Prediction of Resistance to 177 Lu-PSMA Therapy by Assessment of Baseline Circulating Tumor DNA Biomarkers

• Published in: Journal of Nuclear Medicine Vol. 64; no. 11; pp. 1721 - 1725
• Main Authors: Sartor, Oliver, Ledet, Elisa, Huang, Minqi, Schwartz, Jennifer, Lieberman, Alex, Lewis, Brian, Layton, Jodi, Barata, Pedro, Jang, Albert, Hawkins, Madeline, Pocha, Olivia, Lanka, Sree, Harris, Kendra
• Format: Journal Article
• Language: English
• Published: United States 01.11.2023
• Subjects: Circulating Tumor DNA - genetics; Dipeptides - adverse effects; Heterocyclic Compounds, 1-Ring - adverse effects; Humans; Lutetium - therapeutic use; Male; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant - genetics; Prostatic Neoplasms, Castration-Resistant - radiotherapy; Radiopharmaceuticals - adverse effects; Retrospective Studies; Treatment Outcome; radiopharmaceuticals; PSMA; prostate cancer; Lu-177; biomarkers; ctDNA
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.123.266167

Lu-PSMA-617 and Lu-PSMA I&T (collectively termed Lu-PSMA) are currently being used for the treatment of selected metastatic castration-resistant prostate cancer (mCRPC) patients with PSMA PET-positive disease, but biomarkers for these agents remain incompletely understood. Pretreatment circulating tumor DNA (ctDNA) samples were collected from 44 mCRPC patients receiving Lu-PSMA treatment. Prostate-specific antigen responders and nonresponders were assessed relative to the ctDNA findings at baseline. The ctDNA findings indicated that nonresponders were more likely to have gene amplifications than were responders (75% vs. 39.2%, = 0.03). In particular, amplifications in (25% vs. 0%, = 0.01) and (31.2% vs. 0%, = 0.001) were more likely to be present in nonresponders. mutations were more likely to be present in nonresponders (25% vs. 3.6%, = 0.05). Our analyses indicate that ctDNA assays may contain specific biomarkers predictive of response or resistance for Lu-PSMA-treated mCRPC patients. Additional confirmatory studies are required before clinicians can use these findings to make personalized treatment decisions.