Buyyounouski Mark K, Hanlon Alexandra L, Eisenberg Debra F, Horwitz Eric M, Feigenberg Steven J, Uzzo Robert G, Pollack Alan
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1455-62. doi: 10.1016/j.ijrobp.2005.05.053. Epub 2005 Sep 19.
To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer.
From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared.
The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test).
The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length.
比较前列腺癌放疗（RT）联合或不联合雄激素剥夺治疗（ADT）后长期随访的男性患者中，生化失败（BF）的几种替代定义的特征。
1991年12月1日至1998年4月30日，688例T1c - T3NX - N0M0期前列腺癌男性患者接受单纯放疗（n = 586）或放疗加ADT（n = 102），最短随访4年且有5次或更多次“无ADT”的治疗后前列腺特异性抗原水平。BF通过三种方法定义：（1）美国放射肿瘤学会（ASTRO）定义（前列腺特异性抗原水平连续三次升高）；（2）改良的美国放射肿瘤学会（ASTRO）定义，即连续三次升高后紧接着出现下降时，还需要另外连续两次升高；（3）“休斯顿”或最低点加2 ng/mL定义（比最低点至少升高2 ng/mL）。以临床进展为终点，确定每种定义的敏感性、特异性、阳性预测值、阴性预测值和总体准确性。此外比较了前列腺特异性抗原水平持续升高时的错误分类率、满足比例风险（放疗联合或不联合ADT）的能力、短随访的影响以及BF诊断间隔。
与改良ASTRO定义的0%和0%，以及ASTRO定义的5%和23%相比（分别为单纯放疗和放疗加ADT），最低点加2 ng/mL定义的BF错误分类率分别为2%和零。仅最低点加2 ng/mL定义的单纯放疗和放疗加ADT的风险率呈比例，且似乎不受随访时间长度的影响。对于放疗联合或不联合ADT，最低点加2 ng/mL定义最具特异性（单纯放疗为80%，放疗加ADT为75%），阳性预测值最高（单纯放疗为36%，放疗加ADT为25%），总体准确性最高（单纯放疗为81%，放疗加ADT为77%）。与ASTRO定义相比，最低点加2 ng/mL定义在随访的前2年诊断出的BF比例更高（13%对5%，p = 0.0138，卡方检验）。
最低点加2 ng/mL定义是持续、真实、生化和临床失败的最佳预测指标，不受ADT使用或随访时间长度的影响。
