University Medical Center Utrecht, Radiation Oncology, Utrecht, the Netherlands.
Radboud University Medical Center, Radiation Oncology, Nijmegen, the Netherlands.
J Clin Oncol. 2021 Mar 1;39(7):787-796. doi: 10.1200/JCO.20.02873. Epub 2021 Jan 20.
This study investigates whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized prostate cancer.
In the phase III, multicenter, randomized controlled Focal Lesion Ablative Microboost in Prostate Cancer trial, 571 patients with intermediate- and high-risk prostate cancer were enrolled between 2009 and 2015. Patients assigned to standard treatment received 77 Gy (fractions of 2.2 Gy) to the entire prostate. The focal boost arm received an additional simultaneous integrated focal boost up to 95 Gy (fractions up to 2.7 Gy) to the intraprostatic lesion visible on multiparametric magnetic resonance imaging. Organ at risk constraints were prioritized over the focal boost dose. The primary end point was 5-year bDFS. Secondary end points were disease-free survival (DFS), distant metastases-free survival, prostate cancer-specific survival, overall survival, toxicity, and health-related quality of life.
Median follow-up was 72 months. Biochemical DFS was significantly higher in the focal boost compared with the standard arm (hazard ratio 0.45, 95% CI, 0.28 to 0.71, < .001). At 5-year follow-up bDFS was 92% and 85%, respectively. We did not observe differences in prostate cancer-specific survival ( = .49) and overall survival ( = .50). The cumulative incidence of late genitourinary and GI toxicity grade ≥ 2 was 23% and 12% in the standard arm versus 28% and 13% in the focal boost arm, respectively. Both for late toxicity as health-related quality of life, differences were small and not statistically significant.
The addition of a focal boost to the intraprostatic lesion improved bDFS for patients with localized intermediate- and high-risk prostate cancer without impacting toxicity and quality of life. The Focal Lesion Ablative Microboost in Prostate Cancer study shows that a high focal boost strategy to improve tumor control while respecting organ at risk dose constraints is effective and safe.
本研究旨在探讨局部前列腺癌患者采用外照射放疗对宏观可见肿瘤进行局部加量能否提高生化无病生存（bDFS）。
在 2009 年至 2015 年间，共纳入 571 例中高危前列腺癌患者参加这项 III 期、多中心、随机对照的前列腺癌局部病灶消融微加量研究。标准治疗组患者接受 77Gy（2.2Gy 分次）全前列腺照射。局部加量组则在多参数磁共振成像显示的前列腺内病灶上接受额外的同步整合局部加量至 95Gy（2.7Gy 分次）。在考虑局部加量剂量的同时，优先考虑危及器官剂量限制。主要终点为 5 年 bDFS。次要终点包括无病生存（DFS）、远处转移无病生存、前列腺癌特异性生存、总生存、毒性和健康相关生活质量。
中位随访时间为 72 个月。与标准治疗组相比，局部加量组的生化无病生存率显著提高（风险比 0.45，95%CI：0.28 至 0.71，<0.001）。5 年 bDFS 分别为 92%和 85%。我们未观察到前列腺癌特异性生存（=0.49）和总生存（=0.50）的差异。标准治疗组和局部加量组的晚期泌尿生殖系统和胃肠道毒性≥2 级的累积发生率分别为 23%和 12%，28%和 13%。在晚期毒性和健康相关生活质量方面，差异较小且无统计学意义。
对于局部中高危前列腺癌患者，在前列腺内病灶上增加局部加量可提高生化无病生存率，而不会影响毒性和生活质量。Focal Lesion Ablative Microboost in Prostate Cancer 研究表明，在尊重危及器官剂量限制的同时采用高局部加量策略提高肿瘤控制效果是有效且安全的。
