Journal club #7 | proPSMA and Penile Fractures(!)

0:00It's time for another journal club and we have lots of reasons to celebrate today. Yes, it's the first journal club after the EAU. Is that what you're talking about? Well, that's one, but you will see that the studio today is quite full. It's a crowd. It's exactly right. In the GUCAS studio. A Lena Berg is with us in-person. A Lena, welcome to Australia. So great to be here, to be in the real studio. That's time. You'll remember, Lena has been joining us on Zoom for all these past journal clubs, but she's now a brand-newly-minted fellow at Peter Mack. And so it's great to have you, Lena. There you have it. It should be here. And wonderful to have the whole team in the studio. Yeah, it feels great, doesn't it? So in case you're not watching on YouTube, you got for myself and Renew. As usual here, in our seats, we have Carlos Delgado. Carlos, one of our journal club editors who's been on fellowship here for a while. Carlos, welcome back. Thank you, Layton. A pleasure being here.

1:00Yeah, but yeah, it's so exciting to have a Lena. Behind the scenes, we have our partnership and content manager, David Chen. We should do that. Hello, David. You can shout out. We'll hear you. He's already sending through some behind-the-scenes footage. He sure is. Yeah, so we got the whole game together in person. And that's right. And we've, you know, we've all just returned from a huge EAU in London, with our first live stage show. So, you know, we had a great time over there. What did you guys think? Did you think it went well? Well, very nice. You guys, you guys were very good at, I strategically planted that question. You did. For compliments for Renew. So, you know, EAU was great because we interviewed you, you know, in the audience, you know, with that very immersive kind of stage that we had there that Martin Albison and the team had set up for us. And we talked all about journal club. And how difficult it is to pick the papers for each episode of the journal club. You know, you always want to talk about prostate cancer. And we sort of have to tell you to back off a bed. And so, we decided while we had the whole audience for, you know, our live stage show,

2:03we might get their help in picking the papers. And, you know, we committed to doing these papers. So, Declan, how did they pick the papers? Well, yes. So, if you haven't seen the live event that we posted last week, we did an audience poll while we had Carlos and Elena there. So, we put up five papers. I think that you guys had picked out and let's watch how that vote went. Everyone get out your phones. There's a QR code there. And we have a few suggestions. Pick your favorite paper. And the top two will feature in our next GUCAS journal club. So, get voting. Please start now. So, the options are radical prostatectomy or watchful waiting in early prostate cancer. This is the SPCG4 trial. The ProPSMA study. We love that study. Swag337, Intravis cycle gem site of being for low grade non-muscle invasive bladder cancer. Camina, site of reductive nephrectomy. Or, is that right? Penal fractures. The price of a Merry Christmas. So, vote everyone. We've got a few seconds here. Penal fractures. That's not your oncology. Did you put that up there?

3:04All right. Few more seconds to get your votes in. Let's see. Penal fractures. Penal fractures and ProPSMA. Well, there you go. You guys have to present those two papers now. That's our next journal club sorted out. We should do this every month, right? Excellent. Thank you, Carlos Salina. Back to you, Deque. Yes, so now we're committed to these papers. So, that's a ProPSMA, a proper big paper. And then, what's it called, the... What's it called, the native? And the price of a Merry Christmas. The price of a Merry Christmas. And that's going to be about penal fractures. Very archaeological. What that has to do with Geochology. I'm not quite sure, but there it is. So, there are the two papers. They're going to be treated like proper classic journal club papers. Thanks again to our friends at MSD who support the journal club. And, oh, gee, the feedback we got at the EAU was fantastic about journal club. Yeah. Thank you to everyone who looks journal club. And thank you for all the suggestions. We know that these go around the trainee WhatsApp groups in Erology, Radiation College, Medical Oncology. And we love that feedback. So, hopefully you'll enjoy this one.

4:05Yeah, I'm sure you will. And I'm thinking part of the charm really is that you guys take all the work out of it for everyone else. So, let's get straight into it. I think we might start with the ProPSMA job. With the oncology. With the oncology one. Awesome. Well, we cannot start a Geochast journal club without that prostate cancer paper. Yay. So, I'm going to talk about the ProPSMA trial. This is a land set published at the land set in 2020. I'm sure you guys know it very well. This is a landmark study that fundamentally changed how we estates men in high risk prostate cancer. For many years, the standard of staging approach relied on conventional imaging with CT and bone scan. However, these modalities have relatively poor sensitivity in detecting small lymph node metastasis and early bone metastasis. As a result, a proportion of patients who appear to have localized disease actually harbor or cult metastatic disease.

