Brachytherapy (radioactive seed implantation) has very high cure rates and comes with a low risk of side effects. If that’s true then why isn’t seed radiation more popular? What is seed radiation anyways?
This episode explores and defines brachytherapy from the difference between HDR (temporary) and LDR (permanent) seeds, to who is eligible and why seeds might be an appealing treatment choice.
Dr. Scholz: [00:03] Welcome to PROSTATE PROS. I’m Dr. Mark Scholz and this is my cohost Liz Graves.
Liz: [00:08] I wanted to delve into treatment options starting with brachytherapy, or seed implants. When it comes to seed implants, you have a couple of options: LDR, permanent or HDR, temporary. You may also have a choice between using brachytherapy as a monotherapy or in combination.
Dr. Lam: [0:31] Prostate cancer has always been a very complicated condition because it’s really not your typical disease. That’s why, I can spend full time in one cancer; I don’t have to do any other cancers because this cancer so complicated. We’re always trying to figure out ways to help patients understand their condition better. Perhaps help them concentrate their efforts on learning about their specific situation without being bombarded by this overwhelming amount of knowledge, especially on the World Wide Web. So this was an update published in JAMA comparing the cure rates of AZURE patients, in that paper they call it very High-risk patients. When they did surgery versus radiation versus seeds plus radiation and based on this study at seven and a half years for 1800 men, the remission rate of the combination group was 90% as opposed to 80% for the other two groups. So there is an improvement in cure rate with the combination of seeds plus radiation. Hence for our AZURE patients, we recommend this group this combination over radiation by itself or surgery by itself.
Dr. Scholz: [02:07] Yes, exactly, in combination with the standard beam radiation which we’re going to cover in our next podcast in greater detail. One of the questions that comes up is, “why seed implants?” Many doctors don’t even mention them anymore. Back in 2005, seed implants were the most popular form of prostate cancer treatment. Then along came robotic surgery and along came IMRT and both of which doctors got real excited about it and seeds sort of got left by the side of the road. The reason that we’re putting this ahead of IMRT in our sequence is because the cure rates are better with seed implants than with IMRT. That’s a rather shocking statement. But the quality of studies showing better cure rates is excellent. Excellence, meaning that they’ve done comparative randomized prospective trials showing about a 20% higher cure rate with seed implants rather than IMRT alone. Now in those studies they gave a combination of seed implants plus IMRT, but there are also studies giving seed implants alone compared to IMRT. So that’s why we’re taking up the topic of seed implants first.
Liz: [03:26] Even though seed implants have higher cure rates. Why aren’t they more popular?
Dr. Scholz: [03:31] Well, the problem comes back to finances. The seed implant doctors are paid very poorly by insurance companies for doing seed implants. IMRT, which many of their seed implant doctors do as well, is paid extremely well. So when IMRT came along, the doctors were financially incentivized to use IMRT exclusively. In the early years there was no proof that IMRT had lower cure rates. So, it was perfectly justifiable from an ethical point of view to use IMRT, but now the studies are in and people have been using IMRT for so long that many people have simply forgotten about seed implants.
Liz: [04:13] Can you tell us a little bit about how seed implants work?
Dr. Scholz: [04:17] The technology behind seed implants is very elegant because the radiation stays exclusively inside the prostate gland. This is a beautiful thing because when you beam radiation in with IMRT or proton therapy, small amounts of radiation hit all the surrounding bones and the intestines and typically those don’t cause problems. The beauty of seed implants is 100% of the radiation stays exclusively in the prostate. The advantage of course is that you can turn up the dose of radiation without damaging surrounding structures. This is why the cure rates are better.
Liz: [04:52] There are about 40 to 100 seeds implanted in the prostate and each seed is about the size of a grain of rice.
Dr. Scholz: [04:58] Right. So what you’re referring to as the permanent seed implants or you called it the LDR, that means low-dose-rate. So these little seeds emit radiation for about 30 days, some longer, some shorter depending on whether you use palladium, iodine, or cesium. The seeds slowly burn out over a period of time and then they remain there, inert in the prostate for the rest of your life. They space these seeds out with very careful technical acumen and the seeds, therefore immerse the whole gland in a uniform dose of radiation.
