Introduction

In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy.

Materials and methods

In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan–Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle).

Results

Sixty-one out of one hundred seventy-six (34.7%) patients showed a sustained increase and 86/176 (48.8%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95% CI 0.22–0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95% CI 0.30–0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95% CI 0.78–2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95% CI 0.38–4.05; P = 0.68).

Conclusion

Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression.

中文翻译：

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放射配体治疗下 PSA 波动的 mCRPC 患者与 PSA 持续下降的患者相比具有相当的生存获益

介绍

在计划接受前列腺特异性膜抗原 (PSMA) 靶向放射配体治疗 (RLT) 的转移性去势抵抗性前列腺癌 (mCRPC) 患者中，根据前列腺特异性抗原 (PSA) 水平的重复测量来评估生化反应。我们的目的是确定在治疗期间经历 PSA 持续升高、降低或波动的患者的总生存期 (OS)。

材料和方法

在这项双中心研究中，我们纳入了 176 名接受 PSMA 定向 RLT 治疗的 mCRPC 患者。PSA 水平是在第一次 RLT 之前和随后周期的入院日使用血液样本确定的。我们计算了与基线相比 PSA 水平的相对变化。Kaplan-Meier 曲线和对数秩检验用于比较不同亚组的 OS，包括 PSA 持续增加、减少或波动（定义为初始减少后的变化或第一个周期后增加）的患者。

结果

一百七十六名 (34.7%) 患者中有六十一名患者的 PSA 水平持续升高，86/176 (48.8%) 名患者的 PSA 水平持续下降。在剩余的 29/176 (16.5%) 中观察到 PSA 波动。在这个亚组中，22/29 经历了最初的 PSA 下降然后增加（7/29，最初增加然后减少）。与 PSA 水平持续升高的患者相比，PSA 水平持续降低的患者的中位 OS 明显更长（19 个月与 8 个月；HR 0.35，95% CI 0.22–0.56；P  < 0.001）。与 PSA 水平持续升高的患者相比，PSA 波动患者的中位 OS 显着延长（18 个月与 8 个月；HR 0.49，95% CI 0.30–0.80；P < 0.01)，但与 PSA 持续下降的男性相比无显着差异（18 个月与 19 个月；HR 1.4，95% CI 0.78–2.49；P  = 0.20）。此外，在经历 PSA 波动的男性中，中位 OS 在肿瘤标志物水平初始降低或初始升高的患者之间没有显着差异（16 个月与 18 个月；HR 1.2，95% CI 0.38–4.05；P  = 0.68）。

结论

在接受 RLT 的大多数患者中，PSA 水平的初始升高或降低是持续的。持续的 PSA 降低与延长的生存期有关，并且接受治疗的 PSA 波动的男性经历了相当的生存益处。因此，RLT 下的短暂肿瘤标志物振荡不应导致治疗中断，尤其是在没有放射学进展的情况下。