Radium-223, known by the brand name Xofigo, is a radiopharmaceutical, a drug that emits radiation as a targeted therapy. It is used for patients whose prostate cancer no longer responds to hormonal treatments, a condition known as castration-resistant prostate cancer (CRPC), and has spread to the bones. Radium-223 mimics calcium, allowing it to be absorbed by bone tissue, particularly in areas with high turnover like bone metastases. It then releases short-range alpha particle radiation that damages the DNA of nearby cancer cells. The success of this treatment is evaluated through several important outcomes for patients.
Survival Benefits of Radium-223
A primary measure of success for any cancer treatment is its effect on survival. The ALSYMPCA clinical trial provided data on this topic by comparing patients with castration-resistant prostate cancer and bone metastases. One group received Radium-223 plus the best standard of care, while the other received a placebo with the same standard of care to determine if the treatment extended overall survival.
The results of the ALSYMPCA trial were significant. The updated analysis showed that patients treated with Radium-223 had a median overall survival of 14.9 months, compared to 11.3 months for those in the placebo group. This improvement was observed across different patient subgroups, including whether or not they had previously received chemotherapy like docetaxel.
While an increase of 3.6 months may appear modest, it represents a meaningful improvement in the context of advanced, late-stage cancer. In the ALSYMPCA trial, the positive survival data were clear enough during an interim analysis that the study was stopped early. This allowed the patients who were originally receiving the placebo to be offered Radium-223. The findings led to the FDA’s approval of the drug for men with symptomatic bone metastases from CRPC.
Impact on Quality of Life and Skeletal Events
Beyond extending life, Radium-223 also improves a patient’s daily experience by preventing painful complications. It has demonstrated positive effects by delaying what are known as symptomatic skeletal events (SSEs). These are complications from bone metastases and can include the need for radiation to a bone to relieve pain, bone fractures, or compression of the spinal cord.
The ALSYMPCA trial showed that Radium-223 significantly postponed the first occurrence of an SSE. Patients receiving the treatment had a median time to their first skeletal event of 15.6 months, compared to 9.8 months for patients in the placebo group. This extension helps preserve a patient’s mobility and reduces the need for interventions to manage severe bone pain or fractures.
The impact on patient well-being was also measured in the trial using a standard assessment questionnaire. A greater percentage of patients in the Radium-223 group reported a meaningful improvement in their quality of life compared to those receiving the placebo (25% vs 16%). Patients receiving Radium-223 also experienced less of a decline in their quality-of-life scores and had fewer serious adverse events than the placebo.
How Treatment Success Is Monitored
For many prostate cancer therapies, doctors rely on the prostate-specific antigen (PSA) blood test to gauge how well a treatment is working. However, for patients undergoing Radium-223 therapy, the PSA level is not a reliable indicator of effectiveness. Patients should be aware that their PSA levels might not decrease and could even temporarily increase, an event known as a PSA flare, even when the treatment is providing a benefit.
Instead of PSA, clinicians often turn to a different blood marker called alkaline phosphatase (ALP). ALP is an enzyme found in high concentrations in the liver and bone, and levels are often elevated in patients with active bone metastases. A significant decrease in ALP levels during Radium-223 treatment is more closely associated with a positive response and longer survival. In one study, 56% of patients had an ALP response.
In addition to blood markers, physicians monitor treatment success by assessing a patient’s symptoms, particularly bone pain. A reduction in pain or a decreased need for pain medication is a positive sign. Imaging tests, such as bone scans, are also used to evaluate the status of the metastases. A partial response or disease stability on a bone scan after treatment is correlated with better survival outcomes.
Patient Factors That Influence Outcomes
The success of Radium-223 therapy can be influenced by individual patient factors. A person’s overall health at the start of treatment, measured by an ECOG performance status, is one such factor. Patients who are healthier and more active (with a lower ECOG score) tend to have better survival outcomes with Radium-223.
The extent of the cancer in the bones, referred to as the disease burden, also plays a role. Patients with a lower burden of disease when starting Radium-223 tend to fare better, which highlights the importance of timing in the treatment course.
Previous treatments can also affect the outcome. While Radium-223 was shown to be effective regardless of whether patients had previously received chemotherapy, some real-world data suggest that completing the full six-injection course is associated with better overall survival. Factors like having had prior chemotherapy can sometimes impact a patient’s ability to complete all cycles.