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Prostate Biopsy

A prostate biopsy can come with anxiety and uncertainty. In this webinar, experienced urologists dispel common myths, walk through the experience from preparation to recovery, and equip men with key questions to ask their doctor at each step.

Dr. Phillip Koo leads a conversation with Dr. David Albala, urologist at Associated Medical Professionals and Chief of Urology at Crouse Hospital in New York, and Dr. Matthew Cooperberg, Professor of Urology at UCSF.

Learn about:

  • Transperineal vs. transrectal biopsy: Understand the two main approaches to prostate biopsy: differences in technique, infection risk, discomfort, and why the experience and preference of your urologist matters most in choosing between them.
  • The role of imaging in biopsy accuracy: Learn how MRI and ultrasound help doctors target suspicious areas of the prostate rather than relying on sampling alone.
  • What to watch for after your biopsy: Seeing blood in your urine, semen, and stool is normal for a few days, or even weeks. If you have fever or significant bleeding, seek help right away.
  • What your pathology report means: Walk through a real biopsy report and understand Gleason scores, percent tumor involvement, and risk of cancer outside the prostate.
  • When a negative biopsy isn’t the whole story: A biopsy that shows no cancer isn’t always the end of the conversation. For men whose PSA or other factors still raise concern, the ConfirmMDx test can help show whether a significant cancer may have been missed.

Thank you to MDX Health for their support of this program.

Transcript:

Phillip Koo, MD [00:00:00] Thank you all for joining. As Becky talked about, this is one of the first times we’re actually talking about a topic before diagnosis. Many of you are actually going through the journey right now and hopefully there’s a lot you’ll learn from this, but for those of you who may have already gone through the journey of a biopsy, I think you’ll just learn a lot from this, and if people do approach you and have questions about what to do after an abnormal PSA when the recommending a biopsy, please refer them to this video, which will be enduring on the PCF website. So, thank you, David. Thank you, Matt, for joining us. Let’s get right into it. So, this is a great topic. Patients, we get screened. You get your PSA drawn, you know, maybe every year, ideally every year. Maybe every other year. It comes back abnormal more often than not, or oftentimes if it’s abnormal, you get an MRI. But at some point, we’re not gonna go through all the details. A decision is made that you need a prostate biopsy. And then all these questions start going through your head. You start going to Dr. Google and trying to figure out what does that mean? I think the biggest question that comes up is, how are these done and the different types of approaches? And I think a lot of times patients think, oh, a biopsy is a biopsy, but the sort of a big fork in the road is this idea of a transperineal biopsy versus a transrectal biopsy. So Matt, let me start with you. Give us an overview of you know, these two, what sort of the different approaches and what are some of the pros and cons for both? 
 
Matthew Cooperberg, MD, MPH [00:01:32] Yeah, so these are two different ways of getting to the prostate. The prostate sits right on top of the rectum anatomically and kind of under the bladder and also sits very close to the skin of what we call the perineum. That’s the skin between the scrotum and the rectum. So, it can be reached from either of those trajectories. In either case, whether we pass needles through the rectums, that’s a transrectal biopsy, or through the skin of the perineum. Either way, we’re doing a transrectal ultrasound. So that has been our primary modality for visualizing the prostate for decades at this point. A transrectal ultrasound is done by an ultrasound, a plastic probe that’s passed into the rectum. That is typically uncomfortable, but not painful. And then the needle is passed either right along that probe across the rectum into the prostate or through the skin of the perineum. Historically transrectal was by far the most common way to do this. We would occasionally do transperineal ones for folks who had been through several biopsies, and we were looking for something missed, or prior, you know, extensive rectal surgeries. There would be exceptions, but transrectal has been historically, you know by far, the one that’s out there the most. Over the last few years, there’s been a lot of interest in transperineal, again, going through the skin rather than going through the rectum, mostly in the hopes of reducing the infection risk from a transrectal biopsy. Transrectal, of course, the rectum is not the cleanest place in the body. There are millions of bacteria per square millimeter in the rectum, and there’s always been the concern of carrying bacteria from the rectum into the prostate or into the blood. And in fact, there is about a 1%, depending on what you read and which study it is, about a one percent chance of infection after a transrectal prostate biopsy. Despite the antibiotics that we typically give. So, there’s been a lot of interest recently in transperineal and just in the last year and a half, there’ve been a few very large, randomized trials published where men were actually randomized between doing a transrectal and a transperineal biopsy. And at the end of the day, the differences are probably a little bit more subtle than a lot of people expected them to be. So, there is a lower infection risk in the transperineal approach than the transrectal approach, but only by a few tenths of a percent. There’s really no real difference in the ability to find the aggressive prostate cancer that we’re looking for in doing the biopsy. And the trade-off is the transperineal is more uncomfortable. There’s more pain. The way we’ve always done a transrectal biopsy, it’s done with a dense local anesthetic with a lidocaine injection. It’s a little bit like going to the dentist for the Novocain that, you know, the injection of the Novocain hurts. After that you’re numb and you feel pressure but should not feel any pain. The same applies with the transrectal biopsy. It is possible, but a lot more difficult to get the same density of local anesthesia with the transperineal approach. So many colleagues I have that are doing a lot of transperineal have taken to doing them in the operating room or under sedation in the office rather than just with local anesthesia. There’s nothing inherently wrong with that, but it’s converting it from a 15-minute outpatient procedure to a few hours in a surgery center with multiple providers involved in that sort of thing. So bottom line is these are both still very much valid approaches. There is a lot of hype out there. Sometimes there are specific anatomic reasons, given a specific lesion that might be easier to get to for the transrectal approach versus the transperineal approach. So sometimes there are specific reasons to choose one over the other. Otherwise, there’s usually a lot of room for discussion with the docs. And I would say the most important thing is it be a procedure that the urologist has done many, many, many times before and is comfortable with. 
 
