BACKGROUND The importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown. OBJECTIVE To evaluate the clinical implications of LF after definitive RT. DESIGN, SETTING, AND PARTICIPANTS Individual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable Cox proportional hazard models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were developed to evaluate the impact of specific transitions between disease states on these endpoints. RESULTS AND LIMITATIONS Median follow-up was 6.4 yr overall and 7.2 yr for surviving patients. LF was significantly associated with OS (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.37-2.10]), PCSS (3.10 [95% CI 2.33-4.12]), and DMFS (HR 1.92 [95% CI 1.54-2.39]), p < 0.001 for all). Patients who had not transitioned to the LF state had a significantly lower hazard of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.13 [95% CI 0.04-0.41], p < 0.001). Additionally, patients who transitioned to the LF state had a greater hazard of DM or death (HR 2.46 [95% CI 1.22-4.93], p = 0.01) than those who did not. CONCLUSIONS LF is an independent prognosticator of OS, PCSS, and DMFS in high-grade localized PCa and a subset of DM events that are anteceded by LF events. LF events warrant consideration for intervention, potentially suggesting a rationale for upfront treatment intensification. However, whether these findings apply to all men or just those without significant comorbidity remains to be determined. PATIENT SUMMARY Men who experience a local recurrence of high-grade prostate cancer after receiving upfront radiation therapy are at significantly increased risks of developing metastases and dying of prostate cancer.

中文翻译：

---

侵袭性前列腺癌明确放疗后的局部衰竭和生存：六个随机试验的个体患者水平荟萃分析。

背景技术用确定性放射疗法（RT）治疗高级前列腺癌（PCa）后局部衰竭（LF）的重要性仍然未知。目的评估明确RT后LF的临床意义。设计，地点和参与者参加六项随机临床试验的992例患者（593 Gleason分级组[GG] 4和399 GG 5）的患者数据进行了荟萃分析。结果测量和统计分析建立了多变量Cox比例风险模型，以评估总生存期（OS），PCa特异性生存期（PCSS），无远处转移（DM）生存期（DMFS）和LF之间的关系。协变量 开发了马尔可夫比例风险模型以评估疾病状态之间特定转变对这些终点的影响。结果与局限性中位随访总体为6.4年，存活患者为7.2年。LF与OS（危险比[HR] 1.70 [95％置信区间{CI} 1.37-2.10]），PCSS（3.10 [95％CI 2.33-4.12]）和DMFS（HR 1.92 [95％CI 1.54] -2.39]），对于所有p <0.001）。未转变为LF状态的患者与转变为LF状态的患者相比，转变为PCa特异性死亡状态的危险要低得多（HR 0.13 [95％CI 0.04-0.41]，p <0.001）。此外，与未转移的患者相比，转移至LF状态的患者有更大的DM或死亡风险（HR 2.46 [95％CI 1.22-4.93]，p = 0.01）。结论LF是高级局部PCa和由LF事件引起的DM事件子集中OS，PCSS和DMFS的独立预测者。LF事件值得考虑进行干预，这可能暗示了加强前期治疗的理由。但是，这些发现是适用于所有男性还是仅适用于无明显合并症的男性，尚待确定。患者总结接受前期放射治疗后经历局部前列腺癌局部复发的男性患前列腺癌转移和死亡的风险显着增加。