A year of apalutamide plus ADT around prostatectomy delays events in high-risk disease

Design

Open-label randomised substudy (1:3), PROTEUS programme

Population

408 men with high-risk localised or locally advanced prostate cancer having prostatectomy

Primary outcome

Event-free survival

Effect

3-year EFS 63% vs 41%; HR 0.38 (95% CI 0.26 to 0.55)

This open-label substudy of the PROTEUS programme randomised 408 men with high-risk localised or locally advanced prostate cancer, in a 1:3 ratio, to apalutamide 240 mg daily plus androgen-deprivation therapy for six 28-day cycles before and six after radical prostatectomy with lymph node dissection, or to surgery alone. The main, blinded PROTEUS trial had already reported benefit against placebo.

Event-free survival, counting biochemical failure, recurrence, metastasis or death, was better with perioperative treatment (3-year rates 63% vs 41%; HR 0.38, 95% CI 0.26 to 0.55). Because the hazards were not proportional, a restricted mean analysis estimated about 11 more months event-free over the first three years. Metastasis-free survival including PSMA imaging favoured treatment (87% vs 78%; HR 0.49), and the need for subsequent therapy fell (HR 0.29). Metastasis-free survival on conventional imaging did not differ (94% vs 92%). Grade 3 to 4 adverse events were more frequent (31% vs 22%).

The result supports perioperative apalutamide plus ADT as an option for fit men choosing surgery for high-risk disease, mainly by delaying PSA failure and further treatment. Overall survival data are not yet available, and the comparison here was open-label against surgery alone.

Cost and a year of hormonal side effects are real trade-offs; check local availability and pricing before discussing it.

• Consider discussing perioperative apalutamide plus ADT with fit men having prostatectomy for high-risk disease.
• Explain that the benefit is mainly delayed PSA failure and later treatment, not proven longer life.
• Counsel on a year of hormonal effects; serious adverse events were more common.
• Metastasis-free survival on conventional imaging was not different.
• Plan with medical oncology, given cost and monitoring needs.

Why it matters

Surgery for high-risk disease may work better as part of a combined plan than on its own.

Don't overread it

Open-label, with no overall survival result yet; conventional-imaging metastasis-free survival did not differ.

The statistics, in plain English

An HR of 0.38 means a much lower event rate overall, but the effect changed over time, which is why the authors also report average event-free time: about 11 extra months in the first three years. Endpoints driven by PSA can move earlier than survival.

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