2025 Update on Prostate Cancer - YouTube
Summary of Dr. Richard Lam's Presentation on Updates in Prostate Cancer Treatment
New Targeted Therapies
Dr. Lam discussed several targeted therapies for prostate cancer, including the traditional androgen receptor (AR) targeting with medications such as Lupron, Orgovix, Zytiga (abiraterone), Xtandi (enzalutamide), Darolutamide, and Erleada (apalutamide).
He explained newer targets like PARP enzymes which help cancer DNA replicate. PARP inhibitors (olaparib, rucaparib, niraparib, and a newly approved fourth drug) only work in patients with mutations in homologous recombinant repair genes (about 20% of advanced cases). These inhibitors show benefit in about one-third of patients when used alone, but when combined with AR inhibitors like enzalutamide or abiraterone, they can double the duration of benefit.
Another important target is Prostate-Specific Membrane Antigen (PSMA), a molecule found on most cancer cell surfaces. The FDA-approved Lutetium-177 (Pluvicto) delivers radiation directly to cancer cells. It's currently approved for metastatic castrate-resistant prostate cancer patients who have had chemotherapy (even if it didn't work or caused side effects). Lutetium works in about 60% of patients, with benefits lasting from 4-6 months to up to 2 years. Side effects include dry mouth, nausea, and potential bone marrow and kidney impacts.
A newer radioactive treatment, Actinium-225, is currently being studied. It's about 100 times stronger than Lutetium but creates less radiation spread from the cancer cell, potentially causing fewer side effects. It's currently being studied for use after Lutetium treatment fails.
Combination Therapies
Dr. Lam discussed combination therapies for metastatic castrate-sensitive prostate cancer (where Lupron/Orgovix still works). Combining ADT (androgen deprivation therapy) with abiraterone, enzalutamide, darolutamide, or apalutamide improves survival and delays resistance. ADT with chemotherapy offers similar benefits. For more aggressive cases with high PSA, high Gleason scores, or extensive metastatic disease, a triple therapy of ADT, chemotherapy, and darolutamide might be recommended.
For castrate-resistant prostate cancer, PARP inhibitors combined with abiraterone or enzalutamide work better than these drugs alone, doubling the duration of response. Promising new research shows PSMA-targeting therapies plus enzalutamide may allow Lutetium use before chemotherapy.
Immunotherapy Advances
Dr. Lam characterized prostate cancer as a "cold cancer" where T-cells don't naturally attack the cancer cells, making immunotherapy less effective than in other cancers. Provenge, developed 15 years ago, is still used for castrate-resistant, low-volume, medium-growing prostate cancer.
Keytruda (pembrolizumab) works by getting T-cells into cancer cells, but only in about 5% of metastatic castrate-resistant patients who have specific genetic features (high microsatellite instability, high tumor mutation burden, or defects in MMR family genes). When it works, the response rate is about 40%.
Next-generation T-cell immunotherapy includes T-cell bi-specifics from Amgen, which attaches to T-cells and directs them to prostate cancer cells with the STEAP1 protein. This has shown a 50% PSA drop in about half of men, with visible tumor shrinkage in 25%. CAR-T therapy, which modifies a patient's T-cells to target specific proteins like PSMA, shows about a 20% success rate but has severe side effects.
Minimally Invasive Treatment Options
Dr. Lam discussed focal therapy approaches that treat only the cancerous portion of the prostate rather than removing or treating the entire gland. These include cryotherapy (freezing), HIFU (high-intensity focused ultrasound), and laser therapy. While these have fewer side effects, they have success rates of 60-80%, sometimes requiring retreatment.
He favors HDR brachytherapy, which inserts filaments into the prostate to deliver precise radiation. Dr. Lam shared case studies of focal HDR brachytherapy patients with Gleason 9 and Gleason 7 cancers who responded well to treatment targeting only the affected areas of their prostates.
Dr. Lam also discussed Stereotactic Body Radiation Therapy (SBRT), which delivers radiation in just 5 treatments over two weeks instead of the traditional 28-42 treatments. A trial comparing 5-day SBRT to 28-day conventional radiation showed equivalent cancer control rates (over 95%). Both had similar serious bowel side effect rates (1%), but SBRT had slightly higher short-term urinary symptoms (26% vs. 18%). Sexual dysfunction occurred in about 30% of patients in both groups after five years.
A smaller study comparing SBRT to radical prostatectomy found significantly lower incontinence rates with SBRT (6% vs. 50% of men using daily pads at the five-year mark).
