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Enzalutamide combined with androgen deprivation therapy (ADT) significantly prolonged metastasis-free survival and overall survival (OS) versus ADT alone in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) with rapidly rising prostate-specific antigen (PSA). The objective of this post hoc analysis of the PROSPER trial is to evaluate OS benefit and safety of enzalutamide in patients across age and regional subgroups. Eligible men with nmCRPC, PSA doubling time ≤10 months and PSA ≥2 ng/mL with continued ADT use were randomised 2:1 to enzalutamide 160 mg or placebo. OS and safety were examined by age (<70 vs ≥70 years) and region (North America, Europe, Asia or the rest of the world). The impact of prior and subsequent therapy was also examined. In total, 1401 men were enrolled (median age, 74 years). Enzalutamide plus ADT reduced the risk of death, independent of age or region. Multivariate analyses identified Eastern Cooperative Oncology Group (ECOG) status (P < 0.0001), log (PSA; P = 0.0002) and subsequent therapy (P < 0.0001) as statistically significant factors impacting OS. Safety was consistent across age and regional subgroups. Any grade treatment-emergent adverse events were similar across age groups, were more common in the placebo group and had regional variation. In men with nmCRPC and rapidly rising PSA, the benefit and safety of enzalutamide were consistent across age and regional subgroups. Variables impacting OS included ECOG status, log (PSA) and subsequent therapy. NCT02003924. [Display omitted] • Enzalutamide plus androgen deprivation therapy reduced the risk of death in non-metastatic castration-resistant prostate cancer. • Overall survival with enzalutamide was similar across age and geographical regions. • Three factors were identified that improved overall survival. • The safety of enzalutamide was similar across age but varied with geography. [ABSTRACT FROM AUTHOR]

Purpose: To investigate pathological stage at radical prostatectomy (RP) using the "Partin tables" approach in NCCN high-risk (HR) prostate cancer (PCa) patients., Materials and Methods: Within the SEER 2010 to 2016 database, we identified 7,718 NCCN HR PCa patients. Cross-tabulation was used to illustrate the distribution of organ confined disease (OC, pT2), extra-prostatic extension (EPE, pT3a), seminal vesicles invasion (SVI, pT3b), lymph node invasion (LNI, pT2N1), extra-prostatic and lymph node invasion (EPE + LNI, pT3aN1), and seminal vescicale and lymph node invasion (SVI + LNI, pT3bN1), according to preoperative criteria, which consisted in PSA, clinical T stage, biopsy Gleason Score (GS). Binomial 95%CI was constructed for the reported proportions., Results: Median (IQR) PSA levels was 9 (6-20) ng/ml. The majority of patient harbored cT1c (51%) followed by cT2 (35%) and cT3 (14%) stage. Most patients exhibited GS 4+4 (43%). Overall, 87 vs. 15 vs. 2% of patients harbored only 1 vs. 2 vs. all 3 HR criteria. At RP, OC, EPE, SVI, and LNI rates were respectively 36%, 27%, 17%, and 19%. Highest levels of OC were recorded for cT1c, PSA <10 ng/mL and biopsy GS4+4. Conversely, EPE, SVI and LNI were the highest in patients with cT3, PSA ≥20 ng/mL and GS 5+5. After stratification according to clinical stages, OC rates decreased with increasing PSA levels and GS. Conversely, EPE, SVI and LNI rates increased with increasing PSA and GS., Conclusion: We provide a lookup table to illustrate the relationship between clinical and pathological characteristics in NCCN HR PCa patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To examine the effect of specific Asian ethnic subgroups on stage at presentation and cancer-specific mortality in non-metastatic upper tract urothelial carcinoma among North American upper tract urothelial carcinoma Asian patients treated with radical nephroureterectomy., Methods: We relied on the Surveillance, Epidemiology and End Results database, from 2004 to 2016. Kaplan-Meier plots and multivariable Cox regression models predicting cancer-specific mortality were used., Results: Of 584 upper tract urothelial carcinoma patients, 173 (29.6%) were Chinese versus 130 (22.3%) Japanese versus 68 (11.6%) Korean versus 64 (11.0%) Filipino versus 40 (6.8%) Vietnamese versus 109 (18.7%) other. Vietnamese and Chinese patients showed the highest rates of T 4 N 0 M 0 and/or T 1-4 N 1-2 M 0 (25.0% and 18.5%, respectively), relative to other Asian ethnic subgroups. In Kaplan-Meier plots, Vietnamese patients showed the highest cancer-specific mortality rate. In multivariable models, Vietnamese ethnicity also independently predicted higher cancer-specific mortality (hazard ratio 2.15, P = 0.02 and hazard ratio 1.96, P = 0.03), relative to Japanese and Chinese patients. All other Asian ethnic subgroups showed similar cancer-specific mortality patterns., Conclusion: Vietnamese and Chinese patients are at a stage disadvantage at upper tract urothelial carcinoma diagnosis, relative to all other Asian ethnicities. After adjustment for stage, only Vietnamese patients showed a survival disadvantage relative to all other Asian ethnic subgroups. As a result, it appears that Vietnamese patients not only present at a higher upper tract urothelial carcinoma stage, but additionally appear to harbor upper tract urothelial carcinoma that progresses at a faster rate than in other Asian ethnic subgroups., (© 2021 The Japanese Urological Association.)

