Systemic radiation is injected radiation that circulates through the body to target metastasis. There are several types of systemic radiation all of which have been shown to prolong life with limited side effects. This episode covers current systemic radiation options as well as exciting, new advancements on the horizon.
If you have advanced prostate cancer, you don’t want to miss this episode!
Dr. Scholz: [00:04] Welcome to PROSTATE PROS. I'm Dr. Mark Scholz and this is my cohost Liz Graves.
Liz: [00:10] We've talked about computerized beam radiation and seed radiation, but there's yet another category of radiation called systemic radiation. This is radiation that can be injected into the bloodstream to target metastasis throughout the body. Dr. Scholz, can you start off by talking about some benefits of systemic radiation?
Dr. Scholz: [00:31] Injectable radiation offers some specific opportunities that we can't do with beam radiation. We've talked about oligometastatic disease and how if there's only a limited number of spots, radiation therapists can target those spots with beam radiation, but when you have multiple spots, beam radiation will cause excess suppression of the immune system. This is the advantage of injectable radiation, that it can target multiple spots throughout the body.
Liz: [01:09] So how this works is it gets injected via infusion into the bloodstream.
Dr. Scholz: [01:15] Yes, and it's quote, smart enough, unquote, to be able to go seek out the metastasis in different areas of the body and radiate them directly.
Liz: [01:27] We're talking about metastatic disease, which means the types of systemic radiation we'll be talking about today are typically for men with advanced prostate cancer that's usually resistant to hormone therapy.
Dr. Scholz: [01:40] That's entirely correct. There is some very preliminary research looking at preventing future metastases, but that is only at the very beginning stage.
Liz: [01:52] Before we get into the different types, can you talk a little bit about which kind of doctor administers these radiations?
Dr. Scholz: [01:59] So most men with advanced metastatic prostate cancer are going to be seeing either a urologist or a medical oncologist, but neither of these specialties actually give this type of treatment. You're typically going to see either a radiation therapist or a nuclear medicine specialist. Nuclear medicine specialists are the same doctors that administer bone scans, pet scans, and other nuclear based treatments.
Liz: [02:27] So the first type we're going to talk about today is Xofigo, which might be familiar to listeners. It was FDA approved for prostate cancer in 2013.
Dr. Scholz: [02:37] So Xofigo is a clever invention. Some doctors discovered that radium behaves very similar to calcium. When people have metastatic disease in the bones, the calcium metabolism is accelerated, the body incorporates the calcium into the bones at an accelerated rate. Since radium is mistaken for calcium, the radium gets incorporated into the bones right next to the tumor. Radium-223 is a very powerful alpha particle and just a single hit of an alpha particle can kill a cancer cell.
Liz: [03:19] So, Xofigo treats only bone mets, which means patients and doctors need to be selective in who is getting this treatment. How do we find out if someone has bone mets, Dr. Scholz?
Dr. Scholz: [03:32] So there's a variety of different scans. Of course, these again are people that have elevated PSAs, but bone scans, CAT scans, and PET scans can all detect bone mets. It's important that the prostate cancer patient has mostly bone mets, a few small lymph node mets are acceptable because lymph node mets are not as dangerous as bone mets. But if people have lung mets or liver mets, fortunately those are less common, but if they are present, Xofigo may not be the optimal treatment.
Liz: [04:04] So let's say you have a patient and you decide to put them on Xofigo, what's the protocol? What are some important side effects to note?
Dr. Scholz: [04:12] So Xofigo is pretty simple. It's an injection, a very brief injection, given once a month, typically for up to six treatments. The most common side effects are a little bit of nausea for a few days afterwards and maybe some loose stools. Not everybody gets those problems, but they can occur. Then people also have to have their blood counts checked. We talked earlier about how radiation can suppress the immune system and Xofigo doesn't have prominent effects in that regard, but certain patients may be susceptible. So their CBC, to check their hematocrit, and their platelet counts, to make sure that those aren't dropping excessively, is a necessary component of the monitoring process.
Liz: [04:55] If PSA doesn't decrease on Xofigo, does it mean it's not working?
Dr. Scholz: [05:00] No, interestingly, both Xofigo and another immune medicine called PROVENGE have been shown to prolong life, but there isn't necessarily a PSA decline. This raised speculation about the effectiveness, but the trials that prove longer survival are pretty unequivocal. I mean these are randomized, prospective double-blind trials. So not having a PSA decline is a little bit confusing. I think what's going on is that the rate of cancer progression is being retarded. So rather than knocking out huge amounts of cancer, what we're doing is we're stopping the growth, slowing it down. This is the mechanism as to how people can live longer with these medicines without dramatic PSA declines.
Liz: [05:52] So Xofigo does have a survival advantage and is mainly used for men with bone mets. But what about for men that have a more wide reaching metastasis, but beyond just the bones, but are there things men haven't heard of?