Diagnostic Innovations
PSMA PET scans can detect cancer that conventional imaging misses, allowing for treatment of oligometastatic disease (limited metastases). Dr. Lam noted that if a patient has limited metastatic spread and receives both treatment of the primary tumor and SBRT to the metastatic spots, there's still about a 30% chance of cure.
Dr. Lam explained two types of genetic testing: somatic testing (examining cancer cell DNA to identify treatment options like PARP inhibitors or Keytruda) and germline testing (checking the patient's inherited DNA for mutations that might respond to certain treatments). Genetic testing can also help predict radiation treatment side effects.
Artificial Intelligence in Prostate Cancer
AI is helping radiologists interpret MRIs and PET scans more efficiently and accurately, and helping pathologists examine slides more effectively. Dr. Lam highlighted the Artera AI system, which uses biopsy slides to help predict long-term outcomes and guide treatment decisions, including whether patients should undergo active surveillance or receive hormone therapy with radiation.
Dr. Lam expressed optimism that AI will soon help with more complex decisions such as treatment sequencing, chemotherapy selection, and optimal timing for PET scans and Lutetium treatment, expecting wider implementation within 4-5 years.
Q&A Following Dr. Lam's Presentation
Proton Therapy
Q: Could you comment on the effectiveness of proton therapy?
A: Proton therapy is very effective at treating cancer within the prostate, with success rates above 90% for getting rid of the cancer. Success rates vary by Gleason score - higher scores might have 80% success, lower scores could be 95%. Side effects are probably equivalent to SBRT and IMRT.
Clinical Trials for Advanced Treatments
Q: Where are the centers for clinical trials of advanced medications, particularly radiopharmaceuticals, in Southern California?
A: Lutetium is widely available. For actinium trials after lutetium failure, Hoag in Orange County is conducting them, UCLA has three trials ongoing, and possibly UCSD as well. Some trials for lutetium before chemotherapy are also happening, but they fill up quickly.
SBRT vs. Surgery Incontinence Rates
Q: Regarding the PACE-A trial comparing SBRT to surgery, was the surgery open or robotic?
A: About 90% or more of surgeries now are robotic. The study was small (60 men in each group) but showed a significant difference in incontinence rates (6% for SBRT vs. 50% for surgery). Dr. Lam noted that some surgical patients later receive radiation, which can increase incontinence rates.
Treatment for Vertebral Metastasis After Radiation
Q: What alternatives exist for treating a vertebra (S2) that has already received maximum radiation dose and now has cancer relapse?
A: This is a difficult situation with limited options for localized treatment. Some doctors inject cement to support the area or add scaffolding to prevent collapse. The best approach might be systemic therapy to treat the whole body, including that spot. Dr. Lam recommended getting a second opinion, as some centers might be able to deliver more radiation, but warned that additional treatments might weaken the vertebrae's structural integrity.
Decipher Test for Active Surveillance
Q: How much weight do you give the Decipher test score for those on active surveillance?
A: The Decipher test looks at cancer genetics from prostate biopsy samples. Dr. Lam stated that PSA, MRI/ultrasound findings, and Gleason score carry more weight in decision-making. The Decipher test influences decisions in about 1 out of 10 cases.
Adding PARP Inhibitors to Existing Treatment
Q: A patient's son asked about adding olaparib (PARP inhibitor) to his father's current treatment of Lupron and bicalutamide for castrate-resistant metastatic prostate cancer.
A: Dr. Lam confirmed this could be appropriate if genetic testing showed the patient qualified for PARP inhibitors. He noted that side effects and quality of life should be considered, but cost shouldn't be a barrier since Medicare's new law caps out-of-pocket expenses at $2,000 per year, even for drugs like olaparib that cost $150,000 annually.
HDR Brachytherapy Side Effects and Availability
Q: Could you elaborate on HDR brachytherapy side effects and availability?
A: Side effects primarily include urinary issues (frequent urination, nocturia, urgency, burning sensation) that typically resolve within 1-2 months. Sexual dysfunction occurs in about 20% of focal therapy cases and 40% of whole-gland treatment. The treatment requires technical expertise and doesn't pay well, so it's not offered everywhere. UCLA has "an amazing doctor" for this procedure, and UCSD offers brachytherapy but Dr. Lam wasn't certain if they specifically offer HDR brachytherapy.
Discrepancy Between PET-CT and Diagnostic CT
Q: A patient with S2 vertebral cancer relapse noted that while his SUV max on PET increased, the diagnostic CT showed nothing. Dr. Lam was asked if he'd encountered this situation.
