Castrate-Sensitive Prostate Cancer: Frontline Therapy


Current treatment options available to treat hormone-sensitive prostate cancer in the first-line setting and factors that impact treatment selection.

Nicholas Vogelzang, MD, FASCO, FACP: This patient has fairly good-risk disease, and in the CHAARTED study, good-risk disease did not have a major benefit from docetaxel therapy. That was not the case with either the STAMPEDE docetaxel study or the GETUG trial. Those 2 trials showed benefit for docetaxel in lower-volume disease, so I tend to be somewhat skeptical that chemotherapy should not be given. I tend to think that chemotherapy has a role in all these patients, but nonetheless, an elderly man is often somewhat frail. We do not know a lot about his other conditions, comorbidities, etc.

In his case, he was apparently fairly clear that he did not want to have chemotherapy. Many people come in having strong biases against chemotherapy, so that tends to lean heavily on our decision. As long as he does not have a lot of cardiovascular disease, hormone therapy is usually the way to go. In the United States certainly, over 90% of patients do not get an LHRH [luteinizing hormone-releasing hormone] agonist and docetaxel. They get a LHRH agonist and one of the hormone agents to complement that. In general, the patient’s age, comorbidities, and ECOG performance status generally lead us to give a hormone doublet rather than a LHRH agonist and docetaxel. That makes life pretty easy for most of us.

On the other hand, if the patient is young, fit, and has a long life expectancy, then chemotherapy at the beginning is quite favorable. I tend to favor it. In the TITAN trial published by Kim Chi, [MD,] about 17% of the patients got 3 drugs: they got leuprolide, docetaxel, and apalutamide. Those patients did not have any better outcome than the patients on 2 drugs, leuprolide and apalutamide. There will be an upcoming study called PEACE-3, and that will look at 2 drugs vs 3 drugs, and we do not yet have the answer.

The bottom line is that, for the majority of patients with hormone-sensitive disease, the androgen receptor-targeted therapy is used. Of the 3 agents, leuprolide and abiraterone, leuprolide and enzalutamide, and leuprolide and apalutamide, they all seem to be pretty similar. The study that seemed to be the most striking and hit the target fastest, mainly with the lowest PSA [prostate-specific antigen], the longest duration of response, was the TITAN trial published in The New England Journal of Medicine by Dr Chi. Therefore, that is one of the regimens that I routinely discuss with the patients. The quality of life was a superior outcome, and the PSA nadir, particularly in terms of early onset of PSA nadir, was superior for that regimen. I have been using apalutamide as my androgen receptor-targeted therapy choice more and more.

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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