At ASCO 2026, Neeraj Agarwal, MD, FASCO, highlighted breakthrough Phase 3 data from the PROTEUS trial evaluating a perioperative hormone-based strategy for men with high-risk localized or locally advanced prostate cancer who are planning to undergo radical prostatectomy. The update focuses on adding apalutamide to a perioperative course of androgen deprivation therapy (ADT) and assesses whether the combination can improve key disease-control outcomes compared with standard perioperative management.
High-risk localized and locally advanced prostate cancer represents a difficult clinical group because the risk of microscopic spread and later metastatic recurrence remains substantial even when definitive local therapy such as surgery is performed. Radical prostatectomy can remove the primary tumor, but patients with aggressive disease features may still harbor residual microscopic cancer. For that reason, treatment intensification around the time of surgery—often termed perioperative or neoadjuvant/adjuvant systemic therapy—has been an area of intense research. PROTEUS is designed to test whether a more robust androgen blockade during the perioperative window can translate into stronger pathologic and longer-term clinical outcomes.
In the Phase 3 PROTEUS study, patients with high-risk localized or locally advanced prostate cancer received perioperative ADT combined with apalutamide, then proceeded to radical prostatectomy. The central efficacy message from the ASCO 2026 update is that the regimen produced a notable improvement in pathologic response—an important surrogate marker reflecting how much of the tumor is eliminated by treatment before or around surgery.
The results reported show an increase in pathologic response rates of 8.9% versus 1.0% when comparing the apalutamide-containing perioperative regimen to the reference control approach. While the absolute percentages may appear modest, the relative improvement is substantial and suggests that the addition of apalutamide meaningfully enhances tumor eradication in the pre-surgical or peri-surgical setting. In prostate cancer research, pathologic response can be particularly relevant because it can provide an early signal that systemic therapy is effectively suppressing or eliminating cancer cells even when the disease is managed with surgery.
Beyond the pathologic findings, the PROTEUS update also reports outcomes related to metastasis-free survival at 5 years. The reported 5-year metastasis-free survival was 78.2% for patients treated with perioperative ADT plus apalutamide, compared with 73.5% for the comparator group. The hazard ratio (HR) reported was 0.80, indicating a 20% relative reduction in the hazard of developing metastases (or related progression events depending on how metastasis-free survival was defined in the trial) with the apalutamide strategy. This signal is clinically meaningful because preventing or delaying metastatic disease is often the primary goal in high-risk prostate cancer—since metastasis is strongly associated with disease progression, complications, and mortality.
Importantly, the trial’s findings connect an early biologic response (pathologic response) with a longer-term disease-control endpoint (metastasis-free survival). The combination of improved pathologic response and a favorable metastasis-free survival trend supports the rationale that more intensive androgen receptor pathway inhibition during the perioperative period may improve patient outcomes rather than only changing short-term markers.
The key takeaway from the ASCO 2026 announcement is that perioperative ADT plus apalutamide may represent a new systemic intensification option for patients with high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy. By improving tumor response at the surgical stage and demonstrating a positive metastasis-free survival effect at 5 years, the regimen appears to strengthen the curative intent approach of surgery with an added systemic component.
As the oncology community digests the PROTEUS Phase 3 data, subsequent attention will likely center on the durability of benefit, safety and tolerability in the perioperative setting, and how these results compare with or complement other intensification strategies used in high-risk prostate cancer. Still, the reported improvements provide momentum for the use of androgen receptor pathway inhibitors as part of perioperative treatment, aiming to reduce the chance that aggressive disease will persist beyond the operating field.
Overall, this ASCO 2026 update from Neeraj Agarwal, MD, FASCO, presents compelling Phase 3 evidence for perioperative ADT combined with apalutamide in high-risk localized/locally advanced prostate cancer treated with radical prostatectomy—showing improved pathologic response (8.9% vs 1.0%) and favorable 5-year metastasis-free survival outcomes (78.2% vs 73.5%; HR 0.80). According to UroToday.
Neeraj Agarwal, MD, FASCO: Breaking news #ASCO26 👉Ph3 PROTEUS trial👉Periop ADT + apalutamide in high-risk localized/locally advanced #prostatecancer undergoing radical prostatectomy👉↑ pathologic response (8.9% vs 1.0%) & 5-yr metastasis-free survival (78.2% vs 73.5%; HR 0.80) @urotoday @OncoAlert. #breaking
— @neerajaiims May 1, 2026
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