A: This is not uncommon. PET scans can detect cancer earlier when other scans don't show changes. Dr. Lam suggested considering an MRI, which might provide better detail of the vertebrae than a CT scan, waiting for sequential scans to clarify the situation, or performing a needle biopsy.
Post-Radiation PSA Increase
Q: A patient mentioned his father-in-law had his prostate removed, finished radiation treatment, but his PSA went up afterward. Is that expected?
A: The goal of radiation after surgery is for PSA not to increase. A rising PSA indicates there's still cancer somewhere in the body producing PSA, though it doesn't specify the location.
Finding Knowledgeable Doctors
Q: How do patients find doctors who are as knowledgeable about the latest treatments?
A: Dr. Lam suggested learning from the support group and bringing that knowledge to your current doctors, who are often willing to try suggested approaches. He noted that urologists are surgeons, radiation oncologists specialize in radiation, while medical oncologists handle broader treatment management. For comprehensive care, especially for advanced or recurrent cases, a medical oncologist might be most appropriate. Dr. Lam mentioned his practice sees patients from diagnosis through treatment and beyond, and offers telemedicine consultations.
Neuroendocrine Cancer After Lupron
Q: How common is neuroendocrine cancer after years of Lupron?
A: About 5% of cases. The longer cancer is contained, the more time it has to mutate. With newer treatments extending survival, doctors are seeing more unusual manifestations of prostate cancer, including spread to lungs and liver, and neuroendocrine mutations. In newly diagnosed patients who've never had Lupron, neuroendocrine variants appear in only 1-2% of cases.
Artera AI Coverage
Q: Is the Artera AI tool covered by Medicare?
A: Yes, Medicare does cover it.
Cleaned/Punctuated Transcript of Dr. Richard Lam's Presentation
"Good morning. I think this is like my 15th or 18th time. 17? Somewhere in the teens. It's always a pleasure and honor to come here. I'm usually very proud to come here because you guys are such a successful and big group. Despite COVID and changes in the whole system with the internet and everything, seeing so many people in person is inspiring.
With that in mind, let's get started. My topic today is an update on what's new in the field. We're going to talk about new targeted therapies, radiopharmaceuticals, combination therapies, immunotherapy advances, minimally invasive options, some diagnostic innovations, and we'll talk a little bit about artificial intelligence since that seems to be the buzzword nowadays. Pretty soon you'll have a robot lecturing you guys.
Let's talk about targeted therapies first. The old classic target for prostate cancer is the androgen receptor. We target that receptor with various medications for the last 40 years. It's all related to blocking the hormones. So we call that androgen deprivation, some people call it hormone blockade, and there's lots of drugs that work on that target.
There are some new targets that we're going to touch on today. One is the PARP enzyme. It's an enzyme that plays a role in DNA repair of the cancer cell. When the enzyme works, it's good for the cancer, so we want to inhibit this target, which would be bad for the cancer.
These are four drugs - three drugs, there's a fourth one actually that just got approved. You notice they all end with the two letters IB, so that's olaparib, rucaparib, niraparib, and talazoparib. All these drugs are called inhibitors and we'll talk about how they work in a second.
Another target is the PSMA or prostate-specific membrane antigen. This is a molecule found on most cancer cell surfaces, but not all. We're using what we call radiopharmaceuticals to target this PSMA molecule and deliver radiation to the cancer cells directly. The FDA-approved drug currently is called Lutetium-177, some people have heard it as Pluvicto. The next generation radiopharmaceutical is called Actinium, and it is currently actively being studied at multiple places - UCLA among them, possibly Hoag and maybe UCSD.
Let's go back to this slide. I'm going to talk about PARP inhibition, but let's talk a little bit about the androgen receptor target, the original target that we use.
Let's look at this green box here. We call it the androgen receptor. When testosterone or dihydrotestosterone - they're all related male hormones in the bloodstream - go onto the androgen receptor, this complex, the AR testosterone complex, goes into the nucleus of the cancer cell, attaches to the DNA, and blocks the DNA from replicating. When the DNA starts replicating, cancer dies. This is the typical approach we use for prostate cancer.
On this androgen receptor pathway, there are various drugs that inhibit this pathway. One drug is Lupron or Orgovix, or in the olden days, chemical or surgical castration. That basically removes testosterone from the body.
There are other ways to remove testosterone from the body. It turns out that cholesterol gets converted to testosterone, so by blocking this enzyme that converts cholesterol to testosterone, that's called CYP17, that's how abiraterone works. Zytiga/abiraterone works by blocking the conversion of cholesterol to testosterone. It turns out that abiraterone works so well, even in the testicles, that a lot of people who take abiraterone, we could even stop Lupron. That's a take-home message.
