Prof Declan Murphy on interpreting the PROTEUS trial in localized prostate cancer

In this video, Declan Murphy, MB, BCH, BaO, FRACS, FRCS, Urol, discusses the significance of the phase 3 PROTEUS trial (NCT03767244), explains why its presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting drew widespread attention, and addresses questions surrounding the trial's use of androgen deprivation therapy (ADT) in the control arm. Murphy is a urologist and the director of GU Oncology at the Peter McCallum Cancer Center in Melbourne, Australia.

Murphy emphasized that the PROTEUS trial represents a landmark study in localized prostate cancer, citing its presentation during the ASCO plenary session and simultaneous publication in the New England Journal of Medicine¹ as indicators of its importance. He noted that the international, double-blind, randomized trial enrolled more than 2100 patients, making it the largest surgical study ever conducted in high-risk localized prostate cancer. According to Murphy, the trial addresses a longstanding unmet need by evaluating whether perioperative hormonal therapy administered before and after radical prostatectomy can reduce the high rates of relapse experienced by patients with high-risk disease.

Overall, the study met its co-primary end points, showing that percentage of patients with a pathological complete response or minimal residual disease was significantly higher in the apalutamide group than in the placebo group (8.9% vs. 1.0%; OR, 10.17; 95% CI, 5.27 to 19.64; P < .001). The probability of metastasis-free survival at 5 years was also greater in the treatment arm (78.2% vs. 73.5%; HR for distant metastasis or death, 0.80; 95% CI, 0.67 to 0.96; P = .02).

One of the primary points of debate surrounding the study, however, is the inclusion of 6 months of ADT before and after surgery in the control arm, rather than surgery alone. Murphy acknowledged that ADT is not the current standard of care in this setting, but he explained that the design was chosen to preserve the trial's double-blind structure and improve patient retention.

Despite concerns raised by some observers, Murphy said he does not believe the use of ADT in the control arm complicates interpretation of the trial's findings. He noted that prior neoadjuvant ADT studies have demonstrated improvements in pathologic outcomes, such as surgical margin status and lymph node involvement. He also pointed to an ongoing PROTEUS substudy comparing radical prostatectomy alone with the investigational perioperative regimen, explaining that those forthcoming data should provide additional context regarding the impact of ADT in the control arm.

REFERENCE
1. Taplin ME, Gleave M, Shore ND, et al; PROTEUS Investigators. Perioperative apalutamide in high-risk localized prostate cancer. N Engl J Med. 2026. doi:10.1056/NEJMoa2603878