Objective: To test whether radical prostatectomy might result in better survival than external beam radiation therapy in metastatic prostate cancer patients., Methods: Newly diagnosed metastatic prostate cancer patients with M1a/b substages, treated with radical prostatectomy or external beam radiation therapy were abstracted from the Surveillance, Epidemiology and End Results database (2004-2016). Temporal trend analyses, propensity score matching, cumulative incidence plots, multivariate competing risks regression models and landmark analyses were used., Results: Of 4280 patients, 954 (22.3%) were treated with radical prostatectomy. After propensity score matching, 5-year cancer-specific mortality was 47.0 versus 53.0% in radical prostatectomy versus external beam radiation therapy patients (P = 0.003). In propensity score matched competing risks regression models, radical prostatectomy was associated with lower cancer-specific mortality versus external beam radiation therapy (hazard ratio 0.79, 95% confidence interval 0.79-0.90; P = 0.001). Finally, landmark analyses rejected the bias favoring radical prostatectomy. Finally, in subgroup analyses, we relied on selection criteria that most closely resembled the STAMPEDE criteria and a similar hazard ratio of 0.8 (P < 0.001) was recorded., Conclusion: In metastatic prostate cancer, radical prostatectomy results in lower cancer-specific mortality relative to external beam radiation therapy. Even after adjustment for age at diagnosis, prostate-specific antigen and biopsy Gleason grade grouping, lower cancer-specific mortality rates are recorded in radical prostatectomy patients than in external beam radiation therapy patients. As a result, radical prostatectomy should be considered as a treatment option in selected metastatic prostate cancer patients. However, further validation will be provided by ongoing clinical trials., (© 2021 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

Background: We hypothesized that the survival benefit of external beam radiation therapy (EBRT) recorded in European low-volume metastatic prostate cancer (mPCA) patients, will apply to similar North American patients., Methods: Newly diagnosed mPCa patients with M1a/b substages, treated with EBRT or no EBRT were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Kaplan-Meier plots and Cox-regression models targeted overall mortality (OM) and cancer specific-mortality (CSM) according to EBRT administration. M1 substages and PSA stratified analyses were performed. Internal validation relied on 2000 bootstrap resamples., Results: Of 15,494 patients, 1156 (7.5%) were M1a vs 14,338 (92.5%) were M1b. PSA at diagnosis ≤10.0 ng/ml was recorded in 1463 (9.4%) patients. In all 15,494 patients, EBRT did not affect OM (hazard ratio [HR] 1.0; p = 0.5). However, in M1a patients and M1b patients with PSA ≤ 10.0 ng/ml EBRT was associated with lower OM (HR 0.73, CI 0.62-0.86; p < 0.001) but not in M1b patients with PSA > 10.0 ng/ml. The PSA cut-off of ≤ 10.0 ng/ml represented the most statistically significant cut-off for OM prediction in M1b patients. Moreover, internal validation with 2000 bootstrap resamples confirmed these findings. Finally, all results were virtually the same, when CSM represented the endpoint of interest., Conclusions: We validated the OM reduction associated with EBRT in M1a and M1b patients with PSA ≤ 10.0 ng/ml but not in M1b patients with PSA > 10.0 ng/ml. In consequence, it appears that a smaller subset of North American mPCa patients benefit of EBRT than originally reported in European patients. Further North American validation studies are essential.