Unfortunately, lowering cholesterol hasn't been a very successful option. If you think about "if I lower the cholesterol, I should lower the testosterone, that should be good for cancer" - it turns out it's really difficult to lower it so well that there's an anti-cancer effect. But potentially, there's people who've been taking cholesterol medicines for a long time. They seem to have better outcomes and better statistics with regards to prostate cancer. So potentially there's a connection between statins being good against prostate cancer. That's the mechanism.
Other ways to block the AR testosterone pathway is preventing the testosterone or dihydrotestosterone from attaching to the receptor. So it blocks the red dot attaching to the green box, and we use many drugs such as enzalutamide, darolutamide, apalutamide, or in the olden days, Casodex/bicalutamide. These are all AR receptor blockers.
When the androgen receptor complex hits the DNA, it turns out that this PARP enzyme helps the DNA replicate. So if you use PARP inhibitors, it actually is another target to block the DNA from replicating.
Unfortunately, PARP inhibitors have been studied and only work in certain patients. This applies to breast cancer, ovarian, and prostate cancer. This drug works for these three cancers primarily. If you have these three cancers, you also need to have mutations in the homologous recombinant repair genes. If you have mutations in these genes, then you can consider PARP inhibitors.
In prostate cancer, it turns out that in advanced cases, about 20% of men will have these gene mutations. So one out of five men may use these PARP inhibitors. If you use it alone, about one out of three men get a benefit. If you use it in conjunction with the classic AR inhibitors, when you combine these drugs with enzalutamide or abiraterone, it improves the response duration by about 100%. It doubles the duration of benefit.
How to test for these genes? We'll talk about that a little bit more later on, but there's two types of testing: one is germline testing and one is somatic testing.
The other target that we're going to touch upon today is the PSMA molecule. This molecule is found on most cancer cells as I mentioned earlier, and the drug that's been approved is Lutetium/Pluvicto. It basically delivers radiation to the cancer cells.
This drug is currently approved for people with metastatic castrate-resistant prostate cancer who have had chemotherapy. I use the word "have had chemotherapy," meaning you could have had it and it didn't work, you could have had it and it worked but now the cancer's back, or you could have had chemotherapy and you stopped because of side effects. So the criteria is pretty broad - you just have to have a whiff of chemo to qualify for Pluvicto.
It has been shown so far to improve survival in these men. It works in about 60% of men who take it, and when it works, it works from anywhere between four to six months, which is so-so, but it also works up to like two years. So it all kind of depends on the luck of the draw.
It's fairly well tolerated. It basically goes wherever the treatment's injected into the veins, and the side effects are related to wherever this drug goes. It goes through your parotid glands, so one of the side effects is dry mouth. It goes a little bit in your intestines, so some people get nausea. It goes into the bone marrow, so one of the bigger side effects is it could affect your red counts and white counts. One of the rare side effects that we've discovered recently is it could really hurt the kidneys. Every drug has potential side effects.
They are studying this drug in combination with other drugs such as PARP inhibitors, AR receptor blockers, and possibly using it before chemotherapy.
The newer version of Lutetium is Actinium-225. It came out about three years after Lutetium. All this started in Europe. Lutetium came out in Europe in the trials about 10 years ago. Actinium came out about seven years ago, and it just takes a long time to work its way through the trial process.
Currently, we know that Actinium is stronger than Lutetium, maybe a hundred times stronger. We also know that the alpha particles that Actinium emits don't spread the radiation too far from the cancer cell, so hopefully it has a smaller area of damage.
Currently, it's being studied after Lutetium. Hopefully, they'll be... once it's approved for after Lutetium, then the next step is typically the researchers will do it in comparison to Lutetium. All these things take years, so hopefully in about a year and a half or two years, we'll have really good data, and it might get approved at that time.
Going back a little bit, just to remind you schematically how Lutetium works: the round blue circle here is the cancer cell, and on the surface of the cancer cell is the PSMA molecule. The drug Lutetium is actually this whole thing here. It's an antibody that is a radioactive Lutetium isotope attached to the antibody, and this complex is injected into the veins. This whole complex goes to the purple PSMA receptor, and when that happens, the Lutetium gets released near the cancer cells.
A couple of caveats: it's made like a couple hours before injection. It only lasts for a few hours, so when the doctor orders it, you have to go in at a certain time. You've got to get it on time, or else the stuff wears off really quickly. The delivery requires a little bit of good coordination, and you can't miss your appointment because that's $10,000 down the drain.
