Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer

Abstract

The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks—particularly in patients with a modest effect of ADT and poor performance status.

Real-World Treatment Patterns in Metastatic Castration-Resistant Prostate Cancer Across Europe (France, Germany, Italy, Spain, and the United Kingdom) and Japan

“…The higher use of enzalutamide highlighted through our analysis compared with the cited source might reflect differences in the timing of data collection in the two studies, as well as the more recent approval of enzalutamide compared with the other two treatments. A recent analysis of medical records for 422 patients with mCRPC from a number of Japanese centres reported 32%, 36%, and 32% receiving abiraterone, enzalutamide, and docetaxel, respectively, in the 1L mCRPC setting [24], compared with 25%, 33%, and 10%, respectively, of current 1L treatment of Japanese patients in our dataset.…”

Dynamic changes in PSA levels predict prognostic outcomes in prostate cancer patients undergoing androgen -deprivation therapy: A multicenter retrospective analysis

“…Early PSA responses to ADT (>30% reduction after 4 or 12 weeks) are frequently used to gauge patient prognosis ( 32 , 33 ). Dynamic shifts in serum PSA concentrations have been used as tools both to explore the prognosis of hormone-sensitive prostate cancer patients and monitor CRPC patients undergoing second-line ADT ( 34 , 35 ) while also providing an approach for assessing the prognosis of CRPC patients undergoing chemotherapy ( 36 ).…”

Dynamic Changes in Prostate-Specific Antigen After Androgen Deprivation Therapy for Prostate Cancer are Strongly Associated with Biochemical Progression-Free Survival: A Multicenter Retrospective Analysis

“…[8] In addition to the above observations, early PSA response to androgen deprivation therapy for prostate cancer (PSA decline > 30% at the rst 4 weeks or > 30% at 12 weeks) is commonly used as a prognostic indicator. [20,21] Kinetic changes in serum PSA levels have been applied not only for the prognosis of hormone-sensitive prostate cancer, but also for second-line androgen deprivation therapy in castrationresistant prostate cancer, [22,23] or as a prognostic monitoring indicator for chemotherapy in castrationresistant prostate cancer. [24] Limitations of this study include its retrospective design, the small number of patients, and possible differences in criteria between the two centers during follow-up observations, all of which may have had an impact on the conclusions.…”