Liz: [05:36] If these seeds are staying in the prostate, does that mean the patient is radioactive and should stay away from people who are at risk?
Dr. Scholz: [05:44] Well, people are certainly warned of that. However, it’s kind of ridiculous because even the surrounding structures like the bladder and the rectum are minimally exposed and how much less people outside of you are exposed. But in this litigious society, people always warn people that you have to be careful for about 30 days and, and don’t let any baby sit on your lap and whatnot. I think it’s an extreme precaution and it’s reasonable, I suppose to deny yourself your grandchildren for 30 days. But, it’s mostly about the litigious society we live in.
Liz: [06:19] Okay, so low-dose-rate seeds or LDR are the permanent seed implants and this happens over a one to two hour outpatient procedure. How long does the radiation continue emitting from the seeds?
Dr. Scholz: [06:35] About 30 days. I like how you emphasize the, the relative simplicity of administering the seeds. It’s rather remarkable. Someone can go in for an implant in the afternoon, walk out and have dinner with his wife without any immediate side effects. Over the next month or so, there probably will be some irritation of urination that can drag on for four to eight weeks, something like that. But the outpatient procedure as opposed to something like surgery or even external beam radiation, which can take five to eight weeks, is amazingly convenient.
Liz: [07:14] Can you tell us a little bit about how they’re implanting the seeds into the prostate?
Dr. Scholz: [07:19] So what happens is they put these seeds in a long needle with spacers in between. That long needle is inserted through the perineum. So the person’s sort of in a stirrup position and the needles go through the skin between the scrotum and the anus into the prostate. They put a stylet over the end of the, of this long needle, and they pull the needle back, leaving a line of seeds equally spaced inside the gland. One of the questions that comes up is, will the seeds migrate or go to other parts of the body? And in their early years, they didn’t string the seeds together as they do in this modern era. And so yes, sometimes seeds would migrate. They never really demonstrated any specific danger from that. People just felt uncomfortable with that idea, but that problem’s been solved now. So the migration of seeds issue is behind us now.
Liz: [08:14] Okay. So we’ve talked about low-dose-rates, seeds. Can we talk about the temporary high-dose-rate version?
Dr. Scholz: [08:21] So for every patient who has a low-dose, or I’d say every hundred patients that have Low-dose seed implants, probably only one or two have the high-dose-rate seed implants. High-dose-rate seeds are a hospital procedure where you have to go in overnight and small catheters instead of needles, they put small catheters through the skin of the perineum into the prostate, and those remain in the prostate throughout the hospitalization, which may last 12 to 18 to 24 hours. Then that catheter is used as a passageway for these super intense high-dose seeds that are on the end of a wire, which is pushed up to the end of the catheter. Then in a timed computerized sense, slowly pulled back, emitting radiation throughout the gland as it’s pulled through the gland. The treatments are repeated two or three times in the hospitalization. Then all the catheters are removed so that nothing remains in the patient’s body after the treatment is finished. The high-dose-rate seeds are somewhat more complex, as you can imagine, somewhat more uncomfortable. And there’s no evidence that they’re more effective except maybe in certain exceptional circumstances. So this is why in general, high-dose-rate seeds are not used as frequently as the permanent or low-dose-rate seeds.
Liz: [09:43] So, one thing that people get worried about are micrometastasis. The interesting thing about the seeds during high-dose-rate is you can guide them around the edges of the gland more easily and that kind of targets the potential micromets.
Dr. Scholz: [10:03] That’s the potential advantage. When you’re putting permanent seeds into the prostate, you can’t put them outside the edge of the gland very conveniently because there’s no tissue there for them too to be sustained by. With high-dose-rate catheters, they can wind the catheters outside the prostate, they can put them up in the seminal vesicles, the little rabbit ears on top of the prostate. For high grade cancers and cancers that appear that appear to be extracapsular or invading the seminal vesicles, the high-dose-rate, temporary seeds are probably a better way to go.