Phillip Koo, MD [00:05:18] You know, I think that’s a great point. It’s about sort of what the urologist is comfortable with, what they’ve done over and over, and with practice comes better results. David, from your perspective, I think this creates a lot of confusing situations for patients because they might read something and someone might say, you absolutely have to get a transperineal. How should patients handle that? You know they might have friends telling them, oh, why are you getting a transrectal? Why are you getting a transperineal? What advice do you have for patients in this situation? 
 
David Albala, MD [00:05:48] I think the most important thing is to, and again, thanks for inviting me, Phil, it’s really a pleasure. I think that the most thing is that to have a discussion with your treating provider. I mean, you have to feel comfortable first with the biopsy. And I think, the important question is to ask them, does he do transrectal or transperineal? There are many older urologists that have not done transperineal biopsies. They’ve done transrectal all of their careers. And as Matt said, most of those are done typically under an anesthetic, just like going to the dentist. They’re tolerated well. The probe is a little uncomfortable, as Matt said, but you can get good tissue. And that’s been really, there’s been many, many more transrectal biopsies done over the years than what we’ve seen with transperineal. The transperineal approach is great. If you have a treating provider that does that, you know, ask them how many they’ve done. I think that, you know, the most important thing is though, the urologist has to feel comfortable with the approach. The tissue that they’re going to get with either biopsy is probably going to be identical. As Matt said, my experience with transperineal biopsies is that they are more painful and we typically do them under anesthesia, you know at our surgery center, for example, and we find that that works pretty well. But, again, I don’t think there’s a real major difference in the quality of the biopsy as long as the person is experienced. And I think that’s the overriding factor. But that’s like with any procedure that you’re gonna have. If you’re going to have a robotic prostatectomy, the questions you’re to ask is, how many have you done? What are your outcomes like? Again, the risks with these biopsies, as Matt alluded to, are extremely low. Bleeding and infection are the biggest risks. And you can have an infection with a transperineal, that’s much lower than we see with transrectal. But as Matt also said, there are biopsy randomized studies that have been done. For example, there was a nice study done at Albany Medical Center, just down the street from Syracuse. And what they did is they got groups of patients, and they randomized into transrectal and transperineal. And there was no difference in the outcomes and infection rate was very, very minimal. So, I would tell you, now, one thing that Matt alluded to is typically these biopsies need to be done either with an ultrasound or with MRI fusion, where you get an MRI first and then fuse the images with the ultrasound. So, you can have it just a straight, like for example, transrectal ultrasound where the ultrasound probe is in the rectum and taking pictures, or you can get an MRI and fuse those images with the ultrasound. So, if there’s an abnormality that’s picked up on the MRI, that’ll be seen on the ultrasound, and we can do targeted versus just random biopsies. So, I think that’s an important question to ask. Are they doing MRI fusion biopsies or are they just doing an ultrasound biopsy by itself? 
 
Phillip Koo, MD [00:09:11] You know, I think that’s a great point and a great transition into this idea of image-guided biopsy versus random biopsies, and what we do know is when you take these biopsies, you’re only taking a very small sample of the entire prostate. So, in some ways it’s kind of a shot in the dark, but there is some structure to it. So, Matt, maybe demystify and explain this idea of image- guided versus random. 
 
Matthew Cooperberg, MD, MPH [00:09:33] Yeah. So first of all, they should never be random. You know, the other term is systematic. So, you know, image, I know it’s true, people use the term random all the time. You know at UCSF, we are blessed to have an ultrasound program led by Katsuto Shinohara who has really been one of the international sort of founding opinion leaders in terms of how to do a good prostate ultrasound. And it’s really important to recognize that ultrasound itself is a very good imaging modality, especially with modern equipment. There used to be this one-liner that the ultrasound was the way to find the prostate, not to find the tumor. And that is really not the case in contemporary practice. At my center and at most centers, we uncommonly do a biopsy without having an MRI first, because the MRI can identify lesions that the ultrasound might miss. And we do use a fusion system to help identify the cancer. But the reality is most of the aggressive lesions that we see on MRI, you can see on an ultrasound. If it’s good quality equipment and you’ve got an experienced urologist doing it. So, the idea with image-guided versus systematic, the image-guided biopsy means whatever we can see, whether we’re seeing it on the MRI in advance or through a fusion system or seeing it on ultrasound, we target that spot and take anywhere from one to four biopsy cores of that area. The systematic biopsy recognizes that we don’t see everything, and we will take somewhere between in modern practices, somewhere between eight and fourteen cores typically from the different parts of the prostate, right left, front back, what we call kind of apex and base that sort of thing, mapping out the prostate mentally into these different sectors. It’s a little bit controversial now, do you still do the systematic biopsy? Most people on this side of the Atlantic feel the answer is yes. There’s some very good data from the NIH from Peter Pinto’s group. We have data at UCSF. There’s data from a variety of studies showing that the imaging does not always find the highest-grade cancer. In the UK and other places, there is this movement to say we’re only going to biopsy what we see on imaging. I don’t think we’re quite there yet in terms of the quality of the imaging. The last thing I wanna say about imaging and about MRI in general is the quality of the MR is incredibly important and incredibly variable. So, the reads on the MRs can be hugely variable from radiologist to radiologist. And there’s a lot of variability in quality from machine to machine. And you would much rather have a good quality ultrasound than a bad MR. And in fact, there’s newer technology called micro ultrasound that a lot of urologists are adopting that, especially in areas where you don’t have access to great quality MRI, is probably a better way to go. And it’s fewer trips for the patient because you don’t have to make your way to the MRI center and then come in for the ultrasound. So, it’s really a question of image guidance through some combination of MRI and ultrasound. And then, yeah, I’m still in the camp of doing the systematic biopsies as well as the targeted. 
 
