What's New in Active Surveillance for Prostate Cancer

Well, it's wonderful to be here. Thank you, everyone, for joining. I'm glad to be here with you and everyone who's helped organize this.

This is really special. I usually give talks in front of large groups of people, physicians, scientists, trainees, but it's actually more joyful and actually more pressure to speak in front of all of you. So, it's really a pleasure being with you for the next hour.

Where we'll go through a presentation and also answer some of your questions that have been sent earlier today and this week. So, with that said, I think we can get started here.

So, I'm sure all of you know me. I'm a physician at Sloan Kettering, a surgeon. Ten years ago, we decided to really focus on active surveillance. Develop it as a program at MSK, and create a team of excellence that will be dedicated to patients like yourselves, to care for patients with cancer, which is unique for not only our hospital, but any hospital in the world.

Our team now, as most of you have met, includes Kenny Lin and Natalie Wolchasty, some of the most superb nurse practitioners in the world, who probably have more experience with active surveillance than any physician or nurse practitioner in the world.

We've published together. We meet every week. We discuss cases. We review articles, and it's been a true pleasure working with them. I hope they're delivering excellent care with all of you every day.

Before we get started, some administrative tasks. Everything today that's shared is really for general information purposes only. It's not a personalized guide.

We try to personalize your management when we meet you in our clinics, but this provides more information for a broader audience. If you want to learn more about any of these treatments discussed today, please just discuss it with us, and we'll be happy to share more.

So really, the story of prostate cancer begins about 30 years ago when the PSA test was first introduced. PSA is a normal enzyme. It’s produced by the prostate gland. Its purpose is to liquefy semen.

And in the 80s, they realized many men who were presenting with very advanced prostate cancer, one of the markers that was being checked in the blood was PSA, and those numbers were incredibly elevated. Some numbers in the thousands were in men with metastatic, or cancer that spread beyond the prostate gland.

It was subsequently thought and utilized to say, “Why can't we use that test to screen men?”

Take normal men with no symptoms at a certain age and provide them a test. And if it's above a certain threshold, we can further interrogate or do investigations on those patients.

Well, it turns out the test was not only good, it was almost too good. What we see here on the left is a graph that demonstrates the diagnosis of prostate cancer over the past 40 years.

And at the time the PSA test was introduced, approximately 1988, 1989, the diagnosis of prostate cancer in this country, which is the black top line that's going upwards, really increased sevenfold.

So as urologists and urologic oncologists, we patted ourselves on the back and said, “Well, this is the breakthrough. And we should immediately see a reduction of prostate cancer death because we're finding and treating all these cancer patients so early.”

Well, it turned out when we look at prostate cancer death, we did see a decrease in prostate cancer mortality, but it did not mirror the magnitude of the increase in detection of prostate cancer during this period.

Which meant that many men were being diagnosed with cancers that probably would have never affected their life, and treating those cancers immediately did not translate into any prolonged survival or decrease in prostate cancer mortality.

Where is the prostate cancer located, or the prostate gland located? I think we should start off with anatomy.

It's located right above the bladder and between the bladder and the penis. As you can see, the urethra passes through the prostate gland, and where urine flows. The prostate gland is right above the rectum.

So, this is why we do a rectal examination. We can basically feel the entire posterior aspect of the prostate gland with our finger in the rectum. And we know that almost 80% of cancers, if detected, will be found in this position. So therefore, they would be detected with our fingers.

Going back to the slide regarding prostate cancer incidence, one of the most interesting studies conducted was looking at the concept that many men will die with prostate cancer and not because of prostate cancer.

And if we look at autopsy studies of men who died of other causes, we see that the incidence of prostate cancer is common across all age groups. Men above age 70 and 80 who die of heart disease or stroke, we see that the incidence of prostate cancer can be as high as 50 to 60% when their prostate glands are examined.

We look at men between age 20 and 29 who die in car accidents or violence. We see that about 9 to 10% of those gentlemen have prostate cancer.

So prostate cancer, or at least what we call prostate cancer based on how the cells look under microscope, can be quite common based on your age.

How do we define prostate cancer? It comes down to the simple concept of how these cells look under a microscope.

The more organized-looking cells, we consider to be a lower pattern. So, patterns 1, 2, and 3. And if they're less organized, they're higher patterns, 4 and 5.

This was developed by Dr. Gleason, who was a pathologist at the University of Minnesota in the 60s, who examined many men with advanced prostate cancer and designated these drawings in his own notebook to be associated with prostate cancer.

As we can see here, this system was updated in 2000, in which many men with pattern 3 cells, or pattern 3 cells that were considered more unorganized in the old system, were pushed to call pattern 4 cells.

So, a pattern 3, or Gleason grade 3 cancer of today, really resembles a pattern 2 cell of 20, 30 years ago.

It's important to realize patterns 1 and 2 we don't even consider cancer based on the Gleason grading system. It's really patterns 3,4, and 5 which encompass the diagnosis.

How do we come up with the Gleason patterns? Well, we look at your biopsy cores under a microscope, look at the area where there's cancer, and ask a simple question: What's the most common pattern in that area that's cancer?

That's designated the first number. Let's say a pattern 3. Then, we would look and see what other patterns there are in the biopsy.

If the second most common pattern is a pattern 4, your diagnosis will be Gleason three plus four. If the pathologist only sees a pattern 3, then you would be designated 3 plus 3.

Well, how do men do with active surveillance? The story really begins back in 2000, when our active surveillance program really began to get started.

