Karen Hoffman: Thank you very much. I appreciate the opportunity to chat with you today.
Neeraj Agarwal: So we really enjoy your presentation at the 2026 annual American Urology Association meeting in Washington, DC, especially your discussion on biochemically recurrent prostate cancer. Taking a step back, if I look at our discussions, ongoing discussions, in the tumor boards, in the meetings, I think the most time is spent on how to manage these patients with biochemically recurrent disease, because there are so many nuances, so many ways to treat them. So please tell us about your approach on salvage radiation therapy.
But let's start with salvage radiation therapy. So you see a patient with biochemical recurrence and you are contemplating salvage radiation. Who should get it? Who may not get it? If I do it, what is the optimal duration of ADT? Short, long? How do we decide?
Karen Hoffman: To help me reflect on what I think about in clinic every week with my patients, so we can take the first piece of that with regards to who should be receiving salvage radiation therapy.
Now, as a radiation oncologist, the patients are often initially followed by my urology colleagues and then referred to me when they're considered for salvage radiation therapy. These days, as you know, we're looking to do salvage when the PSA is still quite low if possible, 0.1, 0.2, 0.3, when it's the kind of patient where we think that we will truly be able to benefit them.
So the things that I'm looking for as to whether or not to do salvage treatment or not is I certainly look to try to understand what was the aggressiveness of their disease when they had their prostate removed and looking to try to follow, hey, what is the PSA looking like? Is it a slow change or rise? Was their cancer removed 5 years ago, 10 years ago? Just trying to get a real sense of is this a cancer that's going to grow or change or cause an issue for the patient down the road.
So the other thing that I look to is I look to say, "Hey, is this the kind of patient that would've been a candidate for those old adjuvant radiation trials, the kind of patient that would've had involved margins or disease spread outside the prostate where we're able to show benefit in that population?"
So it's ultimately you're also of course taking into account how is the patient's overall health? Do we think they're going to be with us long enough to potentially benefit from salvage radiation therapy? Because we know it does have side effects, it does have toxicities. So I think that sometimes is the most challenging initial decision is whether or not to move forward with salvage treatment or not.
In my world as a radiation oncologist, I feel like they've been followed initially for a bit with the urologist before they come to see me to have that discussion, but we want to make sure that it was someone that we believe could benefit. Then the piece that we think about then, as you alluded to, is do we give just radiation therapy-
Neeraj Agarwal: So before we go there, those are great points. Thank you. Any role of PSMA PET scan? I know earlier we do salvage, higher are the chances of salvage radiation therapy succeeding, 0.1, 0.2, 0.3, rather than waiting for PSA to go up to two or three.
Karen Hoffman: Mm-hmm.
Neeraj Agarwal: So that was a great point. Any role of PSMA PET scan for our colleagues out there in the community who are seeing these patients? Should we be ordering PSMA PET scan or not?
Karen Hoffman: So I routinely get PSMA PET scan on my patients that have biochemical recurrence. I actually get both PSMA PET scan and I still get a pelvic MRI as well, because it's uncommon, but sometimes I'll pick up something on pelvic MRI that we're not actually picking up on a PSMA PET.
Now we realize, we appreciate when these PSAs are quite low, we may not see something on that PSMA PET. But when we do, it really impacts or it changes management. When these molecular-based imaging first came out, it actually was studied compared to conventional imaging, and we saw that when we got that as radiation oncologists, it actually changed our approach to our patients. We were more likely particularly to pick up nodal disease that we hadn't appreciated before, which was changing our radiation treatment fields, and that ultimately led to actually better outcomes for our patients.
So we do get it. We don't always see something, but when we do, it can really impact our approach to the patient.
Neeraj Agarwal: So MRI of the pelvis and PSMA PET scan are the two modalities we like to use before making decision on radiation therapy to the fossa and the pelvis.
Karen Hoffman: Mm-hmm.
Neeraj Agarwal: Now, let's talk about androgen deprivation therapy with salvage radiation.
Karen Hoffman: Mm-hmm.
Neeraj Agarwal: Duration? 6 months, 18 months? Who should get it? Who may avoid it? And are there any molecular testing which can help us, molecular or digital imaging testing or pathology testing, which can help us in determining who may or may not get it and for how long?
Karen Hoffman: So certainly this is a very active area of investigation. We do want men to receive androgen excess therapy when we think it's truly going to benefit them with regards to disease control, but we also know the negative impacts it can have on our patients, the fatigue, the hot flashes, and so forth.
I think the most commonly used regimen when we use androgen deprivation therapy currently is six months of ADT, supported by GETUG, supported by the SPPORT trials, as we use most commonly in our practice. I do think we probably are using it a bit more than we necessarily need to, but I think sometimes it's hard not to give it because we know this could be the last chance of eradicating the cancer for patients.
But, thankfully, we do think coming down the road, we will have good genomic tests that will help us understand who can be spared ADT. There was an important study that was presented at our ASTRO meeting last year, GU006, which was using PAM50 to identify those men most likely to benefit from androgen excess therapy.
What they found is those patients with luminal B cancer actually were the ones that benefited from the addition of six months of apalutamide compared to no treatment. So I think once that data is published, that's going to be very useful for us in terms of understanding who definitely benefits from that treatment.
