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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 AP sa 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 work, if 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 diffuse. He 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 none 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 androgen 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 what he started at 65. As you 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 PS 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 external ra 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 those bowel movements as well as fatigue. Um, those are things that can acutely happen while the 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, s 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