PSA Biochemical Response as Prognostic Factor in Metastatic Castration-Sensitive Prostate Cancer

Overview

Prostate cancer remains the most common malignancy in men in Europe. Over the last two decades, the treatment landscape for both localized and metastatic prostate cancer has been revolutionized. For patients with metastatic castration-sensitive prostate cancer (mCSPC), the primary treatment objectives are to delay progression to metastatic castration-resistant prostate cancer (mCRPC) and to improve overall survival (OS). Although patients with PC may initially respond to androgen deprivation therapy (ADT), progression to castration resistance occurs in 10-20% of patients within 5 years. Primary ADT has been the standard of care for over 50 years. However, recent advancements have shifted treatment from ADT monotherapy for all mHSPC/mCRPC patients to more intensive approaches, which include combinations of ADT with new androgen receptor pathway inhibitors (ARPIs), chemotherapy, or both, tailored to tumor characteristics such as metastatic burden. In clinical practice, a reduction in prostatic specific antigen (PSA) levels from baseline is commonly used to monitor disease control, particularly in the castration sensitive phase (both early and metastatic). For patients with mCSPC, a decrease in PSA levels signifies that the treatment is effective. Moreover, the depth, time and duration of this PSA reduction are linked to better clinical outcomes, including OS. Although more patients achieved an optimal PSA response with intensified ADT (with ARPI or docetaxel), those with a suboptimal response have a significantly worse survival rate. Several key studies have demonstrated that achieving undetectable PSA (≤0.2 ng/mL) is associated with better OS, irrespective of subgroups. This study aims to evaluate patient survival based on PSA response and to describe baseline characteristics among patients with or without PSA response. Specifically, patients will be divided into two groups based on the achievement of PSA values ≤ 0.2 ng/dl, and overall survival (OS) and progression free survival (PFS) for each group will be evaluated. Clinical and laboratory information at baseline will be compared between the two groups. Baseline characteristics considered are histology, Gleason score, stage of disease, presence of genetic alterations, PSA values, sites and number of metastases, de novo or metachronous disease, high/low risk disease, high/low volume disease.