Treatment Recommendations Upon Metastasis in CRPC - Episode 2

Monitoring Response to ADT in Prostate Cancer

October 29, 2018

Daniel J. George, MD:There are a couple of things that are really interesting and concerning about this case, in terms of PSA [prostate specific antigen]. PSA is a really good marker of disease response for our patients, but it’s also a very worrisome prognostic marker of lack of response. There’s a nice study that was done by the SWOG [Southwest Oncology Group] that demonstrated that patients who start primary hormonal therapy and don’t drop their PSA to less than 4 have very poor outcomes and prognoses. Patients like that rapidly progress to castrate-resistant disease and die early from this disease. This is the type of patient who may fit that profile. This would raise my concerns that they’re going to have an accelerated course, and we’re going to need to think about layering our therapies because we may not be able to get through 5 different disease progressions to use each treatment modality that we have as a monotherapy.

The enzalutamide use in this patient was actually a bit ahead of its time. This patient presented with a rapidly rising PSA. Within just a few months, his PSA went from a very low level up to 47. In that space of time, the patient hadn’t yet developed bone metastasis by the standard CT [computed tomography]/bone scan. If we’re going to use molecular imaging like PSMA PET [prostate-specific membrane antigen positron emission tomography] or Axumin PET, we know that we might actually see that metastatic disease burden better. But, it’s probably evolving so quickly that it wasn’t there yet. These are exactly the kinds of patients with very short PSA doubling times who were enrolled in the trials like PROSPER and SPARTAN, which demonstrated the clinical benefits associated with enzalutamide or apalutamide. In 2016, that would have been enzalutamide. Rightly, I think this patient was treated proactively for those kinds of complications. What’s interesting and what wasn’t commonly seen in those studies is patients having a relatively short response. Within 6 months, this patient developed metastatic disease. We saw that in the placebo arms but not as much in the treatment arms. It really speaks of the inherent resistance to mechanisms like enzalutamide and the lack of dependence of this patient’s particular tumor on the androgen receptor pathway.

Transcript edited for clarity.


mCRPC Treated With Radium-223 Therapy

January 2015

H&P:

  • A 71-year old gentleman presented with urinary incontinence
  • Past medical history: HBP controlled with lisinopril
  • On digital rectal examination prostate was enlarged
  • Patient was asymptomatic

Imaging:

  • Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with a Gleason score 9 [4+5] with 9 of 12 cores positive
    • PSA, 10.2 ng/mL
  • CT scan was negative for metastases
  • He was started on a 3-month depot injection of leuprolide 22.5 mg and treated with 7800 cGy IMRT

April 2016

  • Patient returned for 3-month injection; his PSA level increased to 47 ng/mL
    • CT/Bone scans were negative for metastases
  • He was started on enzalutamide
    • PSA, 12 ng/mL

October 2016

  • 6 months later the patient complained of severe fatigue and lower back pain
    • Imaging with CT and bone scan showed multiple metastases of the spine and pelvis
    • PSA levels increased to 76 ng/mL
    • ALP, 268 U/I
  • Radium-223 therapy was initiated in addition to continuing enzalutamide
  • After 3 infusions of radium-223
    • PSA declined to 31 ng/mL
    • ALP decreased to 80 U/l
    • CT scan showed no new bone metastases
    • Fatigue decreased, and patient’s physical activity increased