177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study.

We aimed to assess whether the addition of neoadjuvant prostate-specific membrane antigen (PSMA)-targeting radioligand therapy to SBRT would improve outcomes.

我们旨在评估是否将前列腺特异性膜抗原（PSMA）靶向放射配体治疗作为新辅助治疗添加到SBRT中，能否改善治疗结果。

Methods

The LUNAR trial was a single-center, randomized, open-label, controlled phase II trial conducted at the University of California, Los Angeles.

LUNAR试验是一项在加州大学洛杉矶分校进行的单中心、随机、开放标签、对照的II期临床试验。

Eligible participants had orHSPC as determined by the presence of one to five lesions identified on PSMA positron emission tomography/computed tomography (PET/CT).

符合条件的参与者被确定为有或HSPC，这是通过在PSMA正电子发射断层扫描/计算机断层扫描（PET/CT）上识别出一到五个病变来确定的。

After stratifying by stage (N1/M1a v M1b) and lesion count (1 v 2-3 v 4-5), we randomly assigned patients 1:1 to receive SBRT to all lesions or two cycles of 177Lu-PNT2002 (6.8 GBq/cycle, 2 weeks apart) followed by SBRT to all lesions.

在按阶段（N1/M1a与M1b）和病灶数量（1个与2-3个与4-5个）分层后，我们按1:1的比例随机分配患者接受SBRT治疗所有病灶或接受两个周期的177Lu-PNT2002治疗（每个周期6.8 GBq，间隔2周），随后对所有病灶进行SBRT治疗。

The primary end point was progression-free survival(PFS), defined by PSMA PET/CT, salvage hormonal therapy, or death.

主要终点是无进展生存（PFS），通过PSMA PET/CT、挽救性激素治疗或死亡来定义。

PSMA PET/CT was acquired systematically at prostate-specific antigen progression and/or 12 months after SBRT.

PSMA PET/CT在前列腺特异性抗原进展和/或立体定向放疗后12个月时系统性获取。

All analyses were done in the intention-to-treatpopulation.

所有分析均在意向治疗人群中进行。

The study is registered with ClinicalTrials.gov (identifier: NCT05496959).

该研究已在ClinicalTrials.gov注册（注册号：NCT05496959）。

Results

From September 2, 2022, to November 9, 2023, 92 patients were randomly assigned (SBRT n = 47 and 177Lu + SBRT n = 45), with 87 evaluable patients (SBRT n = 42 and 177Lu + SBRT n = 45).

从2022年9月2日至2023年11月9日，共有92名患者被随机分配（SBRT组47人，177Lu + SBRT组45人），其中87名患者可进行评估（SBRT组42人，177Lu + SBRT组45人）。

At a median follow-up of 22 months, the addition of 177Lu to SBRT significantly improved PFS (17.6 months [95% CI 15 months to not reached] v 7.4 months [95% CI, 6.0 to 13.5 months]; hazard ratio, 0.37 [95% CI, 0.22 to 0.61], P < .0001).

在中位随访22个月时，177Lu联合SBRT显著改善了无进展生存期（PFS）（17.6个月 [95% 置信区间 15个月至未达到] 对比 7.4个月 [95% 置信区间, 6.0至13.5个月]；风险比，0.37 [95% 置信区间, 0.22至0.61]，P < .0001）。

The only grade 3 adverse events were lymphopenia (two patients [4.8%] in the SBRT group and three patients [6.7%] in the 177Lu + SBRT group).

唯一的3级不良事件是淋巴细胞减少症（SBRT组有两名患者[4.8%]，177Lu + SBRT组有三名患者[6.7%]）。

Prognostic biomarkers for PFS were identified.

鉴别出了影响无进展生存期（PFS）的预后生物标志物。

Conclusions

Compared with SBRT alone, the addition of 177Lu-PNT2002 to SBRT significantly improved PFS in patients with orHSPC without an attendant increase in toxicity.

与单纯立体定向放疗（SBRT）相比，加入177Lu-PNT2002到SBRT显著改善了有或无去势抵抗性前列腺癌（orHSPC）患者的PFS，且没有增加毒性。