Phillip Koo, MD [00:12:31] Great.  
 
David Albala, MD [00:12:33] I might just add one thing, you know, we talked about the risks, you know, bleeding, infection, a common question that comes up is, if you have a prostate biopsy and there’s a cancer and you biopsy it, can you see, you know, do you spread the cancer? Is that a risk factor? And, and that’s come up multiple times with patients that come in that are always concerned. And we’ve done hundreds of thousands of biopsies. And that risk is it’s not zero, but it’s so small. You probably have a greater chance of walking in a grocery store parking lot and getting killed by a car, you know, than that happening. It’s very, very unusual. So, the biopsies are safe. You, you know, we’re getting small pieces of tissue to look under the microscope, make the diagnosis, and that risk of spreading is essentially negligible and I just want to, because that’s a common question that comes up to many, many patients who come in. 
 
Phillip Koo, MD [00:13:34] So, you were reading my mind and there are actually several questions about that that came up before and during it about potentially spreading the disease, so that’s great. Dr. Cooperberg, you brought up a great point about experience. So, even the MRI piece, it’s really important to go to a center that’s experienced, you know. Whether it’s 3T, 1.5T, you now, that’s just a tool. They have to be able to use that tool effectively. So, just don’t exclude a center just because you’re using a 1.50T magnet as opposed to a 3T. It’s really about experience and that comfort level and that communication with the urology team, which is also vitally important. So, David, I’m gonna ask you this. So, a lot of patients are gonna be told they need a biopsy, they’re reading about it, they’re real anxious and they’re thinking to myself, how do I prepare, how do make sure I decrease any of those risks as much as possible? How can I contribute to make sure I have the best outcome? So basically, how should they prepare before biopsy? 
 
David Albala, MD [00:14:31] Well, typically most practices will have a standard protocol of what they tell the patient. If you’re on any aspirin or blood thinning medications like anticoagulants, we typically have those patients stop those medications. Our practice, we do rectal swabs. So, patients two weeks before their biopsy, come in and we get essentially a Q-tip, and essentially get a piece of stool and place that on a culture plate so we can actually look at the antibiotics and make sure that we provide an appropriate antibiotic that’s going to kill the typical bacteria that would be in the rectal flora. So, we typically have done that. When I was at Duke, our infection rate went, you know, dropped dramatically once we started this rectal swab program. So, it’s one other step to try to minimize that risk of infection. Patients on the day of the biopsy give themselves an enema and then they come in and then the biopsy is done. So, there’s not a whole lot to prepare for. Understand when the biopsy is done, the probe is put in the rectum and when the biopsy gun is you know engaged it makes a little clicking noise and I like to tell the patients you’re gonna hear a clicking noise because it doesn’t really hurt. But it can startle the patients and make them jump up a little bit. So, I try to educate them that way to be prepared. But my experience is if the biopsy is painful during the biopsy, you need to speak up because we can give you more lidocaine to provide a better block. But we have very experienced people that do our biopsies. You know, they’ve done many, many ultrasounds. You know, and usually those are the things that we usually try to do and prepare our patients for. 
 
Phillip Koo, MD [00:16:36] Alright, so you’re setting yourself up, preparing so you can decrease your risk of bleeding, decrease your risks of infection. Is there any role for enemas, David, for preparing? 
 
David Albala, MD [00:16:46] We have given enemas to our patients, and we tell them, you know, and it just makes it easier. So, when they put the probe in, there’s not a lot of stool there. I don’t know, I’d be curious to see what Matt does, but we typically have been, you now, having our patients give them a Fleets enema two hours before the biopsy. 
 
Matthew Cooperberg, MD, MPH [00:17:06] We generally have as well. If it’s early in the day biopsy, the patient’s had a bowel movement and really wants to avoid the enema, we will sometimes skip it, but most of the time we do. Otherwise, the prep is similar. We don’t do the rectal swab culture, but we have adopted a protocol from the Music Consortium in Michigan where they are literally just sort of wiping the needle in on alcohol preps. Prep pads between each biopsy, and they showed in this Michigan quality initiative, they dropped the infection rates almost 50% by that sort of simple step. So, we’ve started doing that. It’s hard to prove, because the infections are so uncommon, it’s hard show that you’re making a difference in any six-month period, but we have adopted that practice too. 
 
Phillip Koo, MD [00:17:47] You know, we covered a little bit about what happens during the procedure. There’s the transperineal approach versus the transrectal. You know, we talked about general anesthesia versus local anesthesia. Matt, anything we missed and also if you could touch quickly on you, know, we talked about not random but systematic biopsy versus image-guided There’s something called mapping biopsies or saturation biopsies that’s out there. Can you sort of demystify that for us as well? 
 
