A 68-year-old man is diagnosed with prostate cancer (Gleason score 4+4=8, PSA 15 ng/mL, clinical stage T2cN0M0). He receives radical radiotherapy combined with androgen deprivation therapy (ADT). The STAMPEDE and ENZAMET trials have established that for high-risk localised or metastatic hormone-sensitive prostate cancer, which treatment intensification strategy demonstrates the greatest overall survival benefit beyond standard ADT?

• A Adding docetaxel chemotherapy from the outset of ADT
• B Addition of zoledronic acid for bone protection prolongs survival
• C Radium-223 added upfront to ADT for bone micrometastases
• D Adding an androgen receptor pathway inhibitor (ARPI): enzalutamide, apalutamide, or darolutamide ✓

Explanation

Multiple phase III trials (ENZAMET, TITAN, ARCHES, ARASENS, PEACE-1) have shown that adding an ARPI (enzalutamide, apalutamide, darolutamide) to standard ADT significantly improves overall survival in hormone-sensitive prostate cancer, with hazard ratios around 0.60–0.72. The STAMPEDE trial demonstrated docetaxel benefit primarily in high-volume metastatic disease, not all comers. For this high-risk localised patient, intensification with an ARPI plus ADT (and radiotherapy) represents the most practice-changing contemporary evidence. Zoledronic acid reduces skeletal events but does not prolong overall survival in hormone-sensitive disease. Radium-223 is indicated for bone-dominant castration-resistant disease.

Reference: Bailey & Love's Short Practice of Surgery, 27th ed.

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Written and medically reviewed by the StethoPrep medical team.