Hanlon A L, Moore D F, Hanks G E
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Cancer. 1998 Jul 1;83(1):130-4.
The goals of this study are twofold: 1) to describe the postradiation kinetics of nonrecurring prostate carcinoma based on prostate specific antigen (PSA) levels in men who remain biochemically free of disease; and 2) to determine predictors of all three components of the resulting piecewise exponential model based on pretreatment and treatment characteristics.
Between March 1988 and May 1994, 153 patients with T1-T3 nonmetastatic prostate carcinoma were treated definitively with radiation therapy and at last follow-up had not failed biochemically (PSA rising on 2 consecutive occasions to a level > 1.0 ng/mL or 3 consecutive elevations). All patients were required to have at least 6 posttreatment PSA determinations and a minimum follow-up of 36 months. The median follow-up was 53 months (range, 36-94 months). A piecewise exponential model was used to describe the mean PSA levels because 1) the kinetics of postradiation PSA levels appear to follow first-order rate processes, and 2) there is evidence that PSA levels may rise slightly several years after treatment. Nonlinear mixed effects modeling was used in this situation because of the aforementioned nonlinearity and because variability between patients and within patients (PSA variation) must be taken into account. In addition, this methodology allows for modeling parameters as a function of patient and treatment characteristics.
The random effects model based on the entire patient population demonstrated that PSA levels do not continue to drop 3 years after treatment, and that in fact the levels begin to rise slowly between 2-3 years after treatment. Pretreatment PSA was the only independent predictor of baseline PSA at time zero (end of radiation therapy). Gleason score was the only independent predictor of the rate of PSA decline after treatment, in which tumors with Gleason scores 7-10 drop at a slower rate than do tumors with Gleason scores 2-6. Finally, pretreatment prostate volume was the only independent predictor of the postnadir rise in PSA level, in which larger volumes translate to a steeper slope.
The fact that pretreatment PSA level is the only independent predictor of the baseline PSA at time zero is not surprising. The observation that patients with tumors with higher Gleason scores have a slower rate of decline is in agreement with previous reports that these tumors contribute less PSA per unit volume than do tumors with moderate to well differentiation. Finally, the fact that no tumor-related characteristic (only pretreatment prostate volume) was predictive independently of the observed postnadir rise in PSA level suggests that these patients were cured.
本研究有两个目标：1）基于生化无疾病男性的前列腺特异性抗原（PSA）水平，描述非复发性前列腺癌放疗后的动力学；2）根据治疗前和治疗特征，确定所得分段指数模型所有三个组成部分的预测因素。
1988年3月至1994年5月期间，153例T1 - T3期非转移性前列腺癌患者接受了根治性放疗，最后一次随访时生化检查未失败（PSA连续2次升至>1.0 ng/mL或连续3次升高）。所有患者至少需要有6次治疗后的PSA测定结果，且最短随访时间为36个月。中位随访时间为53个月（范围36 - 94个月）。采用分段指数模型描述平均PSA水平，原因如下：1）放疗后PSA水平的动力学似乎遵循一级速率过程；2）有证据表明治疗后数年PSA水平可能会略有上升。由于上述非线性以及必须考虑患者之间和患者内部的变异性（PSA变异），因此在此情况下使用非线性混合效应模型。此外，该方法允许将模型参数作为患者和治疗特征的函数进行建模。
基于全体患者人群的随机效应模型表明，治疗3年后PSA水平不会持续下降，实际上在治疗后2 - 3年开始缓慢上升。治疗前PSA是放疗结束时（时间零点）基线PSA的唯一独立预测因素。Gleason评分是治疗后PSA下降速率的唯一独立预测因素，其中Gleason评分为7 - 10分的肿瘤下降速率比Gleason评分为2 - 6分的肿瘤慢。最后，治疗前前列腺体积是PSA水平最低点后上升的唯一独立预测因素，前列腺体积越大，斜率越陡。
治疗前PSA水平是时间零点基线PSA的唯一独立预测因素这一事实并不令人惊讶。高Gleason评分肿瘤患者下降速率较慢的观察结果与先前报道一致，即这些肿瘤每单位体积产生的PSA比中分化至高分化肿瘤少。最后，没有肿瘤相关特征（仅治疗前前列腺体积）能独立预测PSA水平最低点后上升，这一事实表明这些患者已治愈。
