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Jan Vanwelkenhuyzen1,2,3, Eva Van Bos4, Siska Van Bruwaene4

  • 1Department of Human Structure and Repair, Ghent University, Ghent, Belgium.

European Urology Open Science
|June 9, 2023
PubMed
Summary

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This summary is machine-generated.

Circulating tumor DNA (ctDNA) profiling in metastatic castration-resistant prostate cancer (mCRPC) patients receiving lutetium-177 prostate-specific membrane antigen radioligands (177Lu-PSMA) can predict treatment outcomes. Genetic alterations in AR and PI3K pathways are linked to poor prognosis.

Area of Science:

  • Oncology
  • Genomics
  • Radioligand Therapy

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) is an advanced stage of prostate cancer.
  • Lutetium-177 prostate-specific membrane antigen radioligands (177Lu-PSMA) represent a novel therapeutic approach for mCRPC.
  • Predictive biomarkers for 177Lu-PSMA treatment response are crucial for patient management.

Purpose of the Study:

  • To evaluate the prognostic value of circulating tumor DNA (ctDNA) profiling in patients with mCRPC undergoing 177Lu-PSMA therapy.
  • To identify specific genomic alterations associated with progression-free survival (PFS) and treatment response.

Main Methods:

  • An observational cohort study included 57 patients with late-stage mCRPC treated with 177Lu-PSMA I&T.
  • ctDNA profiling was performed on blood samples collected before treatment.
Keywords:
BiomarkerCell-free DNACirculating tumour DNALiquid biopsyLutetium-177-PSMAMetastatic castration-resistant prostate cancer

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  • Genomic alterations in AR, PI3K pathway, TP53, and TMPRSS2-ERG were analyzed.
  • Progression-free survival (PFS) was assessed using Kaplan-Meier and Cox regression analyses.

    • Main Results:

    • Median PFS was 3.84 months.
    • A prostate-specific antigen response of ≥50% was observed in 37.5% of patients.
    • ctDNA was detected in 84.8% of profiled patients, with higher ctDNA levels correlating with shorter PFS.
    • Genomic structural rearrangements in the AR gene (HR 9.74) and alterations in the PI3K pathway (HR 3.58) were independently associated with poor prognosis.

    Conclusions:

    • ctDNA profiling holds prognostic value in mCRPC patients treated with 177Lu-PSMA.
    • Specific genomic alterations, particularly in the AR gene and PI3K pathway, predict unfavorable outcomes.
    • Prospective validation in biomarker-driven trials is warranted to confirm these findings.