Matthew Cooperberg, MD, MPH [00:18:13] Yeah, there’s a question in the Q&A about that too. A saturation biopsy, I think we’re doing less and less in the MRI era. It used to be something you would do when you’ve gone through a couple biopsies, and we haven’t found the cancer and the PSA is still going up. You would take the patient to the OR and literally do one biopsy per cubic centimeter of prostate tissue or something along those lines. So, take a lot of biopsies, making sure you’re covering every little nook and cranny of the prostate. Again, in this era of image guidance, we’ve got better MRI, we’re even doing PSMA PET sometimes when we’re onto like the third biopsy and looking for a hidden cancer. It’s been a while since we’ve done one of those. I should say, having said that, the systematic biopsies we tend to do on a template regardless of the size of the prostate, which has never made all that much sense, but it’s what we do. And if you do a 14-core biopsy from a 20-gram prostate, you’re gonna sample that prostate much more extensively than if you do the same 14 cores in a hundred-gram prostate. So, when it comes to saturation, I think the cases where we would still do that are typically gonna be in a really big prostate where we really need to pull out all the stops to explore all corners of it. I would make one more comment on the prep, which is that one of the most important aspects of preparing for biopsy is that in many cases these days you’re going to get the pathology report before we talk to you because many centers have open access to charts now and it is essential to understand that what we’re looking for is aggressive prostate cancer and along the way we might find grade group one or Gleason 6 or 3 plus 3 and a lot of us are starting to say that shouldn’t even be called cancer. It is low grade it almost never needs treatment and it’s really really important to understand that that readout the pathology report is not “yes/no” it’s “yes/no/sort of”. If we find a higher-grade cancer, we have the conversation about what to do. If it’s all negative, that’s great. If we find grade group one or three plus three, in almost all cases, that’s something we’re going to watch and should not trigger alarm bells. 
 
Phillip Koo, MD [00:20:11] You know, I think you’re teasing a discussion we’re gonna have in a few minutes, so this is good, so everyone listening, get your buckle up, we’re going to have some good discussions. So, alright, David, you get the biopsy, it’s an outpatient procedure, whether you’re getting a transperineal versus transrectal, you’re going home that day. It’s always anxiety provoking when you have some weird symptoms or certain things are happening after you get home. Talk to us about recovery, what is normal, what is not normal. You know, there’s a question in the chat about, you know, someone actually a friend of someone being given a catheter after a biopsy. Talk to us about all this. 
 
David Albala, MD [00:20:48] So, I would tell you, if you have a fever, that’s abnormal. That to me is a, you know, red light goes off. If you develop a fever after a prostate biopsy, you need to be seen, either by the person that did the biopsy or going to the emergency room. Because if you become septic, you can slide very quickly, you know, into where the treatment is going to be much more difficult. You know, people can die from prostate biopsies. Rare, but it can happen. So, to me, if you have a fever, that’s a golden rule. You need to be seen right away or go to the emergency room. There are patients that have bleeding. That’s not uncommon. If it’s profuse bleeding and your clots are coming out, and I’ve seen that over the years, not very common again, that would be another indication that you probably need to be seen right away. Again, in the emergency room or by the person that did the biopsy if they can get you in, you know, call the office or where your biopsy was done. So, to me, those are the two big, you know stop signs. You may have a little burning with urination. That’s not uncommon. People have some urgency and frequency. Again, not all that uncommon, but to me fever and significant bleeding would be things that would drive me to see my treating provider as soon as possible. 
 
Phillip Koo, MD [00:22:20] Great, so, you know, I don’t think there are any real I mean long-term adverse events here are probably exceedingly, exceedingly rare, so I don’t even think it’s worth our time to discuss that. So, alright, you get the biopsy, they process it, in a couple days, as Dr. Cooperberg said, maybe a little longer, who knows. Patients in MyChart are gonna get that report. You’re gonna be sitting there refreshing probably every minute wanting to see the results, and the results sometimes are complicated. So, Dr. Albala actually was gracious enough to bring up a de-identified sample report. So, let’s sort of walk through the information that comes from this report. David, I’ll turn it over to you. 
 
David Albala, MD [00:23:00] Sure, so this is a report that our pathologists generate and, you know, every different practice is going to be different. I like this because it tells me all the information. It’s got the patient’s name up at the top. It tells me what the PSA is. And then it looks at what we call the clinical stage. And that helps the treating provider think about the kind of treatments that may be available to the patient. But as Matt said, so in this particular diagnostic biopsy, on the frame on the left is a model of the prostate. It shows the landmarks, you know, the base of the prostate and the apex of the prostate. And it’s reversed. It’s a little funny because, you now, most people think the base is the bottom and the apex is the top, but this is how it’s reported on our pathology reports. The stars represent normal prostate tissue. So, in this particular individual, he had one, two, three, four, five biopsies that were completely normal. You know, we do look at cells that are atypical. That would be represented with a triangle. In here, we don’t have that in this particular patient, but those cells aren’t truly cancer cells, but they have a high likelihood of progressing into cancer cells. So, if you had triangles on this biopsy, you know, the treating provider would say, yes, you know there is no definitive cancer, but these cells are not normal, they’re slightly abnormal and atypical, and we need to have a high index of suspicion. But for us, the biopsies are shown here in two things. Anything that’s red is a positive biopsy. So, there’s one, two, three, four, five, six, seven, eight of these biopsies are, out of the 13, are positive. Now, if you look underneath it, it says GS: 3 + 3 = 6, or GS: 3 + 4 = 7. That stands for Gleason score, and we’ll talk a little bit about the Gleason score. The Gleason score is a way of determining the aggressiveness of a particular tumor. And underneath that is the initials PTI, and there’s a percentage. So, if you look at that right base, it’s about, I think it’s 60%. PTI is about 60%. So, what that means, if this is the prostate and I stick a needle in, 60% of that biopsy is cancerous, 40% is normal. So, it gives us an idea of how much cancer is present in that specific core that we biopsied. So, you can see down at the apex on the left, or look at actually the left base, you can say there’s a 5% involvement. So, 95% of the biopsy is normal, 5% had a cancer and it looks like it’s a Gleason 3 + 4 = 7 up there. So again, these are all tools that help the treating provider, you know, educate you about your disease, about the aggressiveness of the tumor, how much cancer is present. We then on the opposite side, and this is what our practice does, we use the Partin table. It’s a nomogram that that Alan Partin, who was the chair at Hopkins. Essentially it looks at four component factors. It looks at lymph node involvement, which is the top one, the mark that’s red. The yellow looks at seminal vesicle involvement, and remember, the seminal vesicles sit on the backside of the prostate. And then the two bottom ones are extra prosthetic extension, and the green at the bottom is organ confinement. So, what this tells us is for people that had this kind of biopsy, the Partin table, the nomogram says that the risk of lymph node involvement is extremely low, the risk of seminal vesicle involvement is extremely low. You know, the organ confinement is 68% I think looking at that. And then you can see extra prosthetic extension which is, you know, think of the prostate as an orange, what’s the chance of the disease getting outside that orange peel or penetrating that orange peel. That’s what the EPE is. So, it just is a tool to give patients an idea when I’m sitting and counseling them, what their risk factors are for these factors. Now, this is just, again, population based on patients that we’re seeing at Johns Hopkins. And so, it’s just a talking point to give us a discussion. But again, I think the real discussion is gonna happen with your treating provider. And they’re going to go into all these details, Gleason score, percent tumor involvement, and then if you have higher grade disease, are you a better candidate for surgery versus radiation? And so that’s how I start the discussion, but you can see it’s relatively involved and that’s what you’ll see our MyChart. 
 
