Dr Saad on the Importance of Timing When Incorporating Radium-223 Into Prostate Cancer Treatment

“If we want to get a window of opportunity for radium 223, and if we wait for post chemotherapy, patients [will often have] more advanced [stages of disease and be] a little bit weaker. Their performance status and their bone marrow quality might [also] be in worse shape.”

Fred Saad, CQ, MD, FRCS, FCAHS, director of prostate cancer research at Montreal Cancer Institute, as well as a full professor in the Department of Surgery and a uro-oncologist in the Department of Urology at the University of Montreal Hospital Center, discussed how findings from the phase 3 PEACE-3 trial (NCT02194842) inform the optimal timing of radium-223 dichloride (Xofigo) administration when used in combination with existing prostate cancer regimens.

The PEACE-3 trial evaluated the combination of radium-223 plus enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone-predominant disease. The trial sought to optimize the integration of radium-223 into contemporary treatment sequences and to clarify its safety and efficacy when used alongside androgen receptor pathway inhibitors (ARPIs).

According to Saad, one of the principal messages from the study is the importance of timing when incorporating radium-223 into the treatment continuum. Radium-223 is often been administered late in the disease course—typically after chemotherapy—when patients may have already experienced significant bone marrow suppression, declining performance status, or extensive skeletal disease burden. Saad emphasized that such delayed use can limit both the tolerability and efficacy of the agent, as patients may be unable to complete the recommended 5 or 6 treatment cycles required to achieve full therapeutic benefit.

He noted that an earlier integration of radium-223, particularly after progression on first-line ARPI therapy, may represent a more optimal strategy. In this setting, patients generally retain sufficient bone marrow reserve and functional status to tolerate treatment effectively. Administering radium-223 at this juncture could maximize the potential for disease control while minimizing the risk of treatment-limiting hematologic toxicity. Saad underscored that clinicians should identify patients likely to experience rapid disease progression—especially those with symptomatic or extensive bone metastases—and consider initiating radium-223 before clinical deterioration restricts eligibility.

Saad further cautioned against delaying treatment until after chemotherapy, as this may narrow the therapeutic window. Patients who progress quickly following cytotoxic therapy may lack the 6-month timeframe typically required to complete the radium-223 regimen, thereby reducing the likelihood of achieving durable skeletal and survival benefits.