5:07This is technically important because inaccurate staging may lead to inaccurate treatments. Around the time of this study, PSMA PET City was emerging as a promising imaging modality with the potential to detect much smaller deposits of metastatic disease. However, prior to the ProPSMA trial, most of the evidence supporting PSMA PET City in the staging situation were retrospective or single center studies. And there were no prospective randomized trials comparing it directly with conventional imaging. The ProPSMA trial was a prospective randomized multi center phase trial conducted across 10 centers in Australia. The investigators enrolled men with newly diagnosed high risk prostate cancer who were being considered for curative treatment with either surgery or radiotherapy. Patients had to meet at least one of the high risk features PSA above 20 or higher.

6:08I subgrade group 3 to 5 or clinical stage T3 or greater. After all of 300 and two men were randomized one and one into groups. First group underwent conventional imaging consisting on CT and CT abdomen and pelvis and technician bones can and expect CT. The second group underwent a gallium 68 PSMA PET City and an interesting feature of the study was a crossover design. So after the initial imaging test, most patients underwent alternative morality as a second line imaging unless widespread metastatic disease was detected in the first one. The primary endpoint was diagnostic accuracy for detecting pelvic node or pelvic nodal metastasis or distant metastatic disease assessed using the area under the rock group. The reference standard including histopathology, imaging findings and clinical follow-up at six months. Basel and characteristics were well balanced between the three groups,

7:09median age was 68 years, 98% of the patients had great group. Three or higher, about 22% had PSA above 20 and 27% had clinical T3 disease. Overall about 30% of the patients were ultimately found to have nodal or distant metastasis based on the reference standard. The results were that PSMA PET City achieved an accuracy of 92% compared with 65% for conventional imaging. This represents an absolute improvement of 27%, which was highly statistically significant. Looking more closely at the test performance, the sensitivity for detecting metastatic disease for the PSMA PET was 85% compared with 38% for conventional imaging. A specificity was also higher for PSMA PET, was 98% versus 91% on the conventional imaging.

8:10PSMA PET also identified different types of metastasis baseline and among patients who scan with PSMA PET, 20% had pelvic nodal disease, 9% had abdominal nodal disease, 10% had bone metastasis, and 1% had visual metastasis. Many of these would likely have been missed with conventional imaging. This is very important for the patients. Conventional imaging produced equivocal results in about 23% of the patients, whereas PSMA PET reduced this equivocal results to only 7%. This is clinically relevant because equivocal scans often trigger additional tests and delayed treatment decisions. The study also evaluated impact on clinical management. PSMA PET led to changes in management in 28% of the patients compared with 15% after conventional imaging. And interestingly, PSMA PET was also associated with lower radiation exposure.

9:10Strengths of this trial, this was a randomized perspective, multi-center design. This is the first phase three randomized control trial, comparing PSMA PET city, head-to-head with conventional imaging, which was the long-standing goal standard for staging in high risk prostate cancer. The investigators use a composite reference standard with follow-up imaging, which is often necessary in diagnostic accuracy studies where biopsy confirmation is not always feasible. High inter-rider agreement of a capital of 0.87 for nodal and 0.88 for distant metastasis on PSMA PET, which this supports replicability of the study. Patients had an excellent follow-up, 98% of the patients had reference standard as accessible at six months. And pre-specified long-term follow-up has since confirmed the prognostic value of PSMA PET city nodal findings.

10:14However, there were also some limitations that are worth mentioning. Not all metastatic lesions had histopathological confirmation. So the reference standard was partly based on imaging and clinical follow-up. And the sensitivity was likely overestimated. The pelvic lymph node section was performed in only 66% of prostatectomy patients. Subsequent studies using histopathology as the goal standard report PSMA PET sensitivity lower than the 85% reported in the pro-PSMA study. However, we know that pelvic lymph node the section is also inaccurate because we often miss some sites of metastasis that we are not detecting in the regular templates of the pelvic lymph node section. And despite these limitations, the clinical implications of the pro-PSMA trial were substantial. The study demonstrated that PSMA PET city is significantly more accurate than city

11:15and bone scan for staging in high-risk prostate cancer. And it also, it also reduces equivocal findings, influences management decisions more often, and exposed patients to less radiation. As a result, PSMA PET has rapidly been incorporated into major international prostate cancer guidelines. And in most part of the world, it has effectively replaced conventional imaging for primary staging. PSMA PET city provides substantially more accurate staging that conventional imaging in men with high-risk prostate cancer and should be considered the first line imaging morality before curative treatment. This trial represents one of the most important advances in prostate cancer imaging over the past decade. It has been cited more than 2,000 times since it was published in the Lancet. Excellent. Very nice summary of the pro-PSMA study. For sure. Really a landmark study. Do you remember, Declan, this was our first ever podcast?

