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So I'll get underway here with my presentation. Um but we'll start by talking about a clinical case and this is a patient um by the name of Mister Smith. He's a 65 year old man who came to his primary care doctor for his annual checkup and he has his P SA or prostate specific antigen labs drawn as along with other uh routine laboratory checks. And he's noticed a, a rise in his, his P SA and we see his P SA trend has been uh steadily rising to where in January of 2024. It's now 12.2. Ok. Um The rest of his clinical case, he reports a um some increased urinary frequency, um some nocturia which means he gets up in the middle of the night to urinate. His past medical history is significant for hypertension and gastroesophageal reflux. He takes Lisinopril and omeprazole for, for those problems and then a bit about his social life. He's married with two grown Children. He is a retired teacher. He is enjoys a glass of wine with dinner. Occasionally, no history of tobacco or drug use and he's very active. He enjoys things like hiking and cycling. Um, his primary care doctor does a physical exam, not notices that there's no uh, mass or, and he has normal rectal tone, his prostate nontender, but he does have some firmness on the left side of his prostate. Uh Mister Smith then gets referred to a urologist and he um undergoes an MRI of his prostate. And on his MRI, the radiologist discovers a lesion in the left posterior, what we call the posterior peripheral zone where he has this nodule. Here, here's the normal outline of the prostate and it's this nodule here on this sequence. And you can really see it light up on this separate MRI sequencing. So it's um the report reads that there's a loss of the defined capsule that's overlying the, the um overlying the prostate. Um and that the, the lesion is suggested that there may be some extra prosthetic extension, meaning that it's popped out of that, that capsule. Uh So he returns to his urologist and his urologist uses the MRI uh as part of the prostate biopsy. And Mr MRI fusion biopsy, they take 13 cores with three that are targeted based on the MRI of that nodule. So we see the pathology results here and he does indeed have prostate cancer and the Gleason score, which is the way that we grade prostate cancer comes back as what we call a grade group four and grade group three here with Gleason three plus uh G Gleason four plus four and Gleason three plus four and then a separate region that wasn't uh seen on the um MRI also came back as having uh Gleason three plus four and four plus four prostate cancer. So what all this means uh based off the biopsy is that Mister Smith has newly diagnosed uh high-risk prostate cancer due to the high Gleason score. And then that indicates uh when patients have high-risk prostate cancer, that they need additional imaging of their, of their entire body. And he uh elects to undergo um PS ma pet scan uh where an avid uh lymph node and avid sclerotic bone metastasis are identified. So, here are the pet scan results and PS ma pet scan is a special type of pet scan. Uh that's newer in the prostate cancer world as having a specific marker and tracer for prostate cancer specifically. So the scan will pick up uh areas of activity that are specific for, for prostate cancer. So, in his pet scan, we see that in the prostate, he has two areas that are what we call avid or, or picking up the dye or tracer um here in his, his rib and that's near the spine, it's also added and then also a lymph node that's in the pelvis. Um Here. So, in summary, uh Mister Smith is a 73 year old man with overall good health who's been newly diagnosed early or oligo metastatic prostate cancer. Um what are his treatment options? And what do those treatments entail? Is surgery an option? Can he get radiation androgen deprivation therapy or a DT um or even chemotherapy? And how do these treatments fit into Mister Smith's uh care goals and his, his overall life goals. So, the treatment option for, for men with all of the metastatic prostate cancer or that early uh stage of metastatic prostate cancer um involve a lot of uh s uh specialist. Uh The oncology treatment team involve can involve urologists, radiologists, have we, as we have already seen in this clinical case, as well as medical oncologists, pathologists, radiation oncologists, even, and even cardiologists. Um So his treatment options will involve input from and expertise from multiple specialties. Uh And typically the best outcomes are involve a combination and multi uh and a multimodality of treatment strategies. And there's been several recent clinical trials that drive uh the current treatment standard in this space. So looking at some of these uh uh these uh clinical trial data, we have the Stampede trial, which is a trial that was um a very large trial comple