Rosar Florian, Hau Fabian, Bartholomä Mark, Maus Stephan, Stemler Tobias, Linxweiler Johannes, Ezziddin Samer, Khreish Fadi
Department of Nuclear Medicine, Saarland University - Medical Center, Homburg, Germany.
Department of Urology, Saarland University - Medical Center, Homburg, Germany.
Theranostics. 2021 Feb 16;11(9):4050-4060. doi: 10.7150/thno.56211. eCollection 2021.
Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted Lu radioligand therapy in metastatic castration-resistant prostate carcinoma (mCRPC), some patients do not respond and other patients with initially good response develop resistance to this treatment. In this study, we investigated molecular imaging and biochemical responses after a single cycle of [Ac]Ac-PSMA-617/[Lu]Lu-PSMA-617 tandem therapy in patients who had progressed on [Lu]Lu-PSMA-617 monotherapy. Seventeen patients with mCRPC were included in a retrospective, monocenter study. Molecular imaging-based response was assessed by modified PERCIST criteria using the whole-body total lesion PSMA (TLP) and molecular tumour volume (MTV) derived from [Ga]Ga-PSMA-11 PET/CT. Biochemical response was evaluated according to PCWG3 criteria using the prostate-specific antigen (PSA) serum value. Concordance and correlation statistics as well as survival analyses were performed. Based on the molecular imaging-based response assessment, 5 (29.4%) patients showed partial remission and 7 (41.2%) had stable disease. The remaining 5 (29.4%) patients had further progression, four with an increase in TLP/MTV of >30% and one with stable TLP/MTV but appearance of new metastases. Based on the biochemical response assessment, 5 (29.4%), 8 (47.1%), and 4 (23.5%) patients showed partial remission, stable disease, and progressive disease, respectively. A comparison of the response assessment methods showed a concordance of 100% (17/17) between TLP and MTV and 70.6% (12/17) between TLP/MTV and PSA. Patients with partial remission, independently assessed by each method, had better overall survival (OS) than patients with either stable or progressive disease. The difference in OS was statistically significant for the molecular imaging response assessment (median OS not reached vs. 8.3 m, = 0.044), but not for the biochemical response assessment (median OS 18.1 m vs. 9.4 m, = 0.468). Based on both assessment methods, [Ac]Ac-PSMA-617/[Lu]Lu-PSMA-617 tandem therapy is an effective treatment for the highly challenging cohort of patients with mCRPC who have progressed on [Lu]Lu-PSMA-617 monotherapy. Molecular imaging response and biochemical PSA response were mostly concordant, though a considerable number of cases (29.4%) were discordant. Molecular imaging response reflecting the change in total viable tumour burden appears to be superior to PSA change in estimating survival outcome after tandem therapy.
尽管前列腺特异性膜抗原（PSMA）靶向的镥放射性配体疗法在转移性去势抵抗性前列腺癌（mCRPC）中取得了令人鼓舞的结果，但一些患者没有反应，而其他最初反应良好的患者则对这种治疗产生了耐药性。在本研究中，我们调查了在[镥]Lu-PSMA-617单药治疗中病情进展的患者接受单周期[锕]Ac-PSMA-617/[镥]Lu-PSMA-617串联治疗后的分子影像学和生化反应。17例mCRPC患者纳入一项回顾性单中心研究。基于分子影像学的反应通过改良的PERCIST标准进行评估，使用全身总病灶PSMA（TLP）和源自[镓]Ga-PSMA-11 PET/CT的分子肿瘤体积（MTV）。生化反应根据PCWG3标准使用前列腺特异性抗原（PSA）血清值进行评估。进行了一致性和相关性统计以及生存分析。基于分子影像学的反应评估，5例（29.4%）患者显示部分缓解，7例（41.2%）病情稳定。其余5例（29.4%）患者病情进一步进展，4例TLP/MTV增加>30%，1例TLP/MTV稳定但出现新转移灶。基于生化反应评估，5例（29.4%）、8例（47.1%）和4例（23.5%）患者分别显示部分缓解、病情稳定和疾病进展。反应评估方法的比较显示，TLP和MTV之间的一致性为100%（17/17），TLP/MTV和PSA之间的一致性为70.6%（12/17）。经每种方法独立评估为部分缓解的患者总生存期（OS）优于病情稳定或进展的患者。分子影像学反应评估的OS差异具有统计学意义（中位OS未达到 vs. 8.3个月，P = 0.044），但生化反应评估的OS差异无统计学意义（中位OS 18.1个月 vs. 9.4个月，P = 0.468）。基于两种评估方法，[锕]Ac-PSMA-617/[镥]Lu-PSMA-617串联疗法是治疗在[镥]Lu-PSMA-617单药治疗中病情进展的极具挑战性的mCRPC患者队列的有效疗法。分子影像学反应和生化PSA反应大多一致，尽管有相当数量的病例（29.4%）不一致。反映总存活肿瘤负荷变化的分子影像学反应在估计串联治疗后的生存结果方面似乎优于PSA变化。
