Practical application of biochemical failure definitions: What to do and when to do it
Practical application of biochemical failure definitions: What to do and when to do it
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DOI：
10.1016/s0360-3016(02)02707-4
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发表时间：
2002-06-01
影响因子：
7
通讯作者：
Martinez, AA
中科院分区：
文献类型：
--
作者：
Kestin, LL;Vicini, FA;Martinez, AA
目的：治疗后前列腺特异性抗原（PSA）的档案往往是很难解释后外照射放射治疗前列腺癌。我们对放疗后PSA测量进行了广泛的分析，以确定生化衰竭（BF）的临床意义以及BF与临床衰竭（CF）和原因特异性死亡（CSD）的相关性。材料和方法：在1987年至1997年期间，727例临床分期为T1-T3 N 0 M0前列腺癌患者在William博蒙医院接受了明确的外照射放疗，放疗后PSA水平至少为5，并且未接受激素治疗。仅放疗PSA升高（CF证据出现前）。所有患者仅接受外照射放疗（无辅助激素治疗），前列腺总剂量中位数为66.6戈伊。超过20个BF定义与CF（任何局部失败或远处转移）和CSD的相关性进行了测试。对所有BF定义进行了敏感性、特异性、准确性以及预测随后CF和CSD的阳性和阴性值的测试。中位随访时间为5.0年。结果：连续三次PSA升高预测CF的敏感性为73%，特异性为76%，总体准确性为75%。251例显示连续3次升高（BF）的患者的10年CF率（从完成放疗开始）为64%，而未出现3次升高（生化控制）的患者为14%。将BF定义为最低点后增加至高于最低点大于或等于3 ng/ml，准确度最高，为87%。此外，该定义似乎也有利于CF率的最大分离：放疗后10年，BF为82%，生化控制为5%。CF率也从BF日期开始计算（例如，第三次崛起）。第三次PSA升高后6个月和2年的CF率分别为9%和27%。在增加至高于最低点2：3 ng/ml后6个月和2年的CF率分别为23%和54%。一旦患者被归类为BF，无论BF定义如何，CF率都有明显变化，这取决于治疗前的特征。考克斯多元回归分析显示，对于每种BF定义，诊断时年龄较小、治疗前PSA较高和Gleason评分较高独立预测BF后CF。例如，治疗前PSA < 4.0 ng/ml的患者在第三次PSA升高后2年的CF率为11%，而治疗前PSA大于或等于20.0 ng/ml的患者在三次升高后的CF率为46%。同样，Gleason 2-4组患者在最低值大于或等于1.0 ng/ml后的2年CF率仅为3%，而Gleason 8-10组患者在最低值大于或等于1.0 ng/ml后的2年CF率为47%。虽然当使用高于最低值大于或等于3 ng/ml时，CF率也与治疗前特征一致，但即使对于低风险患者，CF率仍然很高（例如，2-PSA < 10.0 ng/ml的年CF为48%，Gleason 2-4的年CF为41%）。此外，从最低点到最低点+ 1 ng/ml或从最低点到最低点+ 3 ng/ml的时间间隔较短（对应于PSA曲线中的更陡斜率）独立预测CF。结论：一旦放射治疗后PSA曲线达到高于最低点大于或等于3 ng/ml，则在相对短的时间段内存在临床吸引力的高风险，无论治疗前的特征如何，都可以考虑进行治疗干预。在最低值大于或等于1.0 ng/ml或连续3次升高后，可考虑在治疗干预前对部分患者（尤其是具有低风险治疗前特征的患者）进行进一步PSA观察。(C)2002年爱思唯尔科技有限公司
Purpose: The posttreatment prostate-specific antigen (PSA) profile can often be difficult to interpret after external beam radiotherapy for prostate cancer. We performed an extensive analysis of post-radiotherapy PSA measurements to determine the clinical significance of biochemical failure (BF) and the correlation of BF with clinical failure (CF) and cause-specific death (CSD).Materials and Methods: Between 1987 and 1997, 727 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with definitive external beam radiotherapy at William Beaumont Hospital and had at least five post-radiotherapy PSA levels and did not receive hormonal therapy for post-radiotherapy PSA elevations only (before evidence of CF). All patients received external beam radiotherapy alone (no adjuvant hormonal therapy) to a median total prostate dose of 66.6 Gy. More than 20 BF definitions were tested for their correlation with CF (any local failure or distant metastasis) and CSD. All BF definitions were tested for sensitivity, specificity, accuracy, and positive and negative value of predicting subsequent CF and CSD. The median follow-up was 5.0 years.Results: Three consecutive PSA rises yielded a 73% sensitivity, 76% specificity, and 75% overall accuracy for predicting CF. The 10-year CF rate (from the completion of radiotherapy) for those 251 patients demonstrating three consecutive rises (BF) was 64% vs. 14% for those patients who did not have three rises (biochemically controlled). Defining BF as a post-nadir increase to greater than or equal to 3 ng/ml above the nadir yielded the highest accuracy of 87%. In addition, this definition also seemed to pro-tide the greatest separation in CF rates: 82% for BF vs. 5% for biochemically controlled at 10 years after radiotherapy. CF rates were also calculated from the date of BF (e.g., date of third rise). The CF rates at 6 months and 2 years after the third PSA rise were 9% and 27%, respectively. The CF rates at 6 months and 2 years after an increase to 2:3 ng/ml above the nadir were 23% and 54%, respectively. Once a patient was classified as a BF, regardless of the BF definition, the CF rate varied markedly, depending on the pretreatment characteristics. For each BF definition, younger age at diagnosis, higher pretreatment PSA, and higher Gleason score independently predicted for CF after BF on Cox multiple regression analysis. For instance, patients with a pretreatment PSA < 4.0 ng/ml demonstrated an 11% CF rate at 2 years after the third PSA rise vs. 46% after three rises with a pretreatment PSA greater than or equal to 20.0 ng/ml. Similarly, patients with Gleason 2-4 had a 2-year CF rate of only 3% after a nadir greater than or equal to 1.0 ng/ml vs. 47% for Gleason 8-10 at 2 years after a nadir greater than or equal to 1.0 ng/ml. Although the CF rate also coincided with pretreatment characteristics when using greater than or equal to 3 ng/ml above the nadir, CF rates remained high even for low-risk patients (e.g., 2-year CF of 48% for PSA < 10.0 ng/ml, 41% for Gleason 2-4). In addition, a shorter time interval from nadir to nadir + 1 ng/ml or from nadir to nadir + 3 ng/ml (corresponding to a steeper slope in the PSA profile) independently predicted for CF.Conclusion: Once the post-radiotherapy PSA profile reaches greater than or equal to 3 ng/ml above the nadir, there is a high risk of clinical allure within a relatively short time period, for which treatment intervention may be considered, regardless of pretreatment characteristics. After a nadir greater than or equal to 1.0 ng/ml or three consecutive rises, some patients (especially with low-risk pretreatment characteristics) may be considered for further PSA observation before treatment intervention. (C) 2002 Elsevier Science Inc.