ABSTRACT
OBJECTIVES: The objective of this study is to assess the trends in treatment selection for patients with de novo metastatic castration-sensitive prostate cancer in the era of upfront combination therapy. METHODS: This multicenter retrospective study included 595 patients treated with either upfront combination therapy (upfront novel hormonal therapies and taxane-based chemotherapy) or vintage therapy (androgen deprivation therapy with or without bicalutamide) between 2016 and 2021. High tumor burden metastatic disease was defined when a patient met the CHAARTED or LATITUDE criteria. We evaluated trends in treatment selection and reasons for selecting vintage therapy. RESULTS: Of the 595, 123 and 472 patients were classified as having low and high tumor-burden disease, respectively. The Use of upfront combination therapy was found to be rapidly increasing with utilization rates of 72% and 54% in 2021 for high and low tumor-burden disease, respectively. Multivariable logistic regression analysis found older age, poor performance status, and nonacademic center were significantly associated with the selection of vintage therapy. Of the 163 patients who received vintage hormone therapy after approval of upfront therapy, 74.2% had a specific reason for avoiding upfront therapy. The reasons for selecting vintage therapy included refusal (39.8%), older age (67.6%), frailty (56.3%), and comorbidity (40.8%). Furthermore, 16.9% of patients declined upfront combination therapy due to cost concerns. CONCLUSION: Upfront combination therapy use has 72% and 54% prevalence among patients with high and low tumor burden diseases, respectively, in this current practice. Older age, poor performance status, and facility bias were negatively associated with the use of upfront combination therapy.
ABSTRACT
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.