J&J's apalutamide around prostate surgery cuts recurrence or death risk by 62% in PROTEUS substudy

Johnson & Johnson reported on 24 October 2026 that giving apalutamide with androgen deprivation therapy (ADT) for six months either side of surgery cut the risk of recurrence or death by 62% against radical prostatectomy alone in high-risk localised or locally advanced prostate cancer. The data come from a substudy of the Phase 3 PROTEUS programme and were shown as a late-breaking abstract (#LBA53) at the ESMO Congress 2026 ¹².

What the substudy found

The substudy was randomised and open-label, with 408 patients who had newly diagnosed, non-metastatic disease and were fit for both surgery and systemic therapy. Of these, 102 received apalutamide plus ADT and 306 had radical prostatectomy with pelvic lymph node dissection, followed by standard institutional practice or observation. The drug arm took 240 mg of apalutamide daily for six 28-day cycles before surgery and six after ¹.

The primary endpoint was event-free survival, counting biochemical failure, local or regional recurrence, distant metastasis or death. At a median follow-up of 37.8 months the hazard ratio was 0.38 (95% CI 0.26-0.55; p<0.0001). Median event-free survival had not been reached in the apalutamide arm, against 19.1 months with surgery alone. At three years 63% of the drug arm were event-free, compared with 41.4% of the surgery arm ¹.

Secondary and exploratory measures pointed the same way, though J&J describes them as numerical improvements with nominal p-values. Metastasis-free survival showed a hazard ratio of 0.49 (95% CI 0.26-0.90; nominal p=0.0193). Time to first subsequent therapy had a hazard ratio of 0.29, and at three years 64.6% of the drug arm had needed no further treatment against 32% after surgery alone ¹.

Grade 3 or 4 treatment-emergent adverse events affected 31% of patients on apalutamide plus ADT and 22% of those who had surgery only. No adverse event led to death in either arm. Hot flush (64%) and urinary incontinence (63%) were the commonest adverse events with apalutamide ¹.

What it means for the market

The substudy answers a narrower question than the main PROTEUS trial, whose primary results J&J presented in the plenary session at ASCO 2026. Here the comparator is surgery with no systemic treatment, which J&J calls a longstanding standard of care, so the result speaks directly to whether hormone therapy should be added around prostatectomy at all ¹.

The commercial stakes sit in where apalutamide is used. The drug is currently approved only in advanced disease, in metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer. Use around surgery in high-risk localised disease has not been approved by any regulator, and J&J's statement does not set out a filing plan or timetable ¹. For urology and oncology services, the halving of the share of patients needing subsequent therapy at three years is the figure most relevant to treatment pathways and downstream drug spending, should the indication be granted.

Alberto Briganti of IRCCS San Raffaele Hospital in Milan, an investigator, said the reduction in recurrence and metastases "suggests we may be able to build on surgery and help more patients achieve lasting disease control" ¹.

Caveats

The study was open-label and the arms were unequal in size, with three times as many patients in the surgery arm. The metastasis-free survival and subsequent-therapy results carry only nominal significance, and adverse events were more frequent with the drug. Overall survival is still being followed and has not been reported ¹. A manuscript of the results has been accepted by European Urology ¹².