Case 1: An 80-Year-Old Man With mCSPC

Dan Petrylak, MD: This patient is an 80-year-old male who presents with nocturia and decreased appetite. He has mild pain in his hip and lower back. Upon further examination, he does not have any family history of prostate cancer. He's a widower who does not have transportation for regular medical visits. He's frail, but his cognition is good. Transrectal ultrasound-guided biopsy revealed an adenocarcinoma of the prostate, Gleason grade group 3 with 8 of 12 cores positive. His PSA [prostate-specific antigen] is 500 with a hemoglobin of 9.4 and ANC of 1.5. His bone and CT scan demonstrated 1 metastatic lesion in the pelvis. He had negative germline testing and he was diagnosed as having de novo metastatic castration-resistant prostate cancer. He was started on antigen deprivation therapy with initial PSA decrease and did not want chemotherapy in addition to the antigen deprivation therapy; he was started on apalutamide based upon these reasons. At a 1-year follow up the patient's PSA remained undetectable, and he continues to have good quality of life.

This is a typical course, and I agree with the management of this patient. He has metastatic disease; he was treated on it with antigen deprivation therapy. He had a decline in his PSA on ADT plus apalutamide. For the most part, I do agree here. The one thing based upon the STAMPEDE data that one could also consider is in a patient who has low burden metastatic disease, which this patient does and that's defined as less than 4 lesions on bone scan, that radiation therapy to the prostate may also improve survival over those patients who do not receive local radiation therapy. I think that that's another consideration that I would put for this patient; I agree with the management at this point.

There are several different options to consider for this patient. There are 3 FDA [Food and Drug Administration]-approved next-generation antiandrogen agents that could be used within 3 months of the initiation of antigen deprivation therapy. Those include apalutamide, enzalutamide, and the combination of abiraterone and prednisone. Then, the chemotherapy is also considered for these patients with docetaxel for 6 cycles. That is, for patients who have more than 4 lesions on bone scan or visceral disease. How do we choose from one versus the other? With chemotherapy, 1 issue with the volume of disease, as I just mentioned, is some patients may not want to have to take an oral pill regularly; some patients just simply want the treatment over and done with. Docetaxel is finished within 18 weeks. Most patients will choose antiandrogen therapy. How do we decide between these 3 different agents? Firstly, the side effect profile. Abiraterone and prednisone can cause transaminitis, hyperemia, hypertension, as well as edema. There's more data that has been coming out over the last years, particularly from Jefferson, where they've found that patients with preexisting cardiac conditions may actually have increased cardiac risk if they receive abiraterone, prednisone. Those are factors to consider for a patient that is hypertensive, and if you're having trouble controlling their blood pressure. If they have diabetes, even though the dose of steroids is low, that may influence that if they have cardiovascular disease. I tend to choose the antigens over abiraterone and prednisone. Although, there are cases where we do see hypertension with the antiandrogens as well. Enzalutamide and apalutamide are similar drugs. However, enzalutamide may have a little bit more fatigue. Apalutamide has hypothyroidism as well as fatigue as a side effect, but perhaps not as much as enzalutamide. Darolutamide was of the subject of a phase 3 trial in this clinical space, and showed a similar survival benefit to what we're seeing with these other agents. However, it's not yet FDA-approved in this situation. The advantage of darolutamide is that it does not cross the blood-brain barrier and theoretically, it has less fatigue than the other agents.

I agree with the frontline treatment for this patient. He has low-volume metastatic disease. All patients do tend to benefit from these antigens regardless of volume. I agree with the use of apalutamide. One could have used any of the other 3 agents that we spoke about before that have FDA approval; I agree with the use of apalutamide.

PSA is one of the drivers in doing imaging. They've been studies such as the RADAR consensus group that have looked at the use of imaging in these patients. For the most part, I will image the patient when their PSA starts to rise. Usually, 3 consecutive PSA rises; that's to determine whether these patients do have progression in bone or in other lesions. Generally, what I would do is a PSA level every 3 months to see if the patient is having any changes in their PSA. However, the imaging is generally triggered by a PSA rise. Some recommend imaging the patient on a yearly basis; there really is no consensus on what to do before these patients become castration-resistant.

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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