Surgery vs Radiation for Prostate Cancer: New PACE-A Trial Results

0:01 Surgery versus radiation therapy. This is an exciting trial that was just presented at the National Radiation Oncology Meeting in North America. This is the ASTRO 2026 meeting. This is the big meeting that all the radiation oncologists go to around the country and many oncologists come from around the world to this meeting. So, this year it was held in Boston and my favorite trial was presented. there this year. It compared surgery versus radiation therapy for prostate cancer. So if you've been watching a lot of my other videos, you know that one of the big questions that men face is, should I get surgery or radiation therapy for my prostate cancer? And this is a question that many men will face,

0:49 and it's present among multiple risk groups. So here are the national guidelines. This is for favorable multiple risk groups. So here are the national intermediate risk disease. RP means radical prostatectomy. RT means radiation therapy. So the guidelines tell you you can do either one for favorable intermediate risk disease on top of active surveillance. We're going to get to that in just a little bit. But they don't really tell you which ones to choose. They just say that both are an option. And you would think, well, maybe for unfavorable intermediate risk disease, it's going to be different. And you would think, well, maybe for unfavorable intermediate risk disease, it's going to be different. But no, unfavorable intermediate risk disease, same selection, same choices. But no. Really, the main thing that changes is that now you're potentially adding hormone therapy if you're receiving radiation therapy. And what

1:37 about for high risk disease or very high risk disease? So the options are radiation therapy or radical prostatectomy. And now the main thing that's different is that the hormones are longer, now 12 to 36 months. If you've been watching my other videos, you know that I'm a big proponent of the shortest amount of hormones possible, so maybe 12 months, and maybe for very high -risk disease, we're adding this drug called abiraterone. More on this in just a little bit. So all these risk groups, same question, and the plenary presentation, so plenary is kind of like the highest type of abstract or highest presentation at the meeting. It's presented to everyone at the meeting on the national stage. presentation at the meeting. It's presented to everyone. This is the efficacy of radical prostatectomy versus stereotactic body radiation therapy for localized prostate cancer, the results of an international

2:27 phase three randomized controlled trial. And that trial is PACE -A. And Nick Van As is the first author here. You can see that the trial is largely run from the United Kingdom. And this has been presented and published in various forums before, and I want to go through all the parts of this trial and what I think is important for men to consider. Okay, so how do we put this trial in perspective? This is a figure that you'll see in my other presentations for men of how we define the risk groups and the treatment options, and so what you'll remember is that PROTECT, which is the trial that also compared surgery versus is that PROTECT, which is a trial that also compared surgery versus radiation therapy versus radiation therapy, active surveillance, was mostly low -risk and favorable intermediate

3:14 -risk disease. PACE -A is now mostly intermediate -risk disease. And for high -risk disease, we currently have a post -hoc analysis of the PUNCH and RTOG trials that's done by Dr. Sam Roy. And there is a randomized trial that is pending, but we're slowly filling in the gaps for all the risk groups. Okay. So where does PACE -A fit in? And I'm going to go through all the parts of this abstract and the figures that were presented at the meeting. Okay. So the authors state that the purpose of the trial, they know that the treatment selection is often influenced by expected functional outcomes because we assume that the cancer control is

4:03 relatively similar between the treatments. is relatively similar. So there is no evidence right now or limited evidence that compares radical prostatectomy versus stereotactic body radiation therapy or SBRT. SBRT is just kind of like the quote unquote newest form of radiation therapy. It just means that you're getting the treatment in five treatments or less. Typically it's five. And it's technically pretty similar to IMRT. It's just that the treatment is condensed. Instead of getting 40 treatments or 20 treatments, you're getting a much larger dose each day and you're done with the treatment in basically like two -ish weeks. treatment is condensed instead of getting 40 treatments. So the background, they are presenting the five -year efficacy data and the side effect data of this trial. And these slides are taken from the investigators, so I

4:53 have to give major kudos and shout out to the investigators. These are not my slides. I'm just relaying the These are not my slides. message so everyone else gets to see it. The PACE trials are addressing various questions. So if you saw before in my other talks, we talk about the PACE -B and PACE -C trials. PACE -A is all the way on the left side here, and this is comparing radical prostatectomy versus SBRT, and it is no hormones, no ADT. And that's important because ADT affects your PSA control. So more on this in just a little bit, because the side effects, ADT also has side effects. It's kind of