12:16It was. That's the pro-PSMA study. Yeah, a fun fact, because it was due to be presented in the EU, wasn't it? It was. It was. COVID shut everything down. March 2020. That's right. And Michael Hoffman, the lead author, was supposed to present it in the practice changing cleaner at the EU in Amsterdam. And then two weeks before that, everything's cancelled. We're locked down in Australia. And we happen to be about to launch the podcast. So our very first podcast, end of March 2020, just six years ago, was pro-PSMA. So it's a special trial for us, isn't it? Very special. It was a reason. I mean, yeah, that's right. And I mean, it completely changed our practice. I mean, this was published in 2020, and we got reimbursement for PSMA PET in the stage in a couple of years later. July 2022, I remember. So a great way to stage patients with, you know, intermediate and high-risk prostate cancer. But it also meant that we, we, you know, the rate of no-disection went straight down because now we have this amazing staging tool. We didn't need to rely on a morbid operation like a no-disection degree.

13:17And so it has made such a huge difference for us in practice. Yeah, and it's great to see guidelines accepted around the world and reimbursement following. Few additional points about it. I like the way you refer to these equivocal findings on the CT in bone scan, because, you know, you forget like it was 23%. And this is, remember, on a prospective trial where all the quality controls are in place for the, you know, conventional imaging as well as the PET imaging. And what informant that you stage with unfavorable intermediate-risk or high-risk prostate cancer have an equivocal finding? And, you know, they, things on a bone scan, equivocal lymph nodes, this, that, the other, which in itself lead to more scans or biopsies or whatever it would be. We're trying to make them as metastatic. And people out there listening to the podcast who still stage or remember staging with them, remember that one and four? What are the equivocal findings? Whereas that's 9% in PSMA PET CCs. That was very important. Because we get the big end point of accuracy. That's, that's way better. The other one of the low radiation dose mattered when it came to reimbursement as well.

14:17You know, if you only have one scan as a PSMA PET CT, one scan, quick time in the hospital, it's a significantly less radiation dose. Does, you know, that matters as well. And, and the concordance on the central reading was very, very high. So these are all secondary important secondary endpoints to why it matters. And there was a, there was a separate health economics paper we wrote out of this. It was a pre-specified health economic analysis where we factor in everything, you know, cameras breaking down and blah, blah, blah. And at least in the Australian setting, we showed it was cast effective, you know, from a management point of view. An interesting point that we were asked about recently is the randomization way. So what's this randomization thing? So the randomization was for which scan do people have first? Do you have CT and bone scan or PET scan? And the reason for that was we were recording the management plan after each line of imaging, and even actually before imaging. And the reason for that is that that's important to get reimbursement in imaging studies. So it's not just about accuracy or clinical endpoints, people actually, you know, apparently want to know about management impact.

15:17So the reason we randomized was we were able to show in the trial that if you had a CT and bone scan first and then you cross over and have a PET scan, there was even still a high management impact. You've already had management impact by having one round of basic imaging. But even then, a PET CT further changed the management in more than 20% of patients. The other way around, of course, doing a PET CT, management impact, 28% or whatever. And then when you crossed over and had a CT and bone scan, like negligible management impact, it didn't make any difference. So multiple reasons why it then led to, you know, it's a very, very strong place in guidelines for staging on favorable intermediate and high risk prostate cancer. Yeah, it's great, isn't it? And it's, you know, this paper is now 60 years old, and yet I have not been to a non-college meeting where this hasn't come up, you know, it hasn't been relevant, you know, to this day. Colors, a question for you. So you mentioned that it should be the first line in staging. Do you think CT and bone scan have any role anymore in staging localized prostate cancer? Well, if you don't have a PSM8 bed, that honestly...

16:19Be the only time. Yeah. Because I mean, there's no need to stage low risk disease and for intermediate and high risk now we've got this. I guess, Declan, one of the things, I mean, we had a great time here because we were so used to these scans already by the time pro PSMA was published. But around the world, there were a lot of significant challenges in A-axis, but also once you had the scan, you know, what do you make of these results? I mean, are there experienced people reading these scans? Yeah, reporting systems. Reporting systems. And, you know, patients who, you know, the flip side of the coin is that they have a clear CT and bone scan and all of a sudden this pesky little node comes up on a PSMA pit CT. You know, what do you make of that? So it has been a challenge, you know, to have this kind of more widely accepted around the world. And on that point, people often talk about, yeah, the greater sensitivity, you're going to see these smaller lesions and management impact and controversy about that. But the flip side was also through, as you said, the specificity is higher. So these vague things on a bone scan that condemn someone to, oh, now you've got metastatic disease. You know, and you talked about this

