Background: [¹⁷⁷Lu]-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./nMethods: Patients with metastatic castration-resistant prostate cancer who received Lu-PSMA therapy were reviewed for this analysis. All patients with available baseline and interim [⁶⁸Ga]-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_max of all metastases), total tumor volume (PSMA-TV) and TLQ (quotients of tumor volume and SUV_mean 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./nResults: 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 vs. 15.6 months, p = 0.1). In the subgroup of patients with PSMA-TV response, mean SUV_max 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)./nConclusion: 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.

中文翻译：

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接受 Lu-PSMA 治疗的患者的总肿瘤体积减少和低 PSMA 表达

背景： [ ¹⁷⁷ Lu]-PSMA-617 (Lu-PSMA) 疗法是终末期前列腺癌患者的一种有前途的治疗选择。两个治疗周期后第一次再分期的早期治疗反应可能与高治疗效果和长总生存期 (OS) 相关。因此，本研究的目的是评估早期肿瘤体积缩小是否是 OS 的积极预测指标。为此，比较了治疗前（基线）和两个治疗周期（中间；即 12 周）后第一次再分期时的 PSMA PET。/n方法：接受 Lu-PSMA 治疗的转移性去势抵抗性前列腺癌患者被对此分析进行了审查。所有具有可用基线和中期的患者 [ ⁶⁸Ga]-PSMA-11 PET/CT 包括在该分析中 (n = 33)。基线和中期 PET 中的所有 PSMA 转移灶均被半自动分割。在基线和中间时间点对平均 PSMA 表达（所有转移灶的平均 SUV_最大值）、总肿瘤体积（PSMA-TV）和 TLQ（肿瘤体积的商和所有转移灶的SUV_{平均值之和）进行量化。}当出现下降 > 30% 时，假定 PSMA-TV 中的响应。所有患者均可获得 OS 和生化反应。/n结果：基线 PSMA-TV 是 OS 具有统计学意义的预测指标（HR = 1.618 95%CI：1.117 - 2.343，p = 0.011）。在整个队列中，PSMA-TV 的降低并不是 OS 的统计学显着阳性预测指标（HR = 0.829 95%CI：0.559 - 1.230，p = 0.352）。同样，PSMA-TV 反应患者与无 PSMA-TV 反应患者的生存时间没有统计学差异（13.2个月与15.6 个月，p = 0.1）。在有 PSMA-TV 反应的患者亚组中，平均 SUV _max是 OS 具有统计学意义的预测指标（按中位数二值化；HR = 0.15；95%CI：0.03 - 0.83；p < 0.05）。如果将基线时 PSMA 表达低的患者排除在分析之外，则 PSMA-TV 的降低成为单变量和多变量 Cox 回归中 OS 的阳性预测指标（HR = 0.290；95% CI：0.108 - 0.782；p = 0.015）。 /n结论：只有在排除低 PSMA 表达的患者时，PSMA-TV 降低才是 OS 的阳性预测指标。这可能表明低 PSMA 表达患者的 PSMA-PET 可能不适合评估 PSMA-TV 减少。未来研究 PSMA-TV 和低 PSMA 表达反应的相互作用是必要的。