Early PSA decline as a predictor of progression in patients with metastatic castration-naïve prostate cancer (mCNPC) treated with abiraterone acetate and prednisone (AA/P)

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Journal of Clinical Oncology


Background: Treatment intensification with androgen deprivation therapy (ADT) plus AA/P is a standard of care in patients with metastatic castration naïve prostate cancer (mCNPC). Despite initial responses, nearly all men will eventually progress to castration resistant disease (CRPC). Early changes in PSA while on ADT plus AA/P has significant clinical and therapeutic implications for mCNPC patients, yet limited data is available. We aimed to assess PSA patterns while on therapy with ADT plus AA/P and time to CRPC. Methods: mCNPC patients treated with ADT plus AA/P between June 2017 and February 2019 at the Cleveland Clinic, were included. The primary objective was to describe patterns of PSA change evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months from AA/P initiation. Other endpoints of interest included PSA progression by PCWG3 and CRPC-free survival at 12 and 18 months. Results: A total of 130 patients, 82% Caucasian, median age 69 years, with 50% with de-novo mCNPC, 47% high-volume (60.8% Gleason score ≥8, 16.2% visceral disease, and 53.8%had ≥3 bony lesions) were included. Half of the patients achieved undetectable PSA ( < 0.03) while on therapy. The median time to PSA < 0.03 was 13.1 months (95%CI, 7.6-NE). The greatest PSA reduction occurred at the first 3 months (80%, p < 0.0001), changes after 3 months were small, (4% from 3 to 6 months, p < 0.0001; 3% from 6 to 9 months, p < 0.0001) and not significant from 9 to 12 months. The 12 and 18-months mCRPC-free survival after initiation of ADT plus AA/P was 88.1% and 81.3%, respectively. A PSA > 0.2 at 3 months was associated with a shorter time to mCRPC (p = 0.002). Similarly, a PSA reduction < 98% at 3 months was associated with worse outcomes (12 mo CRPC survival 68.0% vs. 94.9%, respectively; p < 0.001). Conclusions: In this data set, timing and depth of serologic response predicted the early development of CRPC in patients receiving ADT plus AA/P. Further validation is ongoing using data from large randomized clinical trials.




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