Phillip Koo, MD [00:28:18] So, it’s a very complicated discussion, lots of information. When you open that report, just make sure you schedule that appointment or you have a time to go speak to your urologist to clear all this confusion up. So, one other point I’d like to sort of emphasize is, again, these biopsies are only taking a very, very, very small percent sample of your entire prostate. So, we’re taking, using that small sample to make a very big conclusion. But it’s getting better, as Dr. Cooperberg said, now that we have image guidance to sort of target the more suspicious areas better. So, all right, you get the biopsy. In this case, it’s clearly positive. We’ve talked a lot about positive biopsies. Then you have prostate cancer. We’ve talked about that in other webinars. That’s where Decipher and other biomarker genomic tests come into play. So, we’re not gonna get into that today. That being said, Matt, there are times where it is indeterminate. What does indeterminant mean? 
 
Matthew Cooperberg, MD, MPH [00:29:18] Yeah, well, indeterminate, first of all, there are the other patterns that David just mentioned, which may show up on a pathology report. Things like atypia, or ASAP, atypical small acinar proliferation, that is thought to be an area, maybe suspicious for cancer, but too small for the pathologist to actually cull. It’s been controversial over the years where there’s something called high-grade PIN, H-G PIN, is an indicator of possibly having missed a cancer. So, there are these indeterminant things we can see on the pathology. But there’s also sort of indeterminate clinical situations where, for example, there was a clear spot on an MRI, if you had an MRI and yet the biopsy is all negative or you had some other biomarkers suggesting we would find something and we didn’t, or we go back to following the PSA and it’s going up quickly. And these are all sort of varying degrees of gray zone situations in terms of what we actually recommend the patient do next. 
 
Phillip Koo, MD [00:30:12] Alright, so it can get confusing, alright, another result, potential result is your biopsy comes back negative, which, okay, you breathe a sigh of relief, thank goodness, but then there’s also this sense of, hmm, I had all this stuff before the biopsy that was suspicious that I had to get a biopsy and now you’re telling me I don’t have cancer, so what the hell’s going on? So, David, what do you do with this? 
 
David Albala, MD [00:30:39] So there are, obviously you need to have a discussion with your treating provider and you’re gonna sit there and obviously most people are very happy that the biopsy is negative. But as a clinician, if the PSA is super high or as Matt alluded to, things just don’t fit, there are some commercially available tests that we can do to further determine if perhaps maybe we missed the cancer. And one test that comes to mind is the Confirm MDx test. This is a methylation test. So, say Matt comes in to see me, he has a biopsy done, the biopsy is negative, and he’s still, you know, anxious, and he’s like, doc, you know, my father had prostate cancer, my brother, you know my PSA is really high. What this test does is I will get the biopsy samples and send them out to a laboratory, I believe it’s in San Francisco, and what they will do is they will methylate the specimen. And the thought process is that, if you have a prostate nodule, there’s abnormal cells around that nodule that if the biopsy doesn’t go directly into the nodule, but maybe alongside it, that with the methylation test that would come up positive. And so, I can send his biopsies off, they can do the methylation tests, and it will give me a map of the prostate, and it’ll tell me whether it’s positive or negative. If it’s negative that means the methylation test nothing lit up on the methylation test. If it’s positive, what’s really nice about these reports is, they break down the risk of the significant, you know, lesions that we worry about, and they break down the lesions that might be prostate cancer, but we don’t worry about that. As Matt alluded to, the Gleason 3 + 3s, or the low-risk prostate cancer versus the higher-risk prostate cancer. And I think, Phil, maybe you can put up the slide.
 
Phillip Koo, MD [00:32:57] Yes, we’ll get to those in a moment. So, before we get there are multiple tests. This is the only tissue-based test. I believe there are urine-based tests that are often performed before the biopsy, but that’s a different topic of discussion. Matt, David brought up a topic of missed. Maybe patients have heard that and that probably brings some anxiety. Talk to us about this idea of misdiagnosis. 
 
