First-Line Therapy Options for mCRPC


An expert oncologist outlines first-line treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC).

Case: A 65-Year-Old Man With Prostate Cancer

January 2018

Initial Presentation

  • A 65-year-old man was diagnosed with localized prostate cancer
  • Biopsy revealed adenocarcinoma of the prostate gland, Gleason score 7 [4+3]
  • PSA 15.7 ng/mL
  • Baseline staging: T3bN1M0 with right seminal vesicle and pelvic lymph node involvement

Initial Treatment

  • He undergoes radical prostatectomy with PLND
    • PSA nadir of 0.4 ng/mL post-surgery
    • Gleason 7 (4 + 3) confirmed
    • Positive surgical margins
    • Baseline staging confirmed – AJCC Stage IVA

February 2019

Follow-Up Notes

  • Serum PSA, 38 ng/mL; ALP, 289 IU/L
    • Metastatic retroperitoneal LNs outside resection field
    • Abdominal nodes
    • Bone mets in ribs and thoracic spine
  • Genetic testing: BRCA2 mutation-positive

Additional Treatment

  • Abiraterone + prednisone initiated
  • Improved pain, PSA, and ALP

October 2019

Follow-Up Notes

  • Patient reported bone pain
  • Laboratory testing revealed rising PSA and ALP (serum PSA, 350 ng/mL; ALP, 2500 IU/L)
  • Imaging showed radiologic progression
  • ECOG PS 1
  • PSMA PET CT: increased uptake in retroperitoneal and abdominal LNs

mCRPC Treatment

  • Treated with docetaxel x4 cycles and denosumab
    • Serum PSA, 38 ng/mL; ALP, 289 IU/L
    • Reporting bone pain increased in back, now reporting pain in hip area
  • Bone scan and CT scan:
    • Enlargement of retroperitoneal and abdominal LNs
    • Additional bone mets noted in pelvic region


Daniel J. George, MD: When I have a patient that is diagnosed with metastatic CRPC [castration-resistant prostate cancer], first-line treatment options are predicated on a couple of factors. The first is, what were their prior treatments. To be metastatic castrate-resistant, you’ve had to had androgen deprivation therapy. But in that earlier disease settings, patients could be also treated with several other therapies, from androgen receptor inhibitors or androgen biosynthesis inhibitors, to chemotherapies, to even investigational agents. These are important considerations in the selection of our first line for metastatic CRPC.

I like to also think about the disease burden that patients have and the disease course. If this is rapid progression from initial hormonal therapy to castration resistance, they’re much more likely to have a resistant biology to other hormonal manipulations. If this is somebody that has relatively slow progression and low-volume disease, they’re patients that may respond to additional hormonal manipulations, or even immunotherapies, like sipuleucel-t. These are some of my considerations.

Then the other end of the spectrum would be our symptomatic high-volume patients, patients like this gentleman that we presented, where painful bone metastases is a phenotypic characteristic of their disease and something that’s affecting their quality of life. It’s also highly prognostic, and it’s why we chose a cytotoxic therapy like docetaxel in this case. To me, those characteristics, what they had for prior therapies, the pace of disease and the volume and symptoms of disease, determines my approaches.

When I can, I’ll use secondary hormonal therapies as a frontline agent if they’ve not received that before, or if they received it in the past and had a break and had a very slow progression, this is a treatment of choice along with immunotherapy. If they’ve got more higher volume, symptomatic disease, and they’ve had that novel hormonal agent already, then I’m more likely to choose a cytotoxic therapy like chemotherapy or a radiopharmaceutical. Then if they haven’t had a novel hormonal agent yet in the metastatic castrate-resistant space, those are the patients where I feel good about starting a novel hormonal agent on them. We also consider clinical trials of course in this space, but where I feel confident they have a high likelihood of benefiting from that frontline novel hormonal agent.

Transcript edited for clarity.

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