A Novel ADT Strategy Without Conventional Anti-Androgen Pretreatment: An Observational Study of Abiraterone Combined With Castration Therapy
Abiraterone combined with LHRH agonists rapidly achieves castration-level testosterone, potentially eliminating the need for anti-androgen pretreatment in prostate cancer therapy.
Where it sits
this study against the rest of the goserelin corpusSummary and findings
This observational study evaluated the combination of goserelin and abiraterone acetate in 35 patients with advanced prostate cancer. The primary endpoint was achieving castration-level serum testosterone, which was met by all patients by Day 28. Secondary endpoints included PSA reduction and adverse event monitoring.
Abstract
<title>Abstract</title> <p> <bold>Purpose</bold> Prostate cancer(PCa) ranks among the most common malignancies in men, with ~ 30% of Chinese patients with advanced disease at diagnosis. LHRH agonist-based castration is the the cornerstone of ADT, but may induce transient "flare-up effect" at initiation, which increases the risk of disease progression and adverse events. We aims to evaluate the dynamic changes in serum testosterone with synchronous abiraterone and LHRH agonists, instead of anti-androgen, providing evidence for initial ADT strategies. <bold>Patients and Methods:</bold> This single-center observational cohort enrolled 35 patients with locally advanced or metastatic PCa. All patients received goserelin(10.8mg) plus abiraterone acetate(1000mg daily) and prednisone(5mg twice daily). The primary endpoint was the proportion of patients achieving castration-level serum testosterone(< 0.5ng/mL) at predefined timepoints(days 1, 2, 3, 7, 14, 28). Secondary endpoints included PSA changes at day 28, hepatic function, and adverse events. <bold>Results</bold> By Day 28, all patients(100%) achieved castration-level testosterone. Except for 2 patients(5.7%) showing mild testosterone elevation on Day 1, 94.3% patients exhibited immediate testosterone decline(6.2%–96.6% from baseline). The proportions of patients reaching castration levels on Day 2, 3, 7, 14 and 28 were 74.3%(26/35), 94.2%(33/35), 97.1%(34/35), 100%(35/35), and 100%(35/35), respectively. No grade 3–5 adverse events were observed. Most common treatment-related adverse events were grade 1–2 flushing(20%), facial edema(2.9%), and grade 2 hepatic dysfunction(2.9%). All patients demonstrated PSA decline at day 28, with a median reduction of 95.4%(IQR: 90.2%–98.9%). <bold>Conclusion</bold> Abiraterone plus LHRH agonist rapidly suppresses testosterone, and may obviate the need for traditional anti-androgen pretreatment. This strategy demonstrates streamlines initial treatment workflows, warranting further validation in multi-center trials. </p>
Background
Prostate cancer is a prevalent malignancy among men, with a significant portion of Chinese patients presenting with advanced disease. LHRH agonist-based castration is a standard treatment but can cause a transient flare-up effect, potentially worsening the disease. This study explores the use of abiraterone combined with LHRH agonists as an alternative initial ADT strategy, aiming to mitigate the flare-up effect.
Methods
This was a single-center observational cohort study involving 35 patients with locally advanced or metastatic prostate cancer. Patients were treated with goserelin (10.8 mg) and abiraterone acetate (1000 mg daily) plus prednisone (5 mg twice daily). The primary endpoint was the proportion of patients achieving castration-level serum testosterone at various timepoints. Secondary endpoints included PSA changes, hepatic function, and adverse events.
Results
By Day 28, all patients achieved castration-level testosterone. On Day 1, 94.3% of patients showed an immediate testosterone decline, with 74.3% reaching castration levels by Day 2. PSA levels declined in all patients by Day 28, with a median reduction of 95.4%. No grade 3–5 adverse events were reported, with the most common being grade 1–2 flushing.
Interpretation
The combination of abiraterone and LHRH agonists effectively suppresses testosterone levels without the need for traditional anti-androgen pretreatment. While the results are promising, the clinical significance is limited by the small sample size and single-center nature of the study. Larger, multi-center trials are necessary to confirm these findings and establish clinical guidelines.
Key findings
- 100% of patients achieved castration-level testosterone by Day 28.
- 74.3% reached castration levels by Day 2.
- Median PSA reduction was 95.4% at Day 28.
- No grade 3–5 adverse events were observed.
- Most common adverse event was grade 1–2 flushing (20%).
Limitations
- small n=35
- single-center study
- observational design
- short follow-up
- no control group