Hodgson D C, Catton C N, Warde P, Gospodarowicz M K, Milosevic M F, McLean M B M, Catton P
Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.
Int J Radiat Oncol Biol Phys. 2001 Mar 15;49(4):957-63. doi: 10.1016/s0360-3016(00)01431-0.
To examine the impact of irregularly rising prostate-specific antigen (PSA) and "impending" biochemical failure on the apparent rate of biochemical relapse following radiotherapy for localized prostate cancer.
We analyzed the outcome of 572 patients with T1/T2 prostate cancer treated with radiotherapy alone at the Princess Margaret Hospital (median follow-up, 4.21 years). Biochemical outcomes were analyzed using 2 different definitions of failure: (1) the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and (2) a modified definition that included 2 consecutive rises in PSA, with a minimum rise of 1.5 ng/mL above the nadir, or a nadir value of greater than 4 ng/mL. Patients were defined as having "impending failure" when the last 2 PSA measurements taken demonstrated 2 consecutive rises.
Two-hundred and thirty patients (40%) met the ASTRO definition of failure; 258 patients (48%) failed by the modified definition (p = 0.001). Five-year biochemical relapse-free rate (bNED) rate was 55% using the ASTRO definition, and 49% using the modified definition. This difference in 5-year bNED was greatest for patients with high-risk disease (ASTRO definition 30% vs. modified definition 15%). Twenty-four of the 38 additional cases identified as biochemical failures by the modified definition had irregularly rising PSA levels; 14 were "impending failures." These additional 38 patients had a median PSA elevation 5.4 ng/mL above the nadir, and a high risk of subsequent clinical failure (4-year clinical failure-free rate of 63%). The ASTRO definition had a sensitivity of 87% and specificity of 74% for predicting clinical relapse. The modified definition had a sensitivity of 95% and a specificity of 70%.
A definition of biochemical failure that includes an absolute allowable rise in PSA above the nadir can identify patients with rising PSA who are at substantial risk of clinical relapse, but who are not defined as biochemical failures by the ASTRO definition. This is particularly true for patients with high-risk disease. The use of a uniform definition of biochemical failure is crucial to ensure that differences in apparent outcome are not due to differences in the definition of relapse. Currently, the ASTRO definition should remain the standard. Large cohort studies with long follow-up can be utilized to optimize the definition of biochemical failure following radiotherapy for prostate cancer.
探讨前列腺特异性抗原（PSA）不规则升高及“即将发生”的生化失败对局限性前列腺癌放疗后生化复发表观率的影响。
我们分析了在玛格丽特公主医院仅接受放疗的572例T1/T2期前列腺癌患者的治疗结果（中位随访时间为4.21年）。使用两种不同的失败定义分析生化结果：（1）美国放射肿瘤学会（ASTRO）定义，以及（2）一种改良定义，包括PSA连续两次升高，最低升高幅度比最低点高1.5 ng/mL，或最低点值大于4 ng/mL。当最后两次PSA测量显示连续两次升高时，患者被定义为“即将失败”。
230例患者（40%）符合ASTRO失败定义；258例患者（48%）根据改良定义失败（p = 0.001）。使用ASTRO定义的5年生化无复发生存率（bNED）为55%，使用改良定义的为49%。对于高危疾病患者，5年bNED的这种差异最为显著（ASTRO定义为30%，改良定义为15%）。根据改良定义被确定为生化失败的38例额外病例中，24例PSA水平不规则升高；14例为“即将失败”。这38例额外患者的PSA中位升高幅度比最低点高5.4 ng/mL，且随后临床失败风险高（4年临床无失败率为63%）。ASTRO定义预测临床复发的敏感性为87%，特异性为74%。改良定义的敏感性为95%，特异性为70%。
一种包括允许PSA相对于最低点有绝对升高幅度的生化失败定义，可以识别出PSA升高但根据ASTRO定义未被定义为生化失败、却有较高临床复发风险的患者。对于高危疾病患者尤其如此。使用统一的生化失败定义对于确保表观结果的差异不是由于复发定义的差异至关重要。目前，ASTRO定义应仍然是标准。可以利用长期随访的大型队列研究来优化前列腺癌放疗后生化失败的定义。
