Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital, Sydney, New South Wales, Australia.
St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
J Nucl Med. 2023 Mar;64(3):410-415. doi: 10.2967/jnumed.122.264677. Epub 2022 Sep 8.
Lu-PSMA is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC). Our ability to assess response rates and adjust treatment may be improved using predictive tools. This study aimed to evaluate change in Lu-PSMA SPECT quantitative parameters to monitor treatment response. One hundred twenty-seven men with progressive mCRPC previously treated with androgen-signaling inhibition (99%) and chemotherapy (71%) received a median of 3 (interquartile range [IQR], 2-5) 8-GBq (IQR, 8-8.5 GBq) doses of Lu-PSMA-I&T. Imaging included Ga-PSMA-11 PET/CT (SUV > 15 at a single site and > 10 at all sites > 2 cm), diagnostic CT, and Lu SPECT/CT from vertex to mid thigh (24 h after treatment). Lu SPECT/CT quantitative analysis was undertaken at cycles 1 (baseline) and 2 (week 6) of treatment. Clinical and biochemical results were assessed to evaluate prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival (OS). A PSA reduction of more than 50% was seen in 58% (74/127). The median PSA PFS was 6.1 mo (95% CI, 5.5-6.7), and OS was 16.8 mo (95% CI, 13.5-20.1). At the time of analysis, 41% (52/127) were deceased. At baseline and week 6, 76% (96/127) had analyzable serial Lu SPECT/CT imaging. SPECT total tumor volume (TTV) was reduced between baseline and week 6 in 74% (71/96; median, -193; IQR, -486 to -41). Any increase in SPECT TTV between baseline and week 6 was associated with significantly shorter PSA PFS (hazard ratio, 2.5; 95% CI, 1.5-4.2; = 0.0008) but not OS. Median PSA PFS in those with an increase in SPECT TTV was 3.7 mo (95% CI, 2.8-6.8), compared with 6.7 mo (95% CI, 5.8-10.6) in those with no increase in SPECT TTV. An increase in SPECT TTV greater than 20% was also associated with PSA PFS (hazard ratio, 1.9; 95% CI, 1.2-3.0; = 0.008) but less significantly than any change in SPECT TTV. There was a significant difference in PSA PFS between patients with both increased PSA and SPECT TTV and patients with reduced SPECT TTV and PSA (median, 2.8 vs. 9.0 mo; < 0.0001). Increasing PSMA SPECT TTV on quantitative Lu SPECT/CT predicts short progression-free survival and may play a future role as an imaging response biomarker, identifying when to cease or intensify Lu-PSMA therapy.
Lu-PSMA 是转移性去势抵抗性前列腺癌（mCRPC）的有效治疗方法。我们使用预测工具评估反应率并调整治疗的能力可能会得到提高。本研究旨在评估 Lu-PSMA SPECT 定量参数的变化，以监测治疗反应。
127 名先前接受过雄激素信号抑制（99%）和化疗（71%）治疗的进展性 mCRPC 男性接受了中位数为 3（四分位距 [IQR]，2-5）的 8-GBq（IQR，8-8.5 GBq）剂量的 Lu-PSMA-I&T。成像包括 Ga-PSMA-11 PET/CT（单个部位 SUV > 15，所有部位 SUV > 10，且 > 2 cm）、诊断 CT 和 Lu SPECT/CT（从头顶到大腿中部，治疗后 24 小时）。在治疗的第 1 周期（基线）和第 2 周期（第 6 周）进行 Lu SPECT/CT 定量分析。评估临床和生化结果以评估前列腺特异性抗原（PSA）无进展生存期（PFS）和总生存期（OS）。
58%（74/127）的患者 PSA 降低超过 50%。中位 PSA PFS 为 6.1 个月（95%CI，5.5-6.7），OS 为 16.8 个月（95%CI，13.5-20.1）。在分析时，41%（52/127）的患者死亡。在基线和第 6 周，76%（96/127）有可分析的连续 Lu SPECT/CT 成像。Lu SPECT 总肿瘤体积（TTV）在基线和第 6 周之间减少了 74%（71/96；中位数，-193；IQR，-486 至-41）。基线和第 6 周之间 Lu SPECT TTV 的任何增加均与 PSA PFS 显著缩短相关（危险比，2.5；95%CI，1.5-4.2； = 0.0008），但与 OS 无关。Lu SPECT TTV 增加的患者中位 PSA PFS 为 3.7 个月（95%CI，2.8-6.8），而 Lu SPECT TTV 无增加的患者中位 PSA PFS 为 6.7 个月（95%CI，5.8-10.6）。Lu SPECT TTV 增加大于 20%也与 PSA PFS 相关（危险比，1.9；95%CI，1.2-3.0； = 0.008），但与 Lu SPECT TTV 的任何变化相比，其相关性较小。PSA 和 Lu SPECT TTV 均增加的患者与 Lu SPECT TTV 和 PSA 均减少的患者的 PSA PFS 存在显著差异（中位数，2.8 与 9.0 个月； < 0.0001）。
Lu SPECT 上 PSMA SPECT TTV 的增加预测无进展生存期较短，可能在未来作为影像学反应生物标志物发挥作用，识别何时停止或加强 Lu-PSMA 治疗。
