Case Review: Rationale and Methods in mCRPC - Episode 1

Case Review: 66-Year-Old Develops mCRPC

Evan Y. Yu, MD: Today we have a very interesting case of a 66-year-old gentleman who, unfortunately, develops metastatic castration-resistant prostate cancer. At initial presentation, he had developed some difficulty walking and sleeping on his back due to some lower back and hip discomfort.

His past medical history included hypertension that was medically controlled. He had no known family history of cancer. He went to see his primary care physician who, given the patient’s pain and the fact that the patient had never been screened before for prostate cancer, did think about that on the differential diagnosis.

He performed a digital rectal exam that showed a nodular prostate, so he referred him to a urologist who went ahead and found, on a prostate needle biopsy, that he had stage T2N0M0 adenocarcinoma of the prostate. This was grade 4. While this is of high-risk disease, he still has an excellent prognosis, certainly more than 5 years.

Because of the excitement with germline testing, and because it’s now been shown to be seen in about 12% of those with metastatic prostate cancer, and maybe 3% to 7% for those with high-risk localized disease, this patient did undergo germline testing that included multiple genes, such as MLH1, MSH2, MSH6, PMS2, BRCA1 and BRCA2, ATM, PALB2, and CHEK2. This was unremarkable testing.

He did undergo staging studies with a chest, abdomen, and pelvic CT scan. They showed no evidence of distant metastases or lymph node involvement. His bone scan was unremarkable. However, of note, his PSA [prostate-specific antigen] was 26 [ng/mL], and he clearly, by grade and PSA, had high-risk localized disease.

Multiple treatment options were discussed with the patient, including radical prostatectomy and radiation. He decided to embark upon radiation therapy. He underwent 8 weeks of external beam radiation therapy and neoadjuvant concurrent and adjuvant androgen deprivation therapy for 2 years.

His PSA went undetectable during the time he was undergoing treatment, but then, after he stopped androgen deprivation therapy, surprisingly 6 months later his testosterone had recovered and his PSA had gone up to 5.9 [ng/mL]. It was felt that he should be observed for a period of time. At 12 months, his PSA was found to be 16 [ng/mL].

He underwent some restaging scans at that time. It was shown that he actually had some metastases on the bone scan that included the right femur and the pelvis. At that point, he went on combined androgen deprivation therapy with an LHRH [luteinizing hormone-releasing hormone] agonist, also with abiraterone acetate.

He had a period of nice response, with a PSA that went undetectable for approximately a year before his PSA began to rise again rather aggressively. And surprisingly, at this point, he began to develop some pain. This pain was mostly in the right femur where he had known bone metastases before.

He was not requiring any narcotic pain medication, but he was using intermittent Tylenol and ibuprofen. At this point, abiraterone was ceased but the LHRH agonist therapy was continued. Treatment with radium-223 dichloride was initiated. He did receive 6 infusions successfully, and treatment was well tolerated at post-infusion follow-up.

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