completed in the UK. Uh We have the specific arm arm H that sh that looks at patients like Mister Smith. So this I have patients with early uh oligo metastatic prostate cancer and all these patients are traditionally treated with androgen deprivation therapy or a DT for the rest of their lives or as long as they can tolerate it. And what this trial looked at is if we add radiation to the prostate specifically, um versus no radiation, what, what would those outcomes be? And what we saw is that radiation therapy improved all cancer outcomes and overall survival in patients with uh low metastatic burning. Mean they had less than uh three or four sites of metastases um when they had radiation to the prostate. Um this was kind of groundbreaking research um at the time, which is a, a few years ago and has really changed the way we, we deal with these patients. Um Interestingly though patients with a high metastatic burden, uh we do not see that same oncologic benefit. Um in, in addition to that patients uh and another trial called the latitude trial um also trains this type of drug therapy we use in these patients. So, uh again, all patients on this trial were treated with uh lifelong androgen deprivation therapy and then the Abiraterone arm, they got abiraterone and predniSONE and then the control arm, they got two placebo drugs. And again, we see men with this newly diagnosed metastatic prostate cancer, receiving abiraterone and predniSONE increased overall survival and lowered the chance of disease progression on uh radiographic or imaging findings. So I get another groundbreaking uh study that changed uh how we take care of these patients. And then the Oreo trial uh which is trial completed um out of Baltimore um out of Johns Hopkins we again see men who have o metastatic prostate cancer. Um And in this trial, they did not receive any a uh androgen deprivation therapy. And instead got a special type of radiation called saber or SPR T. And that was uh used to target the specific sites of metastasis. So, in the stampede trial, they targeted the prostate. And in this trial, they targeted the sites of metastasis um versus an observation arm that received no uh treatment for the metastasis. And they saw that uh speci radiation to these sites, specifically using this style called SS P RT or Saber uh were less likely to have progression uh overall and that some men had as much as two years um cancer uh without cancer progression and remind you that these patients did not receive any hormone or androgen deprivation therapy. So, uh Metastasis directed therapy was enough to keep these men um essentially cancer free uh for longer periods of time. Um So, based off of those uh those clinic that clinical data, we extrapolate uh to kinda combine all those, all those findings and, and we would offer radiation uh to these patients both as prostate, the pelvic lymph nodes and sites metastasis. Um and then also add abiraterone and androgen deprivation therapy all in combination. Um This is a more aggressive stylish treatment and you can tailor back pretty much any point of those treatments for patients that uh may want to avoid uh radiation. Um for, for specific reasons. Um So potential side effects, um the androgen deprivation therapy. This is typically prescribed by urologist, medical oncologist or even uh radiation oncologist. Um They have some sexual side effects. Basically what these drugs do is uh deplete the body of testosterone. So, men without testosterone will have se sexual side effects like loss of libido, erectile dysfunction and hot flashes. Um they can also have some physiologic effects like weight gain, uh changes in your lipid levels and increased cholesterol. And then things like loss of bone density anemia, uh changes in hair texture. And then uh one of the more serious ones is cardiovascular side effects such as increased risk of cardiovascular disease and diabetes. And uh a lot of times patients who have a strong history of cardiac uh conditions like heart failure or coronary artery disease, we may ask them to see a cardiologist to get specific cardiac uh clearance. Uh Before starting this medication, uh radiotherapy, which is given by a radiation oncologist. This is a local therapy and radiation tends to affect the tissues that are directly within the radiation field. So for treating things within the pelvis or the prostate, acutely, men can have increased uh urinary frequency can have increased urinary urgency, like feeling like they have to urinate more often and go more frequently. Uh they can have loose stools, diarrhea, maybe some blood in the urine or bowel movements and also some fatigue and then chronic uh, and then some late, uh, side effects, uh, months to years after treatment, men can have uh, chronic urinary or bowel changes, uh, like that frequency and urgency. We, we just talked about, uh, and