Background and objectives: Prostate-specific antigen (PSA) concentration is considered an important prognostic marker, with rapid and large reductions associated with a favorable outcome and prolonged survival. Material and Methods: We conducted a single institution and tertiary cancer center retrospective analysis of metastatic hormone-sensitive prostate cancer (mHSPC) patients undergoing active treatment at Division of Oncology and Radiotherapy, University Hospital Dubrava, between December 2022 and August 2025. This study aimed to assess the association between the PSA levels and survival in mHSPC patients undergoing active treatment. Results: A total of 42 (59.2%) in our cohort achieved UL PSA levels, while 29 patients (40.8%) had PSA levels > 0.2 ng/mL. Cox regression analysis identified age > 71 years at the diagnosis of mHSPC and UL PSA levels as statistically significant factors associated with favorable outcome. Conclusions: Our real-world data demonstrated that UL PSA is a favorable prognostic factor associated with prolonged survival and improved prognosis. However, we identified patients achieving UL PSA levels, who experienced radiographic progression. Our finding suggests that even among “best” PSA responders, some might develop resistant clones that manifest via imaging progression without PSA rise.

Background/Objectives: Prostate-specific antigen (PSA) concentration is considered an important prognostic marker, with rapid and large reductions associated with a favorable outcome and prolonged survival. Methods: We conducted a single institution and tertiary cancer center retrospective analysis of mHSPC patients undergoing active treatment at Division of Oncology and Radiotherapy, University Hospital Dubrava between December 2022 and August 2025. This study aimed to assess the association between the PSA levels and survival in mHSPC patients undergoing active treatment. Results: A total of 42 (59.2%) of our cohort achieved UL PSA levels, while 29 patients (40.8%) had PSA levels > 0.2 ng/mL. Cox regression analysis identified age >71 years at the diagnosis of mHSPC and UL PSA levels as statistically significant factors associated with favorable outcome. Conclusions: Our real-world data demonstrated that UL PSA is a favorable prognostic factor associated with prolonged survival and improved prognosis. However, we have identified patients achieving UL PSA levels which experienced radiographic progression. Our finding suggests that even among “best” PSA responders, some might develop resistant clones that manifest via imaging progression without PSA rise.