Transcript:David I. Quinn, MBBS, PhD: I think that what we think is the definition for candidacy for chemotherapy in this setting is likely to evolve. We’ve got data that show that the old SWOG (Southwest Oncology Group) definition of high risk certainly predicts a good incremental survival for early chemotherapy with docetaxel. So, we’d all agree on that. But, we’re sitting here looking at this gentleman, who’s presented from the ER to the urologist, thinking, you know, this guy’s got poor-risk disease. And the sort of things that I’d look at is he’s got a really big lymph node in his pelvis, he’s got at least one metastasis, but he doesn’t fit the ECOG (Eastern Cooperative Oncology Group) 3805 Sweeney definition of high risk. If you look at some other data that’s coming forward about aggressive variant prostate cancer from MD Anderson—from Paul Corn and Ana Aparicio—they looked at patients where this guy would fit the definition because he’s got a big node. And we need some other information. If he’s in my clinic, I’m thinking, how big is his prostate? So, big primary unusual features like a big lymph node in the pelvis on its own, elevated CEA (carcinoembryonic antigen), some other things that maybe are going to come into practice, and we have to look at those.
I’d be thinking about, in terms of giving this guy a 6-month turn on systemic therapy to work out, whether he’s going to be a responder or not, whether I add chemotherapy. But I’d probably just end up doing androgen-deprivation therapy (ADT) because the SWOG trial by Maha Hussain—9346—showed that the nadir at 6 to 7 months in the PSA (prostate-specific antigen) and also assessment of other RECIST (Response Evaluation Criteria in Solid Tumors) response shrinkage predicted the survival of the patient. This guy is maybe going to live 1 year, and if he’s a nonresponder, that’s what that data would predict. If he’s a really good responder or even an intermediate responder, he’s going to live somewhere between 3 and 7 years. And those latitude groups are the areas where I think we need to be trying to address the question as to whether treating the primary with surgery or with radiation therapy is appropriate. And we are actually planning a SWOG trial to look at surgery, and surgeons are either totally dubious or really enthusiastic about the trial. Because we don’t know whether there’s a benefit, but the big question to me is how big this guy’s prostate is and what are his urinary tract symptoms.
Raoul S. Concepcion, MD: To me, I always thought anecdotally it was better—especially in a young person—to get rid of the primary just because you know he’s going to progress and just to control local disease, especially urethral obstruction, hematuria down the road. So, Mike, Neal had mentioned some of the more advanced scans. Are you guys using any advanced scanning in Oklahoma? What do you guys have available?
Michael S. Cookson, MD, MMHC: No, we haven’t really used the PSMA (prostate-specific membrane antigen). I was just at a meeting in Australia and I think it’s like standard of care over there for the PSMA-type of study for looking for metastases. We don’t have our own cyclotrons, we don’t have the choline PET. We’re looking for new things and I think things are coming, but I would say in routine practice, sodium fluoride for the bone scan for looking for small early metastases is one technique we use. And, of course, we use a lot of local imaging and MRI for assessing resectability of large aggressive primaries.
Raoul S. Concepcion, MD: David, let’s say he had advanced imaging using sodium fluoride—which I think many people believe is more sensitive, especially for bone—and he had 10 lesions in his axial skeleton versus what they only see as 1 on bone scan. Does that sway your treatment? Would you push him more towards chemo-hormonal therapy?
David I. Quinn, MBBS, PhD: I think it would, but I think when we go back to our evidence base. We don’t have that data, so it’s a big problem. When we did a comparison of FDG (fludeoxyglucose)—sugar PET—sodium fluoride PET, and technetium scanning, it was quite clear that in patients with just PSA-rising disease, the bone PET—the sodium fluoride PET—was 30% more sensitive, so we found more lesions. And when we found more lesions, usually we at least doubled the lesion count compared with the technetium scan. The issue, of course, is whether that alters practice, but I think we all are sitting here looking at this guy saying, ‘Look, his PSA is 125. We know he’s got de novo metastatic disease. He’s got to have more metastases.’ Our imaging studies are just not good enough to find them.
Raoul S. Concepcion, MD: Dan, in the CHAARTED data, we know that there clearly was an advantage of chemo-hormonal therapy with delayed mCRPC (metastatic castration-resistant prostate cancer) and a survival benefit. Let’s just say this gentleman received 6 cycles of docetaxel plus ADT, is followed along, and then progresses. What is the role then of rechallenging with docetaxel at that point? How does the medical oncology world think about that now?
Daniel P. Petrylak, MD: The way I think about this in terms of timeframes, if this is a relapse that’s a couple of years after the initial treatment, I’m inclined to run the castrate resistant playbook the way I would as if they’ve never received the adjuvant chemotherapy at the beginning. If this patient progresses within a couple of months of stopping the chemotherapy, this is somebody who is not going to do well overall. I would not re-induce docetaxel. I probably would go to cabazitaxel or make sure that I have next-generation sequencing of his tumor to look for an oncogene target, such as BRCA- or any DNA-repair mutations, because this patient is not going to do well with standard therapy. And he probably will not do well with second-generation hormone therapy either because he’s most likely de novo hormone resistant.
Raoul S. Concepcion, MD: Neal, thoughts?
Neal D. Shore, MD: I think Dan brings up a very interesting point regarding the genomic sequencing, especially in biopsying someone like this, and his metastatic sites to get a better understanding of the right target. And, I think a lot of our colleagues in the community don’t typically have access to that; but I think that’s going to change a lot in the future as to actually get the right genomic sequencing of the metastases. It will help better inform us, I completely agree. In patients that I’ve had who’ve progressed very rapidly with chemo-hormonal therapy—younger patients typically—it’s very worrisome. If they don’t have liver metastases, these patients, I have started them on combined therapy with radium and/or novel hormonal therapy. But, I’m following them extremely closely, more vigilantly than I normally would some of my other patients, and they’re very, very tough. But I think what Dan brings up is a great point. Ultimately, will these patients do better if they have certain types of mutations with DNA-repair mechanisms, as carboplatin or perhaps some of the new PARP (poly ADP ribose polymerase) inhibitors that are coming down the lane?
Transcript Edited for Clarity