mCRPC Case Impressions & ADT + Abiraterone Response

Nicholas J. Vogelzang, MD, FASCO, FACP:This is a 76-year-old man who presented with urinary outflow symptoms and back pain to his urologist. He had a digital rectal exam showing a clearly abnormal rectal—a T3 or T4; the urologist referred him for biopsy, which revealed a Gleason grade group 4, or what we call a grade group 4—Gleason 8 prostate cancer in 9 of 12 cores. Preoperatively his PSA [prostate-specific antigen] was 85. His testosterone was noncastrate at 300. He had a bone scan and a CT scan showing multiple bone metastases and no soft tissue or lymph node involvement.

Using the data from STAMPEDE and LATITUDE trials, the patient was treated with LHRH [luteinizing hormone-releasing hormone] agonist therapy and abiraterone. The patient had a dramatic PSA and clinical and symptomatic response; his PSA dropped to undetectable. He felt very well, and as expected his testosterone also progressed to a very low level. This response lasted for about 3 years, and then at around that time his PSA began to slowly climb—initially from a 0.1 to 0.2, then with a doubling time of about 3 to 4 months—ultimately reaching a level of around 5, after which he became slightly symptomatic: His appetite was decreasing and fatigue increasing; he didn’t describe bone pain per se, but he did say, “Well, I’m needing a little bit more aspirin or Advil,” and I started to talk to him about stopping abiraterone and moving on to radium-223 [dichloride; Xofigo].

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