Genotype is linked to outcomes in low-volume prostate cancer

  • Hearn JWD & al.
  • JAMA Oncol
  • 13 Feb 2020

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • The adrenal-permissive HSD3B1 genotype in patients with low-volume metastatic prostate cancer is associated with earlier castration resistance and shorter OS.
  • Docetaxel is associated with prolonged freedom from castration-resistant prostate cancer (CRPC) and OS in high-volume disease regardless of HSD3B1 genotype.

Why this matters

  • The HSD3B1 genotype can be used to risk stratify patients with low-volume disease in future trials.

Study design

  • Phase 3 E3805 CHAARTED trial of 790 patients (mean age, 63 years) with newly diagnosed metastatic CRPC, randomly assigned to androgen deprivation therapy±docetaxel.
  • Funding: National Cancer Institute.

Key results

  • Median follow-up:
    • Low-volume group: 64.4 months.
    • High-volume group: 42.6 months.
  • In patients with low-volume disease, adrenal-permissive vs adrenal-restrictive genotype was associated with significantly lower:
    • 2-year freedom from CRPC: 51.0% vs 70.5% (P=.01).
    • 5-year OS: 57.5% vs 70.8% (P=.03).
  • Adrenal-permissive genotype was associated with a higher risk for CRPC (adjusted HR, 1.89; P=.02) and mortality (adjusted HR, 1.74; P=.045) in low-volume disease.
  • With high-volume disease, no difference was observed in 2-year freedom from CRPC (P=.89) and 5-year OS between genotypes (P=.65).
  • Docetaxel was associated with prolonged freedom from CRPC and with OS in high-volume disease:
    • Adrenal-permissive genotype: P<.001 and p=".02," respectively.>
    • Adrenal-restrictive genotype: P=.003 and P=.008, respectively.

Limitations

  • Only white men included.