- 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.
- 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.
- 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.
- Only white men included.