Spratt Daniel E, Zumsteg Zachary S, Pei Xin, Romesser Paul B, Yamada Josh, Kollmeier Marisa A, Woo Kaitlin, Zhang Zhigang, Zelefsky Michael J
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York.
Prostate. 2015 Feb;75(2):175-82. doi: 10.1002/pros.22902. Epub 2014 Oct 18.
Castration-resistant prostate cancer (CRPC) is a near uniformly fatal form of prostate cancer; however, information on time to development and predictors for progression to CRPC is limited. We report a detailed longitudinal study for development of CRPC in men initially treated with external beam radiotherapy (EBRT).
During 1991-2008, 2,478 patients with clinically localized prostate cancer were treated with dose-escalated EBRT at a single institution. The primary objective was to determine predictors of CRPC among men who failed definitive EBRT and progressed to salvage androgen-deprivation therapy (ADT). CRPC was defined as castrate levels of testosterone (<50 ng/dl) with progressive biochemical or radiographic disease.
For the entire cohort (n = 2,478), the 10-year cumulative incidence rate for developing CRPC was 9.9%. For those that progressed to salvage ADT (n = 362), the 7-year cumulative incidence rates for developing CRPC from time of salvage ADT was 33.7%. Amongst this cohort, multivariable analysis demonstrated that PSA doubling-time (continuous; hazard ratio [HR], 0.98 [0.97-0.99], P < 0.001), higher Gleason score (HR, 1.96 [1.12-3.43]; P = 0.034), and duration of ADT at time of EBRT (continuous; HR, 1.02 [1.01-1.03]; P = 0.007) were associated with development of CRPC.
This represents the first report of predictors of CRPC for patients treated with modern dose-escalated EBRT. We demonstrate that among the minority of patients not initially cured after EBRT, those treated with longer-course ADT have higher rates of resistance to the re-introduction of ADT. Future trials will need to test this subgroup with more aggressive or alternative forms of salvage therapies.
去势抵抗性前列腺癌（CRPC）是一种几乎必死无疑的前列腺癌形式；然而，关于其发生时间以及进展为CRPC的预测因素的信息有限。我们报告了一项针对最初接受外照射放疗（EBRT）的男性发生CRPC的详细纵向研究。
在1991年至2008年期间，2478例临床局限性前列腺癌患者在单一机构接受了剂量递增的EBRT治疗。主要目的是确定在确定性EBRT治疗失败并进展为挽救性雄激素剥夺治疗（ADT）的男性中CRPC的预测因素。CRPC定义为睾酮水平处于去势水平（<50 ng/dl）且伴有生化或影像学疾病进展。
在整个队列（n = 2478）中，发生CRPC的10年累积发病率为9.9%。对于那些进展为挽救性ADT的患者（n = 362），从挽救性ADT开始计算，发生CRPC的7年累积发病率为33.7%。在该队列中，多变量分析表明，前列腺特异性抗原（PSA）倍增时间（连续变量；风险比[HR]，0.98[0.97 - 0.99]，P < 0.001）、更高的 Gleason评分（HR，1.96[1.12 - 3.43]；P = 0.034）以及EBRT时ADT的持续时间（连续变量；HR，1.02[1.01 - 1.03]；P = 0.007）与CRPC的发生相关。
这是关于接受现代剂量递增EBRT治疗患者CRPC预测因素的首份报告。我们证明，在EBRT后最初未治愈的少数患者中，接受疗程更长的ADT治疗的患者对再次引入ADT的耐药率更高。未来的试验需要用更积极或替代形式的挽救性治疗来测试这个亚组。