then on the more serious that you can have scarring of the bowel which leads to bowel obstruction and, and pain. Um, that thankfully, those are very, very rare side effects. But, but worth mentioning and then treatment to things like, uh, metastasis within the bone or the ribs, uh, some patients can have worsening pain in that area typically. That's, that's short term, uh, and goes away with time and then kind of after treatment they live with this increased risk of fracture if they were to fall or, or have injury to that area. All right. Thank you for, uh, listening to my presentation. Ok, thanks do. That was brilliant. Uh, really good. Um I hope you're, uh, I hope you're happy with it. Yeah. Can I just grab a swig of water real quick? Absolutely. Yeah, please, please. Ok. Two. No. All right, ready. Ok. Ok. Get your next slide. Perfect. Yeah, that's great. Ok, awesome. Um, so we'll just do the same thing again. Just, uh, just remember just to give us a couple of seconds at the start and then a couple of seconds at the end, uh, with, uh, with a pause. All right. Ok. We're really excited to have doctor Ki Gaines, uh, join us, uh, again, uh to, to this time, talk about facilitating patient centered communication throughout the management management journey in advanced prostate cancer. I'm gonna hand over to Doctor Gaines. All right. Thank you for having me. Um I'll begin my presentation here and we'll start with a clinical case. Um This is Mister Taylor. He's a 79 year old man who presents to his PCP with new back pain and difficulty urinating. Um Mister Taylor hasn't seen his doctor in several years, but his exam reveals a 10 reveals tender mid back pain and uh as part of his workup, he has a psa drawn uh with other labs. And we see that in uh earlier this year in January, he has AP saa very elevated P SA of 65.4. Um So he, he also reports to his doctor that he has some, some urinary obstruction, obstructive uh symptoms. And then his uh past medical history is significant for chronic kidney disease, congestive heart failure and COPD. He had, he takes uh Lisinopril and omeprazole as medications. And then he's married uh has two grown Children. He's a retired chef and he smoked for about 20 years but quit two years ago. Um he does not drink alcohol or use drugs um on physical exam, he does have some back tenderness in his mid back. His prostate is nontender but diffusely enlarged and irregular in, in shape. As part of his workup. He undergoes a bone scan which is a nuclear medicine scan that uh that uh uses a radioactive tracer to detect areas of what we call rapid bone turnover. So this can show uh activity in areas of me uh metastasis areas of fracture or even arthritis. And his bone scan looks something like this where we see these black dots indicating areas of that nuclear medicine, um radiotracer activity. Uh He then gets referred to a urologist and hi urologist, his urologist, uh schedules a biopsy which shows that he has um kind of diffusely has prostate cancer. And these 12 cores that are taken showing high-risk prostate cancer with high Gleason scores like Gleason four plus five equals nine or Gleason four plus four. Also some intermediate prostate cancer as well just uh distributed throughout the prostate. Um So, so he is a 79 year old man with some chronic health conditions with newly diagnosed widespread bony metastatic prostate cancer, what we call a high metastatic bur burden indicating that he has more than uh four sites of bony metastasis. And Mister Taylor wants to know what his treatment options are and what does the those all entail? So, um is surgery an option is radiation an option. Uh would he use antigen deprivation therapy or even chemotherapy? And how do these treatments uh fit into Mister Taylor's uh overall care goals. Um So looking at some of the uh the clinical trial data, recent clinical trial data in in this space in men with a high metastatic burden prostate cancer. Um to traditionally, men just got what we call a DT or in deprivation therapy alone, uh lifelong to start as a therapy. However, in a recent trial called The Stampede Trial, uh three of these arms looked at uh patients like, like ours. And so that if we added a combination of a DT plus DOCEtaxel, uh which is a chemotherapy that men had better overall uh survival than if they got a DT alone. Um And this finding was specific in men with what we call the high metastatic burden. As it wasn't seen in this improvement, wasn't seen in men with uh sites of meta that had less than three less than four sites of metastases. Um So in this ba basically, Mister Taylor's general recommendation would be from the medical oncologist and we will discuss the treatment options as DOCEtaxel plus androgen deprivation therapy, androgen deprivation therapy alone or, and things like external beam radiation would be reserved for things