Case 2: High-Volume Versus Low-Volume Metastatic CSPC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Jorge Garcia, MD:Alicia, for us treating in America, I think that over the last 4, 5 years, whether you agree or disagree with the US Preventive Services Task Force [USPSTF] guidelines for PSA [prostate-specific antigen] screening, we’ve been seeing an increase in the incidence of these patients walking in the office with metastatic disease. What is usually your approach to those patients when they walk into the office in Chicago?

Alicia Morgans, MD:Absolutely, we’ve been seeing an increase. I agree. I think that up until ESMO [European Society for Medical Oncology Congress] 2019, and actually even after ESMO 2019, I have focused initially on defining whether this is high-volume or low-volume metastatic disease. In the CHAARTED study, it was defined as 4 or more bone metastases with at least 1 outside the axial skeleton, or visceral metastases. That more or less is the definition that’s been applied in several groups, though of course LATITUDE used a high-risk definition instead of a high-volume definition. But that definition, I think, was what helped me decide what systemic therapy I was going to offer those patients. Certainly, based on the CHAARTED data at least, this suggested that there was more of a benefit in the high-volume metastatic patient population for docetaxel than for docetaxel use in the low-volume metastatic setting.

Additionally, of course, we know that radiation may be helpful for men with low-volume metastatic disease—radiation to the primary. That’s kind of how I was thinking about it. But surprisingly, perhaps, at ESMO 2019 we saw STAMPEDE data that was reevaluated by that high- or low-volume status, and they suggested that in their patient population, which notably was predominantly de novo metastatic rather than recurrent metastatic hormone-sensitive disease, there was actually no difference in outcome for patients treated with docetaxel, whether they were high volume or low volume. Now, I’m still thinking about high and low volume very much, but I’m also thinking about, just as with this patient, we would recognize de novo metastatic versus not as I’m thinking about systemic therapy.

Neal Shore, MD, FACS:You began by talking about the USPSTF controversy, and I think we all recognize now that we’re starting to catch up with the rest of the world. Our incidence of newly diagnosed prostate cancer and our percentages of metastatic disease are going up, which is unfortunate on a certain level. In 5% to 30% of European countries, patients present that way. And 30% to 60% of African and Middle Eastern countries and parts of Asian and Latin American countries present this way. It’s an interesting phenomenon. The comments you made, Alicia, I think are really important about the recent STAMPEDE trial. Nicholas James presented this at ESMO just a couple of weeks ago, saying that, “Yeah, you know what, we’re putting forward a different thought process that low-volume patients can benefit from ADT [androgen deprivation therapy] and docetaxel as opposed to the CHAARTED long-term data, which say they could not.”

And there was sort of this rigid criteria: 4 or more bone lesions—just kind of picked out of a hat—and 1 had to be axial, or you had to at least have an appendicular lesion as well as axial lesions and/or a visceral metastasis. I bring that up because you think of this globally now. How many patients present with metastatic disease? This high volume/low volume has a certain arbitrariness to it, depending on the imaging you use. Then we have the issue around tried-and-true use of docetaxel, 6 cycles, which is fairly inexpensive, fairly accessible, and ubiquitous around the world. And now up front, we’re confronting all the data that we’re going to talk about with oral therapies. Is the survival, the progression, different? Is the tolerability different? This is a great case to talk about.

Transcript edited for clarity.