基于前列腺特异性膜抗原(PSMA)的放射性配体疗法(RLT)在多中心WARMTH(世界放射性药物和分子疗法协会)研究中显示,骨转移的存在是生存的负面预后因素。当前的多中心回顾性分析旨在评估RLT的反应率,根据骨受累程度,患者的总生存期(OS)和治疗的安全性。
这项研究包括进行性转移性去势抵抗性前列腺癌(mCRPC)患者,使用[177Lu]Lu-PSMA-617进行RLT,并随访至少6个月。在RLT之前,骨骼中的肿瘤负荷分类如下:少于6个病变,6-20个病灶,超过20个病灶和弥漫性受累。在第一个治疗周期后,使用前列腺特异性抗原(PSA)的变化评估反应率。从第一次治疗之日起计算总生存期。根据不良事件通用术语标准(CTCAE)对血液学不良事件进行分类,版本5.0。
总共319名男性被纳入分析。骨转移的程度和PSA反应没有显着相关。在73%的患者中观察到任何PSA下降;44%显示下降≥50%。不同亚组患者的中位OS为18个月(小于6个病灶),13个月(6-20个病灶),11个月(超过20个病灶)和8个月(弥漫性受累),分别(p<0.0001)。先前使用Ra-223治疗的患者在所有亚组中显示出更长的OS,尤其是在6-20个病变的亚组中(OS:16vs.12个月;p=0.038)以及弥漫性受累(OS:11vs.7个月;p=0.034)。OS的显着阴性预后指标是所有亚组中存在肝转移,而<6个骨病变的患者先前接受过化疗。贫血和血小板减少与骨转移的程度呈正相关:p分别<0.0001和0.005。没有患者出现高度白细胞减少症。
骨受累程度与RLT后的OS呈负相关;然而,与PSA缓解率无相关性。使用Ra-223的先前治疗可能对OS具有积极影响。超过20个骨病变的患者血液毒性较高;然而,这些患者中的大多数没有表现出相关的血液毒性.
Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy)
study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement.
The
study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia.
The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.