PT  - JOURNAL ARTICLE
AU  - Sartor, Oliver
AU  - Ledet, Elisa
AU  - Huang, Minqui
AU  - Schwartz, Jennifer
AU  - Lieberman, Alex
AU  - Lewis, Brian
AU  - Layton, Jodi
AU  - Barata, Pedro
AU  - Jang, Albert
AU  - Hawkins, Madeline
AU  - Pocha, Olivia
AU  - Lanka, Sree
AU  - Harris, Kendra
TI  - Prediction of Resistance to <sup>177</sup>Lu-PSMA Therapy by Assessment of Baseline Circulating Tumor DNA Biomarkers
AID  - 10.2967/jnumed.123.266167
DP  - 2023 Sep 28
TA  - Journal of Nuclear Medicine
PG  - jnumed.123.266167
4099  - http://jnm.snmjournals.org/content/early/2023/09/28/jnumed.123.266167.short
4100  - http://jnm.snmjournals.org/content/early/2023/09/28/jnumed.123.266167.full
AB  - 177Lu-PSMA-617 and 177Lu-PSMA I&T (collectively termed 177Lu-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. Methods: Pretreatment circulating tumor DNA (ctDNA) samples were collected from 44 mCRPC patients receiving 177Lu-PSMA treatment. Prostate-specific antigen responders and nonresponders were assessed relative to the ctDNA findings at baseline. Results: The ctDNA findings indicated that nonresponders were more likely to have gene amplifications than were responders (75% vs. 39.2%, P = 0.03). In particular, amplifications in FGFR1 (25% vs. 0%, P = 0.01) and CCNE1 (31.2% vs. 0%, P = 0.001) were more likely to be present in nonresponders. CDK12 mutations were more likely to be present in nonresponders (25% vs. 3.6%, P = 0.05). Conclusion: Our analyses indicate that ctDNA assays may contain specific biomarkers predictive of response or resistance for 177Lu-PSMA–treated mCRPC patients. Additional confirmatory studies are required before clinicians can use these findings to make personalized treatment decisions.