The other nice thing about that study is that they used apalutamide, which we believe has a better toxicity profile than traditional ADT. Now apalutamide is being compared to traditional ADT in PROSTATE-IQ. It'll be a while before that trial's done and reads out, but hopefully we'll better understand who can be spared ADT and then if we're giving it to them. Hopefully we'll have something that is less impactful for our patients.
Neeraj Agarwal: Absolutely. Using these ARPIs compared to ADT allow testosterone recovery to be much quick.
Karen Hoffman: Yeah.
Neeraj Agarwal: In fact, they never suppress their testosterone. So hopefully these patients, as soon as they stop their drug, they are not experiencing the side effects of androgen signaling inhibition.
Karen Hoffman: Mm-hmm.
Neeraj Agarwal: So we just had a nice ... Yes, please.
Karen Hoffman: I was going to say that one side of this, of course, is trying to back off on the androgen excess therapy, but we also know that there's men, despite getting radiation in six months of ADT, that they still have disease recurrence. So that's the other space we've been looking at is who needs that intensified ADT. We don't have a perfect genomic marker yet for this. One thing that people are using now that wasn't available previously is the ArteraAI Prostatectomy Test. It does help better understand risk of metastasis for patients.
But we certainly have trials that have demonstrated improvements when you intensify ADT in different ways. We of course have data showing that 24 months could be better than six months, or intensifying those six months by adding additional agents could be better than just plain six months.
Again, it comes down to patient selection of who should be receiving this intensified therapy, because it can then carry a longer and more intense side effect burden.
Neeraj Agarwal: Right. This ArteraAI, and maybe Decipher and maybe other molecular tests, may be able to allow us to select those patients for more customized therapy.
Karen Hoffman: Mm-hmm.
Neeraj Agarwal: So we discussed the salvage radiation. We discussed the ADT, yes and no, and the duration of that with salvage radiation. Now coming to the next phase of biochemically recurrent prostate cancer, which is the oligometastasis phase detected by the PSMA PET scan.
Karen Hoffman: Mm-hmm.
Neeraj Agarwal: So conventional scan is negative, and this is not very uncommon scenario in the clinic nowadays. So patient has been treated with radical prostatectomy, salvage radiation therapy, androgen deprivation therapy, now PSA is rising, NVC, oligometastatic disease, and for the sake of discussion, let's cap it at five or less number of bone lesions.
Karen Hoffman: Mm-hmm.
Neeraj Agarwal: How do you approach that?
Karen Hoffman: Certainly I want to understand where those lesions are and how safe it is for me to treat as a radiation oncologist. I do think that there can be benefit to the treatment of our patients as long as we can do it safely. We usually can with the oligometastasis, limited side effects, short duration of treatment, so less burdensome on our patients. Then I'll talk to them and often offer it to them, if they're interested, because we do believe it helps with the disease control. It does help with regards to progression-free survival. I think the challenge sometimes is the sequencing and when to use it.
Neeraj Agarwal: So when you're pursuing oligometastatic radiation therapy, which is a very common situation for all of us in the clinic, what is the role of ADT or ADT plus ARPI? And, again, what should be the duration of that treatment?
Karen Hoffman: So I often partner with my medical oncologist to sort that piece, because it is a challenge to figure out what is the best for each individual patient. There are certain patients where I definitely want to treat with radiation before the ADT or in conjunction with starting the ADT, and those are patients who may have lesions that could be difficult to visualize for targeting the radiation if they already start the ADT and then it shrinks. So there's definitely that specific-
Neeraj Agarwal: Very good point, yeah.
Karen Hoffman: .. group of patients that I will do radiation before ADT. Otherwise, it's often my practice to combine the two together, just to try to get a little bit of benefit of both for our patients, but usually short ADT, maybe just six months, so that then they can have a break from it, because that's our intent with the radiation is to help control disease and then give them a time off of therapy.
Neeraj Agarwal: Because technically these patients have metastatic prostate cancer, and they are basically destined for lifelong ADT plus/minus ... Plus ARPI following the guidelines.
Karen Hoffman: Yeah.
Neeraj Agarwal: So if you can allow them to have a life without ADT, that may be the ultimate goal of using oligometastatic-directed radiation therapy.
Karen Hoffman: Mm-hmm.
Neeraj Agarwal: How's the future evolving? How do you think these treatment options or this biochemically recurrent setting ... Before we conclude today's discussion, where are we heading in biochemically recurrent setting?
Karen Hoffman: I think the big space that we're moving, where so many other spaces are moving as well, is to really individualize treatment based on the characteristics of the cancer. So really using genomic classifiers to understand when do we intensify? When do we deintensify? Who actually benefits from that radiation for oligometastatic treatment?
So I think that's where we're going to try to better understand how can we tailor our treatments for our patients so they get the most benefit and hopefully also the least treatment impact or toxicity?
Neeraj Agarwal: Always a great learning experience talking to you. So thank you for joining us and, again, congratulations for the wonderful talk you gave at AUA.
Karen Hoffman: Yeah. My pleasure. Thank you.