This video features Mike Yu, MD, FACNM, FRCPC presenting on New Imaging Technology in Prostate Cancer. This presentation was given at our November 9th Optimizing Treatment Strategies for Localized and Advanced Prostate Cancer CME in 2022.
Thank you for having me here and I'm the last one between you and home. So I'll try to be a quick so I'm the central reviewer for two of the treasure I mentioned and then some of the trees I mentioned is not FDA approved yet. So we're gonna talk about the new imaging technology basically focused on functional imaging and more about the pet. And then we'll get familiarized with several new tracers have been recently approved you know, within two years. And then there are other options and other things we can do. So this is a big data processing cancer still the number one disease for men. You know, one in nine men will have prostate prostate cancer in their lifetime and then the number two death. So the cost is high with the inflation will be even higher. No question about that. And then depends on the initial stage of the tumor. And then the staging The treatment can be very individualized. So with the different treatment options, the response rate has been really good. There were more than 90% cure rate and there is a very good overall survival is about 98% in five years is one of the best cancer survival we can have. There is a problem. The recurrence is really high. There are about a quarter to half of the patient will have biochemical recurrence. You will hear the B. C. R. A lot in this talk. They will have rising P. I say within 10 years after either surgery or radiation therapy. And then the definition for the PcR is a little bit different between relation therapies just like two nanograms. And then for the surgery the 0.2. So it's a different definition. Conventional imaging can be used for initial stadium and we usually use a TMR but they have a low sensitivity for detect nodal involvement. They have a good specificity and then we have a functional imaging basically the bone scan. We do have a processing available for a while but the image quality was not great. So when the patient have a VCR happens we know there's something in the body but we cannot say it very well for a long long time. So the absence of evidence is not evidence of absence. So for the conventional imaging we all know C. T. M. R. And then we rarely use the ultrasound because you know, that's not really an atomic imaging. But we can use that to get biopsy the physiological imaging. We used in the past basically the bone scan. But if you have a P. I say under 10 and you pretty much say nothing. So we only use for high risk higher grade tumors. We do have a processing which is P. S. M. A. Antibody approved by FDA in 1996. And then for the local staging we can use biopsy or we can use the M. P. M. R. I. And then gave us really the details. So the purpose of imaging is for proper staging and evaluate the full extent of disease and the risk stratification and then the management decision. So we need better tracers and we need new tracers. And then there are some places we call the next generation imaging. And then we try the F. D. G. In the past. So F. D. G becomes available in the early 2000 is not very good for prostate cancer is variable result. Maybe only good for the process. I mean for the progressive disease. And then we try the sodium fluoride is very sensitive but it's low specificity after had registry. Uh Medicare decided not covering it. And then we have tried calling and the flow of in and then the other trees are here. The one in blue has FDA approval. So this is a good representation of the trees are available on the cell surface. We can use all different targets. And then all those ones have a nuclear. And the patch trees are available. The one in the red have FDA approval. So the first one is about 10 years ago is a carbon 11 label. The colon government only approved for a male clinic. So the problem for carbon 11 is very short half life is 20 minutes. So it's almost impossible to be delivered. You need to have onset cyclotron. The other one was approved by you know full male clinic. So whoever wants it, you have to you know do a lot of actual work for that. And then there's no intellectual properties are really not of commercial values. So rarely people use that one 2016 We have a human flu sacrament. Got approved. So this is the FADA announcement. But this one is only used for biochemical recurrence. It cannot be used for initial staging and then they put a lot of restriction there. You probably need a negative or equivocal anatomical imaging. You can do this one just a lot of hurdles. So we do after the FDA approval. We do about 100 cases a year and it's a lot of work and then a lot of a peer to peer review is it works pretty good for some patients but not at all. And then this is a you know bell distribution in the radio graphics. So we see a lot of activity in the muscle marrow, the target organs, the liver pancreas. And then it's just not a great treasure. This is a good case. Listen to me, the patient had radical prostatectomy. The P. I. C. Had been undetectable. Then creeping up P. I. C. Is 0.4. So they said can we see something that said by definition we should be able to see after prostatectomy more than 0.2 is considered biochemical recurrence. So I think the projection is not as great. But we do see multiple small lesions in different locations. They have activity higher than the blood hole. So this is the positive and this is the reason the patient has elevated P. I. Say. And then sometimes the time will tell. This is the patient sent to me beginning of last year has a P. S. A. Of one. At that time I see a small region in the sternum and then there are tiny um medicine disease in the pelvis. None of them can be by opposite easily. Nobody can get