Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia3Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
JAMA Oncol. 2015 Oct;1(7):897-906. doi: 10.1001/jamaoncol.2015.2316.
In 5 published randomized clinical trials, dose-escalated external-beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, scarce evidence addresses whether dose escalation improves overall survival.
To examine the association between dose-escalated EBRT and overall survival among men with nonmetastatic prostate cancer.
DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective, nonrandomized comparative effectiveness study of dose-escalated vs standard-dose EBRT for prostate cancer diagnosed from 2004 to 2006 using the National Cancer Database (NCDB), which includes data from patients treated at Commission on Cancer-accredited community, academic, and comprehensive cancer facilities. Three cohorts were evaluated: men with low-risk (n = 12,229), intermediate-risk (n = 16,714), or high-risk (n = 13,538) prostate cancer.
We categorized patients in each risk cohort into 2 treatment groups: standard-dose (from 68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT (1 Gy = 100 rad).
We compared overall survival between treatment groups in each analytic cohort using Cox proportional hazard models with an inverse probability weighted propensity score (IPW-PS) approach. In secondary analyses, we evaluated dose response for survival.
Dose-escalated EBRT was associated with improved survival in the intermediate-risk (IPW-PS adjusted hazard ratio [HR], 0.84; 95% CI, 0.80-0.88; P < .001) and high-risk groups (HR, 0.82; 95% CI, 0.78-0.85; P < .001) but not the low-risk group (HR, 0.98; 95% CI, 0.92-1.05; P = .54). For every incremental increase of about 2 Gy in dose, there was a 7.8% (95% CI, 5.4%-10.2%; P < .001) and 6.3% (95% CI, 3.3%-9.1%; P < .001) reduction in the hazard of death for intermediate- and high-risk patients, respectively.
Dose-escalated EBRT is associated with improved overall survival in men with intermediate- and high-risk prostate cancer but not low-risk prostate cancer. These results add to the evidence questioning aggressive local treatment strategies in men with low-risk prostate cancer but supporting such treatment in men with greater disease severity.
在 5 项已发表的随机临床试验中，前列腺癌的递增剂量外照射放疗（EBRT）可改善生化和局部控制。然而，几乎没有证据表明剂量递增是否能提高总生存率。
研究非转移性前列腺癌患者接受递增剂量 EBRT 与总生存率之间的关系。
设计、地点和参与者：我们使用国家癌症数据库（NCDB）进行了一项回顾性、非随机的比较效果研究，该数据库包括了 2004 年至 2006 年期间在癌症委员会认证的社区、学术和综合癌症设施接受治疗的患者的数据，对递增剂量与标准剂量 EBRT 治疗前列腺癌的情况进行了评估。评估了三个队列：低危（n=12229）、中危（n=16714）和高危（n=13538）前列腺癌患者。
我们将每个风险队列中的患者分为 2 个治疗组：标准剂量（68.4Gy 至 <75.6Gy）或递增剂量（≥75.6Gy 至 90Gy）EBRT（1Gy=100rad）。
我们使用逆概率加权倾向评分（IPW-PS）方法的 Cox 比例风险模型比较了每个分析队列中治疗组之间的总生存率。在二次分析中，我们评估了剂量与生存率的关系。
在中危（IPW-PS 调整后的危险比 [HR]，0.84；95%CI，0.80-0.88；P<0.001）和高危组（HR，0.82；95%CI，0.78-0.85；P<0.001）中，递增剂量 EBRT 与生存率的提高相关，但在低危组中则不相关（HR，0.98；95%CI，0.92-1.05；P=0.54）。每增加约 2Gy 的剂量，中危和高危患者的死亡风险分别降低 7.8%（95%CI，5.4%-10.2%；P<0.001）和 6.3%（95%CI，3.3%-9.1%；P<0.001）。
递增剂量 EBRT 与中危和高危前列腺癌患者的总生存率提高相关，但与低危前列腺癌患者无关。这些结果增加了对低危前列腺癌患者采用积极局部治疗策略的质疑，但支持对疾病严重程度较高的患者采用这种治疗。
