Multidisciplinary Approach Key to Radium-223 Treatment for Metastatic Prostate Cancer

Joseph F. Renzulli, II, MD

Radium-223 dichloride (Xofigo) has shown a significant survival advantage in treating patients with metastatic castration-resistant prostate cancer (mCRPC) who have symptomatic bone metastases.

In the randomized phase III ALSYMPCA study, which examined 921 patients with symptomatic mCRPC and two or more bone metastases, radium-223 demonstrated a median of 14.9 months overall survival (OS) versus 11.3 months with placebo (hazard ratio, 0.70; 95% CI, 0.58-0.83; P <.001) when either was administered with the best standard of care.

Radium-223 is a targeted alpha emitter that is able to bind to materials in the bone and emit radiation directly to bone tumors. The therapy is particularly promising as prostate cancer metastasizes to the bone in approximately 90% of advanced cases of prostate cancer.

However, questions have emerged regarding patient selection, combining treatments with other modalities, and optimal treatment sequencing, including identifying molecular biomarkers to help guide sequencing.

To answer those questions and improve overall patient care, a multidisciplinary approach is needed for radium-223 treatment for patients with mCRPC, says Joseph F. Renzulli, II, MD, director of Prostate Surgery, Miriam Hospital, Adult Urology, and assistant professor of Surgery (Urology) at Alpert Medical School of Brown University. Renzulli was the lead author of a recent paper published in the Journal of Multidisciplinary Healthcare titled, “Radium-223 dichloride: illustrating the benefits of a multidisciplinary approach for patients with metastatic castration-resistant prostate cancer.”

OncLive: What were the goals of the paper?

How can a solo practitioner incorporate a multidisciplinary approach?

Who would be the ideal clinicians to make up the multidisciplinary team?

How does your study further the discussion in terms of proper sequencing?

There are other nucleotide therapies. Why did you choose radium-223?

Urologists are not always trained to administer chemotherapy. However, this is a trend that is growing. What is your advice?

What is the most important finding oncologists should take away from this paper?

In an interview with OncLive, Renzulli explains the efforts of Miriam Hospital’s Genitourinary Multidisciplinary Clinic in the treatment of patients with mCRPC with radium-223 and the benefits of the collaboration between urologists, medical oncologists, radiation oncologists, nuclear medicine physicians, and essential ancillary support services for these patients.Dr Renzulli: Our goal was to demonstrate that the appropriate utilization of radium-223 is more effective in a setting of multidisciplinary care. It is important that all of the disciplines—radiation oncology, medical oncology, and urology&mdash;work as a team to address the problem. There is not one specialty that is able to administer radium-223 because it requires a referral to a radiation oncologist or nuclear medicine practitioner from an oncologist or urologist. These patients are not solely in the hands of a nuclear medicine physician or radiation oncologist. It requires a dual interaction, if not a tri-interaction, between specialties to have a successful integration of radium-223 into the practice and then a successful outcome for patients.For the solo practitioner, there is still a role for multidisciplinary care. The solo practitioner just needs to team up with the medical or radiation oncologist and/or nuclear medicine physician and create a protocol for patients who are candidates for radium-223 and decide how they are going to manage that. I think we need to move away from the constant dogma of multidisciplinary—it doesn’t have to be a “true” multidisciplinary center where patients are seen by all three doctors at once, but rather it should be a collaborative effort where the doctors have created an arrangement where there are going to be multiple doctors caring for the patient in the advanced prostate cancer setting. Obviously, our situation is the purest, where we have the patient being seen by all three doctors in one clinic at one time, but we also recognize that it is just not feasible in a lot of the models. It does not mean that you cannot collaborate in a multidisciplinary fashion to provide better care for these patients with advanced prostate cancer.In my opinion, it would be urology, radiation oncology, and medical oncology. If you think of the continuum of care, you would include the urologist, radiation oncologist, and medical oncologist.There is significant heterogeneity in castration-resistant prostate cancer. We know by the AR-V7 mutation that there are some cancers that may be more resistant to the oral therapy. We know that they may do better with chemotherapy upfront. In terms of sequencing, the one thing that we have definitively started to do is not use oral therapies back-to-back. Therefore, if someone is on an oral therapy, such as abiraterone acetate (Zytiga) and prednisone and it starts to fail, we may use chemotherapy or radium-223 first before going back to an oral therapy. If they have a nice response, they may go back to enzalutamide. However, we are not using them back-to-back because of the cross resistance that we have seen develop.We should emphasize that radium-223 is the only radionucleotide that has an OS advantage. The others are more palliative, so it is important to distinguish them. We are in a scenario now where there are multiple different treatments for mCRPC that have a survival advantage and that is where we are focusing most of our therapies.In light of the STAMPEDE trial and the CHAARTED data, urologists have to be comfortable treating with chemotherapy for metastatic prostate cancer. It is not that they have to be the ones administering the chemotherapy, but they certainly have to coordinate care in a multidisciplinary fashion with an oncologist that they feel they can provide that service to their patients safely and effectively. I think that is of paramount importance now in prostate cancer.Radium-223 is a novel therapy for patients with mCRPC that can provide them a survival advantage and that it is best to coordinate that care between the urologist and the radiation and medical oncologists, so that the patient can complete the therapy and not have issues arise that interfere with completing the 6 cycles.