5:42 like a very pure trial of just surgery versus just radiation therapy. PACE -B was the trial that was comparing conventional fractionation or moderate hypofractionation conventional fractionation or moderate hypofraction. versus SBRT. So basically, this is like, how quickly can we get the radiation done? PACE -C is for higher risk prostate cancer. This is more of a radiation question. And then PACE nodes is for patients with very high risk prostate cancer. And more on this later. So PACE -A is taking patients with lower or intermediate risk prostate cancer. And so they have to have T1C to T2C disease. They can have Gleason 3 plus 4 disease or lower. This is the same thing as Gleason grade group 2. A PSA less than 20.

6:31 They have to have an MRI and no hormone therapy. And then they are randomized one -to -one surgery versus SBRT. And the authors state that there are co -primary patient -reported outcomes at two years, and these are urinary incontinence and bowel bother. They also look at secondary outcomes from the five -year analysis, so they look at the freedom from biochemical or clinical failure. This just means PSA control, overall survival, so this is death from any cause, and then clinician -reported late side effects based on the CTCAE questionnaire. And more on this also in a little bit. Here are the results.

7:16 I'm going to actually go through the results. I want to show you the figures because now they have a median follow -up of eight years. And one of the important things, so there are 60 patients who had a prostatectomy, 63 patients who received SBRT. This is a smaller trial than PROTECT, but it is still a... Smaller trial than PROTECT, but it is still accruing, and I think it's still very good data. The first thing that they present is the baseline characteristics. So they show that the patients are well -balanced. The median age is about 65, and that's pretty normal. That's also basically the same thing that we see in the U .S. versus the U .K. The median pretreatment PSA was about 8, and

8:05 about... was about eight. And about 6 % of patients had low risk disease and about 94 % of patients had intermediate risk disease. So this is the majority of patients had, quote unquote, intermediate risk disease. Now, do they have favorable versus unfavorable intermediate risk disease? This is another question and not totally addressed on this slide. Number one, freedom from biochemical or clinical failure. Here is a Kaplan -Meier plot. This is chemical or clinical failure. Here is a Kaplan -Meier plot. This is showing you what percent of patients have their cancer controlled based on the PSA as a function of time. So basically, it's the same. This is like seven, eight years out. The PSA control

8:52 is the same between the two groups. The p -value is not statistically significant. And this is pretty expected. You know, at this point, this is kind of what we would expect to see. I would be a little bit surprised if we actually didn't see similar PSA outcomes. Okay. Next is overall survival. So this is patients dying from any cause. And you can see that very few patients died. Only four patients died in the prostatectomy group, three patients died in the SBRT group. And so p -value, again, more than 0 .05. It is not statistically significant. This is also very much what we expect. And also, when I counsel patients about their intermediate risk prostate cancer, I usually tell them, you

9:37 know, it is very unlikely that you're going to die in the next five to 10 years, and even more unlikely that you're going to die of prostate cancer. Most likely, men with especially intermediate risk prostate cancer, they're going to die of something else besides the prostate cancer. And this is kind of like the quote that you might hear. that prostate cancer is often a cancer where men die with prostate cancer, not of prostate cancer. Okay. Next slide. So this is one of the more important figures. They are presenting patient reported urinary incontinence at five years. And the way that it is defined is the use of one or more urinary pad per day. So incontinence, I just want to remind everyone. or urinary pad per day. So incontinence, I just want to remind everyone, is the

10:22 inability to control urinary flow. It means that when you sneeze, cough, lift something, urine comes out and you can't control it. And so sometimes patients have to wear a pad or a diaper or something like this. And this is typically an issue that we can see with surgery. It is very unlikely that we see this with radiation therapy. Now, that being said, you can see that about 8 % of patients 8 % had some degree of incontinence at five years versus about 48 % for the prostatectomy group. And here is a figure that is breaking down. So this is prostatectomy versus SBRT, and they're looking at different time points. So this is the baseline, then at four weeks, 12 weeks, six months, nine months, et cetera.

