Horwitz E M, Vicini F A, Ziaja E L, Gonzalez J, Dmuchowski C F, Stromberg J S, Brabbins D S, Hollander J, Chen P Y, Martinez A A
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
Int J Radiat Oncol Biol Phys. 1996 Oct 1;36(3):565-71. doi: 10.1016/s0360-3016(96)00360-4.
Biochemical control using serial posttreatment serum prostate specific antigen (PSA) levels is being increasingly used to assess treatment efficacy for localized prostate cancer. However, no standardized definition of biochemical control has been established. We reviewed our experience treating patients with localized prostate cancer and applied three different commonly used definitions of biochemical control to determine if differences in therapeutic outcome would be observed.
Between January 1987 and December 1991, 480 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital. The median dose to the prostate was 66.6 Gy (range 58-70.4) using a four-field or arc technique. Pretreatment and posttreatment serum PSA levels were recorded. Over 86% (414 of 480) of patients had a pretreatment PSA level available. Three different definitions of biochemical control were used: (a) PSA nadir < 1 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (b) PSA nadir < 1.5 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (c) Posttreatment PSA nadir < 4 ng/ml without a time limit. Once the nadir was achieved, if it did not rise above normal the patient was considered to be biochemically controlled. Clinical local control was defined as no palpable prostate nodularity beyond 18 months, no new prostate nodularity, or a negative prostate biopsy.
Median follow-up was 48 months (range 3-112). Pretreatment PSA values were correlated with treatment outcome using the three definitions of biochemical control as well as clinical local control. Pretreatment PSA values were stratified into five groups (Group 1: PSA < 4; Group 2: PSA 4-10; Group 3: PSA 10-15; Group 4: PSA 15-20; and Group 5: PSA > 20), and 5-year actuarial rates of biochemical control were calculated using the three biochemical control and one clinical local control definitions. For Group 1, 5-year actuarial rates of biochemical control were 84%, 90%, 91%, and 96% for Definitions 1-3 and clinical local control, respectively. For Group 2, 5-year actuarial control rates were 45%, 54%, 74%, and 92% for the four definitions, respectively. For Group 3, 5-year actuarial control rates were 26%, 31%, 63%, and 100% for the four definitions, respectively. For Group 4, 5-year actuarial control rates were 24%, 24%, 50%, and 100% for the four definitions, respectively. Finally, for Group 5, 5-year actuarial control rates were 5%, 14%, 15%, and 89% for the four definitions, respectively. Depending on the definition used, statistically significant differences overall in outcome rates were observed. Differences between all four definitions for all pairwise comparisons ranged from 5 to 53% (p < 0.001).
When different definitions of biochemical control are used in assessing treatment outcome, significantly different rates of success are noted. Until a standardized definition of biochemical control is adopted, differences in treatment outcome cannot be meaningfully compared.
利用系列治疗后血清前列腺特异性抗原（PSA）水平进行生化控制越来越多地用于评估局限性前列腺癌的治疗效果。然而，尚未建立生化控制的标准化定义。我们回顾了治疗局限性前列腺癌患者的经验，并应用三种不同的常用生化控制定义来确定是否会观察到治疗结果的差异。
1987年1月至1991年12月期间，480例临床局限性前列腺癌患者在威廉·博蒙特医院使用局部前列腺野接受外照射放疗（RT）。采用四野或弧形技术，前列腺的中位剂量为66.6 Gy（范围58 - 70.4）。记录治疗前和治疗后的血清PSA水平。超过86%（480例中的414例）患者有治疗前PSA水平数据。使用三种不同的生化控制定义：（a）治疗完成后1年内PSA最低点<1 ng/ml。达到最低点后，如果注意到PSA连续两次升高，则在首次升高时将患者记为失败；（b）治疗完成后1年内PSA最低点<1.5 ng/ml。达到最低点后，如果注意到PSA连续两次升高，则在首次升高时将患者记为失败；（c）治疗后PSA最低点<4 ng/ml，无时间限制。一旦达到最低点，如果未升至正常水平以上，则认为患者生化控制良好。临床局部控制定义为18个月后无可触及的前列腺结节、无新的前列腺结节或前列腺活检阴性。
中位随访时间为48个月（范围3 - 112个月）。使用生化控制的三种定义以及临床局部控制定义，治疗前PSA值与治疗结果相关。将治疗前PSA值分为五组（第1组：PSA<4；第2组：PSA 4 - 10；第3组：PSA 10 - 15；第4组：PSA 15 - 20；第5组：PSA>20），并使用三种生化控制定义和一种临床局部控制定义计算5年生化控制精算率。对于第1组，定义1 - 3和临床局部控制的5年生化控制精算率分别为84%、90%、91%和96%。对于第2组，四种定义的5年精算控制率分别为45%、54%、74%和92%。对于第3组，四种定义的5年精算控制率分别为26%、31%、63%和100%。对于第4组，四种定义的5年精算控制率分别为24%、24%、50%和100%。最后，对于第5组，四种定义的5年精算控制率分别为5%、14%、15%和89%。根据所使用的定义，总体上观察到结果率有统计学显著差异。所有四个定义之间所有两两比较的差异范围为5%至53%（p<0.001）。
在评估治疗结果时使用不同的生化控制定义，会注意到成功率有显著差异。在采用生化控制的标准化定义之前，无法有意义地比较治疗结果的差异。
