Understanding Treatment Options for Prostate Cancer Patients with Symptomatic Bone Metastases

Our ability to offer a multitude of effective therapies for the advanced prostate cancer patient continues forward, enhancing patient outcomes while minimizing quality of life untoward effects. Radium 223 (Xofigo), approved in May 2013, is the most recently approved and efficacious advanced prostate cancer (PCa) treatment, receiving level one guidelines endorsements from AUA, EAU, ASCO, ESMO, and NCCN. This addition of CRPC Bone Metastases: Center of Excellence, highlights 3 important publications, each with novel information which supports the clinician responsible for advanced PCa patients with bone metastases burden, the predominant site of metastatic location with well documented meta-analyses for advanced PCa patients worldwide. 

“The Role of Therapeutic Layering in Optimizing Treatment for Patients With Castration-resistant Prostate Cancer (Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II)” coordinated 16 expert panelists, from medical oncology, urology, radiation oncology, and nuclear medicine, to review the approved the CRPC therapies and provide specific recommendations for both clinician and patients to discuss. Specifically, the concept of layering is described, adding another line of therapy to an existing one, in order to enhance patient clinical outcomes. The notion of layering differs from combination therapy of 2 or more therapies at the initiation or addition of another line of therapy.  Assuredly, regional accessibility and clinician experiences are important rate limiting factors. Nonetheless, the authors review and expound upon the potential versatility for the use of Radium 223 through layering while promoting both multimodality of therapy and multidisciplinary care.

Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial”, provides long term follow of the phase III registrational ALSYMPCA trial safety and tolerability regarding the use of Radium 223. Reassuringly, for patients and clinicians considering earlier use and the potential risk of delayed toxicities, the authors report:  “Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 months after the last injection. No other cases were observed. Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns. Updated Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial findings show that radium-223 remained well tolerated during treatment and up to 3-year after each patient's first injection.”  

Finally, “Radium-223 for primary bone metastases in patients with hormone-sensitive prostate cancer after radical prostatectomy in a multicenter German trial with urology and nuclear medicine collaboration, reports on the feasibility of Ra-223 treatment in patients with metastatic hormone-sensitive prostate cancer (mHSPC) post prostatectomy with symptomatic bone metastases. They report changes in alkaline phosphatase (ALP) and prostate-specific antigen (PSA), pain intensity was evaluated using the self-reporting Brief Pain Inventory (BPI) questionnaire and bone scintigraphy (BS) was performed to assess treatment response.

Given the recent evidence based publications solidifying the roles for both chemohormonal and ADT plus abiraterone acetate/prednisone combinations, we will look forward to additional studies evaluating combining and/or layering the therapeutic benefits of targeted alpha therapy. 

I hope that you find these 3 selected articles not only of educational clinical value but also of intellectual stimulation for present and future therapeutic pathway

Written by: Neal Shore, MD, FACS, Medical Director for the Carolina Urologic Research Center, Myrtle Beach, South Carolina

Published Date: September 12th, 2017