11:08 And the bar plots are showing you what percent of patients were wearing one or more pads at each one of these time points. So this is a similar message to what we saw with PROTECT. And some physicians may say, well, don't radiation oncologists say that the risk of incontinence is essentially zero with radiation therapy? And I would typically agree with that. I think the caveat here is that some men who receive radiation therapy, if they have baseline urinary symptoms or some other reasons, if they have an if they have baseline urinary symptoms or enlarged prostate, if they have a high urinary bother score as measured by the IPSS, they can develop

11:53 urinary frequency urgency. They feel like, hey, I just have to go pee right away, and they can't control it. So this is more of, I would say, like urge incontinence for the men who are receiving radiation therapy. I think it is a different type of incontinence receiving radiation therapy. I think it is. versus that that the surgical group here sees. And if you watch my other presentation on patients who should not receive radiation therapy, one of the first things that we mentioned is the presence of baseline urinary symptoms, a very enlarged prostate, a high IPSS score, and some of these patients should probably get a TURP or HOLIP before, or maybe they're just better candidates bullet before, or maybe they're just better candidates for a prostatectomy. Okay. Next for a prostatectomy. outcome. So this is

12:41 patient reported overall bowel bother score. So this is coming from EPIC 26. This is kind of like a standardized questionnaire. It has been validated. It's used internationally. And the question it's asking is how big a problem is your bowel function? And so one of the things that you might hear is, well, if you receive radiation therapy, you're going to have problems with your bowels. It might be rectal pain, rectal bleeding, etc. Here are the results. It is very similar between the two groups. that you might hear is, well, if you Now, you'll see that a minority of patients said that

13:26 rectal bother symptoms were a, quote -unquote, small problem or a very... small problem in the SBRT group. But if you're asking them, is it a moderate problem, is it a big problem, that is very uncommon. Okay, next is what we call clinician -assessed CTCAE GU toxicity. Okay, so what this is asking is, what do the physicians think the side effects are? Like, how are they grading this? the physicians think the side effects are, like, how are they grading the side effects? And basically, grade two toxicity means that the patient has to take a medication for the side effect. So let's say they have a lot more urinary frequency after radiation therapy, and the radiation doctor says, hey, you should start Tamsulosin or Flomax for this. That's technically a grade

14:13 two toxicity. If they needed to have a TURP or HOLUP, maybe during the radiation course or after, maybe you would code that as a grade three toxicity, because that means that they needed a procedure done. They had to come to the hospital for something. A grade four toxicity is that they almost died. Like basically they were they were in the ICU of the toxicity or the side effect. And then grade five is like they died of the side effect, which is incredibly uncommon in the in the modern era. So. The the main thing that we are interested in, because in general, radiation therapy is tolerated very well. is grade two side effect rates. So this is like the need to take a medication. And you can see that those rates are low. Next is

15:00 the GI toxicity. So here are the rates of GI toxicity, and this is even lower. So this is pretty consistent with, I think, what I would usually counsel men, that very few men will develop rectal symptoms to the point of where they need to take up rectal symptoms to the point of where they need to take a medication or they need to go to the doctor for something like an argon plasma cauterization or an APC because of rectal pain and rectal bleeding. And so here, the grade two toxicity, this is like having to take a medication was only 2%, so one patient. Okay, so the conclusion for this trial is that with a median follow -up of eight years, both SBRT and radical prostate... of eight years, both SBRT and radical prostatectomy demonstrated excellent biochemical and clinical disease

15:49 control. The eight -year biochemical recurrence free rates were numerically favoring SBRT, but they were very few events, and it was not statistically significant. So basically, it's the same. And the authors state that these randomized findings support SBRT as an effective non -surgical treatment option, and the low rates of clinician and patient -reported side effects are present for both options. Okay. The other conclusions that they had was that PACE -B, which is exactly the same eligibility criteria, shows 96 % biochemical control at five years. So the vast majority of patients who are treated with radiation therapy have really good

