¹⁷⁷Lu-PSMA-617 (LuPSMA) is a newly established treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), but survival outcomes vary widely, and predictors of treatment responses are needed. This study investigated the role of total tumor volumes (TTVs) and new lesions (NLs) determined by LuPSMA SPECT/CT in early cycles to predict subsequent outcomes in a real-world practice setting. Methods: Between June and December 2022, consecutive patients with mCRPC who received at least 2 administrations of LuPSMA with SPECT/CT 24 h after treatment were retrospectively reviewed. We evaluated associations between TTVs and the appearance of NLs at cycles 2 and 3 with subsequent prostate-specific antigen (PSA) progression-free survival and overall survival (OS) using multivariate Cox regression. All analyses were adjusted for changes in PSA level relative to baseline. Results: Sixty-six mCRPC patients (median age, 74 y) received a median of 4 (interquartile range, 3–5) cycles of LuPSMA. Median follow-up starting at cycle 2 was 42 wk (interquartile range, 33–48 wk), with 24 of 66 patients deceased at the time of the analysis. Changes in TTV measured at the start of cycles 2 and 3 relative to baseline correlated significantly with corresponding changes in PSA level (r = 0.55 and 0.56), but absolute TTVs did not correlate significantly (r = 0.00 and 0.18). Patients with a higher absolute TTV at the start of cycle 2 had worse PSA progression-free survival and OS (hazard ratio [HR], 1.4 [95% CI, 1.1–1.8] and 2.1 [95% CI, 1.5–2.9]), with consistent results at the start of cycle 3 (HR, 2 [95% CI, 1.4–2.9] and 2 [95% CI, 1.2–3.2]). NLs were identified in 13 of 66 and 11 of 51 patients at the start of cycles 2 and 3. NLs at the start of cycle 2 were associated with worse OS (HR, 5.8 [95% CI, 1.9–17.5]), with consistent results at the start of cycle 3 (HR, 4.9 [95% CI, 1.3–18.6]). In multivariate analysis, a higher TTV and the appearance of NLs at the start of cycles 2 and 3 were independently associated with poorer OS. Conclusion: Higher TTVs and NLs on LuPSMA SPECT/CT at the start of cycles 2 and 3 were independently associated with higher risk of death. These measures provided prognostic information independent of changes in PSA. Development of prognostic and predictive models including TTV, NLs, and PSA changes is warranted.

¹⁷⁷ 元Lu-PSMA-617 （LuPSMA） 是一种针对转移性去势抵抗性前列腺癌 （mCRPC） 患者的新疗法，但生存结果差异很大，需要治疗反应的预测因子。本研究调查了 LuPSMA SPECT/CT 确定的总肿瘤体积 （TTV） 和新病灶 （NLs） 在早期周期中的作用，以预测真实世界实践环境中的后续结果。方法：回顾性回顾性分析了 2022 年 6 月至 2022 年 12 月期间在治疗后 24 小时接受至少 2 次 LuPSMA 联合 SPECT/CT 给药的连续 mCRPC 患者。我们使用多变量 Cox 回归评估了 TTV 与第 2 周期和第 3 周期 NLs 出现与随后的前列腺特异性抗原 （PSA） 无进展生存期和总生存期 （OS） 之间的关联。所有分析均针对 PSA 水平相对于基线的变化进行了调整。结果：66 例 mCRPC 患者 （中位年龄，74 岁） 接受中位 4 （四分位距，3-5） 个周期的 LuPSMA。从第 2 周期开始的中位随访为 42 周（四分位距，33-48 周），分析时 66 名患者中有 24 名死亡。在第 2 周期和第 3 周期开始时测量的 TTV 相对于基线的变化与 PSA 水平的相应变化显着相关 （r = 0.55 和 0.56），但绝对 TTV 不显著相关 （r = 0.00 和 0.18）。第 2 周期开始时绝对 TTV 较高的患者 PSA 无进展生存期和 OS 较差（风险比 [HR]，1.4 [95% CI，1.1-1.8] 和 2.1 [95% CI，1.5-2.9]），第 3 周期开始时的结果一致（HR，2 [95% CI，1.4-2.9] 和 2 [95% CI，1.2-3.2]）。在第 2 周期和第 3 周期开始时，66 名患者中有 13 名和 51 名患者中有 11 名被发现 NLs。 第 2 周期开始时的 NLs 与较差的 OS 相关 （HR，5.8 [95% CI，1.9-17.5]），第 3 周期开始时的结果一致 （HR，4.9 [95% CI，1.3-18.6]）。在多变量分析中，较高的 TTV 和第 2 周期和第 3 周期开始时 NLs 的出现与较差的 OS 独立相关。结论：第 2 周期和第 3 周期开始时 LuPSMA SPECT/CT 上较高的 TTV 和 NLs 与较高的死亡风险独立相关。这些措施提供的预后信息独立于 PSA 的变化。需要开发包括 TTV、NL 和 PSA 变化在内的预后和预测模型。