Optimal Use of Bone-Targeted Therapy for mCRPC

Nicholas J. Vogelzang, MD, FASCO, FACP:This is a 55-year-old who presented with nocturia and a PSA of 4.5. A digital rectal exam revealed a T2 area of hardness. Biopsy was positive for Gleason 3+3, now called combined Gleason scores of 1. Clinical stage was T1c, but he had a lump so maybe it was a d2. Patient went on active surveillance. About a year later, his PSA had risen to 10. Repeat biopsy now showed a Gleason 4+3, and 8 of the 12 cores were positive. So, the patient clearly had more advanced disease. Whether it was there before or not, it is hard to be sure.

He was asymptomatic and started on goserelin. About 6 months or so later, his PSA did not go down. What was unusual is his PSA, in fact, rose to be 34. So, you have a case almost of de novo resistance to hormone therapy. That should only occur in about 5% or less of patients.

CT scan was negative. Because the PSA was rising, they began him on abiraterone and prednisone. Within a short period of time, although his PSA declined to 15, he had a cardiac arrhythmia, which does occur with abiraterone. So, the treating physician decided to switch to enzalutamide. Again, a perfectly appropriate decision. Enzalutamide did not have any negative effects, but also did not lower the PSA much.

So, now another 3 to 4 months goes by and the patient begins to develop back pain—or not even back pain, just an achiness—and some mild fatigue. The doctor says, “Well, let’s reimage.” CT scan shows bone metastases. A fluoride PET bone scan confirms lumbar and pelvic bony metastatic disease. PSA is up to 45, and the ALK phosphatase is starting to rise. The patient has symptoms, mostly fatigue, but also a rising PSA, new findings on x-rays, and new findings on the fluoride PET scan.

At that point, it’s extremely appropriate to begin radium-223. The patient develops a drop in the PSA, which isn’t that common with radium. Normally, the PSA does not drop much, but it fell from 45 to 25. His ALK phosphatase comes down into the normal range, and his symptoms of fatigue begin to improve. He has had 4 doses. The questions are: was this the right sequencing? Should he get additional radium, etc? So, we’re going to cover some of those topics.

Transcript edited for clarity.