ASCO 2023: Post Radical Prostatectomy PSA Outcomes Following 6 vs 18 Months of Perioperative Androgen Deprivation Therapy in Men with Localized High Risk Prostate Cancer: Results of Part 2 of a Randomized Phase 2 Trial

(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Rana McKay presented the results of a phase II trial evaluating post-radical prostatectomy PSA outcomes following 6 versus 18 months of perioperative ADT in men with localized, high-risk prostate cancer.


Definitive local therapy provides excellent oncologic outcomes for most patients with clinically localized prostate cancer; however, patients with high-risk, localized disease treated with radical prostatectomy alone experience high treatment failure rates approaching 65%. As such, there are numerous trials evaluating neoadjuvant hormone-based therapies in this disease space, with inconclusive evidence regarding their efficacy. McKay et al. have previously reported the results of part 1 of a phase II trial evaluating intense androgen deprivation therapy prior to radical prostatectomy in men with high-risk localized prostate cancer.
trial schema
This phase II trial Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease (imaging or physical exam) and lymph nodes <20 mm. In part 1, patients were randomized 1:1 to abiraterone acetate/prednisone and leuprolide +/- for approximately 6 months, followed by radical prostatectomy. This trial failed to meet its primary endpoint of improved pathologic complete response or minimum residual disease, with rates of 22% and 20% (p=0.4) in the intervention and control arms, respectively.1

In part 2, patients were randomized 1:1 to apalutamide, abiraterone/prednisone, and leuprolide for 12 months (Arm 2A) or observation (Arm 2B), stratified by neoadjuvant therapy and pathologic T stage (<ypT3 or ≥ypT3). The primary endpoint was biochemical progression-free survival (bPFS) at 3 years post-radical prostatectomy. bPFS was evaluated from time of randomization to progression, defined as: PSA ≥ 0.2 ng/mL, local/distant disease on CT/MRI or bone scan, or receipt of post-radical prostatectomy therapy or radiation for rising PSA, or death. The Kaplan-Meier estimate of bPFS at 3 years was compared between arms using a Chi-square test. Secondary endpoints included safety and time to testosterone recovery (>200 ng/dL).

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Overall, 82/118 (69%) of patients enrolled to Part 1 were randomized to Part 2. Median follow-up was 47 months post-RP. Patient preference was the main reason for non-randomization in Part 2. In the intent-to-treat analysis, there were no significant differences in 3-year bPFS rates between the two arms (80% versus 72%, p=0.39). Patients who achieved pathologic responses (n=14) had longer bPFS than non-responders (log-rank test two-sided p=0.03; 3-year bPFS 100% versus 72%).
Figure 3
With regards to testosterone recovery, in the per-protocol cohort of 36 patients with available data in the intervention arm, 83% had testosterone recovery and median time to recovery from therapy end was 8.7 months. For patients on observation (n=42), 95% had testosterone recovery, and median time to recovery from RP was 4.0 months. No new safety signals were observed.testosterone recovery 
Dr. McKay concluded that neoadjuvant ADT in localized, high-risk prostate cancer resulted in favorable pathologic responses and 3-year bPFS in a subset of patients. As 30% of patients declined an additional 12 months of adjuvant treatment, the study was underpowered to detect a difference between 6 versus 18 months of treatment. Subsequent analyses will evaluate predictors of improved bPFS.

Presented by: Rana R. McKay, MD, Associate Professor, Department of Medicine, University of California, San Diego, CA

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.

Reference:
  1. McKay R, et al. Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer. J Urol 2021;206(1):80-7.