Depart of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA.
Department of Radiation Oncology, Cedars Sinai, Los Angeles, CA, USA.
Eur Urol. 2022 Nov;82(5):487-498. doi: 10.1016/j.eururo.2022.07.011. Epub 2022 Aug 5.
The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear.
To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT.
A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), distant metastasis-free survival (DMFS), and local failure as a time-dependent covariate. Markov PH models were developed to evaluate the impact of specific transition states.
The median follow-up was 11 yr. There were 795 (13%) local failure events and 1288 (21%) distant metastases for high-risk patients and 449 (7.2%) and 451 (7.2%) for intermediate-risk patients, respectively. For both groups, 81% of distant metastases developed from a clinically relapse-free state (cRF state). Local failure was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06-1.30), PCSS (HR 2.02, 95% CI 1.75-2.33), and DMFS (HR 1.94, 95% CI 1.75-2.15, p < 0.01 for all) in high-risk patients. Local failure was also significantly associated with DMFS (HR 1.57, 95% CI 1.36-1.81) but not with OS in intermediate-risk patients. Patients without local failure had a significantly lower HR of transitioning to a PCa-specific death state than those who had local failure (HR 0.32, 95% CI 0.21-0.50, p < 0.001). At later time points, more distant metastases emerged after a local failure event for both groups.
Local failure is an independent prognosticator of OS, PCSS, and DMFS in high-risk and of DMFS in intermediate-risk PCa. Distant metastasis predominantly developed from the cRF state, underscoring the importance of addressing occult microscopic disease. However a "second wave" of distant metastases occurs subsequent to local failure events, and optimization of local control may reduce the risk of distant metastasis.
Among men receiving definitive radiation therapy for high- and intermediate-risk prostate cancer, about 10% experience local recurrence, and they are at significantly increased risks of further disease progression. About 80% of patients who develop distant metastasis do not have a detectable local recurrence preceding it.
在国家综合癌症网络中，局部失败对明确放疗后中高危前列腺癌（PCa）患者的预后意义仍不清楚。
评估放疗后局部失败和远处转移的发生动力学及其对预后的影响。
对癌症前列腺癌协作组（Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium）中 18 项随机试验（1985 年至 2015 年间进行）的 12533 例 PCa（6288 例高危和 6245 例中危）患者的个体患者数据进行了汇总分析。多变量 Cox 比例风险（PH）模型用于评估总生存（OS）、前列腺癌特异性生存（PCSS）、远处无转移生存（DMFS）与局部失败之间的关系，局部失败作为时变协变量。Markov PH 模型用于评估特定转移状态的影响。
中位随访时间为 11 年。高危患者中，795 例（13%）发生局部失败事件，1288 例（21%）发生远处转移；中危患者中，分别有 449 例（7.2%）和 451 例（7.2%）发生局部失败事件和远处转移。两组中，81%的远处转移发生在临床无复发生存（cRF）状态。局部失败与 OS（风险比[HR]1.17，95%置信区间[CI]1.06-1.30）、PCSS（HR 2.02，95%CI 1.75-2.33）和 DMFS（HR 1.94，95%CI 1.75-2.15，p<0.01）显著相关，高危患者中 p<0.01。局部失败也与 DMFS（HR 1.57，95%CI 1.36-1.81）显著相关，但与中危患者的 OS 无关。无局部失败的患者向前列腺癌特异性死亡状态转移的 HR 显著低于有局部失败的患者（HR 0.32，95%CI 0.21-0.50，p<0.001）。在稍后的时间点，两组患者在发生局部失败后出现更多的远处转移。
在高危患者中，局部失败是 OS、PCSS 和 DMFS 的独立预后因素，在中危患者中是 DMFS 的独立预后因素。远处转移主要来自 cRF 状态，这强调了治疗隐匿性微转移的重要性。然而，在局部失败事件后会出现“第二波”远处转移，优化局部控制可能会降低远处转移的风险。
在接受明确放疗的高危和中危前列腺癌患者中，约 10%的患者会出现局部复发，他们发生进一步疾病进展的风险显著增加。约 80%发生远处转移的患者在远处转移前没有可检测到的局部复发。
