This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy (RP) pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368).
Eligible patients had a Gleason score ≥4+3=7, PSA >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone, and leuprolide, (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by RP. Surgical specimens underwent central review. The primary endpoint was the rate of pathologic complete response (pCR) or minimum residual disease (MRD, tumor ≤5 mm). Secondary endpoints included PSA response, positive margin rate, and safety. MRI and tissue biomarkers of pathologic outcomes were explored.
The study enrolled 118 patients at four sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pCR or MRD rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%, one-sided 95% CI: -11%, 14%, one-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between post-therapy MRI-assessed and pathologically-assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor.
Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor <5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.
The Journal of urology. 2021 Mar 08 [Epub ahead of print]
Rana R McKay, Wanling Xie, Huihui Ye, Fiona M Fennessy, Zhenwei Zhang, Rosina Lis, Carla Calagua, Dana Rathkopf, Vincent P Laudone, Glenn J Bubley, David J Einstein, Peter K Chang, Andrew A Wagner, J Kellogg Parsons, Mark A Preston, Kerry Kilbridge, Steven L Chang, Atish D Choudhury, Mark M Pomerantz, Quoc-Dien Trinh, Adam S Kibel, Mary-Ellen Taplin
University of California San Diego, , La Jolla, California., Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts., University of California Los Angeles, Los Angeles, California., Memorial Sloan Kettering Cancer Center, New York, New York., Beth Israel Deaconess Medical Center, Boston, Massachusetts.