背景 镥 177 [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) 是一种前列腺特异性膜抗原 (PSMA) 靶向放射配体疗法，用于治疗转移性去势抵抗性前列腺癌 (mCRPC)。定量 PSMA PET/CT 分析可以提供有关 177Lu-PSMA-617 治疗益处的信息。目的 探讨 VISION 试验中定量基线镓 68 [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT 参数与治疗反应和结果之间的关联。材料和方法 这是 VISION 试验的探索性二次分析。符合条件的参与者（2018 年 6 月至 2019 年 10 月）以 2:1 的比例随机接受 177Lu-PSMA-617 治疗（每 6 周 7.4 GBq，最多六个周期）加标准护理 (SOC) 或仅接受 SOC。从五个解剖区域和全身提取基线 68Ga-PSMA-11 PET 参数，包括平均和最大标准化摄取值（SUVmean 和 SUVmax）、PSMA 阳性肿瘤体积和肿瘤负荷。使用单变量和多变量分析（治疗作为唯一的其他协变量）研究定量 PET 参数与放射学无进展生存期 (rPFS)、总生存期 (OS)、客观缓解率和前列腺特异性抗原反应的关联。根据 SUV 均值四分位数对亚组的结果进行评估。结果 826 名参与者的定量 PET 参数在研究组之间得到了很好的平衡。全身肿瘤 SUV 平均值中位数为 7.6（IQR，5.8-9.9）。全身肿瘤 SUVmean 是 177Lu-PSMA-617 疗效的最佳预测因子，所有结果的风险比 (HR) 范围为 0.86-1.43（所有 P < .001）。全身肿瘤 SUV 平均增加 1 个单位，rPFS 事件和死亡风险分别降低 12% 和 10%。与仅使用 SOC 相比，177Lu-PSMA-617 加 SOC 延长了所有 SUV 均值四分位数的 rPFS 和 OS，但在接受 177Lu-PSMA-617 的参与者中没有可识别的最佳值。较高的基线 PSMA 阳性肿瘤体积和肿瘤负荷与较差的 rPFS（HR 范围分别为 1.44-1.53​​ [P < .05] 和 1.02-1.03 [P < .001]）和 OS（HR 范围，1.36-2.12）相关分别为 [P < .006] 和 1.04 [P < .001]）。结论 基线 68Ga-PSMA-11 PET/CT 全身肿瘤 SUV 平均值是 VISION 试验参与者中 177Lu-PSMA-617 疗效的最佳预测因子。在全身肿瘤 SUV 均值较高的参与者中，177Lu-PSMA-617 加 SOC 的 rPFS 和 OS 改善更大，有证据表明所有 SUV 均值水平均受益。 ClinicalTrials.gov 标识符：NCT03511664 根据 CC BY 4.0 许可证发布。本文提供了补充材料。

Background Lutetium 177 [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Quantitative PSMA PET/CT analysis could provide information on 177Lu-PSMA-617 treatment benefits. Purpose To explore the association between quantitative baseline gallium 68 [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT parameters and treatment response and outcomes in the VISION trial. Materials and Methods This was an exploratory secondary analysis of the VISION trial. Eligible participants were randomized (June 2018 to October 2019) in a 2:1 ratio to 177Lu-PSMA-617 therapy (7.4 GBq every 6 weeks for up to six cycles) plus standard of care (SOC) or to SOC only. Baseline 68Ga-PSMA-11 PET parameters, including the mean and maximum standardized uptake value (SUVmean and SUVmax), PSMA-positive tumor volume, and tumor load, were extracted from five anatomic regions and the whole body. Associations of quantitative PET parameters with radiographic progression-free survival (rPFS), overall survival (OS), objective response rate, and prostate-specific antigen response were investigated using univariable and multivariable analyses (with treatment as the only other covariate). Outcomes were assessed in subgroups based on SUVmean quartiles. Results Quantitative PET parameters were well balanced between study arms for the 826 participants included. The median whole-body tumor SUVmean was 7.6 (IQR, 5.8-9.9). Whole-body tumor SUVmean was the best predictor of 177Lu-PSMA-617 efficacy, with a hazard ratio (HR) range of 0.86-1.43 for all outcomes (all P < .001). A 1-unit whole-body tumor SUVmean increase was associated with a 12% and 10% decrease in risk of an rPFS event and death, respectively. 177Lu-PSMA-617 plus SOC prolonged rPFS and OS in all SUVmean quartiles versus SOC only, with no identifiable optimum among participants receiving 177Lu-PSMA-617. Higher baseline PSMA-positive tumor volume and tumor load were associated with worse rPFS (HR range, 1.44-1.53 [P < .05] and 1.02-1.03 [P < .001], respectively) and OS (HR range, 1.36-2.12 [P < .006] and 1.04 [P < .001], respectively). Conclusion Baseline 68Ga-PSMA-11 PET/CT whole-body tumor SUVmean was the best predictor of 177Lu-PSMA-617 efficacy in participants in the VISION trial. Improvements in rPFS and OS with 177Lu-PSMA-617 plus SOC were greater among participants with higher whole-body tumor SUVmean, with evidence for benefit at all SUVmean levels. ClinicalTrials.gov identifier: NCT03511664 Published under a CC BY 4.0 license. Supplemental material is available for this article.