Treatment Patterns and Attrition in Metastatic Castration-Resistant Prostate Cancer

Importance: Rapid expansion of the therapeutic landscape for metastatic castration-resistant prostate cancer (mCRPC) has increased the complexity of treatment selection and sequencing. However, large, contemporary studies describing treatment patterns and attrition rates in clinical treatment of mCRPC are lacking. Objective: To investigate treatment patterns and attrition rates in patients with mCRPC from 2021 to 2025. Design, Setting, and Participants: This retrospective multicenter cohort study used the US-based, electronic health record-derived, deidentified Flatiron Health Research Database to identify patients with mCRPC who initiated first-line therapy between January 1, 2021, and June 30, 2025, at approximately 280 centers, primarily community oncology practices. Exposures: Year of first-line treatment initiation and types of treatment for mCRPC. Main Outcomes and Measures: First- through fifth-line treatment and attrition rates were summarized using frequencies and percentages into respective categories: androgen receptor pathway inhibitors (ARPIs), taxanes, poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPIs), platinum-based therapies, lutetium Lu 177-prostate-specific membrane antigen 617 (Lu-177)-based therapies, radium Ra 223, sipuleucel-T, immunotherapy, and other. Results: Of 27 979 patients in the dataset, 5096 with mCRPC initiating first-line therapy were included in the analysis. The median age was 75 (IQR, 68-82) years. Overall, 2731 patients (53.6%) received second-line treatment and 1334 (26.2%) received third-line treatment. ARPI was the most common first-line (4041 of 5096 79.3%) and second-line (1123 of 2731 41.1%) treatment, with decreasing use in subsequent lines. Taxane use increased from 637 of 5096 patients (12.5%) in first-line treatment to 953 of 2731 (34.9%) in second-line treatment and became the most common third-line treatment (485 of 1334 36.4%). Overall, 2192 patients (43.0%) received taxane-based therapies. Use of Lu-177 increased progressively from 113 of 5096 patients (2.2%) in first-line treatment to 71 of 226 patients (31.4%) by fifth-line initiation. PARPI use was limited and peaked at 99 of 1334 patients (7.4%) in third-line treatment. Conclusions and Relevance: In this cohort study of patients with mCRPC, only slightly more than half of patients received second-line treatment, and attrition rose significantly across subsequent treatment lines. ARPIs and taxanes remained the most common first-line treatments, with increased use of Lu-177 and PARPIs in later treatment lines. These findings highlight the evolving complexity of mCRPC management and significant attrition with later lines, underscoring the need for optimized sequencing strategies, more efficacious frontline therapies, and interventions to improve access.