Metastatic Hormone-Sensitive Prostate Cancer: When to Use Doublet vs Triplet Systemic Therapy

Authored by Natalia Gandur, published on 2026-05-06 20:36:24.0

  1. Confirmed mHSPC (Start ADT backbone)
    • Assess Key Variables
      Disease timing: de novo vs metachronous Disease burden: high-volume vs low-volume Disease risk: high-risk vs low-risk Visceral metastases / symptoms ECOG / docetaxel fitness Frailty, comorbidities, access, patient preference
      • Aggressive disease and fit for docetaxel?
        • YES
          • Triplet Therapy Favored
            De novo high-volume and/or high-risk disease Visceral metastases or marked symptoms ECOG 0–1, docetaxel-fit Use when chemotherapy is feasible and accepted Examples: ADT + docetaxel + darolutamide ADT + docetaxel + abiraterone/prednisone
            • Special situation: De novo low-volume disease*
              *Favor ADT + ARPI and separately consider prostate radiotherapy.
        • NO
          • Doublet Therapy Favored
            Low-volume disease Metachronous recurrence Frailty, comorbidities, or docetaxel-unfit Preference to avoid chemotherapy / logistical barriers Examples: ADT + abiraterone/prednisone ADT + enzalutamide ADT + apalutamide ADT + darolutamide (where available)
            • Special situation: De novo low-volume disease*
              *Favor ADT + ARPI and separately consider prostate radiotherapy.
  2. Key Take-Home Points
    Avoid ADT alone when combination therapy is feasible Strongest triplet signal: de novo high-volume/high-risk, docetaxel-fit disease Strongest doublet signal: low-volume and/or metachronous disease
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