Dr. Fonteyne, it is truly such an honor to have you here. Thank you for joining us.
Valerie Fonteyne: Thank you for the invitation.
Leslie Ballas: I know that you started your discussion reviewing some of the data about early salvage radiotherapy. Tell us, that is the standard of care currently. Can you just tell us a little bit about when you initiate early salvage and the data supporting it?
Valerie Fonteyne: Yeah, so I think what is very important is to keep in mind the patient that is sitting in front of you. So if you have a healthy patient with a good life expectancy, I think that early salvage radiotherapy should be initiated once there is a suspicion of biochemical recurrence. And the definitions differ a little bit across the several phase-three trials that have been published. But in general, I think that if you perform your salvage radiotherapy around the threshold of 0.2, it's a very safe threshold, not to over-treat the patients but still to be in time to give your patient the best option to be cured at the end. So threshold of 0.2 is more or less the one that I'm using. Although if there are more aggressive tumor characteristics, I might lower and might wait to treat consecutive PSA rises without really waiting for the threshold of 0.2.
I think we have very nice data to support the use of an early salvage radiotherapy. I think that everyone is familiar with these different trials. So adjuvant radiotherapy for me is definitely not something that we should offer to all of our patients. Again, this is also field of discussion. But for patients who really fit within the early salvage radiotherapy trials, meaning the patients with a positive surgical margin, the lower Gleason scores and the lower PSAs and the pT3, I think that these are patients that should absolutely be offered an early salvage radiotherapy.
Leslie Ballas: And what PSA are you using, if that's even your criteria, to add hormone therapy with the early salvage radiotherapy?
Valerie Fonteyne: Well, that is, of course, a completely other area of debate. And we have now several meta-analysis of the different trials that I've looked at whether or not it makes sense to add a potentially toxic drug to salvage radiotherapy. Based on the latest meta-analysis that was published very recently, it was also a patient individualized analysis. So I think it's very appropriate to take this into consideration. The most benefit is seen for patients with a PSA above 1.6, which is quite high. I tend to be very confident that we might not need a hormonal therapy.
Again, for the patients with the better prognostic tumor characteristics, below a PSA level of 0.5, I think that now we have sufficient evidence to say that below this threshold, patient might not have such a huge amount of benefit. There is no overall survival benefit, and metastasis-free survival benefit is more or less 4% at eight years. So you should really be wondering whether this is enough to give a potentially toxic drug to your patients.
Above 0.6, I always give hormonal therapy, but these are the patients that we see not that often, luckily, are really trying to go for early salvage radiotherapy. And in the threshold between the 0.5 and the 0.6, I also discuss it with the patient, and it also depends on tumor characteristics. So if you have more aggressive tumor characteristics, I will add some form of hormonal therapy. If you have less aggressive tumor characteristics, I think I would abandon hormonal therapy.
Leslie Ballas: Are you using just the PSA or do you also incorporate Decipher into making these decisions for ADT in the post-op space?
Valerie Fonteyne: Well, unluckily, we do not have access to genomic classification tools, but if I would have the possibility to apply them, I would definitely do this even for patients with lower PSAs. So I think it's a very promising tool, but not yet available in our clinics, unfortunately. But we also have some data based on clinical features. We know that also based on the randomized trials, that risk factors such as high Gleason scores, higher PSA, negative surgical margins, pT3, B4 are also reasons if you have two or three of these negative predictive or prognostic characteristics, I think that you can also consider adding ADT even if you don't have a Decipher test.
Leslie Ballas: Yeah. And I guess it's hard because you don't have Decipher, but obviously at ASTRO this past year, Dr. Dan Spratt presented the BALANCE trial, which used the Decipher grid and the luminal AB status to show that there's a benefit in luminal B patients of adding apalutamide in the post-op setting. And so when to use ADT, when do you use apalutamide? Do you have any guidance on that?
Valerie Fonteyne: Well, it's very difficult right now to give the right answer because there are some phase-two randomized trials that have looked at the position of an RP on top of salvage radiotherapy. And although the results seems to be promising, we still need the large phase-three data, of course, before we can really claim that it is superior to what we are doing right now. And again, I'm also not convinced that all patients will need an RP. So further risk classification will also be of great value to decide whether or not radiotherapy alone is sufficient or whether or not we should add something. And if we add something, which product we should give preference to. So I think very promising studies that are ongoing with preliminary results that seems to be very promising, but unfortunately all a little bit un-mature according to me to really claim that one is outperforming another approach.
Leslie Ballas: And what about the argument that we should wait until PSMA is positive before initiating radiotherapy so that there's a target? What do you think about that argument?
Valerie Fonteyne: Well, we do have some data indicating that this is probably not the best way to go. So we have, for example, the Emmett paper, which was a large prospective trial. It was, of course, not randomized, but patient received the PSMA PET/CT at different levels of PSA, also in the area of very low PSAs below the 0.5. And what they found and what was quite interesting, I think, is that even in this era of low PSA, and if you perform a PSMA PET/CT and your PSMA PET/CT is negative, you should go for salvage radiotherapy because the patients with the negative PSMA PET/CT who received salvage radiotherapy had a better biochemical recurrence-free survival when compared to the patient's negative PSMA PET/CT who were not offered salvage radiotherapy.
So PSMA PET/CT, of course, is a very attractive tool, and it might also be very useful to guide, for example, our radiotherapy treatment field, whether or not we should include pelvic nodes areas, whether or not we should perform a boost to the microscopic disease, but having a negative PSMA PET/CT for me is not a reason not to pursue with your decision to go for salvage radiotherapy.
Leslie Ballas: I agree. Thank you for reviewing this data with us and for talking with us after APCCC. We really enjoyed chatting with you and hearing your perspective, so thank you.
Valerie Fonteyne: Thank you very much. It was my pleasure.