Department of Nuclear Medicine, University Hospital Essen, Essen, Germany.
Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.
Theranostics. 2021 Jul 13;11(17):8143-8151. doi: 10.7150/thno.60222. eCollection 2021.
[Lu]-PSMA-617 (Lu-PSMA) therapy is a promising therapeutic option for end-stage prostate cancer patients. Early treatment response at the first restaging after two therapy cycles might correlate with high treatment efficacy and long overall survival (OS). Therefore, the aim of this study was to evaluate whether early reduction in tumor volume is a positive prognosticator for OS. To this end, PSMA PET prior to therapy (baseline) and at first restaging after two therapy cycles (interim; i.e., 12 weeks) were compared. Patients with metastatic castration-resistant prostate cancer who received Lu-PSMA therapy were reviewed for this analysis. All patients with available baseline and interim [Ga]-PSMA-11 PET/CT were included in this analysis (n = 33). All PSMA avid metastases in baseline and interim PETs were semi-automatically segmented. The average PSMA expression (mean SUV of all metastases), total tumor volume (PSMA-TV) and TLQ (quotients of tumor volume and SUV summed over all metastases) were quantified at baseline and interim timepoints. Response in PSMA-TV was assumed when a decline > 30% was present. OS and biochemical response were available for all patients. Baseline PSMA-TV was a statistically significant prognosticator of OS (HR = 1.618 95%CI: 1.117 - 2.343, p = 0.011). Reduction in PSMA-TV was not a statistically significant positive prognosticator of OS in the total cohort (HR = 0.829 95%CI: 0.559 - 1.230, p = 0.352). Likewise, there was no statistical difference in survival time comparing patients with PSMA-TV response to those without (13.2 15.6 months, p = 0.1). In the subgroup of patients with PSMA-TV response, mean SUV was a statistically significant prognosticator of OS (binarized by median; HR = 0.15; 95%CI: 0.03 - 0.83; p < 0.05). If patients with low PSMA expression at baseline were excluded from the analysis, reduction in PSMA-TV became a positive prognosticator of OS in uni- and multivariable Cox regression (HR = 0.290; 95%CI: 0.108 - 0.782; p = 0.015). PSMA-TV reduction was a positive prognosticator of OS only if patients with low PSMA expression were excluded. This might indicate that the PSMA-PETs of patients with low PSMA expression may not be suited for assessing PSMA-TV reduction. Future studies investigating the interplay of PSMA-TV and low PSMA expression response are warranted.
[Lu]-PSMA-617（Lu-PSMA）治疗是晚期前列腺癌患者的一种有前途的治疗选择。在两个治疗周期后的第一次重新分期时早期治疗反应可能与高治疗效果和长期总生存期（OS）相关。因此，本研究的目的是评估肿瘤体积的早期减少是否是 OS 的阳性预后指标。为此，比较了治疗前的 PSMA PET（基线）和两个治疗周期后的第一次重新分期时的 PSMA PET（中期；即 12 周）。对接受 Lu-PSMA 治疗的转移性去势抵抗性前列腺癌患者进行了这项分析。所有具有基线和中期 [Ga]-PSMA-11 PET/CT 检查结果的患者均纳入本分析（n = 33）。所有基线和中期 PET 中的 PSMA 阳性转移灶均采用半自动方法进行分割。在基线和中期时间点量化 PSMA 表达（所有转移灶的平均 SUV）、总肿瘤体积（PSMA-TV）和 TLQ（肿瘤体积和 SUV 总和在所有转移灶中的比值）。当下降> 30%时，假设 PSMA-TV 出现反应。所有患者的 OS 和生化反应均可用。基线 PSMA-TV 是 OS 的统计学显著预后指标（HR = 1.618 95%CI：1.117-2.343，p = 0.011）。在整个队列中，PSMA-TV 的减少不是 OS 的统计学显著阳性预后指标（HR = 0.829 95%CI：0.559-1.230，p = 0.352）。同样，与没有 PSMA-TV 反应的患者相比，PSMA-TV 反应患者的生存时间没有统计学差异（13.2 15.6 个月，p = 0.1）。在 PSMA-TV 反应患者亚组中，平均 SUV 是 OS 的统计学显著预后指标（中位数二分类；HR = 0.15；95%CI：0.03-0.83；p < 0.05）。如果从分析中排除基线时 PSMA 表达较低的患者，PSMA-TV 的减少在单变量和多变量 Cox 回归中成为 OS 的阳性预后指标（HR = 0.290；95%CI：0.108-0.782；p = 0.015）。仅当排除 PSMA 表达较低的患者时，PSMA-TV 的减少才是 OS 的阳性预后指标。这可能表明 PSMA 表达较低的患者的 PSMA-PET 可能不适合评估 PSMA-TV 的减少。需要进一步的研究来探讨 PSMA-TV 和 PSMA 低表达反应之间的相互作用。
