Rapid and Deep Prostate‐Specific Antigen Decline is a Prognostic Marker in Metastatic Hormone‐Sensitive Prostate Cancer: A Real‐World Multi‐Intuitional Analysis

ABSTRACT Background Prostate‐specific antigen (PSA) kinetics has been investigated as a prognostic marker in post hoc analyses of clinical trials. This study validated the prognostic value of rapid and deep PSA decline in metastatic hormone‐sensitive prostate cancer (mHSPC) using real‐world data. Methods In total, 1296 patients with mHSPC were retrospectively reviewed. We assessed the prognostic value of a PSA decline to ≤ 0.2 ng/mL after 12 weeks of treatment and investigated several potential risk factors for a poor PSA response. Results Of 1296 patients, 714 (cohort 1: 55.1%) were treated with conventional hormonal therapy, while 582 (cohort 2: 44.9%) received androgen signaling inhibitors. There were significant differences in progression‐free survival and overall survival between patients with PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment and others ( p < 0.001 for each). In addition, patients with an initial PSA ≥ 200 ng/mL, Clinical T4 and Grade Group 5 were less likely to achieve PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment, with odds ratios of 0.31 ( p < 0.001), 0.67 ( p = 0.039) and 0.70 ( p = 0.043), respectively. Conclusion Our findings suggested that PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment may be a useful prognostic biomarker for mHSPC in the real‐world setting. The prognostic value of this should be further investigated in a prospective cohort, and identification of an optimal cutoff value is necessary for its application in clinical trial design or clinical practice.