BACKGROUND:Darolutamide plus androgen-deprivation therapy (ADT) improved metastasis-free survival (MFS) by 2 years and reduced the risk of death by 31% in nonmetastatic castration-resistant prostate cancer (nmCRPC) in ARAMIS. Prior local therapy may influence the efficacy of subsequent systemic therapy. This post hoc analysis of ARAMIS evaluated the effect of prior local therapy on the efficacy and health-related quality of life (HRQoL) of darolutamide. METHODS:Patients with nmCRPC were randomized to darolutamide (n = 955) or placebo (n = 554) while continuing ADT. MFS, overall survival (OS), time to prostate-specific antigen (PSA) progression, and HRQoL deterioration-free survival (DetFS) were estimated for patients with and without local therapy and by treatment using Kaplan-Meier methods. RESULTS:Darolutamide increased MFS versus placebo in patients with (HR, 0.36; 95% CI, 0.26-0.48) and without (HR, 0.46; 95% CI, 0.36-0.59) local therapy. Median OS was 48.6 months for placebo without local therapy and not reached in either the darolutamide group or placebo group with local therapy. Darolutamide 3-year OS rates were 86.9% (95% CI, 83.0-90.8) and 79.0% (95% CI, 66.2-78.1) in patients with and without local therapy, respectively. Darolutamide showed evidence of improved OS versus placebo in patients with prior local therapy (HR, 0.80; 95% CI, 0.50-1.30) and a greater effect in those without local therapy (HR, 0.67; 95% CI, 0.50-0.90). Darolutamide delayed time to PSA progression and HRQoL deterioration regardless of local therapy. CONCLUSIONS:Darolutamide versus placebo improved MFS, OS, time to PSA progression, and HRQoL DetFS independent of prior local therapy, consistent with the overall ARAMIS population. TRIAL REGISTRATION:ClinicalTrials.gov registration: NCT02200614.
BACKGROUND:Clinical studies have shown that outcomes of patients with prostate cancer could vary depending on race. In this study, the authors sought to determine if the treatment effect of apalutamide, an androgen receptor pathway inhibitor (ARPI), on overall survival (OS) varies depending on the race of the patient. METHODS:This pooled analysis includes individual patient data from two phase 3 trials, TITAN and SPARTAN, which randomized patients to androgen deprivation therapy (ADT) ± apalutamide in metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer, respectively. Race was self-identified and categorized as Asian, Black, White, and Others categories. The authors applied a stratified (stratification for the trial) multivariable Cox proportional hazards regression model to determine heterogeneity of treatment effect on OS after adjustment for age, performance status, body mass index, T- and N-stage, Gleason score, comorbidities, and exposure to statins and metformin. RESULTS:Overall, 2190 patients were included: 16.9% patients were Asian, 3.7% were Black, 67.4% were White, and 12.0% were from the Others category. The authors did not find any significant heterogeneity of treatment effect from apalutamide on OS across racial groups (interaction-p = .46). Among ADT plus apalutamide-treated patients, there was no association of race with OS (hazard ratio for Asian, 0.77 [95% CI, 0.56-1.06]; Black, 0.82 [95% CI, 0.49-1.37]; and Others, 1.00 [95% CI, 0.75-1.34], all compared to White). CONCLUSIONS:In this study, the authors did not find any evidence of difference in the treatment effect of apalutamide on OS across patients of different races, although interpretation remains limited by poor representation of racial minorities. Among apalutamide-treated patients, there was no association of race with OS.
PURPOSE:We assessed the diagnostic performance of semen RNA-based biomarkers for detecting prostate cancer and differentiating cancer grade groups. MATERIALS AND METHODS:In a multicenter prospective study, semen samples were collected from men before undergoing prostate biopsy. RNA was extracted and sequenced to generate exome-wide gene expression profiles. Differentially expressed genes were selected and used to train a machine-learning classifier designed to detect prostate cancer with ≥ 95% sensitivity. The finalized model was locked and independently evaluated in a validation cohort. Histopathological diagnosis served as the reference standard. Model performance was further analyzed in relation to International Society of Urological Pathology Grade Group classification. RESULTS:Of 301 enrolled participants, 279 samples met quality criteria and were included in model development (training set: n = 199; validation set: n = 80). The median age and PSA level were 62 years and 5.70 ng/mL, respectively. In the validation cohort, the classifier achieved an AUC of 0.90, sensitivity of 92%, and specificity of 69%, with no significant performance difference compared with the training cohort. Importantly, high-risk cancers (International Society of Urological Pathology Grade Group ≥3) were ruled out with a negative predictive value of 96% in validation. CONCLUSIONS:This study demonstrates that noninvasive, high-accuracy prostate cancer tests can be developed using semen samples collected at home. The proposed test could potentially eliminate 60% to 70% of unnecessary biopsies, representing a substantial improvement in prostate cancer testing and risk stratification.
