Widjaja Liam, Werner Rudolf A, Ross Tobias L, Bengel Frank M, Derlin Thorsten
Department of Nuclear Medicine, Hannover Medical School, 30625 Hannover, Germany.
Cancers (Basel). 2021 Jun 11;13(12):2938. doi: 10.3390/cancers13122938.
Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with Ga-PSMA-11 prior to two cycles of Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUV), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUV (r = -0.49; < 0.001), but not with PSMA-TV (r = 0.02; = 0.89) or TL-PSMA (r = -0.15; = 0.22). A cut-off of 19.8 for SUV and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age ( < 0.001). Multivariate analysis identified SUV (HR, 7.94, = 0.001) and age (HR, 8.05, = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.
镥-前列腺特异性膜抗原（PSMA）放射性配体疗法（RLT）是转移性去势抵抗性前列腺癌（mCRPC）患者一种有前景的治疗选择。我们旨在确定治疗前PSMA配体正电子发射断层扫描（PET）的预测价值，并确定在两个周期的RLT后早期生化反应的既定临床参数。总共纳入了71例在接受两个周期的镥-PSMA-617 RLT之前接受过Ga-PSMA-11 PET/计算机断层扫描（CT）的mCRPC患者。对治疗前PET/CT上的恶性病变进行手动分割，并计算平均最大PSMA表达（最大标准化摄取值，SUV）、全身PSMA肿瘤体积（TV）和全身总病变（TL）-PSMA。然后，我们测试了这些参数相对于既定临床参数在两个周期的RLT后对早期生化反应（根据PCWG2定义为前列腺特异性抗原（PSA）降低≥50%）的预测性能。在71例患者中有34例观察到早期PSA反应。两个周期的RLT后PSA变化与治疗前SUV相关（r = -0.49；P < 0.001），但与PSMA-TV（r = 0.02；P = 0.89）或TL-PSMA（r = -0.15；P = 0.22）无关。通过受试者工作特征曲线确定SUV的临界值为19.8，年龄的临界值为75.5岁，结果显示PSMA表达极低与高以及年龄低与高的患者在早期生化反应方面存在显著差异（P < 0.001）。多变量分析确定SUV（风险比，7.94，P = 0.001）和年龄（风险比，8.05，P = 0.002）是治疗过程早期PSA反应的独立预测因素。因此，计划接受RLT治疗的患者年龄较大且PSMA表达较高可识别出早期生化反应患者。本研究为进一步探索在选定患者中进行PET引导的治疗强化的前瞻性研究提供了理论依据。
