Looking at real world evidence on PSA testing in prostate cancer

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Published: 2 Jun 2024
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Dr Friederike Schlurmann, Prof Boris Hadaschik and Prof Karim Fizazi

Dr Friederike Schlurmann (Centre Hospitalier Universitaire de Brest, Brest, France), Prof Boris Hadaschik (University of Duisburg-Essen, Essen, Germany), and Prof Karim Fizazi (Institut Gustave Roussy, Villejuif, France) discuss the real-world evidence regarding PSA in prostate cancer.

The panel talks about the real-world prostate-specific antigen (PSA) response and disease progression among patients with non-metastatic castration-resistant prostate cancer and metastatic prostate cancer.

They elaborate on the value of PSA in decision-making and trial design. The panel also discusses the PSA test and the variables associated with false-positive PSA results.

Role of PSA in decision making
Role of PSMA PET in decision making
Analysis of de-escalation studies
The importance of real-world prostate-specific antigen (PSA) response and disease progression amongst patients with prostate cancer

 

This programme is supported by an unrestricted educational grant from Johnson & Johnson

Looking at real world evidence on PSA testing in prostate cancer

Dr Friederike Schlurmann – Centre Hospitalier Universitaire de Brest, Brest, France Prof Boris Hadaschik – University of Duisburg-Essen, Essen, Germany

Prof Karim Fizazi – Institut Gustave Roussy, Villejuif, France

FS:        Hi everybody and welcome to the ecancer round table discussion about PSA and real-world evidence. I’m Friederike Sclurmann, I’m a medical oncologist from the University Hospital in Brest in France and I’m really happy today to be here at the ASCO with two of my colleagues; they will introduce themselves.

KF:        Thanks Friederike. I’m Karim Fizazi, medical oncologist from Institut Gustave Roussy in Paris, France. Delighted to be here today.

BH:        My name is Boris Hadaschik, I’m a urologist from Essen in Germany and I’m also very happy to be here at ASCO and in this format.

FS:        So let’s talk a little bit about PSA. We have had some abstracts that have been presented at this ASCO meeting and clinicians ask themselves a lot of questions about the PSA, what to do with PSA, is there a prognostic factor? What are your views on what we have seen at this ASCO meeting? Karim, let’s start with you.

KF:        Sure, it’s a funny thing because we are in a situation of complex oncology, fancy biomarkers etc. and then we realise that a very easy and cheap biomarker can help us for decision making, or at least to make better decisions for our patients. And it’s PSA simply. Indeed, more and more we have phase III trials reading out, for example in metastatic castration sensitive disease, showing us that a PSA down to zero at 6-8 months is a very strong prognostic factor. So, in other words, just using this biomarker you know what’s going to happen for your patients and you can really separate probably two different populations – one who are good responders where actually we may not need all the treatment we are giving for a long, long time with all its toxicity, and on the other hand the poor responders, if they are responders but still it's not perfect, and they will progress soon. So for these patients there might be opportunities for further intensifying their treatments. What I'm saying for metastatic castration sensitive disease actually applies also in other settings of other disease. So perhaps more and more we will learn to better use PSA for decision-making.

FS:        So what would you do with patients who have a PSA that you cannot dose anymore in the mHSPC setting? What do you think we should do?

KF:        Well, for the practice right now I think we can at least tell the patient that it’s very, very good news. Yes, you had metastatic disease six months ago but really you are responding fantastically well to your treatment and you can envision very nice years, very likely without progression. So of course we will monitor and there are questions about how best to monitor, but you can really, with your heart, basically, tell your patient, ‘You’re good.’

FS:        Which is great news for patients.

KF:        Right. And for trials we should probably think about de-escalations but personally I think this should be done only in the context of a trial, not necessarily in other practice because otherwise we don’t know what we’re doing.

FS:        Okay. And what would you say with patients that are on the other side of the spectrum where the PSA is not going down as quick as we would like and not as far down as we would like, what would you say about those?

KF:        That’s a more tricky situation because right now we don’t have a standard of care for intervening earlier, or early, at that stage. So basically you know you have bad news but you cannot do anything about it. So honestly I don’t want my patients to be anxious so if they are happy because their PSA is going down, even if it’s not perfect, not going down to zero, fine. The only thing is that maybe I will be more cautious with this particular gentleman in terms of follow-up and I will keep on measuring the PSA, maybe intensify the imaging, those things, just to make sure that I can capture an early progression and intervene still not too late.

FS:        So, Boris, what are your views on this topic?

