Identifying Prostate Surface Antigen Patterns of Change in Patients with Metastatic Hormone Sensitive Prostate Cancer Treated with Abiraterone and Prednisone.

Background: Despite treatment with abiraterone acetate and prednisone (AA/P), most patients with metastatic hormone sensitive prostate cancer (mHSPC) will develop castration-resistant disease (metastatic castration-resistant prostate cancer [mCRPC]). The early identification of who will progress on AA/P is limited.

Objective: This study investigates the role of prostate surface antigen (PSA) kinetics as a predictor of progression in mHSPC patients treated with AA/P.

Patients And Methods: All patients with mHSPC who initiated androgen deprivation therapy (ADT) and AA/P from June 2017 to February 2019 at the Cleveland Clinic were eligible. PSA-mCRPC was defined as a PSA rise at two consecutive time points. Patients were followed until first mCRPC or last contact after AA/P. Patterns of PSA change were evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months from AA/P initiation. The association between PSA profile at 3 months and PSA-mCRPC was examined using survival analysis. Radiographic progression (Rad-mCRPC) was also analyzed.

Results: A total of 130 men with follow-up were included. The median (interquartile range [IQR]) follow-up time was 15.3 (10.5, 22.5) months. Eighty-two percent were Caucasian (median age 68.5 years); participants had a median (IQR) PSA of 16.8 (5.3, 48.0) ng/mL. Half of the patients had de novo disease, and 46.2% had high-risk disease (61% had a Gleason score ≥ 8, 16% had visceral disease, and 54% had three or more bony lesions). The greatest PSA percentage reduction from baseline after AA/P initiation occurred at the first 3 months (median 98.3%). The reduction at 6-12 months from baseline was small (99.7-100%). Patients without PSA-mCRPC had a significantly greater 3-month reduction of PSA values compared to patients who developed PSA-mCRPC (p interaction = 0.0002). 50.8% of patients were able to achieve a non-detectable PSA (median 13.1 months). PSA-mCRPC (n = 20) was observed from 4 to 24 months after AA/P, with the majority of events occurring within the first 12 months. Patients with PSA < 0.3 ng/mL (12-month PSA-mCRPC-free 94.5% vs. 69.4%, p = 0.0004) or a ≥ 98% reduction (94.9% vs. 68.0%, p = 0.0002) at 3 months had better PSA-mCRPC-free survival compared to their counterparts. Absolute reduction at 3 months was not associated with PSA-mCRPC. Similar PSA patterns were seen in those who had Rad-mCRPC compared to no Rad-mCRPC (p interaction < 0.05).

Conclusion: The degree of PSA decline at 3 months predicted serologic progression to mCRPC. Those who developed castration-resistant disease had higher PSA and a lower percentage reduction by 3 months. Tracking early PSA pattern changes may alert clinicians to poor treatment effect and potential progression; they should consider frequent PSA measurement and imaging, as well as the initiation of sequential therapy.