镭-223与立体定向消融放疗对比立体定向消融放疗治疗寡转移前列腺癌的疗效：RAVENS II期随机试验
Outcomes of Radium-223 and Stereotactic Ablative Radiotherapy Versus Stereotactic Ablative Radiotherapy for Oligometastatic Prostate Cancers: The RAVENS Phase II Randomized Trial.
作者信息
Wang Jarey H, Sherry Alexander D, Bazyar Soha, Sutera Philip, Radwan Noura, Phillips Ryan M, Deek Matthew P, Lu Jiayun, Dipasquale Shirl, Deville Curtiland, DeWeese Theodore L, Song Daniel Y, Wang Hao, Hobbs Robert F, Malek Reem, Dudley Sara A, Greco Stephen C, Antonarakis Emmanuel S, Marshall Catherine H, Denmeade Samuel, Paller Channing J, Carducci Michael A, Pienta Kenneth J, Oz Orhan K, Ramotar Matthew, Leenstra James L, Park Sean S, Abramowitz Matthew C, Desai Neil, Berlin Alejandro, Stish Bradley J, Tang Chad, Tran Phuoc T, Kiess Ana P
机构信息
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
出版信息
J Clin Oncol. 2025 Jun 20;43(18):2059-2068. doi: 10.1200/JCO-25-00131. Epub 2025 May 7.
PURPOSE
Randomized clinical trials (RCTs) have shown progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) without androgen deprivation therapy for oligometastatic castration-sensitive prostate cancer (omCSPC). Most patients with bone metastatic (BM) omCSPC recur with additional bone disease after MDT. We hypothesized the BM-targeting alpha-emitter radium-223 dichloride (Ra223) could target subclinical bone disease and delay progression.
METHODS
This is an investigator-initiated, multicenter, open-label phase II RCT. Eligible men with recurrent omCSPC with ≥one bone metastasis (≤three on conventional imaging and/or ≤five on molecular imaging) were randomly assigned (1:1) to stereotactic ablative radiation (SABR) MDT alone or SABR MDT with Ra223 (six cycles). Primary end point was composite PFS.
RESULTS
From August 9, 2019, to March 2, 2023, 64 patients were randomly assigned, 33 to SABR MDT and 31 to SABR MDT/Ra223 balancing for key covariates. Most SABR MDT/Ra223 patients (87%) received six cycles of Ra223. The median PFS was 11.8 months with SABR MDT and 10.5 months with SABR MDT/Ra223 (adjusted hazard ratio [aHR], 1.42 [95% CI, 0.79 to 2.56]; = .24). Seven patients (11%) experienced grade 3 treatment-related adverse events (no grade 4 or 5), 2 of 33 (6%) with SABR and 5 of 30 (17%) with SABR MDT/Ra223. Patients with high-risk (HiRi) pathogenic mutations in , , , or had worse PFS (HR, 5.95 [95% CI, 1.83 to 19.3]; = .003). Greater T-cell receptor (TCR) unique productive rearrangements were prognostic for improved PFS independent of the treatment arm (aHR, 0.45 [95% CI, 0.21 to 0.96]; = .04).
CONCLUSION
Adding Ra223 to SABR MDT in BM omCSPC does not delay progression of disease. We provide evidence for an HiRi mutational signature and TCR repertoire as prognostic biomarkers in omCSPC treated with SABR MDT, highlighting the importance of collecting biological correlates in RCTs for omCSPC.
目的
随机临床试验（RCT）表明，对于寡转移去势敏感性前列腺癌（omCSPC），在不进行雄激素剥夺治疗的情况下，转移导向治疗（MDT）可带来无进展生存期（PFS）获益。大多数骨转移（BM）omCSPC患者在MDT后会出现额外的骨病复发。我们推测，靶向骨转移的α发射体二氯化镭-223（Ra223）可靶向亚临床骨病并延缓疾病进展。
方法
这是一项由研究者发起的多中心、开放标签的II期RCT。符合条件的复发性omCSPC男性患者，如有≥一处骨转移（传统影像学检查≤三处和/或分子影像学检查≤五处），被随机分配（1:1）至单纯立体定向消融放疗（SABR）MDT组或SABR MDT联合Ra223组（六个周期）。主要终点为综合PFS。
结果
从2019年8月9日至2023年3月2日，64例患者被随机分配，33例至SABR MDT组，31例至SABR MDT/Ra223组，两组关键协变量均衡。大多数SABR MDT/Ra223组患者（87%）接受了六个周期的Ra223治疗。SABR MDT组的中位PFS为11.8个月，SABR MDT/Ra223组为10.5个月（调整后风险比[aHR]为1.42[95%CI，0.79至2.56]；P = 0.24）。7例患者（11%）出现3级治疗相关不良事件（无4级或5级），SABR组33例中有2例（6%），SABR MDT/Ra223组30例中有5例（17%）。在BRCA1、BRCA2、ATM或CHEK2中存在高风险（HiRi）致病突变的患者PFS较差（HR为5.95[95%CI，1.83至19.3]；P = 0.003）。更高的T细胞受体（TCR）独特有效重排可预测PFS改善，且与治疗组无关（aHR为0.45[95%CI，0.21至0.96]；P = 0.04）。
结论
在BM omCSPC患者中，SABR MDT联合Ra223治疗并不能延缓疾病进展。我们提供了证据表明，HiRi突变特征和TCR库可作为接受SABR MDT治疗的omCSPC患者的预后生物标志物，突出了在omCSPC的RCT中收集生物学相关指标的重要性。
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