Patients with bone metastases often have symptoms that they do not relate to pain, such as an increased difficulty in walking or a reduction in the ability to do daily activities. Additionally, many patients who experience pain do not bring it to the attention of their physician.

We conducted a study of men with metastatic prostate cancer and their caregivers—the largest symptom survey in this population to date—and showed that the most frequently reported symptoms were fatigue, urinary symptoms, sexual function, and bone pain. We found that many patients ignore their pain; more than half of patients surveyed believe that daily pain or discomfort is something they need to endure and admit that they do not always know if their pain is related to cancer or to something else. Indeed, nonspecific symptoms such as fatigue and pain may be attributed to the everyday aches and pains of aging. However, since the presence and characteristics of these very symptoms may indicate disease progression, one is required to address them in a timely manner or risk a suboptimal diagnosis and treatment-planning scenario.

Perhaps a great many patients with CRPC develop bone metastases and no visceral disease, and are thus potential candidates for radium-223 treatment; however, the optimal placement of radium-223 in the current treatment paradigm remains to be determined. There has been a shift in the field toward earlier use of abiraterone or enzalutamide for metastatic CRPC (mCRPC), moving docetaxel and radium-223 later in the sequence; data from ongoing trials are likely to provide additional insights that could further inform and shape the practice of therapeutic layering. Such trials include the Evaluation of Radium-223 dichloride in combination with Abiraterone in CRPC (ERA-223) (NCT02043678) and Prostate Cancer Consortium in Europe trial III (PEACE III) (NCT02194842). Both trials are investigating the first-line combination of radium-223 with abiraterone and/or enzalutamide in patients with asymptomatic/mildly symptomatic mCRPC.

In summary, whether or not patients are experiencing pain from bone metastases, early identification of bone involvement means that treatment can be initiated to prevent or delay the development of skeletal-related events (SREs)—such SREs may be painful and debilitating, greatly impacting patients’ lives. SREs are associated not only with substantial healthcare resource utilization, including hospitalization and surgery, but also with significantly increased mortality in men with mCRPC.