BH:        I’m not sitting here to disagree with Karim, so I share his opinion. I think PSA is a wonderful, cheap biomarker that we really are used to using in clinical practice and we have learned this before from the big phase III trials in castration sensitive disease that there are prognostic groups. Here it has been presented that it also works for M0 CRPC and it works for the high risk biochemical recurrence population in EMBARK and in the real world, which is very important for us. So, yes, there are different groups of patients, they respond very nicely to intensified hormone treatment or not. You said pausing the therapy within the context of a clinical trial, I think this is a very strong and good signal and we should support studies like EORTC de-escalate or the LIBERTAS study where in these patients we stop at least parts of the treatment. But because we saw here data from EMBARK and in EMBARK there was within the clinical trial a therapy pause and now it’s reassuring that despite this trial design a PSA that responds very well is excellent news. On the other hand we must not forget that PSA is just one factor and what we learned in the mCRPC disease space is that we cannot completely rely on PSA so we have to reflect where we are in our continuum of disease.

What I discuss with my patients always are three things. So we have the PSA value which is cheap and easy to measure, we have the fitness of the patient or how he is feeling and doing, so that’s most important, and then we have the imaging to look at and think, we discussed this before, in mCRPC without question because there might be progression without a signal in PSA. Even in M0 CRPC there are some signals that there might be early progression besides a good responding PSA. So there PSA alone is not enough but in the hormone sensitive disease with patients that have such a good prognosis outside of clinical trials I use this information to de-escalate my imaging routine, so I do it less often, and I focus a little bit more in these patients where I know they are on treatment for a long period of time on such things as bone health and keeping them doing sports and things like that because I know that the cancer is most likely not a big problem over the near future.

FS:        I think there are two really important things about what you said. There’s one side of the quality of life for the patient where we can de-intensify the treatment that we have because we have all those side effects and patients who are living a really long time now with their cancer, on the one hand. On the other hand we have those patients that we have to intensify to get the most out of our treatment. So you were talking about imaging, so how do you do your imaging? What do you use as an imaging technique? This is a big question too because we talk about PSA, that’s really easy, quick to do and, on the other hand, we have the imaging. So what do you do in your clinical practice?

BH:        This is a difficult question. Coming from Essen and being involved in a lot of PSMA PET studies, I certainly want to stress that PSMA PET is the most accurate imaging that we can use. But PSMA PET is more cost intensive so I reserve it for situations where I know it will inform my clinical practice. So in most of the patients we are discussing here I like to have an initial PET scan to really understand the disease but we don’t have commonly agreed upon criteria yet to use PET for imaging response and looking at that. We show on Monday, here at ASCO, that at one timepoint PET scan is helping us really also classify our patients. We present, and it will be published in Lancet Oncology at the same time, data that a formal PROMISE score of the PSMA PET can predict outcome in our dataset survivors.

So again here we use imaging to classify our patients into different risk groups. So I’m a PET fan, I have good availability and reimbursement is not a big topic. So I use PET at the initial timepoint and then normally in the hormone sensitive disease space if the PSA is responding nicely I do a conventional CT thorax abdomen after 12 months. I rarely use bone scan because I’m unhappy with the reads and the Prostate Cancer Working Group criteria. Also they acknowledge that there might be false positive signals so the 2+2 rule is in clinical practice, outside of trials, sometimes challenging, if I get the imaging outside and it says, well, there is progression. So I always have to reflect but I think this is still a very open field and we have to now come up. There are various consortia working on this to find the progression criteria on PET and they then need to be validated in the context of trials.

FS:        So you’re in the good position that you have access, it’s reimbursed, that’s really great. It’s not like this in every country. So how is it in France? What do you do, what do you use? How do you image your patients in different settings of the disease?

KF:        Actually right now we have quite broad access to PSMA PET but I’m not using it, actually similar to you, Boris, not using it all the time obviously. Especially for metastatic castration sensitive disease I image my patients at baseline to show that there are metastases. Typically I redo the same imaging six months down the line to assess the response and, to be honest, to provide the good news to the patient. Of course it’s reassuring to them to see that not only their PSA is going down but also that the imaging is also going down on top of feeling better most of the time, thanks to the treatment which is ongoing. But then at six months if things are going well I tend to follow my patients just clinically and by PSA. Unless something bad is happening, either clinically or by PSA, I don’t image them anymore. Honestly, I’ve been doing that for a long time, even at the time of bone scans/CT scans, and I think I was never surprised.

FS:        And that’s in the mHSPC setting, to be clear?

KF:        Correct, yes. In CRPC, in castration resistant disease, I’m much more cautious because I recognise that some patients will progress with very undifferentiated/neuroendocrine differentiations and the PSA will not pick this up. So you need the imaging.

