Comparison of Oncological Outcomes of Conventional Androgen Deprivation Therapy (ADT) and ADT Plus Androgen Receptor Signaling Inhibitor in Older Patients With Metastatic Castration-Sensitive Prostate Cancer

Objectives: Evidence on upfront androgen receptor signaling inhibitor (ARSI) plus androgen deprivation therapy (ADT) in the older population with metastatic castration-sensitive prostate cancer (mCSPC) is scarce. We aimed to compare the oncological outcomes of ARSI plus ADT (upfront doublet therapy) and conventional ADT in mCSPC patients aged ≥ 75 years in a real-world clinical practice. Methods: Subjects were mCSPC patients aged ≥ 75 years who received upfront doublet therapy (upfront doublet group) or ADT, either alone or in combination with bicalutamide (conventional ADT group) as a first-line systemic therapy. Castration-resistant prostate cancer-free survival (CRPC-FS), overall survival (OS), and cancer-specific survival (CSS) were analyzed. Propensity score matching (PSM) was used to adjust the clinicopathological features. Results: After PSM, a total of 200 mCSPC patients, 100 in the upfront doublet group and 100 in the conventional ADT group, were included. In the PSM population, median CRPC-FS was 30.8 months in the upfront doublet group and 12.1 months in the conventional ADT group (p < 0.05). Median OS was N.A. in the upfront doublet group and 45.2 months in the conventional ADT group (p < 0.05). Median CSS was also statistically different between the two groups (N.A. vs. 61.6 months; p < 0.05). In subgroup analyses, the upfront doublet group showed improved oncological outcomes in high-volume disease compared with the conventional ADT group, but not in low-volume disease. Conclusions: The oncological benefits of upfront doublet therapy are not diminished in mCSPC patients, even in the older population; but these benefits are limited when restricted to low-volume disease.