Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer.

Abstract

PURPOSE:

This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368).

MATERIALS AND METHODS:

Eligible patients had a Gleason score ≥4+3=7, prostate specific antigen >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 radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored.

RESULTS:

The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor.

CONCLUSIONS:

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.

• Authors: 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
• Journal: The Journal of urology (J Urol) Vol. 206 Issue 1 Pg. 80-87 (07 2021) ISSN: 1527-3792 [Electronic] United States
• PMID: 33683939 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Antineoplastic Agents, Hormonal
• Thiohydantoins
• apalutamide
• Leuprolide
• Abiraterone Acetate
• Prednisone

Topics

• Abiraterone Acetate (therapeutic use)
• Aged
• Antineoplastic Agents (therapeutic use)
• Antineoplastic Agents, Hormonal (therapeutic use)
• Combined Modality Therapy
• Drug Therapy, Combination
• Humans
• Leuprolide (therapeutic use)
• Male
• Middle Aged
• Prednisone (therapeutic use)
• Preoperative Period
• Prostatectomy
• Prostatic Neoplasms (pathology, surgery)
• Risk Assessment
• Thiohydantoins (therapeutic use)
• Treatment Outcome