Radium-223 for mCRPC: A Radiation Oncologist's Viewpoint

Glen Gejerman, MD:In the past, the radiopharmaceutical agents were typically beta emitters, which were quite good at going into the bone and treating disease so that patients did achieve a palliative effect. Unfortunately, they really were not specific, so there was a lot of bone marrow failure. And, justifiably, a lot of oncologists were reluctant to use the beta emitters, because there was no survival advantage and patients often were precluded from having additional therapies due to their bone marrow compromise. Xofigo, radium-223, is quite different in that it’s an alpha emitter, and because of that, the deposition is different. It’s a calcimimetic. It goes specifically to the parts of the bone that are affected by cancer, but it spares the bone marrow, so there’s much better tolerance and less myelosuppression. The most important thing about this drug is that the ALSYMPCA trial showed there was a survival benefit. So, not only does it relieve pain and prevent secondary skeletal events, but patients who are treated also live longer.

It’s very important that these patients are evaluated in a multimodality clinic. A urologist, a urologic oncologist, and a radiation oncologist should review the patient’s case and determine what the appropriate therapy is. We have so many different treatment options now, and the concept of therapeutic layering is so important. It’s vital that these clinicians decide what the proper order is. A patient who has very bulky lymphadenopathy or visceral disease should be treated with chemotherapy. On the other hand, early on in the castrate-resistant phase, if the patient has bony involvement, that would be a patient who I would strongly consider for radium-223.

For this patient, it’s quite logical to use radium-223. The patient has clear castrate resistance and their PSA is rising despite the fact that they were treated with androgen suppression. Once we get to that phase and there’s bony involvement, we know that we have to intervene in order to improve survival. If the patient has bony involvement but lymph nodes are either not present or less than 3 cm, and there is no visceral involvement, these are the patients who are most appropriate for radium-223.

As a radiation oncologist, it’s very important that I interact with the urologist, urologic oncologist, and the radiologist. And it’s very important that we utilize the latest studies. For example, sometimes patients will have a completely normal looking bone scan, but the sodium fluoride PET/CT scan will show early involvement. That helps us identify patients early in the course of disease who are most appropriate for therapy such as radium-223.

We know from the ALSYMPCA trial that less than 70% of patients received a full 6 cycles of radium-223. That’s a major impact on their outcome. We know the patients who received 1 to 2 cycles did not do as well as the patients who received the full 6 cycles. So, in discussion with a urologic oncologist, I always stress the importance of identifying these patients early and supporting them through the full 6 cycles. Those are the patients who will receive the maximum clinical benefit.

Transcript edited for clarity.

November 2014

• A 55-year old gentleman presented with nocturia and PSA level of 4.5 ng/mL
• PMH: Insignificant
• DRE revealed an abnormal area of hardness
• Biopsy showed adenocarcinoma of the prostate gland with a Gleason score 6 [3+3], clinical tumor stage T1c                                                                                                                                                                  
• The patient remained on active surveillance

November 2015

• When he returned after 1 year:
  • PSA, 10 ng/mL
  • Repeat biopsy showed Gleason 7 [4+3] with 8 of 12 cores positive
  • CT scan was negative for metastases
  • He remained asymptomatic
• He was started on a 3-month depot injection of goserelin

February 2016

• PSA, 34 ng/mL
• CT scan was negative for metastases
• He was started on abiraterone and prednisone
  • PSA declined to 15 ng/mL and remained stable
  • After 4 months, he developed cardiac arrhythmia attributed to prednisone; he was switched to enzalutamide
  • PSA remained stable

August 2016

• 3 months following therapy switch, the patient complained of severe fatigue
  • CT scan showed enlarged lumbar spine and pelvic bone metastases
  • ¹⁸F-FDG PET showed increased FDG uptake in several areas of the lumbar spine and pelvis
  • PSA, 45 ng/mL
  • ALP, 225 U/I
• Radium-223 therapy was initiated and enzalutamide was continued
• After 4 cycles of radium-223:
  • Fatigue decreased significantly
  • PSA, 25 ng/mL
  • ALP, WNL
  • CT showed no new bone metastases