Georgios Agrotis: Oh, thank you. Thank you for having me. Nice to be here. So, what we will discuss today is our recent paper, Radiological T-staging in Prostate Cancer, that was published in the European Journal of Radiology, focusing on the current role and the limitations of MRI in prostate cancer staging. And although we know that prostate MRI is widely used for diagnosis through the PI-RADS system, which is an established risk-stratification tool. In the staging world, we do have a bit of an issue, especially when it comes to distinguishing T2 disease from T3a disease. MRI is not formally integrated into the TNM staging system. The digital rectal examination is the official TNM staging tool. And if we see the fundamental meta-analysis that shows that MRI has modest sensitivity, but relatively high specificity for detecting extraprostatic extension, and this means that small minor imaging signs for identifying pathologic extraprostatic extension are often missed, resulting in interobserver variability even among experienced readers.
And in order to improve the sensitivity, several MRI-based scoring systems have been developed all over the world that predict pathologic extraprostatic extension. And some scoring systems incorporate quantitative metrics such as the capsular contact length or tumor size, in order to achieve higher sensitivity than individual imaging features, often at the expense of specificity. And the reason that I am doing this sensitivity-specificity trade-off is that, it has significant treatment implications. Once a disease is classified as locally advanced, management is usually escalated. Nerve-sparing techniques may no longer be feasible. Radiotherapy might be combined with long-term hormonal therapy that might take two to three years. And so, how we stage the disease directly influences our patient treatment. The thing is that, this current MRI staging practice tends to favor sensitivity over specificity, which this comes at a cost. And these false positives, this overstaging and overtreatment, may lead to escalated treatment strategies with prolonged hormonal therapies, which lead to reduced quality of life for our patients. And long-term data suggests that not all missed extraprostatic extension is clinically significant, especially when it is microscopic or focal. In modern surgery techniques and radiotherapy, such disease is often treated within the radiotherapy margins, and this microscopic or minority disease has better prognosis than the established or the macroscopic extraprostatic extension. And this distinction is already made by the pathologist in their reporting to distinguish between focal and established extraprostatic extension, because they carry different prognostic outcomes.
So, based on these insights, our paper argues that MRI should evolve into a staging tool, one that is biologically and prognostically relevant, offering real guidance for the patient, rather than just identifying a T2-stage disease or a T3a-stage disease. And the end goal, what we are currently working on, is to develop a balanced and clinically meaningful decision-making tool, that is validated on long-term prognostic outcomes. Because MRI has the potential to become this preoperative prognostic tool that can guide treatment choices, much like MRI is already doing in other organs like the rectum, within the TNM framework. Of course, achieving this requires consensus within the community among the radiologists, the pathologists, the radiation oncologists, the medical oncologists, validate MRI features against long-term outcomes of the patients, so we can make better treatment decisions for our patients. Thank you.
Leslie Ballas: Thank you, Dr. Agrotis. I guess I have a couple of questions for you. I think a lot of people are using MRI as a staging tool for clinical T3 disease. Do you think that that's an error?
Georgios Agrotis: No, that's definitely not an error. And that's the reality that we are already using MRI as a staging tool. However, when we look at the official TNM staging, there is no MRI. There is a digital rectal examination. And the problem is, actually the TNM, the ninth version says that you can use MRI, but you need to report it complementary to the DRE, because how we stage with MRI is not the same staging with the digital rectal examination. And because this carries the Will Rogers phenomenon, that we may understage or overstage our patients, if we change the modality of staging, we need to revalidate our patients with new staging techniques with their prognostic outcomes, in order to put this officially into the TNM staging. It's not an error. It's not an error that we use MRI. We just need to be careful what is clinically relevant and what is not clinically relevant for our patients.
Leslie Ballas: And I think it also brings up questions as a clinician, for T3a especially, I see comments in MRI reports, abutting capsule, but no definitive breach of capsule or no definitive extracapsular extension. There's a lot of hedging in the language. And so, how do you suggest clinicians deal with that?
Georgios Agrotis: I think that's a radiological problem, that happens with everything that we tend to be more careful in our wordings, likely, that likely has extraprostatic extension or suggests, might suggest. But the thing is, it's nice to be clear that, if it is established, if it is measurable, then say that, it is much worse for the patient. If it's just abutment, if it's just contact of the pseudocapsule, then also state that there is contact with the pseudocapsule measuring this millimeter. However, no definite extraprostatic extension is seen, because this also alarms the clinician, the radiation oncologist that, okay, there is some suggestion, but it is not definite, in order also to make proper treatment decisions.
Leslie Ballas: And so, you mentioned in your discussion that MRI prioritizes sensitivity, but doesn't have as high of specificity, which is sort of the exact opposite of a DRE. A DRE has like a 50 to 60% sensitivity rate and sort of moderate to high specificity, probably depending, anywhere between 60 to 90%. And so, do you feel that they should be complementary or that MRI really should replace DRE?
Georgios Agrotis: Well, for the time being, it needs to be complementary. We cannot replace DRE because of stage-shift migration. When we introduce the new modality, we need to be aware of that. That's why also the TNM suggests it be reported side by side. And that's what we would also suggest. But for the future, what I see is that MRI should replace DRE. And actually, if we ask the urologists, they tend to use less and less the digital rectal examination, because it is not very informative for them. And we're talking about locally advanced, but seminal vesicles is also something that we need to address, because the digital rectal examination, it is very difficult to touch the seminal vesicles. So, there are a lot of arguments that MRI, in the future, should replace DRE.
Leslie Ballas: I agree.
Georgios Agrotis: What do you think as a radiation oncologist? How do you feel, what should MRI's role be as a radiation oncologist?
Leslie Ballas: Well, we use the MRI for a number of things. It does help dramatically, I think with staging. I think that there's a lot of variability in DRE technique or ability to detect T3 disease. I myself would admit that I'm not great at it. And so I use MRI quite a bit and I use it for decision making in terms of obviously staging, T-staging. We also use MRI in our treatment planning. We use it to help define the apex of the prostate. We use it to help with target delineation for the urethra. So, there's a lot of benefit for us in our treatment planning, that comes from MRI, outside of just staging.
Georgios Agrotis: Nice. Thank you.
Leslie Ballas: Well, listen, thank you so much for joining us and taking the time to talk to us about your paper.
Georgios Agrotis: Well, thank you. Thank you so much.
Leslie Ballas: We hope that your prediction for the future is right and that MRI will replace DRE and we will look out for that time.
Georgios Agrotis: Well, thank you so much. Thank you so much.
Leslie Ballas: Thanks.