16:34 PSA control. And patients considering a radical prostatectomy should be given the information about SBRT before making a decision. And patients considering a radical prostatectomy should be given the. So this is their their conclusion. And it is basically what you just saw. Now, they presented the authors also presented basically a companion study of the sexual outcome. And so here here is the the author line and here is the abstract. I want to show you the results from this study because this was presented in I want to show you the. a different session. So here I am showing you the sexual domain scores from the EPIC 26

17:21 questionnaire and the authors state that the sexual domain scores declined from 62 to 17 after prostatectomy and from 79 to 58 after SVRT. And so it is a statistically significant change, and it is really favoring SVRT. So if erections are important for men, I usually counsel them that they should consider radiation therapy over surgery, which is basically what this trial is showing. Next, a greater proportion of prostatectomy versus SVRT patients had reductions exceeding what they call the minimally clinically important difference or the MCID clinical. in the EPIC26 sexual domain score. So basically, the questionnaire is

18:10 kind of granular. And at some point, the investigators say like, hey, if there's a really big difference between your pre and your post -treatment score, that is what we call the minimally clinically important difference. be a minimally clinically important difference. And so here you can see, you know, for patients what percent have worse scores and what percent have better scores. So in general, I think what you'll see from this plot is that, well, erections after treatment do get worse for both groups. However, it looks like they do get worse for the prostatectomy group more than they get worse for the SBRT group. And so I think part of this is that, yes, erections yeah, they probably are affected by radiation therapy,

18:57 but there is probably also a baseline change, just like we saw in PROTECT. As men age, their erections will go down over time. Okay, the authors also presented the ability to get an erection, and so here we are comparing prostatectomy versus SVRT at baseline, one month, three months, six months, et cetera, and then the patients will rate this as very good, good, fair, poor, very poor, et cetera. And so what you'll see is that there's a lot more red for the prostatectomy group at multiple time points. Patients either stating that it's very poor or poor for their ability to get an erection. And also a similar message for the quality of erection. Basically, it's worse at multiple time points

19:44 for the patients receiving radical prostatectomy. Next is the ability to reach climax. So you'll receiving radical prostatectomy. see a lot more red for the patients who are undergoing a prostatectomy. And so you'll see this big dip. This is at like one month, three months. Now there is a plateau and the patients do get back to more of a baseline. So the erectile function and the ability to reach climax does improve after three months and six months. However, if you're looking at 12 months, prove after three months and six months. However, if you're looking at 12 months, 24 months, it looks like it's favoring SVRT or radiation therapy. The other question is overall sexual bother. And so again, maybe a little bit more red that you'll see in the

20:32 prostatectomy group. Now, this is a really interesting question. I've got a whole separate presentation on sexual function after various treatment options. for prostate cancer. I think the important thing about this trial is that there's no hormone therapy. Hormone therapy affects multiple aspects of sexual function, erections, ability to climax, ability to have an orgasm, et cetera. So this is a very clean trial. It's basically just comparing radiation therapy versus surgery. The other thing that they mention is the surgery. The other thing that they mentioned is the SHIM score or the IIEF score. And so this is the 25 -point questionnaire that men will fill out about their sexual function. A score of

21:20 25 out of 25 is like a perfect score. A score of 21 or less is technically erectile dysfunction. And what this plot is showing you is that there is more erectile dysfunction following prostatectomy than SVRT than SBRT at both six months and at five years. So again, you see a lot more red for the at both six months. prostatectomy patients, and it is statistically significant. So the conclusions for this part of the study is that compared to surgery, SBRT has significant advantages in preserving sexual function and sexual quality of life at five years. And again, the authors state that patients who want to preserve sexual function should be given the option of SBRT. Okay, I want to put this trial given the option of SVRT. Okay. I want to put this trial in perspective and tell you how

22:06 I would frame it. So number one, how do we assess quality of life in oncology or in medicine in general? The best thing that you can do is get patient reported quality of life at multiple time points using a validated questionnaire. That's exactly what the study is doing. And so I think this is kind of like the gold standard of the data. And I think it's much more important than, quote unquote, physician reported toxicity or the CTCAE scores that you saw. And this study was discussed by multiple radiation oncologists at the meeting. Here's Steve Frank, a very prominent radiation oncologist at MD Anderson. And he actually says that radiation therapy

