Castrate-Sensitive Prostate Cancer: Second-Line Therapy


Second-line therapies available to treat hormone-sensitive prostate cancer and recommendations for use based on current clinical data.

Nicholas Vogelzang, MD, FASCO, FACP: When you have used, in this case apalutamide, you have used the best androgen receptor inhibition. The role of second-line androgen receptor therapy with abiraterone or enzalutamide is quite uncertain, and there may not be much left to do. The CARD study, for example, looked at patients who had previous abiraterone or enzalutamide, and randomized them to the alternative androgen receptor inhibitor or to cabazitaxel. Cabazitaxel was superior in those patients. I do not think there is a big role for a second-line androgen receptor inhibitor for these patients. In the majority of patients after failure of abiraterone, enzalutamide, or apalutamide, you are left with having to go to chemotherapy, or radium, sipuleucel-T, or one of those sorts of drugs. For a long time, we were quite enamored with the use of a second androgen receptor inhibitor. The CARD trial has deflated our optimism about that sequence. I would still do it, and most doctors, particularly prostate cancer doctors, would do it, but there is not a high level of benefit for most patients.

I mentioned my patient with Bloom syndrome who has a PSA [prostate-specific antigen] doubling time of 1 month, and I explained to him that this was not a good thing. Yesterday I said to him, “We better be prepared for some bad outcomes.” He feels perfectly well. He has nothing but a fast doubling time and minimal disease. But the Johns Hopkins [University] study many years ago from Mario Eisenberger, [MD,] and that team said that a PSA doubling time of under 3 months is an ominous finding, and you have to be prepared to change therapies if you start seeing a rapid PSA doubling time. As long as you are prepared and as long as you explain the significance of it to the patient, you can be ready for it. We have options, like I said, you have PARP inhibitors, sipuleucel-T, radium, and several types of chemotherapy. You have platinum agents, so those are all good drugs. We simply have to be prepared to deploy them at the right time.

Transcript edited for clarity.

Case: A 76-Year-Old Male With Recurrent Castrate-Sensitive Prostate Cancer


  • A 76-year-old man diagnosed with localized prostate cancer, 4 years ago
  • At that time, he underwent EBRT


  • Patient was lost to follow-up; returns due to intermittent hip pain
  • PMH: obese, BMI 32; prostate cancer; otherwise unremarkable
  • FH: No known family history of cancer
  • PE: left hip tender to palpation, slight limp and evidence of decreased weight bearing on left lower limb

Clinical workup

  • PSA 10 ng/mL; doubling time 3 months
  • Core needle biopsy with TRUS showed adenocarcinoma of prostate
    • Gleason score (4+4)
    • Bone scan revealed 2 bone metastases: 1 in the left femur 1 in the left pelvis
  • Chest/abdominal/pelvic CT scan positive for 4 pelvic lymph node metastases
  • Diagnosis: stage IV mCSPC
  • ECOG PS 1

Treatment and Follow-Up

  • He was started on ADT + apalutimide 240 mg qDay
  • At 3-month follow up: PSA 2 ng/mL
  • Repeat imaging showed no new lesions

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