Matthew Cooperberg, MD, MPH [00:33:23] Yeah, so again, the needle, no matter how big it feels, the needle is very small and is sampling, as you said, only a small amount of the tissue. And if you have a relatively small prostate cancer, it can absolutely be missed, even with a good quality biopsy. And this is why we don’t say go home and forget about it when a biopsy is negative. Now, these get to be very nuanced conversations. And a lot of the process before a first biopsy, tends to be a little bit algorithmic. I think the conversations after a first negative biopsy are a lot more personalized. It depends on what the PSA is doing. It depends on lots of factors. It’s important to remember a few things here. First of all, PSA is prostate specific antigen. It is not prostate cancer specific antigen. And this is where we look for things like the size of the prostate. We look for things like inflammation in the prostate that we might see on the biopsy that can be sources of elevated PSA. And yeah, we have lots of tests available to make sure we haven’t missed anything significant, missed anything meaningful. So first of all, the American Urological Association has a guideline that says pretty clearly, you know, the MRI is optional before a first biopsy. It is not really optional before a second biopsy. So, we would almost always want to see an MR before deciding to get a second biopsy done. And then, yeah, we have lots of markers. We have, as you said, lots of urine and blood tests that are out there. The Confirm MDx test is a terrific one to try to localize what might have been a missed area geographically. But we have, there are questions in the chat about IsoPSA. That’s a blood test along with 4K and PHI, which are looking at subsets of PSA that are a little bit more specific for prostate cancer. There’s urine tests like MPS2 and ExoDx. These are all intended to predict the likelihood of a higher-grade cancer. Both before the initial biopsy and before we think about repeating a biopsy to make sure we haven’t missed anything significant. And again, I emphasize over and over again, missed anything significant. You make it to a man in your 70s as a black man, 80s as white man, there’s a 50-50 chance you’ve got a little bit of Gleason 6, grade group one in there, and you are perfectly happy not knowing about that. And I really cannot emphasize that enough. All these tests we’re talking about, Confirm, MRI, Iso, So all these tests are intended to predict grade group two or higher, what we call clinically significant prostate cancer or higher. And the idea is if the test is negative, it means either there’s nothing or there’s a grade group one. And in either case, we don’t recommend the biopsy. So, we were actually trying pretty hard not to find grade group 1. 
 
Phillip Koo, MD [00:35:58] I think that’s a great point and I know a lot of patients with grade group one, that creates a lot of anxiety there as well, but that’s something, a different topic that we’ve talked about, especially in that active surveillance videos. So, David, to your point, we’re gonna reset now. You had your biopsy, it comes back negative, but there still is a high suspicion or concerning signs that you might have prostate cancer, maybe family history, really high PSA. Can we bring up the first patient story using this type of test and David, I’ll turn it over to you to walk us through how you interpret this and how you sort of walk patients through this report 
 
David Albala, MD [00:36:36] So this is the methylation test. This is the MDx test. And the tissue has been sent out to the laboratory. The methylation test has been done. And essentially, you’re gonna get a report that’s gonna be one of two reports. This is a positive report. So, this a patient, if you can slide it down a little bit, let’s just look at the diagram. You see the prostate diagram here. That’s the area one where the methylation test was positive. In other words, all the clear circles represent the methylation test was negative. But in that left side, you can see the left mid-portion of the prostate, there is a positive methylation tests. So, number one, it localizes where the abnormality is from the biopsy specimens. So everywhere else except that left mid portion of the prostate was completely normal. Then it breaks it down into what the risk is for a low-grade disease versus a high-grade disease. And up at the top, you can see that’s the likelihood where it says 12% for a high-grade tumor. Then down below it is 20%. That’s the likelihood of a low-grade tumor. And those ones we don’t really, again, as Matt and Phil both have alluded to, those are the ones we’re not really interested in as much as that one with that 12%. We’re interested in those high-grade lesions because those are ones that we wanna treat. And then the circle to the right just adds the two numbers together and that’s what gives you that likelihood, if I were to do a repeat biopsy, what the likelihood is of finding a cancer. So, it’s, in this particular patient, It’s 32% if he had a repeat biopsy done with a 12% risk of a high-grade lesion versus a 20% risk of a low-grade of lesion, and the area that’s of concern is the left mid-portion of the prostate. 
 
Phillip Koo, MD [00:38:48] Great, thank you. And then I think the patients and everyone can see how this type of information really would impact how you might be managed, even though your biopsy came back negative and that 12% risk of having something significant needs to be worked up. So, then Matt, let’s switch gears and we’ll bring up the other case story. Alright, so this is the second case, and Matt, walk us through this other scenario. 
 
