mCRPC: Medical and Radiation Oncologist Collaboration

Nicholas J. Vogelzang, MD, FASCO, FACP:At this next juncture, there’s no question that radium-223 has to be given for 6 doses. Then the question is, what do you do next? The radiation oncologist may wish to radiate those bone metastases to consolidate the response. Or, alternatively, a radiation oncologist may have said, “Well, I want to radiate those lesions first.” I don’t have a problem either way with that. In fact, if you wanted to radiate the bone and give radium-223, that would be perfectly appropriate. In ALSYMPCA, that was allowed. In all the expanded access programs, that was allowed. And there was no excess safety signal in those patients who got radium concurrently with external beam radiation. So, there’s no problem. Giving radium with chemotherapy, that’s another story. It’s a little harder to achieve, and so, therefore, you have to be careful.

Now, how do you coordinate that with your radiation oncologist or your nuclear medicine physician who’s giving the radium? Well, the medical oncologist really has to be the one who drives this ship because you’re the one, as a medical oncologist, who has to sequence these agents or layer them. And you’re going to have to say, “I need to get the radium in, I need to give him a little bit of rest, and then I’m going to come in with chemotherapy.” Because although this patient had a nice drop in their PSA from 45 to something in the 20s, that does usually not often occur. And usually, if anything, the PSA is starting to rise after 4 cycles, but stay the course. That’s the take-home message: stay the course, don’t stop after 4 cycles.

Whenever I get to a patient and I say to them, “Okay, you’re going to get 6 doses,” I may have the radiation oncologist go, “Well, their PSA is rising and they don’t feel that good.” I go, “It’s okay, it’s okay, you can finish this up.” Sometimes it’s very difficult to finish, but you insist upon it. You say, “This is what gives optimal survival, optimal quality of life, optimal pain control, and gives you the longest duration of benefit with radium-223.”

So, what are the indications to start radium-223? A lot of my colleagues say, “Well, the patient doesn’t have pain. Therefore, they don’t need to start radium.” That’s wrong. You don’t need symptoms to start radium, you need some minor symptoms. But in ALSYMPCA, the randomized phase III trial, they didn’t need to have pain. All they had to have was symptoms. That could be fatigue, weight loss, appetite loss, any number of minor symptoms. We had patients on ALSYMPCA who only were taking acetaminophen or nonsteroidals. And yet they, in fact, had the greatest degree of benefit.

If you wait to give radium-223 to patients with bone pain, you will be disappointed. Radium is not given for pain; it’s given for improvement in survival, improvement in quality of life. It reduces the need for narcotics. It reduces the time to need for chemotherapy. It has a whole host of benefits, but primarily being given for reduction of pain is not its primary endpoint. Only about 20% or so of patients when given radium will have a drop in their pain. So, you need to give radium as a life-extending, life-prolonging therapy when you have a 6-month window to do so. You don’t want to wait until the very end when the patient has had everything under the sun—including external beam radiation, chemotherapy, abiraterone, sipuleucel-T, and enzalutamide—and then you go, “Well, I guess now I should use radium.” Well, that’s not the right time.

In the old days when we had strontium as the only available radiopharmaceutical, it was given for pain, but it also had severe bone marrow suppression. And so, there was a lot of disappointment with strontium because it would induce severe bone marrow suppression when given too late in the course of the disease. So, again, radium-223 is not the same as a beta admitter, like strontium. Radium-223 is an alpha emitter with minimal bone marrow suppression, albeit you can get bone marrow suppression in the face of a super scan or extensive prior chemotherapy or extensive prior radiotherapy. Again, everything points to give radium earlier in the natural history of the disease.

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