Very deep prostate-specific antigen decline is associated with longer rPFS in patients with metastatic castration-sensitive prostate cancer

Prostate-specific antigen (PSA) is widely used in the diagnosis and monitoring of prostate cancer. The prognostic relevance of very low PSA levels has not been clearly established in metastatic castration-sensitive prostate cancer (mCSPC). More sensitive PSA assays may provide more accurate estimates of clinical outcomes. To evaluate the relationship between achieving very deep PSA levels (⩽0.02 ng/mL) within 6 months of treatment and radiologic progression-free survival (rPFS) in patients with mCSPC. A retrospective, unicenter observational study conducted at a tertiary oncology center. A total of 203 patients with mCSPC who received first-line treatment with luteinizing hormone-releasing hormone analogs, androgen receptor pathway inhibitors, or docetaxel were included. Patients were stratified into four groups based on their PSA nadir levels: ⩽0.02, 0.02-0.2, 0.2-4, and >4 ng/mL. Kaplan-Meier and Cox regression analyses were used to assess the association between PSA nadir and rPFS. Patients achieving PSA ⩽ 0.02 ng/mL had significantly longer rPFS (median: 59.2 months) compared to other PSA groups. Multivariable analysis confirmed PSA ⩽ 0.02 ng/mL as an independent predictor of rPFS (HR: 2.02, p < 0.001). The overall log-rank p-value for group comparison was < 0.001. A very deep PSA response (⩽0.02 ng/mL) is associated with longer rPFS and may serve as a prognostic marker in mCSPC. This threshold could be considered in future clinical trial design and treatment stratification.