Case 2 Introduction: A 62-Year-Old Man With mCSPC and Front-Line Approach

Dan Petrylak, MD: The second case is a 62-year-old man who presents the emergency room with progressive fatigue, low back pain, decreased appetite, weight loss, an abnormal rectal exam, and abnormal urinary retention. His past medical history is unremarkable; he has no family history of prostate cancer. He was biopsied and he was found to have Gleason … adenocarcinoma in 8 out of 12 cores. He had a PSA [Prostate-Specific Antigen test] of 200 and bone and CT scans demonstrated 2 metastatic lesions in the pelvis. He had a hemoglobin of 9.5 and an ANC of 1.7. His performance status was 1. He had de novo metastatic castration-resistant prostate cancer, and he was tested for germline abnormalities, which were negative. The patient started abiraterone and prednisone along with antigen deprivation therapy with an initial decrease in PSA. This another typical case of castration-sensitive prostate cancer. Again, he's got a high PSA of 200 with 2 lesions in the pelvis. As we talked about before, this is the type of patient that may benefit from local radiation therapy to his prostate in addition to his abiraterone and prednisone, and antigen deprivation therapy. I think that the initial impression is this is a typical case of castration-sensitive disease.

I agree with the front-line approach. I think it's appropriate to consider abiraterone and prednisone or any other antiandrogen. Chemotherapy would not be appropriate in this patient because he does have low volume disease. I agree with the approach of abiraterone in this setting. Now, the question I think that's also interesting is: does the use of abiraterone in the front-line setting impacts its use of in castration-resistant disease? The answer my mind is yes; if a patient does develop castration-resistant disease, they've had prolonged exposure to abiraterone and this may influence what you do as the next step. Clearly, although there's only data in the metastatic castration resistance state, there's little data about using enzalutamide or apalutamide after abiraterone in a patient who just becomes castration-resistant. However, I would assume that it's going to be the same as what we see in the overall castration resistance state. Often, using a second antiandrogen will give you a lower response rate than if these patients have seen any of the other next-generation antiandrogens. The duration of response is generally short and the patient’s PSA response rates are generally about 20%-40%. Now, there is a trial called the CARD trial, which has looked at this question in patients who've received docetaxel and a next-generation antiandrogen. That study found that if they've used Abi [abiraterone] first, then they get ENZA [enzalutamide], or ENZA then Abi, and comparing that to cabazitaxel showed a radiographic progression-free survival benefit for cabazitaxel as well as an overall survival benefit. Again, I think that the previous drugs will influence what happens later and how these other treatments are affected, particularly if there is a class effect.

This transcript has been edited for clarity.

Case 1: An 80-Year-Old Man With Metastatic Castration-Sensitive Prostate Cancer

Initial presentation

• An 80-year-old man presents with nocturia and decreased appetite
• He has mild pain in his hip and lower back

Patient History, Lifestyle and Clinical workup

• No family history of prostate cancer
• Patient is a widower without transportation for regular medical visits
• He is physically frail but his cognitive function is good
• TRUS and biopsy revealed adenocarcinoma of the prostate gland, Gleason grade group 3 [3+4] with disease in 8/12 cores.
• PSA 500 ng/mL; Hb 9.4 g/dL; ANC 1.5
• Bone and CT scans showed 1 metastatic lesion in the pelvis

Diagnosis

• Patient is diagnosed with de novo metastatic castration-sensitive prostate cancer
• Germline genetic testing is negative

Treatment

• Patient is started on ADT at diagnosis with initial decrease in PSA
• He expresses interest in receiving more intensive treatment to control his PSA
  • However, he does not want to receive chemotherapy since he has heard about the risk of side effects
  • He is looking for a treatment option that will allow him to have a good quality of life
• Due to his frailty, inability to make frequent medical visits and request not to receive chemotherapy, the patient is treated with ADT + apalutamide
• At his 1-year follow-up, the patient’s PSA remains undetectable, and he continues to report a good quality of life

Case 2: A 62-Year-Old Man With Metastatic Castration-Sensitive Prostate Cancer

Initial Presentation:

• A 62-year-old man presents to the emergency room with progressive fatigue, low back pain, decreased appetite, weight loss, abnormal rectal exam and urinary retention

Patient History, Lifestyle and Clinical workup

• Past medical history is unremarkable
• No family history of prostate cancer
• Biopsy revealed adenocarcinoma of the prostate gland, Gleason grade [4+4] with disease in 8/12 cores.
• PSA 200 ng/mL; Hb 9.5 g/dL; ANC 1.7
• Bone and CT scans showed 2 metastatic lesions in the pelvis
• ECOG PS is 1

Diagnosis

• Patient is diagnosed with de novo metastatic castration-sensitive prostate cancer
• Germline genetic testing is negative

Treatment

• Patient is started on ADT plus abiraterone at diagnosis with initial decrease in PSA

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