University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Cancer. 2012 Apr 15;118(8):2059-68. doi: 10.1002/cncr.26498. Epub 2011 Aug 26.
After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause-specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose-escalated EBRT.
From 1998 to 2008, 710 patients were treated with EBRT (≥75 grays) ± androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/mL). A short interval to biochemical failure was defined as <18 months after completing radiotherapy and/or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause-specific survival (CSS) and overall survival (OS) were evaluated.
There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate-risk or high-risk disease, respectively. Biochemical failure impacted CSS (P < .0001) but not OS (P = .36). However, a short interval to biochemical failure predicted decreased CSS (P < .0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4-13.0) and OS (P < .0001; HR, 4.8; 95% CI, 2.3-10.3) when compared with a long interval to biochemical failure. The 8-year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure (P = .1; HR, 0.7; 95% CI, 0.4-1.1) and 38% with a short interval to biochemical failure (P < .0001; HR, 3.7; 95% CI, 2.3-5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death (P < .0001; HR, 18.1; 95% CI, 8.4-39) and all cause mortality (P = .0027; HR, 1.5; 95% CI, 1.2-2.1), whereas a long interval to biochemical failure did not.
The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose-escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted.
在前列腺癌接受外照射放射治疗（EBRT）后，<18 个月的生化失败间隔时间被提议作为特定于病因的生存的替代指标。由于 EBRT 剂量会影响生化失败，作者研究了在接受剂量递增 EBRT 治疗的患者队列中，生化失败的间隔时间。
1998 年至 2008 年，密歇根大学的 710 名患者接受了 EBRT（≥75 格雷）±雄激素剥夺治疗（ADT）。生化失败使用凤凰共识定义（最低点+2ng/ml）定义。生化失败后完成放疗和/或 ADT 的生化失败间隔时间定义为<18 个月。评估生化失败、生化失败间隔时间与临床因素之间与特定病因的生存（CSS）和总体生存（OS）的关系。
共有 149 例生化失败（21%），在中危或高危疾病患者中，生化失败的间隔时间分别占生化失败的 14%和 40%。生化失败影响 CSS（P<0.0001）但不影响 OS（P=0.36）。然而，与长间隔生化失败相比，短间隔生化失败预测 CSS 降低（P<0.0001；危险比[HR]，5.6；95%置信区间[CI]，2.4-13.0）和 OS（P<0.0001；HR，4.8；95% CI，2.3-10.3）。无生化失败的 8 年 OS 为 78%，而长间隔生化失败的 8 年 OS 为 78%（P=0.1；HR，0.7；95%CI，0.4-1.1）和短间隔生化失败的 8 年 OS 为 38%（P<0.0001；HR，3.7；95% CI，2.3-5.9）。多变量分析显示，短间隔生化失败增加了前列腺癌死亡的风险（P<0.0001；HR，18.1；95% CI，8.4-39）和全因死亡率（P=0.0027；HR，1.5；95% CI，1.2-2.1），而长间隔生化失败则没有。
在接受剂量递增 EBRT 治疗的患者中，生化失败间隔时间与 CSS 和 OS 的关系得到了独立验证。进一步评估生化失败间隔时间作为替代终点是有必要的。