that one. And then the I. R. Doesn't want to do the biopsy of that one. So we just say time will tell less the tumor declare itself. So the P. I. C. W. Very quickly, you know, double every two months. So the patient came back in august numerous small active lesions in the bones and then the power of a collision got a little bit larger, maybe a little bit another one at that time we don't even need biopsy. We believe this is really truly need some treatment at the time. So the most excitement is recently a P. M. S. A. But we do have a P. M. S. A. Antibody many years ago. The current PM essay is all small molecules. So it can be labeled with the different treasure. The data has shown PMS A imaging has been superior to conventional imaging and then better in all stages and two treasures had been approved by FDA. One is the Guardian 68 labeled PMS 11 and then another one is fluent 18 labeled D. C. L. P. L. When you think about the radio tracers we can label it with different compounds for the diagnostic purpose. And then we can label with the therapeutic tracer for the treatment purpose. So we have indian labeled PMS. A. Antibody approved by FDA 1996. And then we tried the technician and even 23 labeled P. M. S. A. The image college is not as good and then usually nuclear scan and data they do not have any quantity value. And then the gallium and everything labeled P. M. S. A. Compound has FDA approval. People are still working in a couple of 64 because they have a longer half life. They can deliver in a longer distance and then the korean labeled tracer has a lot of interest because the longer half life you can take a multiday scan images then you can do the data analysis for the symmetry for the therapeutic. There is a 7 31 labeled P. M. S. A. And then recently just finished the cool we had that travel open but because of the covid we put on hold and then later on we did not participate but that one just finished recently and then the lotus um just got approved this year at the end of the fourth quarter and then still a lot of the places trying each 90 action. Um actually um have a lot of interest because it's the offer particle. They have a highway payload. So this is the indian process isn't as you can see the image quality is really not ideal. And then as you can see there's something in the abdomen here and here and then for the nuclear scan, you need the multi day study to see the clearance of the background to see the better localization of the tumor. And then with the back city is helpful to see localization of the lymph nodes. When FADA approved in 1996, there was no spec city specs city came after 2000. So it's kind of faded out over the years. So P. M. S. A. Has been tried and in different institutions, different companies and then the blue ones are the functional part of it. And then the right one are the radio label because you use a different trees label a little bit differently. You need a key leader or you need something different. But the functional component is very similar. And then we participate. One of this one is a nuclear tracer labeled with technetium 99 M. And then we can see the localization in the prostate. The similar distribution as the galleon as the other P. M. S. A. Is basically salivary gland gland liver spleen and kidneys. So this is the path treasure of the P. M. S. A. You can see the distribution almost exactly the same but with a better target to background ratio local mcclelland salivary gland liver, supreme kidneys and then there was some activity in the bladder. So we like Pat Tracer because usually they do a quicker scan. They have a quantitative data. They have a better target to background ratio. And then I can put another case side by side. So this is the same compound by the same company labeled with nuclear tracer and labeled with pet tracer. So the company decided to abandon the nuclear tracer. But it's still available in other parts of the world because there are definitely much more gamma cameras than the pet scanner. If in the philadelphia we have about 10 15 pet scanners but we have over 100 nuclear gamma cameras. So the utility is still there and it's still available in africa Asia. And then if you see it and say that in the literature just won't be surprised. So FDA approved the P. M. I says the first one is the column labeled as december 2020 but that's only a food for U. C. S. A. And U C L. A. And U C S. F. So we talk about it, we try to do it here but it's a lot of work. We still need to sell our own I N. D. I need to buy a generator is a lot of work and then I know the other tracers coming in so we decided to wait a little bit. So in March 2021 the leak out the pupil flood stet. And if I don't really write, I mean english your first language. So the trade name is called Glorify. They have a two hour half life and can be delivered in the good distance. And then this one has been approved for initial stages so you can use it for pre treatment. So we got a referral from surgery. Urology and then the radiation oncology before treatment. And then this one approved for biochemical recurrence which is similar as Axman. So this is the news released by FDA and the company and to 12 made the FDA approve it. The first one is called Osprey. So basically the prospective phase 23 Study of the treasure in the prostate cancer examined the diagnostic accuracy. They have to group of patients. One group going to the surgery over 250 patients. The other group with imaging evidence of disease. They just want to say if these nutrients are better. So this is the data for the cohort aid for all the patients went to surgery. The sensitivity is okay. You know from 30% to 42 specificity is very good and positive and negative british value is very good. If we take the lymph node less than five out. The sensitivity improved moderately and then the without