TY - JOUR T1 - Neuroendocrine Differentiation and Response to PSMA-Targeted Radioligand Therapy in Advanced Metastatic Castration-Resistant Prostate Cancer: A Single-Center Retrospective Study JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1602 LP - 1606 DO - 10.2967/jnumed.120.241588 VL - 61 IS - 11 AU - Thorsten Derlin AU - Rudolf A. Werner AU - Marcel Lafos AU - Christoph Henkenberens AU - Christoph A.J. von Klot AU - Jan M. Sommerlath Sohns AU - Tobias L. Ross AU - Frank M. Bengel Y1 - 2020/11/01 UR - http://jnm.snmjournals.org/content/61/11/1602.abstract N2 - Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer. We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of prostate-specific membrane antigen (PSMA)–targeted radioligand therapy (RLT). Methods: Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing 177Lu-PSMA-617 RLT. The primary endpoint was a prostate-specific antigen response in relation to baseline neuroendocrine marker profiles. An additional endpoint was progression-free survival. Tumor uptake on posttherapeutic scans, a known predictive marker for response, was used as a control variable. Results: Neuroendocrine biomarker profiles were abnormal in most patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression (P ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response (P = 0.0030) and reduced risk of early progression (P = 0.0111). Conclusion: Neuroendocrine marker profiles do not predict an adverse outcome from RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving a tumor response. ER -