patient care perspectives
The Importance of Early Detection of Bone Metastases
Neal Shore, MD, Director, CPI, Carolina Urologic Research Center, shares his insights on the importance of early detection of bone metastases, noting that the majority (90%) of patients with castration-resistant prostate cancer (CRPC) will develop bone metastases, which are often initially asymptomatic. While optimal therapeutic layering for advanced prostate cancer remains to be determined, the timing and pattern of metastatic spread in patients with CRPC presents a window of opportunity for the use of radium-223 that is much earlier in the disease course than is currently typical, and prior to the development of visceral disease.
Medical Director and CPI Carolina Urologic Research Center Managing Partner, Atlantic Urology Clinics
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.
“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.”
Brodowicz T, Hadji P, Niepel D, Diel I. Early identification and intervention matters: A comprehensive review of current evidence and recommendations for the monitoring of bone health in patients with cancer. Cancer Treat Rev. 2017 Oct 18;61:23–34. doi: 10.1016/j.ctrv.2017.09.008. [Epub ahead of print].
Cathomas R, Bajory Z, Bouzid M, et al. Management of bone metastases in patients with castration-resistant prostate cancer. Urol Int. 2014;92:377–386.
Drudge-Coates L, Oh WK, Tombal B, et al. Recognizing symptom burden in advanced prostate cancer: a global patient and caregiver survey. Clin Genitourin Cancer. 2017 Oct 5. pii: S1558-7673(17)30305-1. doi: 10.1016/j.clgc.2017.09.015. [Epub ahead of print].
Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol. 2014;65:467–479.
Heinrich D, Bektic J, Bergman AM, et al. The contemporary use of radium-223 in metastatic castration-resistant prostate cancer. Clin Genitourin Cancer. 2017 Sep 6. pii: S1558-7673(17)30275-6. doi: 10.1016/j.clgc.2017.08.020. [Epub ahead of print].
Howard LE, De Hoedt AM, Aronson WJ, et al. Do skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer? Prostate Cancer Prostatic Dis. 2016;19:380–384.
Keizman D, Fosboel MO, Reichegger H, et al. Imaging response during therapy with radium-223 for castration-resistant prostate cancer with bone metastases- analysis of an international multicenter database. Prostate Cancer Prostatic Dis. 2017;20:289–293.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Prostate Cancer Version 2.2017. Accessed October 2017.
Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–223.
Pezaro CJ, Omlin A, Lorente D, et al. Visceral disease in castration-resistant prostate cancer. Eur Urol. 2014;65:270–273.
Radium-223 dichloride and abiraterone acetate compared to placebo and abiraterone acetate for men with cancer of the prostate when medical or surgical castration does not work and when the cancer has spread to the bone, has not been treated with chemotherapy and is causing no or only mild symptoms (ERA 223). https://clinicaltrials.gov/ct2/show/NCT02043678. Accessed November 14, 2017.