Case Review: Rationale and Methods in mCRPC - Episode 3

Overall Survival Data in mCRPC

Evan Y. Yu, MD: This patient and physician provider chose to use radium-223. There are certainly many treatment options for metastatic castration-resistant prostate cancer. At this time, for an unenriched all-comers population, there are 6 options that are regulatory approved, FDA approved in the United States, that show a survival benefit. And so, whenever I see a patient, I like to run through what all of those options are.

Now, he’s already received 1 of those options. In the hormone-sensitive setting, he was started on abiraterone and prednisone. There are obviously novel hormonal agents that work via androgen signaling pathways. Abiraterone is a CYP17 lyase inhibitor, and it decreases production of androgens by 1 to 2 logs lower than what LHRH [luteinizing hormone-releasing hormone] therapy can do alone. But he had already received that.

Another androgen signaling inhibitor that he could have received that is approved in this setting is enzalutamide. However, we have good data that show that sequencing 1 novel hormonal agent after the next usually doesn’t lead to outstanding response rates or outstanding outcomes. I think it is very reasonable to consider going to an agent that switches mechanism of action.

Another approved agent in this setting is sipuleucel-T, and that’s an immunotherapy. The idea is you’re basically producing an androgen presenting cell that targets prostatic acid phosphatase, and that leads to a survival benefit. It’s ideal for patients who are asymptomatic or minimally symptomatic. It’s ideal for patients who have lower volume of disease and lower PSA [prostate-specific antigen] levels. In this situation, given that he was starting to become symptomatic—he was minimally symptomatic but was starting to become symptomatic—and because of the treatment course that he had, I think the choice of sipuleucel-T might not have been ideal.

Another option that I think would have been very reasonable to consider in this situation is moving on to cytotoxic chemotherapy. Docetaxel is regulatory approved for metastatic castration-resistant prostate cancer and can also be used to treat metastatic hormone-sensitive prostate cancer. In this setting, they used abiraterone in that situation. So for somebody who’s becoming symptomatic, certainly I think the risk-benefit ratio starts to fall in favor of giving docetaxel. Docetaxel, when efficacious, can improve pain symptoms, and that might be worth the adverse effects of chemotherapy. Cabazitaxel is another microtubule disrupting agent that is regulatory approved after docetaxel. I wouldn’t consider it in this patient since he had not received docetaxel.

Transcript edited for clarity.


Case: A 66-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer

Initial presentation

  • A 66-year-old man presented with increasing difficulty walking and sleeping on his back due to lower back and hip discomfort
  • PMH: hypertension, medically controlled; no known family history of cancer
  • PE: DRE revealed a nodular prostate; otherwise unremarkable

Clinical workup

  • Biopsy with TRUS showed adenocarcinoma of prostate
    • Stage T2N0M0
    • Grade group 4
    • Expected survival > 5 years
  • Germline testing: MLH1, MSH2, MSH6, PMS2, BRCA1/2, ATM, PALB2 and CHEK2
  • Chest/abdominal/pelvic CT scan showed no evidence distant metastases or lymph node involvement
  • Bone scan was negative
  • PSA 26 ng/mL

Treatment and Follow-Up

  • EBRT for 8 weeks + neoadjuvant concurrent, and adjuvant ADT for 2 years
  • At 6 months post-ADT follow-up; PSA 5.9 ng/mL
  • At 12 months follow-up:
    • Patient reported continued back discomfort, difficulty walking and loss of appetite
    • PSA 16 ng/mL
    • Bone scan showed multiple lesions in the right femur and pelvis
    • Abiraterone + ADT was initiated for 1 year
  • At subsequent follow-up:
    • Patient complained of increased bone pain in right femur
    • PSA 18.6 ng/mL
    • Abiraterone was ceased; ADT continued
    • Treatment with radium-223 dichloride was initiated; 6 infusions completed and well-tolerated at post-infusion follow-up