Association of early achievement of ultra-low PSA levels with radiologic progression-free survival (rPFS) in metastatic hormone-sensitive prostate cancer (mHSPC).

73 Background: Ultrasensitive assays allow the measurement of PSA levels below 0.2 ng/mL, which were previously considered undetectable. This may provide a more sensitive assessment of PSA response and treatment efficacy in mHSPC. In the current study, we evaluated the association between early achievement of ultra-low PSA levels and rPFS in patients with mHSPC. Methods: Patients received first-line therapy with androgen receptor pathway inhibitors (ARPIs) plus ADT, ADT with docetaxel, or ADT alone. Serum PSA levels were measured at baseline, 1, 3 months, and thereafter. Patients were stratified into three groups based on the lowest PSA level reached within the first three months: 0.2 ng/mL. Median follow-up and rPFS were estimated using the Kaplan-Meier method. Results: Of 347 patients reviewed, 323 were included in the analysis after excluding 24 with irregular follow-up or incomplete PSA data. The median age was 68 (43–88) years, and the majority of patients (51.7%) had Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0. Of the patients, 50.5% had high-volume disease, and 76.5% had synchronous metastasis. Additionally, 76.5% of the patients had bone metastasis, 12.4% had lung metastasis, and 4.3% had liver metastasis. Treatment distribution among patients was as follows: 25.1% received ADT alone, 24.5% received ADT combined with docetaxel, and 50.5% received ARPIs in combination with ADT. Among patients receiving first-line therapy, 50 (15.5%) achieved ultra-low PSA levels (0.2 ng/mL during the first three months of treatment. Within the first three months, ultra-low PSA levels were achieved in 12.4% of patients receiving ADT alone, 7.6% of those receiving ADT plus docetaxel, and 20.9% of those receiving ARPIs plus ADT. The median rPFS was 34.2 months (95% CI, 27–40 months). The 5-year rPFS rates were 89% for patients with PSA <0.02 ng/mL, 80% for PSA 0.02–0.2 ng/mL, and 18% for PSA ≥0.2 ng/mL (p < 0.001). Conclusions: Early ultra-low PSA (<0.02 ng/mL within the first three months) is associated with longer rPFS in patients with mHSPC and may serve as a novel surrogate endpoint in future clinical trials.