The 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU 2026) has successfully concluded, bringing forward several landmark advances in prostate cancer. Among them, the final overall survival (OS) results from the EORTC 1333/PEACE-3 trial represent a major milestone in the management of metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. 

Led by the European Organisation for Research and Treatment of Cancer (EORTC), this international, multicenter phase III study provides high-level evidence supporting a novel combination strategy. Oncology Frontier – UroStream invited Prof. Enrique Gallardo from Parc Taulí University Hospital (Spain) for an in-depth discussion of the study’s key findings, clinical implications, safety considerations, and future directions.

Oncology Frontier: Thank you, Prof. Gallardo, for accepting our interview. Could you briefly summarize the key findings of the PEACE-3 trial evaluating enzalutamide plus radium-223 in mCRPC?

Prof. Enrique Gallardo:

EORTC 1333/PEACE-3 is an international, randomized, open-label phase III trial evaluating enzalutamide in combination with radium-223 versus enzalutamide alone as first-line treatment in patients with mCRPC and bone metastases.

A total of 446 patients with asymptomatic or minimally symptomatic disease, at least two bone metastases, and no visceral metastases were enrolled. Patients were randomized to receive either radium-223 (55 kBq/kg intravenously every 4 weeks for six cycles) plus enzalutamide (160 mg orally once daily), or enzalutamide monotherapy.

The primary endpoint was radiographic progression-free survival (rPFS), with key secondary endpoints including overall survival (OS), time to next systemic therapy, time to pain progression, symptomatic skeletal events (SSEs), and safety.

The study demonstrated that the combination significantly improved both rPFS and OS. Median rPFS reached 19.2 months, representing an approximately 3-month improvement over enzalutamide alone (HR 0.71). More importantly, the median OS—the gold standard endpoint—was prolonged by 5.6 months, reaching 38.2 months compared to 32.6 months in the monotherapy group (HR 0.76).

These results clearly establish a meaningful survival advantage with the combination strategy.

Oncology Frontier: How do you think these positive OS results will impact clinical practice and the treatment landscape of mCRPC?

Prof. Enrique Gallardo:

The PEACE-3 trial included a broad and clinically relevant patient population, including those previously treated with androgen deprivation therapy (ADT), ADT plus docetaxel, and even patients with prior exposure to abiraterone.

Given this inclusiveness, I believe the combination of enzalutamide plus radium-223 has strong potential to become a standard treatment option for patients with mCRPC and bone metastases.

Importantly, the regimen also showed promising activity in patients who had progressed after abiraterone. It is not only clinically effective but also relatively convenient to administer, making it highly practical in real-world settings.

Therefore, this combination should be considered at least a high-quality first-line option in this population. Even in patients previously exposed to androgen receptor pathway inhibitors (ARPIs), its role should be actively considered in treatment decision-making.

Oncology Frontier: What are the key considerations clinicians should keep in mind when applying this regimen in practice?

Prof. Enrique Gallardo:

The most critical aspect is comprehensive safety management, particularly bone health protection.

Overall, the combination showed a modest increase in adverse events. Grade ≥3 treatment-emergent adverse events occurred in 69.3% of patients in the combination group versus 57.6% in the monotherapy group, while drug-related grade ≥3 events were reported in 28.9% versus 18.8%, respectively.

Fracture risk is especially important. After a protocol amendment in March 2018 mandating the use of bone-protective agents, the incidence of grade 3–4 fractures was reduced, although still higher in the combination group (5.5% vs 1.3%). Overall fracture incidence was 24.3% versus 13.4%.

These findings highlight that bone-protective agents—such as bisphosphonates or denosumab—must be used routinely alongside this regimen.

In fact, beyond this specific combination, all patients with mCRPC and bone metastases should receive systematic bone-protective therapy throughout their treatment course to ensure safety and preserve skeletal integrity.

Oncology Frontier: Based on subgroup analyses, which patients seem to benefit the most from this combination?

Prof. Enrique Gallardo:

Subgroup analyses showed that the survival benefit was consistent across nearly all predefined patient groups.

This means that, in general, all eligible patients with mCRPC and bone metastases should be considered for this combination regimen.

There were some signals suggesting slightly reduced benefit in patients older than 75 years, those previously treated with docetaxel, and those with poorer performance status. However, these subgroups were relatively small, and no definitive conclusions can be drawn.

Overall, patients with bone-predominant disease and no visceral metastases represent the ideal candidates for this treatment approach.

Oncology Frontier: Looking ahead, what are the key future research directions for optimizing this combination?

Prof. Enrique Gallardo:

The next major step is to move this combination earlier in the disease course, particularly into the metastatic hormone-sensitive prostate cancer (mHSPC) setting.

There is a general trend in oncology to shift effective therapies into earlier lines of treatment. However, whether this combination can deliver a survival benefit in mHSPC still requires robust clinical trial evidence.

For now, the priority is to translate the PEACE-3 findings into routine clinical practice, ensure standardized use of the regimen, and optimize safety management—so that more patients with mCRPC can benefit from this important therapeutic advance.

Prof. Enrique Gallardo