In the treatment of metastatic castration-sensitive prostate cancer (mCSPC), achieving ultra-low prostate-specific antigen (PSA) levels is associated with favorable outcomes. This study aims to compare the efficacy of four novel hormonal agents (NHAs)—Apalutamide, Abiraterone, Enzalutamide, and Darolutamide (combined with Docetaxel)—in achieving ultra-low PSA levels and in the time required to reach PSA nadir.

We retrospectively analyzed data from patients diagnosed with mCSPC between June 2019 and April 2025 in a single medical center. Patients were grouped according to the NHA regimen received. The primary outcome was the proportion of patients in each treatment group who achieved ultra-low PSA levels. The secondary outcome was the number of days from treatment initiation to PSA nadir.

A total of 124 patients were included: 54 received Abiraterone, 31 Apalutamide, 21 Enzalutamide, and 18 Darolutamide plus Docetaxel. The highest proportion of ultra-low PSA achievers was observed in the Enzalutamide group (66.7%), followed by Apalutamide (58.1%), Darolutamide plus Docetaxel (44.4%), and Abiraterone (40.7%). Median time to PSA nadir also varied among regimens, with Abiraterone achieving the shortest duration (223 days), followed by Apalutamide (average 588 days), and Enzalutamide (891 days).

Among the four NHA regimens analyzed in a single medical center, Enzalutamide demonstrated the highest efficacy in achieving ultra-low PSA levels, though Abiraterone showed a shorter time to PSA nadir. These findings may aid in tailoring mCSPC treatment strategies based on therapeutic goals.