Alessandro Viti: Thank you for the introduction. Thank you for the invitation. I'm so pleased to be here today to discuss about that.
Leslie Ballas: Of course. First of all, set the stage. Tell us about EMBARK.
Alessandro Viti: All of us knows how EMBARK really redefined the treatment for high-risk BCR patient, and how it's impacting our clinical practice every day. Although, in the last few years, PSMA PET did something like that as well. Right now, all the patient with a BCR are re-staged with PSMA PET and all the patient in the EMBARK setting were re-staged with conventional imaging. This is leading us some doubts about how should we treat those patients, and how should we define an EMBARK-like patient in the PSMA era.
Leslie Ballas: And so, what did this research show?
Alessandro Viti: So, we compared our retrospective cohort from over almost three decades with a new cohort of the last five, six years re-staged with PSMA PET to see how those patients shifted. What were their characteristics comparing the old generation of patient with this new generation of PSMA PET stage patient. And incredibly, that's something expected, but incredibly, the EMBARK-like patient saw doubling time for surgically treated patient. Doubling time equal or smaller than nine month, and PSA level greater or equal to one. Virtually disappear so we don't have those patient anymore. But what it's interesting is that if we go to see how patient that are not EMBARK legible are staged, we can see that most of those patient has already oligomets. So that's really interesting from my point of view. Even in light of the just released 10 years update of the EMBARK study, and their amazing results in term of survival, how we can consider those patients with few mets on PSMA PET.
Are those really compared to what we define according to the STAMPEDE and the CHAARTED that's a low-volume metastatic patient? Or this is a new category of patient, which is in the middle between an EMBARK patient, so non-metastatic high-risk BCR and a really real low-volume metastatic patient stage with conventional imaging. Those should bring us some reflection and probably for sure need further study and further trials to assess how those patient could be better treated and optimized. Even in terms of probably de-escalation instead of escalation of the treatment for those one.
Leslie Ballas: So tell me in your modern cohort of patients that got PSMA PET scans but met EMBARK criteria, were those patients already being treated with androgen deprivation therapy?
Alessandro Viti: No, all those patients were previously surgically treated, never exposed to ADT, never exposed to any kind of neoadjuvant treatment. So all of them were surgically treatment on a pretty large cohort of more than 500 patients, just 26 met the EMBARK criteria. So that's a really short amount of patient. Because us today we know that whenever we have a relapse, if we want to restage our patient, we tend to restage our patient at lower level PSA, which frequently means we never reached a PSA level of one, especially in a surgically treated cohort. And if we compare the doubling time of those patient, they also tend to have a higher PSA doubling time. Which translate in a really small amount of patient that really are considered EMBARK-like. And once again, when we stage this patient, most of them have a really detectable mets.
Leslie Ballas: Because EMBARK, even without the PSMA PET positivity, showed a metastasis-free survival with the combination of ADT and enzalutamide, would you say that the patients who are EMBARK-like even in the era of PSMA PET, even if they have oligomets detected on PSMA PET, that they should all be on ADT and enzalutamide to get that same benefit?
Alessandro Viti: What you're asking me it's if a mets patient need to be on ADT and enzalutamide or any RP, obviously? My answer is, yes. I think that the reflection that should lead us it's whether some oligomet patient can deserve the intensification after two or three year. Similarly to what we saw in the STAMPEDE trial after two years of abiraterone, and 36 month of ADT. If those patient could deserve the intensification of treatment, and that could be a feasible option for patient with few oligomet. Maybe in light of what WOLVERINE suggest us, I think an MDT to those patient. And could be interesting to see if some of those patients could be treated and cured instead of just prolonging their survival, but obviously that's just a speculation, and would be interesting to see what the future is preserving for those patients.
Leslie Ballas: Yes. As a radiation oncologist, when you detect these oligomets on PSMA PET, obviously that's something that we believe there might be a role for MDT and whether or not to combine that with ADT. ADT and an ARPI is of certainly of question. NRG is looking at that. With the Promethean study, there was the publication of RADIOSA, but certainly much more to be learned.
Alessandro Viti: Yeah, that's true.
Leslie Ballas: Thank you so much for talking to us about your abstract. Congratulations.
Alessandro Viti: Thank you.