Liz: [10:40] So it sounds like high-dose-rate and low-dose-rate, there aren’t a ton of differences when it comes to cure. How do you choose which type of seed you want?
Dr. Scholz: [10:51] Well, I think it has to do with what we just talked about in terms of patients that have big scary, high grade prostate cancers the high-dose-rate seeds may be a more appropriate way to go. For our standard run-of-the-mill intermediate risk prostate cancers, the low-dose-rates, these are so much more convenient and they’re thought to be equally efficacious.
Liz: [11:16] These are performed by radiation oncologists and as with all treatment and doctors, the skill varies between doctor. So it’s very important to look for someone who is experienced with seed implants.
Dr. Scholz: [11:29] That’s absolutely right. I mean this is one of the things with the whole field of prostate cancer. It’s such a sensitive area of a man’s body. Doctors that are experienced in doing one thing over and over again, study after study shows that they get better outcomes. You don’t want to be visiting a doctor that’s only doing a few seed implants a year. You really want to be looking for the doctors that have made a career out of doing seed implants.
Liz: [11:59] As we’ve talked about, staging is also hugely important. What kind of candidates are, or what kind of men are candidates for seed implants?
Dr. Scholz: [12:11] So the typical breakdown, Low, Intermediate and High-Risk prostate cancer, we break it down into colors, SKY, TEAL and AZURE. The men that are in the AZURE category almost uniformly should be getting a combination of IMRT plus a seed implant, because cure rates are critically important in the AZURE or High-Risk category. So the patients that are in the TEAL category or the Intermediate-Risk category, many of them have a more modest condition and they perhaps consider just a seed implant by itself. They could consider doing any of the treatments by themselves. IMRT or proton therapy, SBRT or surgery, or whatever their particular preferences. The seed implants are nice as a monotherapy because of their convenience and because of the favorable side effect profile.
Liz: [13:10] Dr. Scholz mentioned IMR T and that’s something we’ll be talking about next time. He also mentioned SKY, TEAL, and AZURE. Those are colors that are associated with the staging quiz which you can take on keytopc.com and find out treatment options that work for your stage. So radiation is different from surgery because there’s still a prostate left in the body. How is monitoring for relapse different with seed implants than it is from surgery?
Dr. Scholz: [13:45] Yes, I’m not a big fan of surgery, but one of the clarifying factors of surgery is since the glands removed, there should be zero PSA after the treatment. That does make monitoring easier, especially since we know that after seed implants, some men can get a phenomenon called a PSA bump. This is delayed radiation prostatitis, one to three years after the seed implant creating temporary rises in PSA. This can cause confusion. So, PSA bumps are going to occur perhaps in one out of three men who have seed implants. This doesn’t present a major issue for me professionally, trying to distinguish a bump from a relapse, but the patients and doctors who perhaps don’t manage as much prostate cancer sometimes see this as a difficulty. One quick solution that is in the offering of these new, very accurate PSMA PET scans. Historically, we sort of had to sit on our hands and just wait it out, hope that PSA would drop down by itself, thus in retrospect, proving that it was a bump and not a cancer relapse. But now with these new scans, if the PSA starts to go up, we can take a check and look if there’s any cancer that still remains in the body. So, I think the advantage of surgery over radiation in monitoring, which has historically been one of the things that people have argued in favor of surgery is perhaps less relevant now given these new scans that will probably be FDA approved in 2020.
Liz: [15:24] Well we’re comparing surgery to radiation, let’s talk a little bit about side effects of seed radiation.
Dr. Scholz: [15:32] Yeah, the main issue of course is erectile dysfunction. I always go back to the Virginia study that compared erectile function two years after either a seed implant or a surgery. Instead of trying to use ambiguous terms like “Do you have some sexual capacities still?” These researchers were very clever. They just simply asked the patients and their spouses: “is sexual function just like it was prior to treatment?” That’s a clear yes or no answer. The patients that had seed implants about 50% said that it’s just like it was prior to treatment. Unfortunately, the patients that went through surgery only about 10 to 20% said that their sexual function had recovered back to baseline.
