Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial

Cancer. 2024 May 1;130(9):1629-1641. doi: 10.1002/cncr.35170. Epub 2024 Jan 1.

Abstract

Background: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2.

Methods: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL).

Results: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms.

Conclusions: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

Keywords: androgen‐deprivation therapy; biochemical recurrence; high‐risk; neoadjuvant hormone therapy; pathologic response; prostate cancer; radical prostatectomy.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • Androgen Antagonists / adverse effects
  • Androgens
  • Humans
  • Leuprolide / therapeutic use
  • Male
  • Neoplasm Recurrence, Local / surgery
  • Prednisone
  • Prostate-Specific Antigen*
  • Prostatectomy / methods
  • Prostatic Neoplasms* / diagnosis
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / surgery
  • Testosterone
  • Treatment Outcome

Substances

  • Prostate-Specific Antigen
  • Leuprolide
  • Androgen Antagonists
  • Androgens
  • Prednisone
  • Testosterone

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