like palliation of bony metastases. Um Mister Taylor once uh gets presented this data and decides to undergo DOCEtaxel which is six cycles uh as, as long uh as well as uh lifelong A DT. So he completes therapy and his P SA drops uh to less than one, which is a great response from when he started at 65. I should tell does well for several years, he tolerates he's tolerating the A A DT reasonably well with, with mild side effects. But unfortunately, three years later, his psa starts to rise again and it goes from 1.0 to 7.4. And when we see, uh prostate cancer begin to uh progress, even after having hormone suppression, we call that castrate resistant prostate cancer. Um So what are his options now? Um, now he can undergo uh second line chemotherapy, um or even undergo something called targeted radionucleotide therapy. And this is again, newer clinical trial data, a newer uh treatment strategy which uh which this trial specifically called the vision trial has looked at men with um metastatic castrate resistant prostate cancer. So again, this is prostate cancer that does not respond to hormone suppression. Um and they looked at the standard of care and compared the standard of care plus the addition of this, uh it's called lutetium ps ma +621 or Pluvicto. Um And when Clavi was added to the standard of care, they prolonged, uh it it prolonged the disease uh from cancer from progressing and also prolonged overall survival. Uh What Pluvicto is is a specific radio tracer that um that can, that has this TS MA tag on it, which targets prostate cancer specifically and it will go deposit this radiopharmaceutical drug. Uh So this has only been looked at so far in men with, with uh the castrate resistant metastatic prostate cancer. But trials are underway and looking at the role of drugs like this in earlier stages of prostate cancer. Um So as far as external radiation, um this this patient will be eligible for external radiation for things like uh palliating pain. So these bone metastases can be quite painful for patients. As we saw in our case here, our patient had uh some significant back pain and this external radiation can be delivered at any point in the treatment course. Um About 75% of patients that get external radiation for pain palliation re report a, a, uh pa at least a partial pain response, meaning that they require less pain medications or require pain medications less frequently. And even about a third of those patients report report a uh complete response, meaning that they no longer need pain medications for whatever they were taking it for. Um, there's newer research on the use of a special technique of externalization called SPR T and how that impacts pain control. And there's some suggestion that it may have a better uh response and better uh more robust uh type of pain control than conventional radiation. Ok. So some potential side effects of these treatments. Um, so starting with the radiation therapy again, this is a, a local type of treatment. Uh So it only affects uh the tissues that are, are direct, that are directly in the radiation field. So if we're talking about treating things in the pelvis or in the prostate or the prostate specifically, um, patients can experience increased urinary frequency, increased, uh urinary urgency, uh loose bowel movements or diarrhea or even some blood or urine in the bowel movements as well as fatigue. Um, those are things that can acutely happen while patients getting radia radiation to about uh 1 to 2 months after and then some late um effects like months to years later. Patients can have uh these chronic urinary and bowel cha uh bowel changes as well as um uh s scarring of the bowels which can lead to things like blockages. Uh But fortunately, those, those types of things are, are, are very rare. And then in the treatment of uh the sites of metastasis like bone, uh you patients can have increased uh bone pain. Uh Usually this is something that is transient and goes away with time. Uh But then they do carry the risk, an increased risk of fracture in whatever area of bone that is treated. Um A DT which is another uh treatment option here. Um And the way this drug works or this, this group of drugs work is by depleting the body. Um the body's testosterone. So things like sexual side effects like the loss of libido or erectile dysfunction and hot flashes are are are common. Um Things like physiologic effects like weight gain and changes in uh uh lipids and and increased cholesterol can occur and things like loss of bone marrow density and anemia. And then more seriously things like cardiovascular side effects like increased risk of, of heart attack or stroke, uh, and also diabetes. So, a cardiac evaluation with a cardiologist may be warranted in patients with, um, with preexisting cardiac conditions. All right. Thank you for, uh, listening to my discussion.