Dr. Scholz: [06:06] Yeah, there are other approaches. We've talked about beam radiation for oligometastasis. So that's been a popular approach for many years, where if there's just two or three spots, beam radiation can target really almost any place in the body. So it's not just bones. You can give a treatment to lymph nodes or to the lung or even in select cases to liver spots. The beam radiation options have been around for a long time. So we'll not spend too much time talking about that. But there is a new, yet to be FDA approved treatment called lutetium-177, which is very exciting because it not only targets spots in the bones, but also any cancer spots in other locations in the body, including lymph nodes, liver, and lung. We're very hopeful about this new treatment that is pending FDA approval. We have seen, of course with some of the preliminary studies that have been published, that men that have run out of all other options are getting good responses to lutetium-177.
Liz: [07:13] Okay. So lutetium-177 isn't FDA approved yet, but it's a really exciting option for men with advanced prostate cancer. Can you talk a little bit about how it works because it is different than Xofigo?
Dr. Scholz: [07:26] So lutetium is based on what's called monoclonal antibody technology. This is used a lot to target specific surface markers on the cancer cell. These medicines are smart enough, if they're injected into the bloodstream, to swim around in the blood until they find these surface markers and then they latch onto the cancer. So the manufacturers of this product were smart enough to connect this little monoclonal antibody to a high energy lutetium-177 molecule. So when it latches onto the surface of the cancer cell, it ends up radiating and destroying the cancer cell.
Liz: [08:10] So prostate cancer cells overexpress what's called the prostate-specific membrane antigen and that's what they're combining the lutetium-177 with.
Dr. Scholz: [08:22] Yes, exactly. That's the target. The neat thing is that patients who are candidates for this type of scan can have a PSMA PET scan first to make sure that the cancer cells have that PSMA marker on their surface to confirm that there will be a target before these patients even embark upon the lutetium therapy.
Liz: [08:47] You have to confirm that patients have PSMA, so some don't?
Dr. Scholz: [08:52] About 10% of patients have cancers that don’t express PSMA and in those individuals, the lutetium would not be an effective treatment.
Liz: [09:02] So you mentioned the PSMA PET scan and this is something we addressed way back in an early episode. Can you talk a little bit about that? I know that's something that our office is very excited about.
Dr.Scholz: [09:14] Yeah. We've been ordering a lot of these scans. They're presently only available on investigational trials, but universities on the East and West coast can do these scans and we're availing ourselves of them frequently because the big question in the world of cancer is always has the cancer spread and if so, where in the body has it spread to? PSMA PET scans far supersede the accuracy of any other scans. They’re better than MRIs, CAT scans, bone scans, and even other types of PET scans. So this is fabulous new technology. We're expecting it to be FDA approved, hopefully within the next year or so.
Liz: [09:54] Before men get the lutetium treatment, they’ll get a PSMA PET scan. What happens next?
Dr. Scholz: [10:01] If they do indeed see targets that light up with the scan, the next step is to embark upon therapy, which is an injection every six to eight weeks perhaps. The patients typically tolerate the treatment very well. The most common side effect has been the development of less saliva or dry mouth because the salivary glands also have PSMA and so they get caught in the crossfire with the radiation treatment.
Liz: [10:34] With Xofigo and lutetium, how are you checking the success of these? Is it just PSA? Are they getting scanned?
Dr. Scholz: [10:43] For the PSMA PET scans, we have indeed seen declines in PSA in a more traditional sense. So that's certainly one way. The other way is to repeat the PSMA PET scans after a course of treatment of two or three injections of lutetium with the expectation that there'll be fewer spots and that the previous spots that were noted would be less prominent.
Liz: [11:06] Lutetium has shown to prolong life by about 13 months. So it is a good option for men who are in those advanced stages.
Dr. Scholz: [11:14] Yes, and for people that are unable to wait, we're hoping this will get approved soon. But, as of the present tense, I believe there may be still a clinical trial ongoing in the United States and then for people that have financial resources, the treatment is available in other countries like Germany and Australia.
Liz: [11:37] But is there still more?
Dr. Scholz: [11:39] Well, there are other targeted radiation treatments for other types of cancers and sometimes you get some crossover and use a treatment that was originally designed for another type of cancer and use it for prostate. One very narrow situation is when prostate cancer patients develop spots in their liver. Fortunately, this is a very uncommon situation, but when it develops, it's very dangerous. The liver is quite sensitive to cancer and it can start malfunctioning quickly if something isn't done. People can coexist with bone metastasis for years sometimes, but not liver metastasis. When you talk about liver, you start thinking about colon cancer because the liver is the most common site of spread for colon cancer. There is an injectable radiation; it's actually injected right into the arterial supply of the liver to control and reverse liver metastasis from colon cancer. It turns out that that same treatment, which is called SIR Spheres, that's S I R, separate word, S p h e r e s. SIR Spheres are effective both for colon cancer and for prostate cancer. The research that has been done for SIR spheres for prostate cancer is somewhat limited, but the preliminary studies were pretty exciting. Men who had progressive colon cancer seem to get nice responses and certainly seem to live a lot longer than was expected.
