(A-108) Impact of Treatment Sequencing, and Age on Survival in Metastatic Castration-Resistant Prostate Cancer: A National Health Insurance Database Study

Background: Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment challenges, particularly in older patients.

Objectives: This study aims to evaluate the optimal treatment sequence for mCRPC and assess the impact of treatment timing on overall and prostate cancer-specific survival.

Methods: This retrospective cohort study utilized data from the Taiwan National Health Insurance Research Database between 2016 and 2022. A total of 1,872 patients diagnosed with mCRPC were included. First-line treatments included abiraterone/enzalutamide (Abi/Enza), docetaxel, or Ra-223, with sequential treatment patterns analyzed. The index date was defined as the earliest prescription date of these agents. Overall and prostate cancer-specific survival were assessed using hazard ratios (HRs) adjusted for clinical factors such as Charlson Comorbidity Index (CCI), treatment age, treatment year, and disease risk stratification. The influence of treatment sequencing and the timing of first-line initiation relative to androgen deprivation therapy (ADT) were also examined. Fine and Gray competing risk models were used to account for competing mortality risks.

Results: Patients receiving Abi/Enza were generally older and had the longest treatment duration compared to those treated with docetaxel or Ra-223. After adjusting for key clinical factors, docetaxel (HR = 1.47, p < 0.0001) and Ra-223 (HR = 1.82, p = 0.0005) were associated with significantly higher overall mortality risk compared to Abi/Enza. However, treatment sequence and patient age influenced survival outcomes. Among patients aged ≤80 years, the sequence of docetaxel followed by Ra-223 was linked to the lowest mortality risk (HR = 0.20, p = 0.025). Conversely, for patients older than 80 years, Abi/Enza followed by Ra-223 provided the greatest prostate cancer-specific survival benefit (HR = 0.46, p = 0.0192). Additionally, the timing of first-line treatment initiation following ADT played a crucial role in survival outcomes. For patients ≤80 years, early initiation of docetaxel ( < 6 months) was associated with a trend toward increased overall mortality, whereas delayed initiation (>6 months) further elevated both overall and prostate cancer-specific mortality. Among patients older than 80 years, the timing of first-line docetaxel or Ra-223 initiation did not significantly impact survival.

Conclusions: This study underscores the importance of age and treatment sequencing in optimizing survival outcomes for mCRPC patients. The findings highlight the need for age-stratified and personalized treatment strategies to enhance survival in mCRPC management.