Matthew Cooperberg, MD, MPH [00:39:20] Yeah, so this one’s a lot easier to read. It’s just negative, which is great. It means there is no abnormal methylation of any of the genes. And by the way, just in case it’s not clear, methylation is one of the tools that the body uses to regulate genes. And one of the early hallmarks of cancer, and one of hallmarks cancer in its early development before it even starts to look funny under the microscope is changes in methylation. It’s literally adding little chemical bits to the genes that make it easier or harder for the body to use those genes, to turn those genes into proteins. So, when we see abnormal methylation, that’s an early sign of genetic changes in the cancer. In this case, it is absolutely clear. You can see they have a nice negative predictive value. That means the confidence that we have in the test of 96% for high-grade disease, meaning we can be 96% confident that the original biopsy did not miss a higher-grade cancer. Okay, now, you know, so in this case we would typically recommend this this patient to not worry and just go back to following PSA with primary care. Now, having said that, no test answers the question all by itself. I’ve always joked when I give these talks, you know, everybody wants these to be pregnancy tests and if it turns blue you do the biopsy if it doesn’t you leave it alone, you know, it’s not that easy. These are all continua, and if the PSA keeps going up, or if there’s an MRI lesion, maybe on top of the prostate, far away from where all the biopsies were done, the conversation might change despite this. But this would, generally speaking, be a very reassuring test. Now, let’s say one more thing about the PSAs being nine here. So, this is where we really look at other things that we have now learned. Either through the MRI or through the ultrasound, we will now have a size on the prostate, and we can calculate what’s called PSA density. That’s literally just the PSA divided by the size of the prostate. If this was a hundred-gram prostate, the density would be 0.09 something. It would be very reassuring. We’d say, listen, the PSA is just high because they have a big prostate. If the prostate is much smaller and the PSA is going up consistently, that would be more worrisome. Once in a while, we will actually use medication specifically to drop the PSA, especially if somebody’s got a very big prostate and a lot of voiding symptoms. There’s medications that shrink the prostate and should stabilize the PSA. If somebody has a history of bladder infections or prostatitis or we see inflammation on the prostate biopsy, we will sometimes use anti-inflammatories, and I’ve seen those drop the PSA by like 70% in some cases. Because again, the PSA is prostate specific, not prostate cancer specific. So, a negative report like this is very reassuring that we can start looking at other explanations for the high PSA. 
 
Phillip Koo, MD [00:42:05] Great, you know that’s really helpful. I think it’s a reminder also though, doesn’t mean you shouldn’t follow up and keep getting your PSAs. Doesn’t mean you’re free and clear. You still need to follow up and make sure you’re getting the appropriate care. So, all right, I think those are really good two cases that show the power of these types of tests in certain clinical scenarios and they’re very, very informative. Obviously impact how you might be managed and the goal is to detect the serious prostate cancer, so it does not impact your life. So, David. From your perspective, we’re gonna go to a little Q&A now. Patients’ second opinions. Patients go to their doctors, oftentimes there are second opinions on pathology, there are second opinions about a lot of things. What’s your advice that you give to patients on when and how to seek out second opinions? 
 
David Albala, MD [00:42:54] Well, I think you have to have a good feel with your treating provider. I have no trouble with any patient that comes in and says, do you mind if I get another opinion? I think as a treating provider, I’m here to provide the information, answer your questions. My goal is to educate you so you can make an informed decision. And if you feel you want another opinion, You know some people like to get another pathologist, you know, most of the patients don’t know the pathologists that, like in our practice, our pathologist just reads GU pathology. When I was at Duke, we just had one pathologist that read prostate biopsies and kidney biopsies and bladder biopsies. But in smaller hospitals, they may not have the benefit of having a specialized pathologist. So, if there’s any concern, there are commercially available labs that are more than happy to give you a second opinion to look at the pathology specimen. But I think you, you know, I think most patients are savvy enough to feel if they feel that they may not have gotten the whole story, I would encourage you to get a second opinion. You know, I think if a physician is reluctant to do that, I’m not saying he’s hiding something, but I bet you, Matt would agree with me on this that, you know, in our practices, we’re comfortable people. If they want to get another opinion, I’d encourage them to do that. If you feel comfortable with your treating provider and you think that you know that the options have all been put on the table, I think that’s great too. You know, and you can, you both need to sit down and make an informed decision on how you want to proceed. As Matt said, there are multiple ways of treating prostate cancer. If it’s low-grade, low-risk disease, you know, we’re going to do active surveillance on those patients. Repeat the PSA at six months, and at some point, get a biopsy maybe a year or two years down the road to kind of see if there’s progression of disease. Obviously, some patients that sent to me are going to have their prostates taken out, you know. And I’ve done 5,000 robotic prostatectomies in my career. You know, we have those discussions talking about the risks and so on of the surgery. All our patients see a radiation oncologist. You know, I’m not an expert on radiation therapy, but I do send them to get them informed to discuss what those options are because radiation has changed over the years. You know we used to do an extended 44 treatments. We now can-do shorter treatments. And I think a radiation oncologist is best, you know, poised to talk about those treatment options because that’s what they do. So, there’s also. If there’s a risk of metastatic disease, scanning, the landscape has changed. We’ve gotten away from bone scans and CT scans or conventional imaging as we referred it to. We now do prostate specific membrane antigen scans. These are very highly specific scans, but again, they’re not 100% foolproof either. So, all of this discussion is pretty robust, and it does take a fair amount of time to go through all these options. 
 
Phillip Koo, MD [00:46:20] There’s a lot to discuss. Just quick, I think you touched on specialization, which I think makes a huge difference. Matt, you had a comment.
 
Matthew Cooperberg, MD, MPH [00:46:28] I wanna make one comment about the pathology second opinion. So, first of all, I agree completely with David. It’s the urologists that try to prevent you from getting, or discourage you from, getting a second opinion that you should worry about. And likewise, anybody that’s telling you it’s an emergency and you don’t have time to get a second opinion, again, that’s especially the scenario where you want a second opinion. This is never an emergency. Even if you have a Gleason nine, you have time to get on a couple of Zoom calls and sort things out. This is a never a cancer that changes in weeks or a couple months. And one comment of the pathology second opinion specifically, it is great to be in a place where you’ve got GU subspecialized folks. But even among GU subspecialists, there can be disagreement, especially in this pattern four category. So, the 3 + 3s are pretty much universally a non-issue. There was a question in the Q&A about the percentage of pattern four. And yet for these 3 + 4, the grade group twos, that is becoming a very important question. How much of it is pattern four? And even more than that, there is a lot of discussion now about the subtypes of pattern four, and I don’t wanna get too far into the weeds here, but there’s different visual patterns that the pathologists see under the microscope that all get lumped under this pattern four. And it’s becoming very clear that some of these matter incredibly more than others. So, when we see terms like large cribriform, intraductal, intraductal is one of the checkboxes on the example that David showed that was not present on that report. So, keywords like that. You really need a pathologist who is ruling them in or out because it turns out it makes a massive difference in the risk of the cancer. So even if you’re not getting a second opinion from another urologist, getting a national reference lab, UCSF does these, Johns Hopkins does these, Memorial, there’s a few other centers, that is well worth the time and usually the few hundred dollars it takes to get the second read. 
 