This is a miracle at Hoag, where a patient had all these spots on his PSMA PET scan. This is the cancer - all these black spots. This is the kidney, so it's not cancer, and these are the parotid glands, this is not cancer, but almost everything else is cancer. This is the bladder, so it gets urinated out into the urine. All the black dots are cancer.
After one treatment, you've already seen a dramatic improvement. This guy had a PSA of over 100. After just two treatments, his PSA was 6, and everything disappeared. Typically, a patient gets six treatments. Is there a consideration to do less if one gets such a good response? You've got to balance the advantages: less side effects, lower risk of kidney damage, but maybe six is better than three in terms of long-term success. Those are little things that doctors are working out.
This is another patient, not as dramatic. He had six treatments at Cornell. I borrowed this slide from Dr. Tagawa. He showed that he had a lot of cancer before, and after six treatments, he still has a decent amount. So this is a good response, not an amazing response. They also did a CTC (circulating tumor cell) count, and it also disappeared. So good response. And of course, there are some bad responses where it doesn't work. It doesn't work in 40% of people.
These are some other targets. We don't need to go into too much detail because who knows which ones will be approved? PI5 P4KA doesn't even have a real name yet. It's an enzyme target that they're targeting. BCL2 protein is excessively produced in about 10% of men with metastatic prostate cancer. It turns out that these people have a worse prognosis. There is finally a drug that targets this protein, and it turns out that this drug with enzalutamide is being studied right now. We'll see if it really makes a difference.
One thing to remember is you could find a target - that's part one. But then you've got to find the drug. It takes a couple of steps. Then you find the drug, and then you have to do the study. That's why these things do take a while.
This was a promising protein. This drug called NXP800 targets a heat shock factor protein, and we need to see if that works. This is pretty promising as well. Of the other surface targets that I mentioned here, this is probably the most promising - the STEAP1 protein - and it might have a role in making immunotherapy work better.
Let's talk a little bit more about combination therapies. Combination therapies typically revolve around hormone-type therapies. I'll divide this in certain categories and try to go through the indication of each combination.
CSPC means castrate-sensitive prostate cancer. These are men for whom Lupron does work, and these are all metastatic patients when we use combinations. It turns out that if you have metastatic castrate-sensitive disease and you use ADT - let's just say Orgovix, let's not even use the word Lupron anymore - when you use Orgovix and you combine it with any of these drugs in the first line - abiraterone, enzalutamide, darolutamide, apalutamide - these are all hormone approaches. Double hormone therapy does improve survival, delays resistance, and delays progression of cancer in the metastatic spots.
It turns out that if you use ADT/Orgovix with chemotherapy, you also get the same benefit. We actually don't know which one is better - ADT plus the first line or ADT plus the second line. We just know all of them are better when you add them to ADT.
But we do know that when you add chemotherapy and darolutamide to ADT, it is better than ADT and chemotherapy alone. So this triplet, not double but triplet, is used for patients who are a little bit sicker, who have high PSAs, high Gleason scores, lots of metastatic disease, and we're worried that the cancer is causing symptoms. We want something to work fast, and we want almost a guarantee it will work - we would use the triplet therapy.
In the CRPC setting (castrate-resistant prostate cancer), we still have to use the backbone treatment, which is Orgovix/Lupron/chemical castration, and we're adding these type of combinations: PARP inhibitors with abiraterone - that's better than abiraterone by itself, as I mentioned earlier. This PARP inhibitor plus enzalutamide - that's better than enzalutamide by itself. They prolong the duration of response by about 100%.
Now there's new research showing that using the PSMA target plus enzalutamide seems very promising as well. This was data just released a few months ago, and this is data used before chemotherapy. Remember I said Lutetium is approved for after chemotherapy? Well, if this data pans out, this may be one situation where you can use Lutetium before chemotherapy.
A little bit about immunotherapy. Immunotherapy is always described as "harnessing the body's immune system to fight the cancer." It sounds amazing, doesn't it? The immune system is primarily T-cells, not B-cells but T-cells, and so we really need the T-cells to step it up and fight our own cancer.
Unfortunately, prostate cancers we call a "cold cancer" - the T-cells don't really go to the cancer. So manipulating the immune system doesn't work that well in prostate cancer. It works amazingly in about 15 different cancers. Jimmy Carter's brain cancer disappeared for many years because of immunotherapy. A lot of melanomas, kidney cancers - there's about 15 different cancers where it's very T-cell heavy. Prostate cancer is not very T-cell heavy, so that's the challenge.
