Case-Based Discussion: Sequencing Prostate Cancer Therapy

Case-based discussion on sequencing prostate cancer therapies for a 72-year-old man with a metastatic adenocarcinoma with small-cell components, a PSA score of 80, and a Gleason score of 10.

A recent panel discussion at the 5th Annual Interdisciplinary Prostate Cancer Congress focused on how best to sequence therapy in prostate cancer. The panel was moderated by Daniel P. Petrylak, MD, and included Robert Dreicer, MD, and Oliver Sartor, MD. To foster further discussion and to build a consensus about the best treatments OncLive is opening up the discussion to our online audience.

The series will be presented in three parts, each representing a unique case. Users are invited to participate both in the poll questions and discussion using the comments below.

First Treatment Option

Case 1

The patient is a 72-year-old man with a PSA score of 80. A biopsy of the prostate reveals Gleason score 10 adenocarcinoma with small-cell components. A bone scan demonstrates extensive metastatic disease, and a CT scan of the abdomen/pelvis demonstrates three hepatic metastases.

Panel Discussion

Dreicer: When you see a patient like this, with hepatic metastases and a hint of small-cell pathology, you worry about a mixed lesion because that is more typical biologic behavior. So, clearly, androgen-deprivation therapy (ADT) is appropriate. Every once in a while, a patient will show up with liver metastases from the adenocarcinoma component, so I think it’s reasonable to start with ADT. I’d probably re-image the patient in eight to 10 weeks, assuming he is asymptomatic. Obviously, if there are symptoms, you’ll start systemic therapy.

Sartor: I’m thinking there are probably two components to the tumor. If small-cell is 80% on the biopsy, that pushes me a bit more toward combined androgen blockade with carboplatin/etoposide.

Second Treatment Option

The patient was treated with combined blockade with six cycles of carboplatin and etoposide up front. His PSA normalized, and a CT scan of the adenocarcinoma showed that his liver metastases went away completely. He was maintained on combined blockade. After one year, his PSA rises to 40 and his liver metastases comes back. He also develops symptomatic bone pain.

Sartor: To me, that PSA rise indicates that the androgen axis is still intact. So I feel that bringing an additional way to attack the androgen axis, like the abiraterone, is very reasonable. We don’t have a lot of data in this sort of setting—in fact, we have almost none—and I wouldn’t fault anybody who would go with the carboplatin/ docetaxel.

Dreicer: It still may be that what we’ve seen here is just mostly adenocarcinoma, so if at this juncture he’s symptomatic, I think abiraterone is a very reasonable choice. I probably would again give him four weeks of therapy and see whether or not there’s any clinical response.

Third Treatment Option

The patient was treated with abiraterone/prednisone. On that treatment, his PSA dropped from 120 to 30, but a CT scan shows continued progression of the disease in his liver. Do you think the patient has a small-cell component at this point? Do you think he has an adenocarcinoma?

Sartor: Is there a role for measuring chromogranin A or neuronspecific enolase? Would that help determine whether to do a re-biopsy at that point?

Petrylak: I’ve found it to be all over the place, and you can’t really get into a trend. Doing another biopsy is not unreasonable, but at the same point, is it going to alter your therapy that much that you want to delay and arrange for a CT-guided biopsy?

The patient was treated with carboplatin and docetaxel, and responded to treatment. The liver lesions are completely gone, although the cancer did progress into his lymph nodes, so he’s now on cabazitaxel.

Closing Commentary

Sartor: I’d like to comment some more on carboplatin/docetaxel. We’ve published studies on that, and it turns out from a PSA perspective that it’s really quite an active combination. We were using it second-line and have some patients getting some pretty reasonable responses. Nobody has pursued this because it’s an old drug and old drugs die, but it’s not a bad combination at all.

Audience member: How would a re-biopsy change your decision?

Petrylak: Well, I think that you may not go forth with a small-cell regimen if you saw that the cancer was adeno-dominant.

Dreicer: The optimal time to do that would have been up front, because if you’ve demonstrated a small-cell component, you already know what you’re going to do. And if it was a pure adenoma, you’d also do something different. By the time you go downstream, you’re really talking about palliation.

Users are invited to share their thoughts below.