Radium-223 Administration and Effective Imaging Studies

Nicholas J. Vogelzang, MD FASCO, FACP:I generally tend to give radium-223 at an earlier stage; I like to give it before chemotherapy—the logic being that the bone marrow is robust. I have not deployed palliative radiotherapy to the bone marrow, which of course will destroy the bone marrow wherever it is given. Ultimately, if we give multiple courses of palliative radiotherapy, the patients will become long-term anemic. Likewise, the chemotherapy option is nice to reserve because many patients are, quite frankly, frightened of chemotherapy. I don’t believe that’s always warranted, but nonetheless there’s the fear of chemotherapy. It’s a lot easier to tell a patient, “Well, we’re going to start by giving you an immune treatment—in this case, sipuleucel-T [Provenge]—and an IV treatment with radium-223.” I usually sequence those very quickly together. I will, for example, begin them on the sipuleucel-T, and at the same time begin prepping them for radium-223. Sipuleucel-T takes only 5 weeks. In this patient I would probably do sipuleucel-T and then transition into radium.

Radium-223 should be given for 6 doses. Multiple studies have shown that fewer than 6 doses result in inferior outcomes. The study presented by Cora N. Sternberg, MD, last year at the American Society of Clinical Oncology [ASCO] 2018 Annual Meeting looked at 3 different ways to give radium-223. One was to give higher doses but still in 6 cycles. Another was to give a longer duration—up to 12 cycles; however, neither of those alternatives showed a significant improvement in outcomes with radium-223. So the standard is still radium-223 for 6 doses.

Imaging in castrate-resistant prostate cancer is an inexact science; bone scans are not particularly helpful. Likewise, CT [computed tomography] scans are not accurate because they cannot distinguish between active cancer and inactive or dormant cancer because the bones look white. You really can’t use regular CT or regular technician scanning. There is a role for a regular PET [positron emission tomography] scan. The FAT in PET scans can be very helpful, but they’re not allowed by most insurance companies. As I mentioned earlier, the fluciclovine [Axumin] or Axiom scan can be very helpful to distinguish which bone metastases are active and which are not. And likewise the PSMA [prostate-specific membrane antigen] scan can be very definitive. For example, you may see a patient who has on his CT scan multiple spots on the bone, and yet when you do the PET scan with either Axumin or F18, you may find that only 1 or 2 of the bone lesions are active—the others are either inactive or eradicated by the hormone therapy. So it’s somewhat unique to see that not all bone metastases seen on CT scan are active.

Transcript edited for clarity.

Hormone Sensitive mPC progressing to mCRPC

March 2015

H&P:

• A 76-year old gentleman presented to his urologist with nocturia and lower back pain
• PMH: unremarkable
• Digital rectal examination revealed an abnormal area of hardness

Imaging:

• Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with a Gleason score 8 [4+4] with 9 of 12 cores positive
  • PSA, 85.3 ng/mL
  • Testosterone, 300 ng/dL
• CT scan showed multiple metastases of the spine
• He was started on abiraterone + prednisone + goserelin
• PSA and testosterone level continued to decline over the next 2 years to PSA, 0.1 ng/ml; testosterone <3 ng/dL.

March 2018

• After 3 years of therapy patient reported increasing fatigue
• PSA and testosterone levels began to rise
  • PSA increased from 0.5 ng/ml to 1.0 ng/ml; 2.0 ng/mg to 4.8 ng/ml at 2-3 month intervals
  • Testosterone, <3 ng/dL
  • CT scan shows several new bone metastasis; others improved
• Patient is diagnosed as castration resistant and abiraterone + prednisone was discontinued
• Radium-223 therapy was initiated