Transcript: Biochemical recurrence

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Last updated:1st May 2025

Published:1st May 2025

Bertrand Tombal, MD, PhD

All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.

So biochemical recurrence is something which is somewhere quite unique to prostate cancer because we have a very good biomarker, which is PSA. So what we're speaking about our patient who had local treatment, prostatectomy, radiotherapy with or without hormone therapy and then see their PSA rising. So it can happen soon, late. Usually we say we should measure PSA for 5 to 10 years, but biochemical means the PSA start rising and that's where it's very, very important to pause, speak with the patient. And the first things to explain is that we are speaking about an extremely heterogeneous process. So the vast majority of patient, the PSA will rise very, very, very thoroughly. I like to call them kitty and they won't get any trouble. We know that if you take all the patient with BCR versus all the patient without BCR, historical series have shown that they don't even have a higher risk of death. So what is very, very important is to explain that to the patient because for a patient, a PSA recurrence means first the patient stress amplifier. Because keep in mind it was diagnosed because his PSA was elevated. So for him, it's extremely difficult to understand that it can be a benign process. Since 1999, we know that basically you should classify patient based on a few elements.

The first and most important is to define at what state of the disease they are. And you're going to need three thing. You're gonna have to look at the PSA kinetic. Is it rising rapidly or slowly? We're gonna have to look at the testosterone. This is mostly the case for patient that were treated with radiotherapy and hormone therapy. And at some point we're gonna have to look whether they have metastasis or not. The testosterone value is important to define whether we are speaking about a patient which is still hormone-sensitive. That's important, that's patient with a normal testosterone. It means that most of the treatment we will be using will be androgen receptor based treatment. Or are we speaking about a patient which is already progressing with a low PSA. And we are gonna speak about, a low testosterone, sorry, and we're gonna speak about castration-resistant prostate cancer. Now, when we refer to BCR, we are speaking mostly about patient who have a normal testosterone. Typically they had surgery, then radiotherapy or radiotherapy and their PSA is rising. So once you have defined that state and most of the patient will be hormone-sensitive prostate cancer, meaning with a normal recurrence, then the next step will be to see whether they have metastasis or not. And so you're gonna have to apply imaging. Conventionally you will use bone scan and CT scan, bone scintigraphy with technetium 99 bisphosphonate. And that's not very sensitive. I wouldn't say we don't use that anymore. But the transition is quick.

We're using modern imaging technology, whether it is PSMA-PET or any PSMA based PET or all body MRI. So that will help you defining metastatic patient from non-metastatic patient and the traditional non-metastatic patients. So these refer as a generic term of BCR, then that's gonna be most of the patient. Then you're gonna have to further stratify into low risk, high risk. So I do repeat the sequence, it's easy. You had a treatment prostatectomy, radiotherapy. First thing you have a normal testosterone or a low testosterone. Let's assume you have a low testosterone, you are hormone-sensitive prostate cancer. Then do you have metastasis or not? If you have metastasis by conventional hormone imaging, you're gonna be metastatic hormone-sensitive. If you have no metastasis, you're gonna be non-metastatic hormone-sensitive prostate cancer. And then the latest step is are you at risk of progression or not at risk of progression? And this is defined primarily by three characteristic. Your initial Gleason score, whether it was lower than 8 or equal or superior to 8, the time at which you had the recurrence.

Is it a recurrence just after the surgery or the radiotherapy? Like you know, one, one and a half year. Conventionally we used 3 years. So was it before 3 years or after 3 years? And the third, and I would say probably the most important one, is your PSA rising rapidly? And we are gonna calculate your PSA doubling time. It's a complicated formula. You can find many calculator on the web. But generally we would say that if your PSA double in more than 12 months, you are at low risk. Many guidelines use strict definition. If you tell, for instance, if you say the EAU guidelines, they use only two attribute. The Gleason score has to be less than 8 for the low risk and the PSA doubling time, which has to be more than 12 months. And for radiotherapy, the interval between the radiotherapy and the rise in PSA, which is 18 months, the high risk being those with a high Gleason and a low PSA doubling time. So that is how you are going to kind of organise that very heterogeneous group of patient, castration-resistant versus hormone-sensitive, metastatic versus non-metastatic, high risk versus low risk. And that's also how you're gonna decide on which treatment you're gonna recommend from actively surveilling. So not recommending any treatment to low risk non-metastatic patient going to intensify systemic treatment plus minus radiotherapy for the very aggressive patient with metastatic deposit to even sometime non-hormonal manipulation when you have very aggressive non-metastatic CRPC. But that first step of classifying the patient is super important.

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