But one of the first T-cell immunotherapy treatments was about 15 years ago. It's called Provenge. It's still being used, and it's used for people with castrate-resistant, low-volume, medium-growing prostate cancer. If you have a cancer that's exploding and it's very aggressive, Provenge will not work because it's not a really strong immunotherapy. But if you have metastatic disease but not too many spots, Provenge could be used on the earlier side, and you tend to get a better benefit.
Since then, there have been very few immunotherapies approved. The only other one is pembrolizumab, otherwise known as Keytruda. The short answer is it gets those T-cells into the cancer cells, but it turns out that it only works in a small group of men whose cancer has specific genetic features such as high microsatellite instability, high tumor mutation burden, or a defect in one of these genes that are part of the MMR family - MLH1, MSH2, MSH6.
In men with metastatic castrate-resistant prostate cancer, 5% of these men qualify for Keytruda. So one out of 20. If you do get it, the response rate's pretty good - about 40%. The key is finding that one out of 20 patient who will benefit because this drug has very little side effects. Testing for these mutations or these characteristics is very simple - it's part of a genetic testing panel, and we'll go into that in a second.
The next generation T-cell immunotherapy treatment is called T-cell bi-specifics. Amgen has a product that is pretty promising. It brings the... it's a drug that goes into the bloodstream, attaches to the T-cells, and takes the T-cells to prostate cancer cells that have the STEAP1 protein that I referred to earlier - that's another target. This drug has been shown to work in about 50% of men in terms of the PSA dropping 50%. A quarter of these men, the cancer actually visibly shrunk. It's in phase three trials now, so we'll probably get some data within two years.
Many of you guys have heard of CAR-T. That's the easy way to pronounce chimeric antigen receptor T-cell. The take-home message is T-cells. The way CAR-T cell treatment is approved for a lot of the blood cancers like lymphomas and leukemias, the way it works is almost like Provenge. It's like a next-generation Provenge. It takes blood out from the patient, isolates their T-cells, and once those cells are isolated, they actually are able to modify these T-cells and inject them back into the patient. The T-cells are modulated and modified to the point where they hunt for specific targets.
One of the targets is PSMA, but they're looking for other targets to create these bespoke T-cell treatments for patients. So far, I'd say 20% success rate, so it's not great yet. We need more targets, and the side effects are fairly severe. So it's probably not something you want to do in the beginning of one's journey. It's going to take a few more years.
Let's switch topics and talk a little bit more, less on the medicines and drugs, but let's talk about minimally invasive techniques and treatment options.
One option is focal therapy, which you guys kind of know about, and you will have some lectures on them. Focal therapy: the theme is, when we treat prostate cancer that's newly diagnosed and has not spread, we want to treat the prostate. We end up removing the whole prostate, we radiate the whole prostate, we heat the whole prostate. Patients are not always aware that we're not just treating the cancer in the prostate - we're treating the whole prostate.
The analogy is: when a lady has breast cancer, we remove the whole breast. So women have advanced the field of partial/focal therapy of breast cancer - we do lumpectomies; we don't take the whole breast. Finally, prostate cancer in the last 10 years is improving upon the lumpectomy approach to prostate cancer, removing part of the prostate.
There are various ways to do focal therapy: HDR brachytherapy, HIFU, cryo, Tulsa-Pro, laser, etc. I'll talk more on the next slide. Another minimally invasive technique is SBRT, and the third minimally invasive technique is treating oligometastatic cancer.
Back to focal therapy - this slide's from UCLA. These are three ways to do focal therapy. One is inserting little sticks into the prostate and dialing down the temperature and freezing the side of the prostate where the cancer is. This is using high-intensity focused ultrasound, like sound waves, focusing it on the cancer. The third method is using laser beams to direct into the cancer.
Laser is not covered by insurance. It's fairly expensive, better for lower-grade cancers, almost the cancers that don't need treatment. So that's kind of lower on my list. HIFU and cryo could be used - they're now FDA approved for both - and they're approved for low-grade, medium-grade, and in certain cases, the more advanced cancers. They're all pretty good.
With HIFU - with all three, you could retreat. But the success rate is anywhere between 60% and 80%. If you do HIFU or cryo, be mentally prepared - "Oh yeah, you get to retreat," but you could also say, "Oh no, I have to retreat." Even though there are less side effects, you really want to do this one and done and be over with.
My favorite is HDR brachytherapy. HDR brachytherapy is basically inserting little filaments into a patient's prostate. This gentleman's laying there playing on his phone, legs in stirrups, and he has these filaments. He's awake, filaments are inserted into the prostate, and on this machine, the doctor is 10 feet away, doing remote control, releases radiation into these filaments, and these filaments deliver radiation. It's a very precise treatment.
