Hormone Sensitivity in Patients With mCRPC

Nicholas J. Vogelzang, MD, FASCO, FACP:The definition of hormone-sensitive prostate cancer has been well-known since the 1940s, when Charles Brenton Huggins, MD, first reported that testosterone ablation therapy—namely surgical castration—induced complete remissions in many patients. His first patient was castrated and had survived 14 years before he died of the disease. Charles Huggins, while at the University of Chicago, was awarded the Nobel Prize for Physiology or Medicine for that work in addition to his progress with hormone-dependent breast cancer. His understanding of hormone-dependent cancer included both breast cancer and prostate cancer.

Hormone-dependent prostate cancer is in many ways similar to hormone-dependent breast cancer. It has a bone-dominant characteristic. It can give you the benefit of therapy without harshness of chemotherapy, with the only adverse effects being the effect of castration on both the woman and the man; this includes hot flashes, changes in body index, increasing weight, and arthralgia. The standard of care for many years has been medical or surgical castration.

In the 1970s, LHRH [luteinizing hormone-releasing hormone antagonists like degarelix; Firmagon] were developed—and then in the 1980s, antiandrogens like bicalutamide [Casodex], flutamide [Eulexin], and nilutamide [Nilandron] were developed, all of which were proven to be marginally valuable; however, some believed it was not enough. It came to about a 5% benefit by adding an antigen receptor antagonist.

The biggest breakthroughs in the treatment of hormone-sensitive disease came with the addition of the CHAARTED, STAMPEDE, and GETUG trials, showing that docetaxel [Docefrez] added to [LHRH] agonists had a major survival advantage measuring on the order of a year or so—sometimes as much as 2 years; this became the new standard. Shortly thereafter, however—2 years ago—it was presented at the American Society of Clinical Oncology Annual Meeting that adding abiraterone [Zytiga] to LHRH agonists improved the median survival by about 2 years. The current state of the art is either giving LHRH agonists and docetaxel, or LHRH agonists and abiraterone; a lot of us debate whether you should give both. Maybe you should give LHRH agonists, chemotherapy, and abiraterone—but those studies need to be done.

This patient is elderly—I therefore ultimately I decided to give him the combination of LHRH agonists and abiraterone. He did very well and had a 3-year duration of response, and then slowly his PSA [prostate-specific antigen] began to rise, showing his tumor had become androgen independent, or castrate resistant.

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