Phillip Koo, MD [00:48:21] And I will also add, as a radiologist, getting a second opinion for your prostate MRI before the biopsy is also helpful. And that’s usually coordinated with the urologist because they will use that test to help guide their biopsy. But I’ve seen a lot of different variations there. And specialization isn’t perfect, but it does make a huge, huge difference. Good, so a question comes up about some other descriptors in pathology. Like, this is a little bit different, but if you are diagnosed with prostate cancer, it’s perineural invasion, vascular invasion. What does that mean? What’s the significance of that? And David, I’ll turn that to you. 
 
David Albala, MD [00:49:00] I mean, those are descriptors, you know, what that means is the cancer is near a nerve, you know bundle on, you, know, the prostate’s got nerve endings, and you can see those nerves. You can see vascular invasion. Again, you know, most of the biopsies that I’ve seen have not reported that. You get a couple that do. Typically, in my practice, it doesn’t significantly change how I’m gonna manage the patient per se. But you know, patients do get concerned. They say, oh, it’s in the vascular system, it’s gonna spread and so on and so forth. That’s really not much of a concern. 
 
Phillip Koo, MD [00:49:48] So, we covered a lot during this hour, all the way from what to expect when you’re getting a biopsy, how to prepare for the biopsy itself, negative biopsies, positive biopsies, indeterminant. Matt, I’ll turn it over to you first. Anything we missed and any closing comments you have for us. 
 
Matthew Cooperberg, MD, MPH [00:50:06] I’m trying to monitor the Q&A. I think we’ve covered a lot of the questions in there. There was a question about blood in the semen, which we did not talk about. Blood in the urine typically lasts a couple days. You gotta drink a lot of water, keep your whole system washed through. Blood in stool, you can see it for a couple of days too. Blood in semen whether it’s transperineal or transrectal can be really dramatic. It can look horrible. It’s typically gonna be red and then gradually fade to brown, then lighter brown, yellow, et cetera. And depending on how often you’re emptying the system, how often you’re ejaculating, it can last for weeks or even a month. So, be aware of that. Beyond that, I would really just emphasize that, you know, this is part of this continuous discussion you have with the urologist and the treating team from that first marginal or elevated PSA on through what do we do? And the entire time, the devil is in the details. Prostate cancer is a huge continuum of risk. Many of them are not that big of a deal. The aggressive ones still kill more men than any cancer except lung cancer. So, you know, the details really do matter. And we are blessed to have this growing armamentarium of things that we can do. Imaging tests, biomarkers, blood tests, urine tests, tissue tests, all to help men make better and more personalized decisions. So, there’s a lot of hope on the horizon across the entire spectrum of decisions. 
 
Phillip Koo, MD [00:51:22] Great. Thank you. Great comments. David?
 
David Albala, MD [00:51:25] You know, the one thing that struck me, if your treating provider wants to get you into the operating room right away, that raises a red flag. Because I think what you need to do as a patient, you need to digest this information. Waiting a week or two weeks or three weeks is not going to increase that risk of disease spread. You need to be methodical. You need to feel comfortable with the decision. You know if you’re choosing surgery you want to make sure you know the surgeon, the number of cases that they’ve done, you know what their you know erectile function rates are, continence rates. So there’s a lot going in you know but this part early on is kind of the gray zone because you know you don’t have cancer, you worry about it, once the biopsy is done and you make that decision I would say if you’re going forward with a biopsy, don’t overthink it, get the biopsy done, it’s tolerated well, and then once you have tissue, then if you do have cancer, you address that head on, or if you don’t have cancer we have another test that might give us some more information to make you feel more comfortable, but have these discussions with your treating provider. There’s no rush, prostate cancer is exceedingly slow growing. And, you know, if somebody’s trying to rush you in, like I’ve had patients come see me and said, you know, Dr. X, you know, wants to do the surgery next week, to me, that should throw a red flag, be methodical, get the information and make an informed decision. 
 
Phillip Koo, MD [00:53:10] Great, I love that. Be methodical, make an informed decision. You know, I like to still think I’m young in this field and looking back, it’s amazing to see all the new tools and all the new advancements that are now available for all of us to make better informed decisions. And that really comes from great research from people like yourselves, people like all the different urologists, medical oncologists, researchers throughout the world who’ve contributed this, that all of these new developments, I think, help get us closer to being able to have a bigger impact on how patients are diagnosed, treated, and managed. And it’s really from all of the listeners out there and people who contribute to the research mission where we are able to make that difference. And it’s always a pleasure to have Young Investigator alumni who are helping to contribute to this as well. So, thank you all for joining. And again, please have anyone who comes to you asking about this who gets diagnosed with an abnormal PSA who needs a biopsy, to watch a video like this just so they are more informed and they can make better decisions. So, thank you all and enjoy your evenings. 
 
David Albala, MD [00:54:18] Thanks for having us, Phil. 
 
Phillip Koo, MD [00:54:19] Thank you.