Bertrand Tombal: Nice to meet you. Always happy discussing with colleagues.
Neeraj Agarwal: You had a very interesting presentation during the 2026 APCCC meeting on the dynamics of testosterone in patients who are being treated with the radiation therapy and a short-term androgen deprivation therapy for either localized to high-risk or locally advanced prostate cancer. And there is increasing recognition that these patients may end up having very low testosterone for very long amount of time, long periods of time, even after completion of their so called limited duration ADT. So Bertrand, first of all, thank you for taking the time, and congratulations for this important presentation. Please tell us more about this.
Bertrand Tombal: Oh, thank you. And indeed, because radiotherapy plus hormone therapy has become more and more popular, especially in younger patient, we start now realizing that using conventional long-term depot LHRH agonist, actually these record extremely powerful and the patient may remain testosterone-suppressed for years.
For many years, we had very little good level information. We knew, as urologists, from the intermittent androgen deprivation studies that sometime, even if you treat somebody with six months, eight months of ADT, it may take months, even years. And especially in elderly patient, in patient with diabetes or comorbidities. And it's interesting also to notice that one of many people who go for radiotherapy, usually one of the side effects they want to avoid from prostatectomy is sexual side effect. And yet, these guys receive androgen deprivation therapy and stay without a libido for years and years and years.
So to me, there are three important point. The first one, as you mentioned also, we should recognize that with standard LHRH agonist, especially long-term depot formulation, three months, six months, that even for short-term duration, six months, and even worse if you go to two, three years, many patient will not recover a normal testosterone over the long run. There are very good data coming from Canada now showing that even with a six months depot injection, 30 to 40% of the patient will remain, I don't like the word, but anyway, castrated for a very long period of time. So we should recognize that and we should tell it to the patient because the way we speak to the patient is that ADT is a transient treatment. Yeah, the administration of the LHRH agonist is transient, but the remaining effect may be very, very long.
So how can we optimize that? I think that I like to have that rule that the best ADT is no ADT. So if you don't need ADT, please don't use it. If you have a favorable intermediate-risk, if you have access to tests like decipher or whatever, if you're treating patient with salvage at low PSA, please don't use ADT. That's the best treatment. And always try to go to the shortest period. We now have good information that some of the high-risk patient with single criteria one year may be enough. So please, use either no or the shortest duration of ADT and inform the patient.
Second, we may optimize the class of drug. We have no drugs like Relugolix, which is an oral antagonist with rapid testosterone recovery. Most of the patient will recover a normal testosterone recovery, normal testosterone within 90 to 120 day. And we have published that you can see early sign of improvement like in sexual activity. So if you have the ability to use this, use this drug. The kind of hypothesis that, yeah, but all the trial were done with drug with that remaining efficacy, I think we have good data from Canada showing that if you don't recover a normal testosterone, your prognostic is actually worse.
And the third one is listen to the patient. And if a patient has been treated as a curative-intent, I would say unfavorable intermediate-risk treated with six months of ADT or a reasonable high risk who has received one and a half to two years of ADT. And after that is still in remission with a low PSA and presenting with hypogonadal symptoms, there is absolutely no reason not to supplement these patient. And we have a growing number of these patients as urologists because this men health activity is part of our portfolio, and they are unbelievably rapidly help with testosterone gels or something like this. And I really believe that with a careful monitoring of the PSA, their quality of life is so good that the patient agrees.
So to me, these are the three most important step. Recognize the fact that it's not six months, three, two, two year, it's much more than that. Second, optimize the class of drug you use. And third, please follow the quality of these patient, ask them if they have sign of hypogonadism and discuss with them testosterone supplementation if they have bothering symptoms. That would be the main take-home message.
Neeraj Agarwal: That's an excellent summary of your talk. And I think the three important messages, as you mentioned, are preferably no ADT, if possible. Number two, shortest duration of ADT if you have to use ADT. And number three, if you have to use ADT, maybe consider class of drugs within the ADT, which allow rapid testosterone recovery such as GnRH antagonists like Relugolix. In fact, we are increasingly using Relugolix in the context of localized prostate cancer, limited duration ADT protocols. And lastly, in patients who have low testosterone levels after one or two years of ADT, and apparently they are done with their treatment, they don't need to be in a so called castrate level. I would say they have the right to recover their testosterone, and what can we do to help them recover their testosterone? And that is an area which has not been investigated fully, but I know everybody is trying their best to help our patients who really want to recover their testosterone after completion of their ADT and radiation therapy, and to achieve the best quality of life.
So those are great points, Bertrand. You mentioned early on that yes, these patients chose radiation therapy, which I found was very interesting, instead of surgery to preserve their sexual function.
Bertrand Tombal: Yeah, we see that more and more. We started discussing with the patient 10 years ago, every patient seeing a urologist, a radiation oncologist, and then a nurse, and we try to expose as honestly as we can, the different side effect. And it's true that if you look at urinary side effect, but you're going to have urinary side effect with both. They're going to be different. But really we have to be honest, for the vast majority of the patient, especially the youngest one, the benefit in sexual preservation has nothing to compare between surgery and radiotherapy, even the best surgery and the highest volume in the best hand, especially know that the patient we do operate, know that we do a lot of active surveillance for ISUP 1, ISUP 2.
The patient we do recommend radical treatment, they're usually a little bit more aggressive disease. So clearly we have to be honest, we see some difference and many young patient more and more are attracted. And these are the one for which quality of life matters the most.
Neeraj Agarwal: The most of all.
Bertrand Tombal: And more and more these patient look at radiotherapy as a preferred treatment. So we've seen that in the last few years. It depend really how you do the information. If you try to expect some equipoise, trying to say what we know in the literature and what we know from our own series, that's easy to draw the picture.
Neeraj Agarwal: Wonderful. Thank you for sharing your insights and-
Bertrand Tombal: Thank you.
Neeraj Agarwal: Appreciate you taking the time.
Bertrand Tombal: My pleasure.
Neeraj Agarwal: And talking about testosterone recovery and dynamics in these patients with limited duration ADT in the context of radiation therapy.
Bertrand Tombal: Thank you so much.