Background: Two recent European studies showed an increasing proportion of non-organ-confined (NOC; pathologic stages T3-4) prostate cancer (PCa) in radical prostatectomy (RP) specimens., Objective: To determine if the trend for NOC and pT3-4 PCa is also evident among contemporary North American patients., Design, Setting, and Participants: Within the Surveillance, Epidemiology, and End Results database (2010-2014), we identified 58 558 patients with clinically localized PCa treated with RP. Only patients with clinical stage T1-2 and biopsy Gleason grade group (GGG) 1-3 PCa were included., Outcome Measurements and Statistical Analysis: Annual trend analyses and multivariable logistic regression models focused on the rate of NOC PCa, the rate of primary pathologic Gleason ≥4 PCa, and the rate of either NOC PCa and/or primary pathologic Gleason ≥4 PCa. Adjustment was made for clinical tumor characteristics (prostatic specific antigen [PSA], clinical stage, and biopsy GGG)., Results and Limitations: The rate of NOC PCa increased during the study period (18.7% vs 24.2%; p=0.002) and remained significant after adjustment (16.9% vs 22.3%; p=0.001) Similarly, the rate of pathologic primary Gleason ≥4 PCa increased during the study period (16.8% vs 23.0%, p=0.001) and remained significant after multivariable adjustment (10.8% vs 14.2%; p=0.002). Moreover, virtually the same findings were recorded when both endpoints were combined. Our results were confirmed in multivariable logistic regression analyses in which year of diagnosis was modeled as a continuous variable or a categorical variable or when a cubic spline approach was used., Conclusions: Rates of NOC PCa and primary Gleason ≥4 PCa increased over time among contemporary North American patients treated with RP. This finding may be related to better acceptance of active surveillance and watchful waiting by North American patients., Patient Summary: In this report, we looked at pathologic outcomes for contemporary North American patients treated with radical prostatectomy. We found an increase in non-organ-confined and more aggressive prostate cancer., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The open-label, single-arm enzalutamide expanded access program (EAP) in the United States and Canada evaluated the safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel., Methods: Patients (n = 507) received enzalutamide 160 mg/day until disease progression, intolerable adverse events (AEs), or commercial availability occurred. AEs and other safety variables were assessed on day 1, weeks 4 and 12, and every 12 weeks thereafter. Data following transition to commercial drug were not collected., Results: Median age was 71 years (range 43-97); 426 patients (83.9%) had a baseline ECOG score of ≤1. In addition to docetaxel, the majority of patients had received prior prostate cancer treatments such as abiraterone (76.1%) or cabazitaxel (28.6%). Median study treatment duration was 2.6 months (range 0.03-9.07). The most frequently reported reasons for discontinuation were commercial availability of enzalutamide (46.7%) and progressive disease (33.7%). A total of 88.2% of patients experienced AEs; 45.4% experienced AEs with a maximum grade of 1 or 2. Fatigue (39.1%), nausea (22.7%), and anorexia (14.8%) were the most commonly reported AEs. Seizure was reported in four patients (0.8%). The most commonly reported event leading to death was progression of metastatic prostate cancer (7.7%)., Conclusion: In this heavily pretreated EAP population with progressive mCRPC, enzalutamide was well tolerated and the safety profile was consistent with that of the AFFIRM trial., (© 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.)

Background: Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer (PCa) after docetaxel in the randomised, phase 3, double-blind, placebo-controlled, multinational Patients with Progressive Castration-Resistant Prostate Cancer Previously Treated with Docetaxel-Based Chemotherapy (AFFIRM) trial (NCT00974311). Prostate-specific antigen (PSA) is commonly used as a marker of PCa disease burden, and the relationship of baseline PSA level to consequent treatment effect is of clinical interest., Objective: Exploratory analysis to evaluate any differences in patient characteristics and efficacy outcomes by baseline PSA level in the AFFIRM trial., Design, Setting, and Participants: Post hoc subanalysis of all randomised patients (n=1199) from the AFFIRM trial., Intervention: Participants were randomly assigned in a two-to-one ratio to receive oral enzalutamide 160 mg/d or placebo., Outcome Measurements and Statistical Analysis: The major clinical efficacy end points were overall survival (OS), radiographic progression-free survival (rPFS), and time to PSA progression (TTPP) versus placebo; baseline characteristics, treatment duration, and subsequent antineoplastic therapy were compared by baseline PSA quartile., Results and Limitations: Baseline PSA quartiles corresponded to the following PSA groups: <40 ng/ml (n=299), 40 to <111 ng/ml (n=300), 111 to <406 ng/ml (n=300), and ≥406 ng/ml (n=300). Enzalutamide consistently improved OS, rPFS, and TTPP compared with placebo across all subgroups, regardless of baseline PSA level. Hazard ratios for improvements in OS were 0.55 (95% confidence interval [CI], 0.36-0.85), 0.69 (95% CI, 0.47-1.02), 0.73 (95% CI, 0.53-1.01), and 0.53 (95% CI, 0.39-0.73) for PSA groups 1-4, respectively. The post hoc design of this analysis was not statistically powered to assess the relationship between baseline PSA and clinical efficacy outcomes., Conclusions: This post hoc analysis of the AFFIRM trial demonstrates consistent benefits in OS, rPFS, and TTPP with enzalutamide regardless of baseline disease severity, as assessed by PSA., Patient Summary: Exploratory post hoc analysis of the AFFIRM trial showed that enzalutamide improves overall survival, radiographic progression-free survival, and time to prostate-specific antigen progression compared with placebo regardless of baseline disease severity, as assessed by prostate-specific antigen., Trial Registration: ClinicalTrials.gov identifier NCT00974311., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)