FS:        An important message.

KF:        So I keep using imaging strategies in CRPC. So in metastatic CRPC typically I would do that every four months or so. In non-metastatic CRPC, if fully the PSA is down to zero, I do it once or twice a year, something like that.

FS:        I think we saw it in the abstract that those patients that have a PSA that’s not doseable anymore, those are the patients that are really doing good and those are the patients where we might do less imaging.

KF:        Yes, I agree.

FS:        So, having said all of that, what’s the outlook, what is going to come? You talked a little bit about the de-escalation studies, are there studies coming to intensify those patients that don’t have a good PSA response? Is there anything on the market?

KF:        Yes, we have an academic trial, the PEACE-6 poor responder trial which is really focussing on patients with metastatic castration sensitive disease with a detectable PSA 6-8 months after the start of systemic treatment. So, again, we know that these patients won’t do well in the short term and the standard of care is just carrying on with their ongoing ADT plus any AR pathway inhibitor we’re using. So we will randomise in this trial, which is just about to start this summer, the standard of care versus the same plus Lutetium-PSMA with the hope that such an early intervention will make a difference in terms of postponing progression and hopefully death. So we’re just about to start this phase III trial in Europe and I know that some companies are also thinking of a similar design with their new treatments.

FS:        That’s great news because those patients really need… and, as you said, as a clinician you’re not really happy with those patients, even if the PSA goes down but not as quickly as you would like. You know that something is coming and you don’t know where it is coming from but you know it’s coming. So this is really reassuring, even as a clinician I feel to have something. So we talked about a lot of things so, Boris, do you want to add something?

BH:        One remark, maybe. Sitting next to you and PEACE and the triplet regimen, I think that’s important because there has been a tradition to start with a doublet and if the PSA is not going down to then add chemotherapy. This is not what has been tested in ARASENS or the PEACE so we don’t know whether chemo is really a good thing to follow-up if the PSA is not going down exactly. So the standard of care if you want to have intensified treatment right now is to start heavy and then… So, from my perspective, the de-escalation studies are at least as important and for the escalation we really have to find out in a more precision medicine like approach which patients benefit from which. Because I don’t think that chemo for all, and you don’t do that in the trial, with that design is perfect. So it’s so nice from year to year we learn more and to more individually speak with our patients and design individual treatment as well as clinical studies. So this cheap biomarker really helps us to do that.

FS:        Do you want to add something?

KF:        No, I think we’ve covered most of it, at least for metastatic castration sensitive disease. But, again, PSA is also helpful in other situations, in earlier situations – biochemical failures – PSA really helps. If it goes down to zero on systemic treatment these patients will live for a long, long time. So really the balance between harming and benefit is there, we need to be cautious. This is probably why most of us are using intermittent therapy in several situations of biochemical failure, for example. This is appropriate indeed.

FS:        I think we can say in general when we have a patient we have the PSA, like you said, we have the patient in front of us, after all, if he has symptoms or not. Then we have imaging. We have to take all of those three things into account when you see the patients; we still have the clinical feeling, I guess. Maybe make a difference between mHSPC, non-metastatic castration resistant prostate cancer, so those are different entities. Now, as you said, we’re in the really lucky position that we start to understand that all cancer patients, prostate cancer patients, are not the same and PSA is saying something to us and that there are studies coming up. I think that’s really great news.

KF:        Absolutely. And maybe if I may add something, we’ve mentioned, the three of us, that we are following all the patients based on those three aspects – clinical, PSA and imaging. Typically patients are asking about the PSA because PSA is good, we’ve said that for 15 minutes, but it’s also generating anxiety. So every time I am telling my patients, yes, I’m following you based on three things but I’m ranking them a different way. First is clinically, I want you to feel good, second is the imaging, third is the PSA.

FS:        I think that’s a super-important message because it’s really, like you said, psychologically speaking really creating anxiety. Those patients have been drilled often before they are metastatic from urologists or oncologists about PSA. So you like to de-sensitise them a little bit about the PSA which is really challenging in the real life setting but is something that we’re working on. But it’s really important to say that, that you still have the patient in front of you and you have to trust your gut feeling a little bit and take into account what we saw in the abstracts. If it’s not working then think about a clinical trial, put your patient in the clinical trial, try to get the best out of the treatments that we have.

KF:        Absolutely.

FS:        So thank you so much. Thank you so much for listening to us today about PSA and the real-world evidence. I hope to see you soon, and I hope that you liked what we’re talking about and that you just learned something for your clinical practice. Thank you so much, thank you Karim, thank you Boris. I hope to see you again soon.