Liz: [13:12] So we've talked about SIR Spheres at Prostate Oncology Specialists together before and you mentioned that we don't really frequently recommend them so much anymore. Why is that?
Dr. Scholz: [13:23] Well, we have a full time prostate cancer practice, but fortunately liver metastases are somewhat uncommon. If we have patients that have prominent disease in the liver, we would certainly consider using SIR Spheres if a lot of the more traditional treatments have already been tried, standard treatments like Xofigo and Taxotere chemotherapy. These things are also effective for liver metastasis and are much more accessible and more commonly used. But, if those treatments stop working, it's nice to know that there is a backup plan for the patients that do have liver mets and the SIR Spheres can be effective.
Liz: [14:04] So we have a lot of options when it comes to systemic radiation. But are they cost effective? Are they easily accessible to patients?
Dr. Scholz: [14:12] Well, certainly Xofigo, which is FDA approved specifically for prostate cancer, doesn't usually present any problem getting payment from insurance companies. The lutetium-177, when it's approved, I anticipate will also be very accessible. But right now, unless you can get it on a clinical trial or you have the resources to go outside the country, obviously there's quite a potential financial barrier. It is pricey. The SIR Spheres interestingly, at least for our Medicare patients have been covered by Medicare for patients that have metastatic prostate cancer in their liver. Then we mentioned briefly spot radiation for oligometastatic disease and that's routinely covered by all insurance companies.
Liz: [14:58] We've talked a lot about moving slow for your prostate cancer, taking time to seek second opinions and redo labs, but when men find out they have metastasis, is there a little bit more of an urgency?
Dr. Scholz: [15:10] Definitely. The crossover point in my mind, as a prostate cancer expert, is the advent of metastasis. A lot of prostate cancers will never spread, and it's unfortunate when those individuals are over-treated with unnecessary aggressive and toxic treatments. But once prostate cancer spreads, it's waving a flag and declaring ‘I have the capacity to cause great harm.’ At that point the whole mindset switches. It's time to pull out all the big guns. Used in a sensible context, of course. You always want to pick the least toxic therapies that are most effective first. You don't want to sit around and wonder what to do. It's time to take action and men should have their disease monitored closely. If an initial treatment that was selected is ineffective, it needs to be switched quickly to another treatment to find something effective. Uncontrolled, metastatic prostate cancer can grow quickly and become dangerous and even life-threatening. Therefore going slow is the opposite mindset for this situation.
Liz: [16:24] We've also talked about how prostate cancer doesn't typically have symptoms, but as it metastasizes, it might cause some bone pain. There was this study done in 2015 that I wanted to talk to you about, Dr. Scholz. It's that seven out of ten men ignore symptoms of prostate cancer progression like pain. How can men get past that? What are some things doctors can do to get these metastasis treated?
Dr. Scholz: [16:51] Historically, metastatic cancer has such a bleak outlook that people address this problem of progressive cancer sometimes with denial. The thinking is ‘Well, doctors can't do much anyway.’ Fortunately in 2020, that's just not true. There's a ton of stuff that can be done. So I think as we encourage people that there are effective options, people will be less prone to rely on denial for what is obviously a serious situation, but thankfully is a treatable situation.
Liz: [17:27] We've talked a lot about complex aspects of managing advanced prostate cancer and the more complex it gets, the more dynamic we remember this disease is. So seeking specialists and second opinions and being sure to see medical oncologists is very important. If you want more on advanced prostate cancer, you can find our blog at prostateoncology.com also, don't forget about the weekly PCRI videos. You can find them on youtube.com/thePCRI
Dr. Scholz: [18:01] The PCRI is also hosting a Mid-Year Update on March 28th at the Marriott near the Los Angeles Airport and the experts that will be speaking on both radiation, Dr. Jeff Demanes and the expert who will talk about advanced prostate cancer, Dr. Evan Yu, are excellent resources for further information about advanced prostate cancer.
Liz: [18:25] Yes, please join us. I'll be there. You can stop by the booth and get a cool sticker about PROSTATE PROS. We've both really enjoyed connecting to listeners through email and social media, so we'd love to meet you there. If you have any topics we should cover or just want to say hi, you can email us at [email protected]. Remember to help us out by rating, reviewing and subscribing on Apple Podcasts. Dr. Scholz, we're coming up to a year anniversary of the podcast. What haven't we talked about that you think we should cover?
Dr. Scholz: [18:59] I do have a speaker at our Mid-Year Update on genetics. This is, probably after immune therapy, the hottest area of development. There are so many aspects to that, we'll only be able to touch on the surface of it, but the new stuff is really exciting.
Liz: [19:18] Awesome. Okay. We'll plan for genetics. I'm looking forward to it.
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