@article{01HMGM6EATB41PN1F0PKTKSNXD,
  abstract     = {{Lutetium-177 prostate-specific membrane antigen radioligands (Lu-177-PSMA) are new therapeutic agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We evaluated the prognostic value of circulating tumour DNA (ctDNA) profiling in patients with mCRPC starting treatment with Lu-177-PSMA I&T. Between January 2020 and October 2022, patients with late-stage mCRPC (n = 57) were enrolled in a single-centre observational cohort study. Genomic alterations in the AR gene, PI3K signalling pathway, TP53, and TMPRSS2-ERG were associated with progression-free survival (PFS) on Kaplan-Meier and multivariable Cox regression analyses. Median PFS of 3.84 mo (95% confidence interval [CI] 3.3-5.4) was observed, and 21/56 (37.5%) evaluable patients experienced a prostate-specific antigen response of >= 50% during treatment. Among 46 patients who provided a blood sample for profiling before Lu-177-PSMA treatment. ctDNA was detected in 39 (84.8%); higher ctDNA was correlated with shorter PFS. Genomic structural rearrangements in the AR gene (hazard ratio [HR] 9.74, 95% confidence interval [CI] 2.4-39.5; p = 0.001) and alterations in the PI3K signalling pathway (HR 3.58, 95% CI 1.41-9.08; p = 0.007) were independently associated with poor Lu-177-PSMA prognosis on multivariable Cox regression. Prospective evaluation of these associations in biomarker-driven trials is warranted. Patient summary: We examined cell-free DNA in blood samples from patients with advanced metastatic prostate cancer who started treatment with lutetium-177-PSMA, a new radioligand therapy. We found that patients with genetic alterations in the androgen receptor gene or PI3K pathway genes did not experience a lasting benefit from lutetium-177-PSMA. (C) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).}},
  author       = {{Vanwelkenhuyzen, Jan and Van Bos, Eva and Van Bruwaene, Siska and Lesage, Karl and Maes, Alex and Üstmert, Sezgin and Lavent, Filip and Beels, Laurence and Grönberg, Henrik and Ost, Piet and Lindberg, Johan and De Laere, Bram}},
  issn         = {{2666-1691}},
  journal      = {{EUROPEAN UROLOGY OPEN SCIENCE}},
  keywords     = {{Urology,Cell-free DNA,Liquid biopsy,Biomarker,Circulating tumour DNA,Lutetium-177-PSMA,Metastatic castration-resistant prostate cancer}},
  language     = {{eng}},
  pages        = {{63--66}},
  publisher    = {{Elsevier BV}},
  title        = {{AR and PI3K genomic profiling of cell-free DNA can identify poor responders to Lutetium-177-PSMA among patients with metastatic castration-resistant prostate cancer}},
  url          = {{http://doi.org/10.1016/j.euros.2023.05.008}},
  volume       = {{53}},
  year         = {{2023}},
}

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