The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA.
Prostate. 2011 Nov;71(15):1608-15. doi: 10.1002/pros.21377. Epub 2011 Mar 22.
We sought to determine the change of PSA doubling time (PSADT) and its association with disease progression during intermittent androgen deprivation (IAD) therapy for prostate cancer.
Data were retrospectively analyzed in 96 patients with biochemically relapsed prostate cancer (BRPC) treated with IAD since 1995. IAD consisted of LHRH-agonists ± antiandrogen given usually at PSA threshold (ng/ml) of 10-20, for 6-9 months. Cycles were repeated until the development of castration resistance. Mixed effects model was used to study PSADT change over cycles. Multivariate cox regression model was used to identify outcome-associated variables.
Patients received a mean of 2.8 treatment cycles over a mean follow-up time of 71 months. Fifty-seven (59%) remain on treatment and 39 (41%) developed PSA refractoriness (n = 8) or positive scans (n = 31). First off treatment interval PSADT (median 2.3 months) was significantly shorter than the baseline (median 7.34) but remained stable in subsequent cycles. Off treatment interval PSADT adjusted for testosterone recovery (median 3.7) was significantly longer than that based on all PSA determinations (median 2). Factors associated with disease progression were pre-treatment PSADT (≥6 vs. <6), first off treatment interval PSADT (≥3 vs. <3), and PSA nadir during the first treatment interval (<0.1 vs. ≥0.1).
During IAD for BRPC, PSADT becomes shorter, and is associated with testosterone recovery. PSADT before treatment and during the first off treatment interval is associated with disease progression. If prospectively validated these data may guide treatment with IAD and clinical trial design.
我们旨在确定前列腺癌间歇性雄激素剥夺（IAD）治疗期间 PSA 倍增时间（PSADT）的变化及其与疾病进展的关系。
回顾性分析了 1995 年以来接受 IAD 治疗的 96 例生化复发性前列腺癌（BRPC）患者的数据。IAD 由 LHRH 激动剂±抗雄激素组成，通常在 PSA 阈值（ng/ml）为 10-20 时使用，持续 6-9 个月。周期重复进行，直到出现去势抵抗。使用混合效应模型研究 PSADT 在周期中的变化。使用多变量 Cox 回归模型确定与结局相关的变量。
患者平均接受了 2.8 个治疗周期，平均随访时间为 71 个月。57 例（59%）仍在接受治疗，39 例（41%）出现 PSA 抵抗（n=8）或阳性扫描（n=31）。首次治疗间隔 PSADT（中位数 2.3 个月）明显短于基线（中位数 7.34），但在后续周期中保持稳定。调整睾酮恢复后的治疗间隔 PSADT（中位数 3.7）明显长于基于所有 PSA 测定的 PSADT（中位数 2）。与疾病进展相关的因素包括治疗前 PSADT（≥6 与 <6）、首次治疗间隔 PSADT（≥3 与 <3）和首次治疗间隔期间的 PSA 最低点（<0.1 与 ≥0.1）。
在 BRPC 的 IAD 中，PSADT 变短，与睾酮恢复有关。治疗前和首次治疗间隔期间的 PSADT 与疾病进展有关。如果前瞻性验证这些数据，可能会指导 IAD 治疗和临床试验设计。