22:52 is the new gold standard. um you know the cure for overall survival and prostate cancer specific survival is the same You know, the cure for overall survival and prostate cancer specific metastasis free survival is the same radiation versus surgery it may actually be better if you're if you have high risk disease and you get radiation therapy plus hormone therapy please check out my other presentation on high risk disease but a randomized trial for this is still pending quality of life we have seen in general in these domains is better for radiation therapy. And one thing that I did not discuss, but you can watch in the sexual therapy and one thing that that i did not discuss function presentation, there is also penile shortening after surgery, at least temporarily, and that is not present with radiation therapy. And overall satisfaction appears to be, at least for the patient and for the

23:40 spouse, better for radiation therapy than it is for surgery. Now, oncologists are on Twitter or X, and so this is discussed and debated, and there's a lot of back and forth people saying, well, surgery, you know, actually the surgery you have to consider was X, Y, and Z. Radiation had these other things, and so there's a lot of caveats to the data, and this is kind of like my take of medical X or Twitter in three sentences. like, I like apples. The other person says, I like oranges. And then The other person says, like, I like apples. The other person says, I like oranges. And then... the first person says, oh, so you said you hate apples, huh? And so there's a lot of caveats to the data. And we will have to see how the manuscript

24:31 is published and a lot more of the granularity. Other big news, Freddie Hamdy became an honorary member of Astro. Freddie Hamdy, if you remember, one of the co -leads of the PROTECT randomized trial. So here he is on stage receiving the award. He gave a great presentation. And here is Tyler Siebert discussing PROTECT. And so congrats to the authors. I think this is a fantastic study. I think this will really help patients. I look forward to seeing this in print. And so patients may, you know, patients may question, well, what happens now? Does this mean all the guidelines change? And may question, well, what happened? the short answer is no. This just

25:17 gives, I think, more information to patients when they're making a selection between the two choices. And so one other big piece of news is that my new book is available, and this is how to write a medical research manuscript. Medical students are not taught how to do research, and so this is in part what I teach. And so what the authors think what I teach. And so what the authors basically are going to be doing next is taking that abstract that you saw that was presented and putting it into paper form. And then it's going to be published as a full manuscript. And so this is a randomized controlled trial. This is like at the very top of the pyramid. So it was at the top of the pyramid for patient reported outcomes. It's the highest level of evidence basically that we can get. So I suspect that this is going to be in a very high

26:06 impact journal, something like a New England Journal of Medicine, JAMA, Lancet, et cetera. And I think, you know, we will all be excited to read it. So this is what you saw so far is what we call an abstract. Abstracts are presented at meetings. They're basically limited to about 300 words or so and are like twelve hundred characters or two thousand. birds or so, or like 1 ,200 characters or 2 ,000 characters, I forget. So this is kind of like an optional route. Like if you do a research study for physicians, you go down this optional route, you submit it to a meeting, you present it at the meeting. Here, in this case, it got a plenary. This is like the highest honor for a submitted abstract. And so what we want to see next is the manuscript, how it's published

26:53 in a paper. And then we can go into the details because there's a lot of limitations. There's a lot of things that we don't know about the study so far that we will know once the paper is out. Okay. As I mentioned, the slides are not mine. Actually, one of our residents, Dr. Brian Johnson, got the slides. So thanks, Dr. Johnson. And here's a picture of many of the radiation oncologists at the meeting. So this is one of the dinners at Astro. Here is me, Dr. Chad Tang and Neil Desai. they help coordinate this each year. And a lot of the folks whose names you see in my presentations, they are shown in this

27:39 picture. There's Sam Roy in the back left. He's one of the docs who did the analysis for surgery versus radiation therapy for high -risk prostate cancer. So this is 2026, and this is Astro. at uh 2025 um so great group of docs um i think everyone's doing their best to try to find the optimal treatment for patients and uh to give uh so to try to find answers about quality of life outcomes data efficacy and help move the guidelines forward and so as always i hope this presentation helped you and i hope it helps you make a decision with respect to surgery versus radiation therapy for your prostate cancer.