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

ABSTRACT 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.