17:19in your oligometastatic plenary at the EAU and the opening plenary. It also does that. It corrects the false positives. That's part of that equivocal finding things. It corrects the false positives that are out there with conventional imaging. And again, points people towards more appropriate management. Absolutely. And also highlights the significance of having a good multidisciplinary team. Because that's the only way that, you know, reading of these scans, you know, you get more experience when you get feedback after patients have been operated on. So, I mean, again, something we do very well here. Lane, any thoughts on it? Because of course, PESMA PET CT really came out of Germany. And we always acknowledge that. And, you know, using gallium PESMA 11, which is what we use, gallium 68, and this came out of work that was done in Heidelberg, in places like that. So, yeah. I still feel like we're a bit, a few years behind Australia, though we've had, yeah, conventional imaging for quite a long time. Now, the reimbursement still isn't very clear.

18:19Most private entrances pay for it, but the general ones still don't. So, yeah, but, yeah, it's going to be good in a few two definitely. And that probably story, even, you know, because Germany's had long, that long experience, but that's still an issue around the world. People listening to this are watching this will, but yeah, I still can't get access, or I can't believe it's changing. And, you know, five years ago, very few people outside certain countries got access. So, it's improving all the time, becoming cheaper. And also, these validated reporting systems, like the SPARK consensus thing that we spoke to Anders Bartel about here recently. All these are helping and keeping the quality high. And PCWG4 has just come out, which is embedding PSME PET CT into clinical trials as well. So, yeah. But thank you, Carlos. That was a very nice overview. Nice for us to hear is, as well as we lived in breathe. But I haven't heard anyone do a journal club on it before. So, that would be nice. We were waiting for the right moment to do pro-PSMA. I don't think we can do that. I think to the crowd of the EU for voting for pro-PSMA. Thank you. But onto the big one, they're nice to vote. Oh, yeah. Okay, yeah. The size of the Merry Christmas,

19:21a little bit different with this paper. This time, but the audience has voted. So, yeah, the paper was published in the VGAI in December 2023 around Christmas. And I'm to evaluate whether the incidence of penal fractures increases during the Christmas period. I'm hypothesizing that the, as the author say, Christmas spirit and the intimacy and euphoria of these holly jolly days might represent a potential risk factor for penal fractures. Oh, yeah. For the Chinese listening, penal fractures defined as the rapture of the Tunica Albuquerinia and surrounding the corporate covenosa, mostly occurring during sexual intercourse and typically presenting with pain, swelling, hematoma, rapid edumacins and sometimes associated also with urethal injuries in about 20 to 25%. So, that study used the germination-wide inpatient data to evaluate that and additionally examined the influence of seasonality and the COVID-19 pandemic, pandemic and lockdown on presentation rates that is called a grand study and it contains all reimbursed inpatient data

20:23of the inpatient cases in Germany. It reveals information on patients and hospital characteristics, comorbidities as well as inpatient procedures, outcomes, complications and is stored and anonymized at the Federal Bureau of Statistics. And the primary outcome was the incidence of penal fractures during Christmas with an admission between the 24th and 26th of December secondary outcomes were the incidence of surgery, poor penal fracture during Christmas, the incidence during New Year's Eve and during COVID-19. A total of 3,421 patients with a median age of 42 years had a penal fracture requiring a hospital stay during between 20, 2005 and 2021. 40 of those occurred during Christmas. The median length of hospital stay was three days for those patients. Most of them, 76% had a surgical correction and for the penal fracture. The daily incidence of the penal fracture during Christmas

21:26was 0.78 compared to 0.45 during the non-Christmas time of the year and that resulted in an IRR of 1.43 which was statistically significant meaning that 43% more penal fractures would have occurred if every day was Christmas in Germany. However, New Year's Eve was not associated with an increased incidence and concerning weekdays, most patients were admitted on a Sunday, followed by a Saturday. It also had a look at seasonality. June was the month with the highest incidence March had the lowest incidence and interestingly the COVID-19 pandemic and the lockdown did not influence this at all. So in conclusion, that's also what the author say. The incidence of penal fractures displays a seasonality. Last Christmas, penal fractures occurred more often this year to save us from tears. We will not do something special than a new Christmas hit of the year. Is that written in the paper? There's written in the paper. That's the conclusion.