Liz: [16:26] That seems like a huge difference.
Dr. Scholz: [16:29] Yeah. It’s something that I’ve seen over and over. Unfortunately men don’t like to talk about this and once the deed is done, people are sort of stuck with whatever they’ve been dealt and as a result they tend to adopt a positive attitude and try and move on with their lives. So we don’t really hear about all the unnecessary suffering that goes on as a result of surgically related impotence.
Liz: [16:54] As far as side effects for seed implants go, there a couple I’d like to talk about. There’s urethritis which is inflammation of the urethra. Is there anything that can be done to prevent that?
Dr. Scholz: [17:10] So the skill of the implant. The doctors try and put the seeds at the edge of the prostate as the urethra goes through the middle. That’s the sensitive area where the urinary passages and inflammation can cause burning and discomfort. This problem is very frequent for a three to six to eight weeks after the seed implant. Fortunately, it dissipates in most everybody, but there is a small risk, five to eight percent risk, of long-term urethral inflammation, which is one of the risks that is associated with the seed implant.
Liz: [17:46] Also for men who have BPH or preexisting urinary difficulty, seed implants might make that a little worse for them.
Dr. Scholz: [17:55] Right. A big prostate requires a greater number of seeds to cover the territory. Therefore, it’s a bigger dose of radiation and thus an increased risk of side effects. Doctors have to calculate exactly how big the gland is and whether a seed implant is feasible for someone with an enlarged gland. In some cases, doctors recommend taking hormonal medicines to shrink the size of the prostate and thus limit the total dose of radiation and make a seed implant treatment feasible in someone that had a preexisting large gland.
Liz: [18:33] So taking all of that into account, if we can go back to the University of Virginia study, they also tested urinary control and four fifths of men who had seed implants recovered to the same degree before treatment. Only one half of men who had surgery recovered to the same degree before treatment.
Dr. Scholz: [18:52] Yeah, as you know, that’s due to the problems with urinary incontinence or urinary leakage after surgery. Urinary incontinence or leakage is quite rare after a seed implant, but it’s extremely common after surgery. This is another way that seed implants really shine when comparing the long-term outcomes with the men who undergo surgery.
Liz: [19:15] Seed implants are an option as a monotherapy or in combination. Can they be used after someone has already gone through previous treatment?
Dr. Scholz: [19:26] Yeah, salvage of men who have had previous IMRT, that’s the beam radiation, is feasible with a seed implant. We’ll be covering that more in our next podcast when we go through IMRT but fortunately IMRT technology has also improved quite a bit. So, dealing with relapses in the prostate is less and less common. Even so, it is nice to know that there is a salvage approach with seed implants that can be used and the need to do an operation which was historically necessary is really no longer the case. Operations for men that have had previous radiation are really problematic.
Liz: [20:08] Next we’re going to continue our discussion on radiation, talking about computerized beam radiation, IMRT, SBRT, and IMPT.
Dr. Scholz: [20:19] I’m so glad we’ve been able to cover this topic of seed implants. There is really underutilization of seed implants in the United States. Outside the United States where there’s a lot of prepaid medicine, socialized medicine because seed implants was so economical in many countries seed implants are the most popular form of therapy. In the United States, it’s important to be aware of this because sometimes seed implantation isn’t even brought up in the discussion about your treatment options and in many ways, studies show that seed implants are going to be the best way to go for many men.
Liz: [20:54] We didn’t have a winner for The Key to Prostate Cancer book giveaway. Amazon required 800 people to enter before the deadline, but we’d really love for listener to get a copy, so we’ll keep you updated via social media on future giveaways. You can find our handles on podcast.prostateoncology.com by scrolling to the bottom of the page. As we sign off, I want to remind you to send any questions or topics to firstname.lastname@example.org. We’d really love to hear from you and learn what you’re interested in hearing about. Also, please help us out by rating, reviewing and subscribing to PROSTATE PROS on Apple podcasts.