Local and Systemic Therapeutic Options in Low-Volume Prostate Cancer

Transcript:Raoul S. Concepcion, MD: Our next case is going to touch on something a little bit different here. This is a 58-year-old African American male who presents with prostate cancer. And as most of you know, a lot of times these patients will show up in the emergency room with some abdominal pain, they don’t really access the system, often times of lower socioeconomic groups. So, this gentleman is a 58-year-old African American. He was referred to urology after he was seen in the emergency room for abdominal pain. And in part of the work-up, he was noted to have a CT scan which showed a 4-cm node to the left-obturator fossa, and he had a suspicious lesion on the CT scan that showed some changes in the L5 vertebral body. When he was seen by urology, his PSA was 125 ng/ml. His rectal exam showed a diffusely firm prostate, very suspicious for carcinoma. In May of 2015, he underwent a transrectal ultrasound of the prostate and traditional sextant needle biopsy, and he had 8 out of 12 cores positive for Gleason pattern 4+4. Again, we had the CT scan which showed a 4-cm node to the left-obturator fossa and a bone scan showed a suspicious lesion to the L5 vertebral body. Still very active, asymptomatic. Neal, what do you think about this patient?

Neal D. Shore, MD: Well, I think this is someone with obviously very, very significant aggressive disease. And so the fact that you have such a large lymph node, you have an obvious lesion on a technetium bone scan, I think it probably goes without saying that if we were to order a more sensitive, more specific, more accurate newer scan—such as a PSMA (prostate specific membrane antigen) gallium scan, a sodium fluoride PET scan, possibly some of the other choline-derived scans—we’d see many more lesions. But that said, the bottom line is, in the United States, the majority of clinicians are still primarily using technetium CT. So, he meets the definition of low-volume, androgen-sensitive metastatic disease, which is the criteria for less than four bone lesions and no evidence of visceral metastases. The chemotherapy hormonal data that everyone is resonating around, which makes great sense in survival improvement, is based upon the high-volume group. But this is somebody that I’d probably give very strong consideration to a combined chemo-hormonal approach. He’s got very worrisome disease. The other flip of that would be to say, ‘Well, he’s got low-volume disease, do we want to treat his primary and treat his oligometastatic disease aggressively, perhaps with either extirpation of the node and/or a focal radiation to his spine in combination with systemic therapy, and/or removal of his prostate, and/or radiating it?’ So, there’s a lot of unanswered questions for some young fellow like him, 58-years-old. But these are some of the unmet answers that we have right now, so it’s a tough call. He needs aggressive therapy.

Raoul S. Concepcion, MD: Mike, what do you think about the role of aggressive treatment of the primary of his prostate in this setting of a very young, healthy gentleman? How aggressive should we be in this oligometastatic patient for the primary tumor of the prostate?

Michael S. Cookson, MD, MMHC: Well, that’s a great question, and one that we do not have all the answers for yet. There are examples in other tumor systems where removal of the primary tumor—the source, the seed for soiling the rest of the body, certainly standard of care—we see a little bit of that with renal cell carcinoma, where we’re often asked to remove the kidney before we go on to additional systemic therapy. However, other than some very small reports and a little bit of registry type data where there’s a hint of survival benefit, we don’t really have high-level evidence of that yet. It’s tempting, and we know that in some patients they may benefit, but I think we’re a long ways away from recommending that as a standard therapy in all patients. I think that, as Neal said, treating him systemically is probably mission critical. And you can split hairs about the development of oligometastatic disease. I think the more we do learn about enhanced imaging and better ways to see these things, many of these patients have lots of metastatic deposits, even if they’re not apparent to us on traditional radiographs. So, I think that most of the strategies that would come about in a clinical trial would be some combination of our most effective systemic therapy, androgen deprivation perhaps with docetaxel. We just finished a large intergroup study in men with high-risk, clinically localized disease to see how that will pan out. It will take a few years for us to get that data, but all of us—as surgeons that participated in that—saw some pretty dramatic responses to the primary. Patients made it through it. So, I guess that, sort of off protocol, I would like to see his response to systemic therapy, reassess him, and then decide whether or not I thought it was appropriate to render local therapy.

Raoul S. Concepcion, MD: Dan, this is based upon he’s got low-volume. He’s got a node, one lesion in the axial skeleton. Again, Neal had mentioned sort of this data now with chemo-hormonal therapy. Expand on that for us.

Daniel P. Petrylak, MD: So, there had been three randomized trials that looked at the combination of androgen blockade with varying number of cycles of docetaxel. The Chris Sweeney trial used 6, the European trial had a median of 8, if I remember correctly, and then there’s the trial that was done in Britain—the STAMPEDE trial—that I believe had 8, as well, if I remember correctly.

Neal D. Shore, MD: Six.

Daniel P. Petrylak, MD: Six. The issue really is, is this an appropriate patient? The only trial that selected patients based upon disease volume is the Sweeney trial, and those data are not yet mature enough to determine whether there is a survival benefit or not. The overall trial turned out to be positive. The patients with high-volume disease had about an 18-month improvement in their median survival. I like the approach that Mike has of giving the systemic treatment up front first, then seeing how the patient does. I think we’re all beginning to have this experience now of seeing some of these patients who blow through chemotherapy and hormone therapy initially, and that would not be a patient I think would be appropriate for a localized therapy. The data are showing that there is a significantly different improvement in survival in favor of the early chemo-hormonal therapy.

Transcript Edited for Clarity