This is a picture of a whole-gland brachytherapy from Dr. Albert Chang. The filaments are here, radiation is released. The different colors refers to the different strength of the radiation, so all the strong radiation is within the prostate, and there is a little bit of a halo effect. The blue radiation is very low and is not dangerous.
Different views of the prostate, but we're here to talk about focal HDR brachytherapy. This is a man actually in our practice. He's 64. He had Gleason 9 disease, high grade. His PSA was 19. His cancer was only on one side. He's fairly young. He wants to have minimal side effects. He does not want to treat the whole prostate.
This is the same cancer on MRI, and this is an ADC view of the MRI. So you see this spot right here - that's the cancer. On PET scan, this is the brightness where the isotope accumulated within the prostate.
Dr. Chang delivered the high-dose radiation to the one side, the left side of the prostate - left side. This is the side view and this is a frontal view, and all the red is the highest dose of the radiation, really concentrated. So the other half of the prostate did not get any radiation.
Six months later, no more brightness, no more spot, and there's some scar tissue. That's it. So success, but yes, we need longer follow-up. At this point, this gentleman's been in remission for about 18 months.
This is another slightly older man. He's 74. His cancer is at the front of the prostate, noticed on the PET scan. The brightness is only slightly more bright than the non-bright areas. This patient's Gleason score is only seven. The cancer is right here in the front. This is the cancer on MRI, the cancer on MRI, and after radiation to the front - this is the urethra, this is the front of the prostate, front of the prostate, front of the prostate - this was done over two treatments, and there's basically no more brightness. I haven't gotten the MRI yet, but we'll see. The brightness is gone.
This is another person. He had SBRT radiation already, and then the cancer still came back on the left side. After radiation, he is in remission. The cancer disappeared after the radiation. I don't have an after slide, but one treatment basically took care of it.
If I had to pick focal therapy, I'd lean towards the HDR brachytherapy.
Another type of minimally invasive treatment is SBRT - stereotactic radiation therapy. I call it minimally invasive because, number one, it's just beam radiation. Number two, instead of going to the radiation doctor 28 days, when I started 20-something years ago, radiation treatment took 42 days to treat the prostate, then it went down to 28 days, and in the last couple years, the research on five days has become more and more accepted. So it's a very simple treatment that takes five treatments over a two-week period.
The big trial that kind of put SBRT on the map as a potential standard of care compared treatment with five treatments for SBRT versus 28 treatments with conventional hypofractionation radiation therapy for 800 men with low and intermediate-risk prostate cancer. So 400 people got SBRT, 400 got five and a half weeks of conventional therapy.
Both groups had a 95% control rate of the cancer - greater than 95%. So cure within the prostate was over 95%. It's really good. 1% of men in both groups had severe to moderate bowel problems - bleeding, mucus coming out, maybe stool incontinence - 1%, and probably because of spacers, the hydrogel has decreased the side effect risk to about 1%.
Both groups had some bowel problems in 10% of both groups in the short term, within the first year. Interestingly, for bladder, 6% of both groups had some moderate to severe urinary problems. This is not incontinence, typically. It's more urinary frequency, urgency, maybe using a pad, but not like wearing six pads a day.
But it does turn out that for the short course, five treatments, you will have up to 26% of men having very annoying urinary symptoms the first year, as opposed to 18% of men having annoying urinary symptoms if you did the 28-day treatment.
The last side effect is sexual dysfunction. Both groups had about a up to 30% likelihood at the five-year mark of saying their sexual function has dramatically dropped.
In summary, the 5-day versus 28-day seems fairly equivalent, except maybe with the five-day treatment, you might have more near-term urinary problems the first year or two.
There's a smaller trial that's accumulating patients, studying SBRT/5 treatments versus radical prostatectomy. 60 people, 60 men in each group. So far, the data shows that 50% of men who had surgery were using daily pads at the five-year mark with surgery. Surprisingly, 6% of men were using pads with radiation.
Part of that is maybe, as we age, we tend to have weaker sphincter muscles, and that might contribute to needing a pad. But the major interesting data out of this study is the incontinence rate is dramatically lower, still there, with the SBRT.
SBRT is also used for the concept of treating oligometastatic disease. This ties in with PET scans, which ties in with the PSMA target. With PET scans, we're able to not only find the cancer but treat it.
With the PSMA PET scans, we're able to find the cancer. In this man, on a CAT scan and bone scan, we didn't know if there was any cancer, but on the PSMA PET scan, there's a faint little dot, and on a different type of view, they found the dot within the lung. So this patient, instead of being relapsed with no metastatic disease, he's a relapse with one metastatic spot.
