Rationale: PSMA-PET-CT enables measuring molecular expression of prostate-specific membrane antigen (PSMA) in vivo, which is the target molecule of ¹⁷⁷Lu-PSMA-617 (Lu-PSMA) therapy. However, the correlation of PSMA expression and overall survival (OS) in patients treated with Lu-PSMA therapy is currently unclear; especially with regard to coexistence of high and low PSMA expressing metastases. To this end, this retrospective single arm study elucidates the correlation of PSMA expression and overall survival in patients treated with Lu-PSMA therapy. Additionally, PET based criteria to define low PSMA expression were explored./nMethods: Eighty-five patients referred to Lu-PSMA therapy were included in the analysis. Pretherapeutic ⁶⁸Ga-PSMA-PET-CT scans were available for all patients. SUV_max of the highest PSMA expressing metastasis (PSMA_max), SUV_max of the lowest PSMA expressing metastasis (PSMA_min), and average SUV_max of all metastases (PSMA_average) amongst other PET parameters were measured for each patient. A log-rank cutoff-finder was used to determine low (lowPSMA_average) and high (highPSMA_average) average PSMA expression as well as low (lowPSMA_min) and high (highPSMA_min) minimal PSMA expression./nResults: PSMA_average was a significant prognosticator of overall survival in contrast to PSMA_max (HR: 0.959; p = 0.047 vs. HR: 0.992; p = 0.231). Optimal log rank cut-offs were: PSMA_average = 14.3; PSMA_min = 10.2. Patients with low average PSMA expression (lowPSMA_average) had significantly shorter survival compared to those with high average expression (highPSMA_average) (5.3 vs. 15.1 months; p < 0.001; HR: 3.738, 95%CI = 1.953-7.154; p < 0.001). Patients with low PSMA expressing metastases (lowPSMA_min) had shorter survival compared to those without a low PSMA expressing metastasis (highPSMA_min) (p = 0.003; 7.9 months vs. 21.3; HR: 4.303, 95%CI = 1.521-12.178; p = 0.006). Patients that were classified as highPSMA_average but with lowPSMA_min had an intermediate overall survival (11.4 months; longer compared to lowPSMA_average, 5.3 months, p = 0.002; but shorter compared to highPSMA_min, 21.3 months, p = 0.02)./nConclusion: Low average PSMA expression is a negative prognosticator of overall survival. Absence of low PSMA expressing metastases is associated with best overall survival and the maximum PSMA expression seems not suited to prognosticate overall survival. Low PSMA expression might therefore be a negative prognosticator for the outcome of patients treated with Lu-PSMA therapy. Future studies are warranted to elucidate the degree of low PSMA expression tolerable for Lu-PSMA therapy.

中文翻译：

---

接受177Lu-PSMA-617放射配体疗法的晚期前列腺癌患者PSMA表达和结局分析。

原理： PSMA-PET-CT能够在体内测量前列腺特异性膜抗原（PSMA）的分子表达，这是¹⁷⁷ Lu-PSMA-617（Lu-PSMA）治疗的目标分子。然而，目前尚不清楚接受Lu-PSMA治疗的患者中PSMA表达与总生存期（OS）的相关性。特别是关于高和低PSMA表达转移的共存。为此，这项回顾性单臂研究阐明了接受Lu-PSMA治疗的患者中PSMA表达与总生存率的相关性。此外，还探讨了定义低PSMA表达的基于PET的标准。/n方法：分析中包括了85名接受Lu-PSMA治疗的患者。治疗前⁶⁸Ga-PSMA-PET-CT扫描可用于所有患者。SUV_最大值的最高表达PSMA的转移（PSMA_最大值），SUV_最大最低PSMA表达转移（PSMA的_分钟），和平均SUV_最大值所有转移（PSMA的_平均）除其他参数PET针对每个患者进行测量。使用对数秩截止器确定平均PSMA的低（lowPSMA_平均数）和高（highPSMA_平均数）高以及最小PSMA最低（lowPSMA _min）和高（highPSMA _min）最低./n结果： PSMA_平均与PSMA _max（HR：0.959; p = 0.047 vs. HR：0.992; p = 0.231）相比，它是总体生存率的重要预测指标。最佳对数秩截止值为：PSMA_平均= 14.3；PSMA _min = 10.2。PSMA平均表达低（lowPSMA _average）的患者的生存期明显短于PSMA平均表达高（highPSMA_平均值）的患者（5.3 vs. 15.1个月； p <0.001； HR：3.738，95％CI = 1.953-7.154； p < 0.001）。患者低表达PSMA转移（lowPSMA_分钟相比那些没有低PSMA表达转移）具有更短的生存期（highPSMA_分钟）（p = 0.003； 7.9个月对21.3； HR：4.303，95％CI = 1.521-12.178； p = 0.006）。被归类为高PSMA_平均但低PSMA _min的患者具有中等总体生存期（11.4个月;相比于低PSMA_平均5.3个月更长，p = 0.002;但与高PSMA _min的21.3个月相比较短，p = 0.02）/ n结论：PSMA平均表达低是总生存率的阴性指标。缺乏低表达PSMA的转移与最佳总生存期有关，最大PSMA表达似乎不适合预测总生存期。因此，PSMA低表达可能是接受Lu-PSMA治疗的患者预后的阴性指标。有必要进行进一步的研究来阐明Lu-PSMA治疗可耐受的PSMA低表达程度。