Background A previous trial involving patients with metastatic prostate cancer that was resistant to androgen pathway modulation (formerly referred to as castration-resistant) showed that adding talazoparib to enzalutamide significantly improved imaging-based progression-free survival and overall survival, with the greatest benefit observed in the cohort with alterations in homologous recombination repair genes. Methods In this ongoing, phase 3, double-blind trial assessing talazoparib in patients with metastatic androgen pathway modulation-sensitive [APMS] prostate cancer harboring alterations in homologous recombination repair genes, we randomly assigned patients in a 1:1 ratio to receive talazoparib at a dose of 0.5 mg plus enzalutamide at a dose of 160 mg once daily (talazoparib group) or placebo plus enzalutamide at a dose of 160 mg once daily (control group). Randomization was stratified according to disease status (new or relapsed), disease volume (high or low), and BRCA (vs. non-BRCA) mutation status. The primary end point was investigator-assessed imaging-based progression-free survival. The key secondary end point was overall survival. Results A total of 300 patients were assigned to the talazoparib group and 299 to the control group. At 3 years, progression-free survival was 77% in the talazoparib group and 56% in the control group (hazard ratio for disease progression or death, 0.48; 95% confidence interval [CI], 0.36 to 0.65; P<0.001). In this interim analysis, overall survival at 3 years was 78% in the talazoparib group and 72% in the control group (hazard ratio for death, 0.77; 95% CI, 0.56 to 1.04). Serious adverse events were reported in 42% and 32% of the patients in the talazoparib group and the control group, respectively. In the talazoparib group, the most common adverse events were anemia, fatigue, and decreased neutrophil count, and the most common event of grade 3 or higher was anemia, reported in 51% of the patients; two treatment-related deaths occurred. Conclusions Talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with metastatic APMS prostate cancer harboring alterations in homologous recombination repair genes. Serious adverse events were more common with talazoparib plus enzalutamide than with placebo plus enzalutamide. (Funded by Pfizer; TALAPRO-3 ClinicalTrials.gov number, NCT04821622.)
# Background External beam radiation therapy (EBRT) and radical prostatectomy (RP) are definitive options for patients with localized or locally advanced prostate cancer (LPC). Limited evidence exists on the post-treatment economic burden in these patients. # Objective This real-world analysis investigated healthcare costs among Medicare beneficiaries with LPC who received EBRT or RP as initial definitive treatment. # Methods This is a retrospective, longitudinal cohort study using Surveillance, Epidemiology, and End Results (SEER)–Medicare database. Included were Medicare Fee-For-Service beneficiaries newly diagnosed with LPC at the age of ≥65 years during 2012-2019 and received either EBRT or RP as an initial definitive therapy. After the initial therapy, all-cause and prostate cancer–related costs were summarized and stratified by the earliest observed definitive therapy (RP vs EBRT) and the National Comprehensive Cancer Network risk classification (low/intermediate-risk [LIR-LPC] vs high-risk [HR-LPC]). # Results Of the 17 066 LPC patients treated with EBRT, 60% (N =10 321) had LIR-LPC and 40% (N = 6745) had HR-LPC. During the follow-up, the mean per-person-per-year all-cause cost was $9837 higher in the HR-LPC cohort than the LIR-LPC cohort ($34 441 vs $24 604; _P_ < .0001). Of the 9479 patients treated with RP, 43% (N = 4120) had LIR-LPC and 57% (N = 5359) had HR-LPC. The mean per-person-per-year all-cause cost during follow-up was $6829 higher in the HR-LPC cohort than the LIR-LPC cohort ($23 820 vs $16 991; _P_ < .0001). Across all cohorts, the largest all-cause healthcare cost category was outpatient, followed by inpatient and prescription drug. # Conclusions This real-world study on healthcare costs in patients with LPC treated with EBRT or RP showed HR-LPC is associated with significant incremental economic burden relative to LIR-LPC. The findings highlight the current unmet need for more cost-effective treatment strategies for HR-LPC.
