Abstract
BackgroundThe magnitude and rapidity of the tumor response to androgen deprivation is known to predict the durability of the therapy. We have investigated the predictive value of categorizing patients by the half-life of PSA under neoadjuvant androgen deprivation therapy in patients with biochemical recurrence after radical prostatectomy.MethodsMedical records of 317 patients who received neoadjuvant androgen deprivation therapy before radical prostatectomy and developed biochemical recurrence were analyzed. The patients were categorized into five groups according to PSA half-life. Risk of developing castration resistance was evaluated by Kaplan-Meier analysis and by Cox proportional risk regression analysis.ResultsThe median follow-up duration was 50.1 months (IQR 31.8–68.7) and median PSA half-life was 22.1 days (IQR 12.7–38.4). Comparison of survival curves revealed that patients in the intermediate response group showed significantly lower 5-year castration-resistant prostate cancer rate (37.5%) compared to non-response and ultra-rapid response groups (63.6%, p = 0.007; 56.1%, p = 0.031; respectively). In the multivariate regression model, intermediate response compared to non-response was associated with significantly reduced risk of castration resistance development (hazard ratio 0.397, 95% confidence interval 0.191–0.823, p = 0.013) and overall mortality (hazard ratio 0.138, 95% confidence interval 0.033–0.584, p = 0.007). When subcategorized by Gleason score, Kaplan-Meier curve revealed that, in the high Gleason score stratum, 5-year castration-resistant prostate cancer rate for intermediate response group (44.0%) was exceptionally lower than that in non-response group (66.7%, p = 0.047), while castration resistance increased in other groups.ConclusionShort PSA half-life as well as no response after androgen deprivation is associated with increased risk of treatment failure compared to intermediate PSA half-life.
Highlights
The magnitude and rapidity of the tumor response to androgen deprivation is known to predict the durability of the therapy
Some prior studies suggest that a shorter time to nadir or prostate-specific antigen halflife (PSAT1⁄2) during Androgen deprivation therapy (ADT) is associated with longer castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival [7, 8]
Under the assumptions that the risk of developing CRPC can be measured by analyzing the PSA response to hormone therapy and that castration resistance is heterogeneous among the individual tumor cells within a patient, we investigated the value of the Prostate-specific antigen half-life (PSAT1⁄2) during neoadjuvant ADT as a predictive factor for CRPC in radical prostatectomy patients who developed biochemical recurrence (BCR)
Summary
The magnitude and rapidity of the tumor response to androgen deprivation is known to predict the durability of the therapy. Androgen deprivation therapy (ADT) has been the preferred therapy for prostate cancer patients with biochemical recurrence (BCR) after definitive local therapy. Regarding the risk of developing CRPC, there has been a notion that the magnitude [5] and rapidity [6] of the tumor response to ADT can reliably predict the durability of the therapy. Because tumor response to ADT may vary [11] and some prostate cancer cells are known to produce little, if any, prostate-specific antigen (PSA) [12], the resultant PSA kinetics can be heterogeneous in nature [3]
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