Final overall survival findings from the phase 3 trial highlight the potential of combination therapy for patients with bone-metastatic castration-resistant prostate cancer, while reinforcing the importance of skeletal protection and coordinated supportive care.

For patients with metastatic castration-resistant prostate cancer (mCRPC), bone metastases are a common and potentially debilitating complication of advanced disease. In addition to contributing to pain, impaired mobility, and skeletal-related events, bone involvement can substantially affect quality of life and increase the complexity of treatment.

New findings from the phase 3 PEACE-3 trial suggest that combining radium-223 with enzalutamide may offer a meaningful survival advantage for selected patients with mCRPC and bone metastases.

The final overall survival analysis, published in Annals of Oncology in 2026, provides important evidence supporting this combination strategy while highlighting the need for careful toxicity management and proactive bone health interventions.

A Survival Benefit With Combination Therapy
PEACE-3 was an international, randomized phase 3 trial evaluating the addition of radium-223, an alpha-emitting radiopharmaceutical that targets areas of increased bone turnover, to enzalutamide in patients with mCRPC and bone metastases.

Patients were randomly assigned to receive enzalutamide alone or enzalutamide in combination with radium-223.

In the final analysis, median overall survival was 38.2 months with the combination compared with 32.6 months with enzalutamide alone, representing a 5.6-month difference.

The combination was associated with a 24% relative reduction in the risk of death (hazard ratio HR, 0.76; 95% CI, 0.60-0.96; P=.0096).

The findings build on earlier PEACE-3 results demonstrating an improvement in radiographic progression-free survival, providing additional evidence that combining therapies with complementary mechanisms of action may improve outcomes in this population.

Importantly, the results apply to the patients enrolled in PEACE-3 and should not be generalized to all individuals with mCRPC, particularly those with visceral metastases or other characteristics outside the trial’s eligibility criteria.

Balancing Survival Gains With Treatment-Related Toxicity
Although the survival findings are encouraging, treatment intensification was associated with a greater burden of adverse events.

Grade 3 or higher treatment-emergent adverse events occurred in 69.3% of patients receiving radium-223 plus enzalutamide, compared with 57.6% of those receiving enzalutamide alone.

These findings emphasize the importance of evaluating potential survival benefits alongside a patient’s overall health, functional status, existing symptoms, and ability to tolerate additional therapy.

Radium-223 also introduces logistical and clinical considerations that may not arise with oral androgen receptor pathway inhibitors alone, including coordination of radiopharmaceutical administration and monitoring for hematologic toxicity.

For clinicians and oncology navigators, these considerations underscore the importance of multidisciplinary communication and early identification of treatment-related complications.

Bone Protection Remains a Critical Component of Care
One of the most clinically relevant aspects of PEACE-3 is its emphasis on bone health. Concerns about increased fracture risk with combinations involving radium-223 prompted changes to the trial protocol requiring the use of bone-protecting agents.

This requirement reflects the importance of skeletal protection in patients with advanced prostate cancer, particularly those receiving therapies that may further affect bone integrity.

For patients, bone health management may involve additional medications, dental evaluations, laboratory monitoring, and ongoing assessment of fracture risk.

These interventions can introduce new barriers related to treatment access, appointment coordination, medication adherence, and patient understanding.

Ensuring that patients receive appropriate education about bone-protecting therapy and understand the importance of continued monitoring is therefore an essential component of comprehensive care.

Implications for Oncology Navigation
The PEACE-3 findings have practical implications for oncology navigators supporting patients with advanced prostate cancer.

As treatment strategies become more complex, members of the care team can help bridge gaps between clinical recommendations and the patient’s ability to follow the treatment plan.

Patients receiving radium-223 plus enzalutamide may require assistance coordinating care among medical oncology, nuclear medicine, infusion or injection services, and supportive care teams. They may also require help with recognizing and reporting new or worsening bone pain, mobility changes, fatigue, and other symptoms that warrant clinical evaluation.

Equally important is helping patients understand the purpose of bone-protecting agents, addressing barriers to accessing prescribed treatments, and reinforcing the need for scheduled monitoring.

For patients already managing the physical and emotional burden of advanced disease, this support can make a complex treatment plan more manageable.

Looking Ahead
The final PEACE-3 overall survival findings add to growing evidence that carefully selected combination strategies can improve outcomes in advanced prostate cancer.

However, the results also reinforce that treatment advances must be accompanied by thoughtful supportive care, particularly when additional therapies introduce new toxicities, logistical demands, or skeletal health considerations.

As prostate cancer treatment continues to evolve, translating clinical progress into meaningful patient benefit will depend not only on selecting effective therapies but also on ensuring that patients have the education, resources, and support needed throughout their treatment journey.

Source
Gillessen S, E Gallardo, A Choudhury, et al. Final overall survival results from EORTC 1333/PEACE-3 trial of enzalutamide plus radium-223 in metastatic castration-resistant prostate cancer. Ann Oncol. 2026;37:736-742.