22:26The trial has a few strengths and limitations. Strength is a creative research question answering something that has not been studied before. In what was a large data set with 3421 patients was a long study period, 17 years, providing temporal stability. Limitations are the limited clinical detail that was administrative data. They have like a mechanism of injury, severity treatment approaches or long-term outcomes that only kept at hospitalised cases, no outpatient or delayed presentations. It was German data only, so may not apply to other countries or healthcare systems. It was small, absolute numbers, only 40 cases during Christmas and had an inconsistent holiday effect, New Year's Eve did not show an increased risk undermining the holiday celebration hypothesis. Oh, my God. And remind me, who are the authors? It was a colleague of mine, Pegidus, et al.

23:28Right, from Munich. Yeah. And how did they get this idea to look into that? That's a very good question. What, you know? Well, it might have been triggered by repairing a peanut fracture at Christmas, because you know what I've just realized, Renew, is I've only repaired two peanut fractures in my career when I was a registrar, one of which was on Christmas morning at Guy's Hospital, and it was like the whole thing broken, big, you reach for a injury, I've got photographs of it. I might see, can I pull out one or two appropriate ones and slip them on in here, but if it's not too brutal. But yeah, they're quite spectacular when you got a proper peanut fracture. When I was a young trainee, like, and it was the middle of COVID, I was on call in-house on the 24th. We had just shifted from 24 hour to 12 hour shifts. So I was expecting a quiet night and because everybody told us that there's nothing happening on Christmas usually and on call shifts. And, but I came there expecting nothing and my colleague, who was there on the day, just you can go straight to the Uber or to theatre.

24:29And there's a peanut fracture that needs repair. So yeah, also on Christmas morning. There you go, it happens. Stodes are building up. Have you repaired any peanut fracture? Not over Christmas. I have done a handful in my training days, but not, I don't think any of them are over Christmas. You go 50% of us at least. Carlos, what about you? Have you had any Christmas peanut fractures? Mexico Independence Day. Is that your Christmas? Yeah. So the clinical implications, I guess, Elena, don't take call on Christmas day. Yeah. Concludes are kind of difficult. Be particularly careful around Christmas. Yeah. Knees, Eve, don't worry about it. But, yeah. What about this Easter, not Christmas, I suppose? I mean, I know, I mean, lots of, obviously, urologists and urology trainees listen to this, but so do radiation oncologists, industry representatives and patients. So if you're a patient out there who's had a peanut fracture or a sympathy, I mean, it's a pretty horrific when it happens. And I remember there used to be like specific risk factors,

25:29reverse cowgirl position. I remember it was one of them. Elena's not like you've done all this reading. And then I remember there was this bizarre paper in the J-eroll in the Journal of Erology. If you're going to talk about the easyology of it, apart from like regular sexual positions, yeah, reverse cowgirl, all this. But don't keep bite. Don't keep bite. That's the one. There's a long this table, one or table two, as a list of reasons why people have a peanut fracture. It was bite from a donkey doctor. And there's another one that was this bizarre kind of masturbation practice in the streets of a certain country, which was like 20% of them. You know, there's young kids hanging around in those street corners with their hands down their pockets. And I can't remember which is bizarre there. So the whole peanut fracture thing, yeah, there you go, you got an airing on to you. Absolutely. And it also goes to show that, you know, if you want to paper published in the BJUI, you just have to have an interesting question. Yeah. I think, I have some interesting questions. That's all for the authors grabbing the moment there.

26:29Yeah, there might be some trainees out there thinking, I could, I've got an idea for a thing like that. And the BMJ- I mean, you never know, it might come up on the exam. It might do. And the BMJ, the British Medical Journal, always has a Christmas edition. And it's chock full of these kind of, you know, humorous stories and there. Well done, Elena. That was very good. Great summary. Very different. Great summary. It was absolutely awesome. And there you go. And thanks very much to the crowd at our live event at the EAU of UICS on Monday news. I don't think we'll do that every month, though. Yeah, I'm having the crowd control of the ship here. Yeah, we did have a few good options on that list. So they may be trials that we decided to do in the future. Yeah, exactly right. But yeah, well done. And great to have the Journal Club editors here in the studio with us for new. It's been really, really good to have them. I must say, instead of having Elena up on the, up on top of the Zoom screen there, that she's normally sitting up there. But here she is with us. And you guys have actually just left the operating theater. You were all doing a robotic partial. Absolutely. So that's what that's what it's like here.

27:30Pre Journal Club. Renew was doing a robotic partial. And it freaked me with Carlos and Elena. And then just peel off. Come out here and do a Journal Club. And now we don't get it by tweet. So that's the way Journal Club now works. We got Elena and Carlos here. Fantastic. Thank you very much again to our Journal Club supporters, MSD, who are great supporters of our Journal Club. Allow us this to happen. And we'll be back again in person. And next month with another edition of the G-Gest Journal Club. Thank you.