Case Review: Rationale and Methods in mCRPC - Episode 2

Initial Impressions of Patient With High-Risk Localized PC

June 2, 2020
Evan Y. Yu, MD

Evan Y. Yu, MD: I think this patient was treated in quite a standard fashion. He had high-risk localized prostate cancer upon diagnosis. Interestingly, his symptoms that brought him to the primary care physician could have been consistent with prostate cancer but were unrelated. But they did lead a primary care physician to do some work-up that led to a prostate cancer diagnosis. His initial pain was certainly not from prostate cancer since he didn’t have bone metastases.

But I think the treatment course that he took was very reasonable. For high-risk localized prostate cancer, one would treat that with androgen deprivation therapy and radiation, or with a radical prostatectomy. He chose to undergo androgen deprivation therapy with radiation.

His prognosis was not great. After he came off androgen deprivation therapy he relapsed quite quickly, with a fairly rapid rise in his PSA [prostate-specific antigen]. So in that situation, after primary local definitive therapy, I think our 2 most important prognostic markers are looking at when the PSA relapses and PSA doubling time. His time to relapse and his PSA doubling time were very short, so it wasn’t surprising that one might find metastatic disease when he underwent reimaging studies.

Treatment with androgen deprivation therapy and abiraterone is reasonable as well. This is based on data for abiraterone and androgen deprivation therapy in combination for new metastatic prostate cancer. I will say the caveat is that he was previously treated with localized disease, and that population usually does better than those who present with de novo metastatic prostate cancer.

But given his rapid course of relapse and his short PSA doubling time, I don’t think it was unreasonable to be aggressive and treat him with androgen deprivation therapy and abiraterone. Per the STAMPEDE and LATITUDE trials, data support that approach.

Now, he was receiving it for the hormone-sensitive disease state, and one would anticipate he might get years of a very low, well-controlled PSA and well-controlled disease. However, about a year later, his PSA started to rise again. This is a short period of response to initial androgen deprivation therapy and abiraterone. One would certainly expect the duration of response for that to be over 2 years, or perhaps in the 3-year range. So again, this was sticking with the trend that he had very aggressive disease.

Additionally, sticking with that trend, when he came back to medical attention and a treatment change was considered, he was already having symptomatic disease. He reported some pain in his femur. He wasn’t requiring narcotic pain medication, but it was clearly in a site where he had prior bone metastases. And so, I think institution of radium-223 was very reasonable there. This approach is regulatory approved and shows a survival benefit for patients with bone metastatic castration-resistant prostate cancer who lack visceral metastases and who have symptoms, and I think that’s exactly his 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