Early characterization of PSA dynamics in patients with metastatic hormone-sensitive prostate cancer receiving apalutamide-based regimens.

Objective: This single-center, real-world study exploratorily compared early PSA kinetics between apalutamide plus androgen deprivation therapy (ADT) and triplet therapy (ADT, apalutamide, and docetaxel). Methods: This study was designed as a single-center retrospective cohort study. A total of 36 patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) and adverse prognostic features between January 2022 and September 2024 were included. Adverse prognostic features were defined as a Gleason score ≥8 and/or high-volume disease according to the CHAARTED criteria. Patients were stratified according to first-line treatment into a doublet group receiving apalutamide plus ADT (n = 17) and a triplet group receiving docetaxel plus apalutamide and ADT (n = 19). All patients received ADT induction for no more than 2 weeks prior to the initiation of apalutamide.The primary endpoints were the time from apalutamide initiation to the first achievement of PSA90 and PSA95, defined as a ≥90% and ≥95% decline in PSA from baseline, respectively. Secondary endpoints included time to PSA <0.2 ng/mL, time to undetectable PSA (PSA <0.09 ng/mL), PSA nadir level, and time to nadir, and PSA levels at predefined time points.Given baseline imbalances in tumor burden and Gleason score between the two groups, multivariable Cox proportional hazards models were applied for adjustment. Restricted sensitivity analyses were conducted to assess the robustness of the findings. Results: The triplet group had a higher proportion of patients with high-volume disease and higher overall Gleason scores, indicating a greater baseline disease risk.Time-to-event analyses showed that the median time to PSA90 was 0.9 months in the triplet group compared with 2.1 months in the doublet group. Similarly, the median time to PSA95 was 1.0 months in the triplet group versus 2.1 months in the doublet group. After adjustment for age, Gleason score, CHAARTED tumor volume, and baseline PSA (log10-transformed) in multivariable Cox regression models, the triplet regimen remained independently associated with a shorter time to achieving PSA90 and PSA95 (PSA90: adjusted hazard ratio [aHR] = 2.50, 95% CI 1.16-5.40; PSA95: aHR = 2.22, 95% CI 1.03-4.78).Regarding secondary endpoints, no statistically significant differences were observed between the two groups in time to PSA <0.2 ng/mL, time to undetectable PSA (PSA <0.09 ng/mL), PSA nadir level, or time to nadir. Likewise, no significant differences were detected in absolute PSA levels at 3, 6, and 12 months after treatment initiation. Restricted sensitivity analyses yielded results consistent in direction with the primary analyses. Conclusion: In this real-world cohort characterized by high-risk features, although patients in the triplet group had a greater baseline disease burden, the addition of docetaxel was associated with a more rapid and deeper decline in PSA. However, PSA levels at subsequent predefined time points converged between the two groups.Given the limitations in sample size and follow-up completeness, the findings of this study should be considered exploratory. Whether the triplet regimen confers long-term benefits in hard clinical endpoints and which patient populations are most likely to benefit, requires validation in larger, well-designed prospective studies with standardized follow-up.