Recently, new androgen pathway inhibitors, abiraterone and enzalutamide, are demonstrated to improve overall survival for metastatic castration-resistant prostate cancer (mCRPC). In Japan, alternative antiandrogen (AA) as second-line hormonal therapy for mCRPC that relapses after initial hormone therapy have been commonly used before new androgen pathway inhibitors. In this study, we attempted to identify the predictive factors for efficacy of AA as second-line hormone therapy.
We identified consecutive 43 metastatic prostate cancer patients treated with AA as second-line hormonal therapy (bicalutamide to flutamide). All patients were treated with maximum androgen blockade (MAB) initially and evaluated antiandrogen withdrawal syndrome after relapse. We analyzed the correlation between progression-free survival (PFS) of AA and clinicopathological characteristics, including patients' age, initial PSA levels, PSA levels at flutamide induction, Gleason scores, T stage, N stage, extent of disease (EOD) classifications on bone scan, and the previous duration of prostate cancer sensitivity to MAB.
The median duration of prostate cancer sensitivity to MAB was 2.8 months (range: 0.0-73.1+ months). In univariate analysis, patients' age and the previous duration of prostate cancer sensitivity to MAB were correlated with poor PFS. In multivariate analysis, two significant risk factors for poor PFS were identified; EOD classifications (3-4 vs 1-2; HR 2.41, 95% CI 1.01-5.76, p = 0.046) and N stage (1 vs 0; HR 2.76, 95% CI 1.00-7.60, p = 0.049). We stratified the patients into two cohorts with low risk (0-1 risk factor present) and high risk (2 risk factors present). We found a significant difference in PFS among risk groups (median PFS 3.6 months vs 0.9, p < 0.000).
EOD classifications on bone scan and N stage were the significant predictive factor for efficacy of AA as second-line hormone therapy in patients with mCRPC. These findings might support that decision-making of when to start the new AR pathway inhibitors.
Clinical trial identification
All authors have declared no conflicts of interest.