In the past, when one has metastatic disease, we used to say, "It's too late, don't even bother treating the prostate, you're incurable now." It turns out that if you have very little cancer, even though it has spread in the lymph nodes or in this case the lung, if you treat the mother ship and you SBRT the spot, there's still about a 30% chance of cure.
The great thing about SBRT is it's minimally invasive when we treat other spots in the body. Three to five treatments of this lung spot - probably 90% it will never come back. And if it never came back within the prostate, hopefully this guy's in remission for a long, long time, if not forever.
The next topic is diagnostic innovations in the last couple years. Again, we talked about PSMA PET scan being able to detect cancer. A little bit more about genetic testing: there's two types of genetic testing. One is somatic testing, and the other type is germline testing.
Just to refresh everyone's memory, I gave a lecture during COVID, a video lecture about three years ago that was all about genetic testing. You guys could refer to that for details, but basically genetic or somatic testing is testing the DNA of the cancer cells. You're trying to find out what characteristics or mutations the cancer has that will allow us to uncover new treatments such as PARP inhibitors, such as Keytruda.
Those are primarily the new treatments, or other mutations that we didn't expect that work for other cancers. Maybe we could use a stomach cancer drug for prostate cancer because these genes have the same mutations.
The DNA can be extracted from the blood. There are multiple companies doing this - Guardant, Caris, Foundation, Myriad - there's like six or seven companies. Tempus. Or you can also, if you had a biopsy of a metastatic lesion, test the sample that you biopsied of the tumor tissue. So that's testing of the cancer cells - somatic testing.
The other genetic testing, which we think of when we hear genetic testing, is the genes of the host, the men who carry the cancer. It turns out that certain men who have certain mutations - typically these mutations were inherited - they can respond to PARP inhibitors, immunotherapy as well. So you check for the host DNA, and for the host DNA, you could do blood testing, and you could also do mouth swabs.
It turns out that when you do mouth swabs, you could also do genetic testing to see if SBRT is going to cause a lot of side effects. So they're using genetic testing not just for treatment selection but side effect prediction.
This is an extreme case where this is the same patient who had a bone scan and they found a couple spots, and he had a sodium fluoride bone scan and they found a couple spots, and then he did a PET scan and they found all these spots.
This is an extreme case, but this is an example of the advantages of PET scan. It actually could make things look worse. It could detect things that are minuscule, but on the other hand, it could give you the truth that things are worse than you thought. Double-edged sword.
Last topic is artificial intelligence/AI. I'm sure half of the guys here are invested in AI stocks, but in the medical field, AI is getting a toehold into the field. Right now, they're using AI to help radiologists interpret MRIs and interpret PET scans quicker, basically, and a little bit more efficiently and more accurately.
These are a couple of companies. They're helping pathologists look at slides quicker, find cancer quicker, and be more accurate. The last two are helping patients, which is more important. They're helping patients predict how to manage their situation, and I'll go over this Artera AI system fairly soon.
The last category where AI is getting a role is helping the radiation oncologists plan radiation better, hopefully with less side effects.
I borrowed this slide from the company Artera. I'm not a spokesperson, but they have a nice slide. Basically, their AI system looks at the biopsy slides and helps patients estimate long-term outcome, helps a patient decide if he should do active surveillance, and helps a patient decide if he should get a little bit of hormone therapy when he does radiation. Those are the three roles of this AI product.
They take the slides - they don't need new biopsies, they just take whatever biopsy was already done from the prostate - they look at it, and you get the results within two days.
This is what their report looks like. This round thing is cancer. A pathologist looks at this and says, "This is cancer, this is a Gleason 6, 7, or 8, this is probably a 7." What AI does is it looks at the cancer, but it actually looks at the pattern of the non-cancer around the cancer, and with that information, along with the patient's age, PSA, clinical stage, they could actually create a prediction, an AI risk score.
This is what their report looks like. High, medium, low risk of metastasis, what's the risk of dying of prostate cancer if this patient should go on active surveillance, and if this patient should get hormone therapy. So it answers a lot of questions to help the patient and the doctor decide what to do next.
Hopefully, AI will help us with picking chemotherapies in the future, sequencing hormone therapy versus PARP inhibitors, help us decide if we should do PSMA PET scans earlier or should we do Lutetium earlier or later. AI is just going to be a supplemental brain for the doctor, and I'm very optimistic that this will indeed be highly implemented in about four or five years.
On that note, I want to end the talk and thank you for paying close attention. No one fell asleep."
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