cancer. Of 284 newly diagnosed patients receiving hormone therapy, 60 patients had specimens with no ‘medullary’ or ‘column-cord’ elements. Twenty-five of these had a ‘fused gland’, while 35 did not. Survival of these patients was analyzed. Cause-specific survival of the patients with no medullary or column-cord elements showed a significantly better prognosis compared to others. Furthermore, the patients whose specimens contained a ‘fused gland’ component had significantly poorer survival than those without that component, suggesting that the ‘fused gland’ component is a poor prognostic factor for survival in patients with hormonally treated prostate cancer.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis.Methods: We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death.Results: A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35; P<0.001). Time to symptomatic progression was significantly longer with apalutamide than with placebo (hazard ratio, 0.45; 95% CI, 0.32 to 0.63; P<0.001). The rate of adverse events leading to discontinuation of the trial regimen was 10.6% in the apalutamide group and 7.0% in the placebo group. The following adverse events occurred at a higher rate with apalutamide than with placebo: rash (23.8% vs. 5.5%), hypothyroidism (8.1% vs. 2.0%), and fracture (11.7% vs. 6.5%).Conclusions: Among men with nonmetastatic castration-resistant prostate cancer, metastasis-free survival and time to symptomatic progression were significantly longer with apalutamide than with placebo. (Funded by Janssen Research and Development; SPARTAN ClinicalTrials.gov number, NCT01946204 .). [ABSTRACT FROM AUTHOR]

Objectives: Recent studies have demonstrated that up-front docetaxel combined with androgen deprivation therapy (ADT) prolongs survival in some patients with metastatic hormone-naïve prostate cancer (mHNPC). However, new biomarkers for selecting personalized treatment strategies for mHNPC are warranted. We evaluated the value of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression as a prognosticator in men with mHNPC.Methods and Materials: A total of 48 men with mHNPC diagnosed from 2003 to 2009 were enrolled in this study. Prostate cancer tissues obtained by needle biopsies were immunohistochemically stained for LMW-PTP. Correlations between LMW-PTP expression and clinicopathological characteristics were then assessed.Results: At the time of analysis, 29 (60.4%) patients were alive, whereas 15 (31.3%) and 4 (8.3%) died of prostate cancer and nonprostate cancer, respectively. Of these, 29 (60.4%) had low LMW-PTP expression and 19 (39.6%) had high expression. Median overall survival (OS) for patients with high LMW-PTP expression was not reached and that for patients with low LMW-PTP expression was 23.8 months. High LMW-PTP expression was significantly correlated with a shorter OS compared with low LMW-PTP expression (P = 0.01). Moreover, multivariate analysis showed that Gleason score (≥8 vs.≤7; HR = 5.8, 95% CI: 1.3-26.5, P = 0.02) and LMW-PTP expression (high vs. low; HR = 2.7, 95% CI: 1.0-7.2, P = 0.04) were independent prognostic factors for OS.Conclusions: LMW-PTP is a potential biomarker to predict OS in patients with mHNPC. [ABSTRACT FROM AUTHOR]