Case Review: Rationale and Methods in mCRPC - Episode 5

Significant Impact of COVID-19 on the Treatment of mCRPC

June 2, 2020
Evan Y. Yu, MD

Evan Y. Yu, MD: Unfortunately, we’re facing challenging times right now. Obviously at the forefront of everyone’s mind is COVID-19 [coronavirus disease 2019]. That has significantly affected oncologic practices across the country, and the world. Being a part of a large comprehensive cancer center, many clinical trials have been put on accrual pause to limit extra visits for the patients and also to limit touch points for our clinical and research staff. I think that has been a challenge, and hopefully will be a short-term issue. We’re starting to come out of our darkest time with COVID-19, and things are starting to ramp up again. I know our center is slowly starting to open up some clinical trials.

There are many other considerations. This includes hospital beds, and ICU [intensive care unit] beds, and ventilators, in particular. Our center has made a real effort to try to limit hospital admissions of patients who don’t absolutely need to be admitted. That includes considerations of inpatient regimens, clinical trials with inpatient regimens, and even the thought of administration of drugs that have high potential for toxicity that might lead to the patients requiring inpatient admissions to the hospital.

This really affects how we think about cytotoxic chemotherapy agents. In some diseases, the myelosuppression can be very pronounced and very long-lasting. And febrile neutropenia risk is very high. We’re fortunate in prostate cancer, where that risk is not as high with single-agent docetaxel or cabazitaxel chemotherapy. However, it still happens, and it needs to be a consideration.

In my practice, it is certainly a discussion that we have. We are concerned that myelosuppression might increase a patient’s risk of COVID-19. And in that situation, when we have good alternative treatment options, we’re discussing this with the patient. And oftentimes, we’re choosing other treatment options.

So if we were to insert the COVID-19 discussion into this patient’s case that I just presented, I already find enough reasons to use radium-223 and to save docetaxel for later. But another consideration would be that I think the myelosuppression that radium-223 causes is at a much lower level and is a much lower risk than with a chemotherapy like docetaxel. And with that consideration, I think that emphasizes that this patient probably gained the best treatment at that time with radium-223.

There is one issue that wasn’t discussed in this case, and that’s the use of bone protective agents. We all know there are very strong data that support both denosumab and bisphosphonates for use to prevent skeletal-related events and the symptomatic skeletal events in those who have bone metastatic cancers. Certainly, that includes castration-resistant prostate cancer. There are also data for use of these agents in patients who might be at high risk for osteoporotic fractures.

Certainly, men treated with androgen deprivation therapy for prostate cancer are at higher risk of osteopenia and osteoporosis, and there are data to show that use of these agents can prevent osteoporotic fractures.

There are also some data from some database and retrospective analyses that show that these agents don’t cause antagonism with radium-223 and may be beneficial in combination. So that is a discussion I would have with this patient. I would personally add either a bisphosphonate or denosumab in that setting. I would probably use denosumab in this situation.

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