losing the specificity negative and positive predictive value. This is another better way of presentation of the data. This is published in the journal of urology last year. So with all the patients the sensitivity about 40%. The specificity negative and positive predictive value is very good. If we take the small notes out The sensitivity improved 20 points without losing any of the other values. By comparison. This new tracer with the C. T. And M. R. Is a similar sensitivity but it's definitely better specificity. You know. C. T. M. R. Has the specificity of 82%. The neutrino has about 97%. There is a significantly better positive and negative predictive value. So that's why the F. D. A. Approved it. And then for the cohort B we know the patient have radiographic evidence of a disease. Then we use this new tracer the sensitivity that more than 95%. And then the positive predictive value was more than 80%. So it's basically saying if you have a vision the nutrients er can say it. So this was published uh as a showcase. The patient has high grade gleason four plus five P. I. C. Is about 14 Ct was negative. Bone scan is fairly negative. There are a little bit something in the left head but the patient had hate processes basically the negative conventional and traditional functional imaging just can show numerous small lesions in the bone. One of them got biopsies of metastatic disease. So thus the Osprey summary basically said this new tracer have a specificity about 98% compared to the conventional imaging about 65%. The overall sensitivity is much better. And then the side effect is really lower because this is the diagnostic scan should have not much of the side effects. So the second trial make FDA approved for the biochemical recurrences called condor prospective phase three multi center open label. And then all the patients will finish a questionnaire to say what are you gonna do? And then they do the scan and then they do a post scan to see the changes. If the patient has a negative one they still sign in. There's no change. If the patient has any positive scan you need to do either biopsy to confirm it or you need to do a scan or other imaging to say this is a relation or you treated with chelation and psychology. And then the P. I. C. Has to go down 50% and then you send in the post and then they use the new term called correct localization rate. The higher the fisa the better correct localization rate. And then there are three independent reader and one of them. So the reading between the three readers very close. So the condo summary basically let me the Primary point they have 85 to 87 uh correct localization rate. They have about 64% of change management, Small lesion, less than five can see it clearly about the background higher than the blood hole. And then the data is published in cancer research. The relation exposure for the new tracer is really fairly low Which is good. And then the gallium labeled Teresa was first approved by use a system and then in December 2021 as approved for nationwide discovered delivery and utility. It's a similar indication. You do a pre treatment scan and you can do a biochemical recurrence. So those is lower. And then the decision made by FDA is basically to 12. I will not go through the details basically the data is fairly similar. They have a six central blended reader. The data is all from U. C. L. A. And UCSF. And they have the sensitivity about 36 to 60% And then the calculated overall is about 47%. So compared to the other one is about 40% is really similar specificity, 74%. The P. V. I. R. Is about 90%. But if you look at the biochemical recurrence is pretty much the similar fundings. So that's why FDA approved it. If you look at the what we call the positivity rate if you have a P. I say less than 0.5 you have only about 36%. And then you're going up with the higher P. I. Say. So overall calculation is about 74%. So about three quarter of the patient will have a positive scan. So I have both of them available. In fact can anybody tell which one is which What do you think? This is A P. Y. L. Or this is the Guardian. Our people say we don't know. So this is the Guardian. This is the devil is very similar distribution is P. M. S. C. Compound. So they will have a similar bell distribution. One is labeled with the galleon and then the other one rating. But both of the pet tracers. So there's another treasure got FDA approved with the vision trial. Because at the time vision trial got approved. They use the 1 77 labeled P. M. S. A. And then they have another Guardian 68 labeled Tracer. But actually the other one is almost exactly as a second tracer. But they have a more indication you can do pre treatment biochemical recurrence and you can use this one to select patient for therapy and N. C. C. And guidelines said you can use either of them to select patients. Society of nuclear medicine basically said you can use either of them. But I do have this one ready. So just in case you have influence issues we have both available. There are other traces have been trying. So this is the P. L. There are number two and number four other traces with very low urine excretion. They're supposed to be better for the prostate bed. This is my last slide. So sometimes when you have the this is the same patient with the different tracers. The patient has prostate cancer with new underground different differentiation. So this is the PMS. A scan. You can see the tumor in the prostate because of new underground differentiation within the governments can with so much receptor, you see much more lesions in different locations. And then we did the f d g for this patient as well, you say, a little bit different things. So sometimes we always try to have the best treasure for the good indication. And then, of course, at the right time, I'm open for questions.