We have men, when we look back at our publications, who were placed or chose active surveillance, now almost 23 years ago. If we look at that data, we see, and this was most recently published, that amongst men with pattern 3 plus 3, very few men either died from prostate cancer or developed cancer spread.

Remember, almost 20 years ago, we did not have the same tools to monitor men as we do today, specifically MRI, advanced biopsy techniques. We didn't even understand fully what active surveillance should encompass.

So, we even consider today's active surveillance more safe than what it was 20 years ago. Despite that, as you can see, given the total number of patients who had started active surveillance, over 2,600 now and counting, only 5 patients in that group developed metastasis.

Partially as well, one of the designations that we consider very important is follow-up, making sure you come to your six-month follow-ups, all your examinations, as a true tenant of active surveillance.

It's also important to remember, historically, we really had a lot of patients who were misdiagnosed or diagnosed with lower-grade cancers and missed higher-grade cancers. That's because our biopsies were truly random biopsies.

As you can see, the arrows pointing, those arrows can miss an area of high-grade cancer, only hit areas of low-grade cancer based on location and size. And so, it was very critical for us to improve our biopsy techniques.

And it wasn't until the advent of the MRI, and the first MRI of prostate was actually performed by the former chairman of radiology here at Sloan Kettering, Dr. Hricak, in 1983 and 1984, when those first publications were introduced.

And subsequently, we've become experts in MRI and led the field out for over three decades. And we brought MRI into the sphere of prostate biopsy for the purposes of improving detection and better mapping a patient's prostate for various treatment options.

As you can see from this image, we can more easily define areas where there's cancer. And they really nicely line up in our earlier studies when the prostate was removed, and we confirmed those indeed were areas that we were seeing the cancer in these men.

And in 2013, when I started at Sloan Kettering and we started the active surveillance program, we really started to incorporate MRI into our biopsies.

We started defining where areas we should target in our biopsies, and we had systems to fuse images from our 3D ultrasound and MRI to be able to place needles in the appropriate areas and do a better job sampling patients.

This has really revolutionized our confidence in men being diagnosed with low-grade cancer and not having other areas of higher-grade cancer somewhere else on the prostate.

So, active surveillance has a definition. It's really deferment of treatment. Hopefully, for many men, we can defer treatment for the rest of their lives.

But we know we want to observe these men carefully with serial examinations, and at the first signs of higher-risk disease, predominantly defined by pathology changes in Gleason grade, those patients are subsequently referred for treatment with surgery, which is what I do, or radiation treatment with our radiation oncology team within the window of cure. And this is critical, and really is a factor associated with follow-ups, monitoring men closely and moving forward.

Although significant variation exists in identifying patients both eligible for active surveillance and detecting disease progression, and this has been the story of active surveillance across the United States and the world.

We have really standardized our tools to detect prostate cancer disease progression. And these tools are: the examination.

We now do a digital rectal examination at least once every year, serial prostate biopsies, which we perform every three years. We look at PSA changes across years, not just six-month intervals, and we look at findings on MRI that may be considered adverse findings.

So, all these things go into our toolbox to detect when a patient should move on to treatment.

People often ask me, “What PSA changes are important?” Well, we did that study, and we published it in 2015.

We looked at across 700 men who are in our program, who had no changes in their prostate biopsy Gleason grade, who remained stable in the active surveillance program, and looked at changes in their PSA over the past 7 years.

What we determined was we saw upwards of 50% changes in PSA at six-month intervals, and this was considered normal.

So, I tell men, if we see a 50% increase in your PSA in a six-month interval, we don't panic. We just repeat that test at your next visit and, based on those values, determine what the next step would be. And if it continues to rise, oftentimes, we would then order an MRI.

The question also asked commonly to me is, “How common is active surveillance?”, or “How often do we place patients or offer active surveillance?” Well, it turns out the acceptance of active surveillance has skyrocketed, and not only in our institution, but across the world.

We have been leaders in advocating for active surveillance, and we see from these numbers from Sloan Kettering really almost a logarithmic increase in the enrollment of patients who have chosen active surveillance.

This is mirrored looking at the National Cancer Database, which is across all NCI, or National Cancer Institute designated centers in the United States. Again, significant increases in active surveillance acceptance.

So, what is the protocol for active surveillance at MSK?

We obtain a serum PSA every six months, an MRI without contrast every 18 months, and obtain an MRI-targeted plus systematic biopsy every 36 months.

These clinic visits are critical. We expect patients to be enrolling in these studies, being part of these visits, not missing follow-ups.

But also, we try to limit the interaction as much as we can, because we know that with every test comes anxiety.

Patients often ask me, “Can I get a PSA every month, or can I do an MRI every six months?” And the answer is, we have shown that there is no benefit to doing those tests more frequently.

In fact, it creates more questions than it does answers.

Ultimately, we also have determined that adding contrast gadolinium to our MRI doesn't improve the detection rate based on our radiologists’ reading of prostate examinations.

So, all of these factors not only have made active surveillance safe, but have also made it non-invasive.

Who is eligible for active surveillance? Well, hopefully all of you, and with that defined that as low-risk patients, any Gleason grade 3 plus 3 cancer, and there's no restrictions on age, PSA levels, or the volume of cancer.

Intermediate-risk patients that we would also consider possible active surveillance candidates are men with very low-volume Gleason grade 3 plus 4. We quantify the volume of pattern 4 with our pathologists.

We look at the MRI and make sure it's not often an invisible lesion with a large area of tumor.

We also consider patients intermediate risk who have variant histologies. So, we have histologies like intraductal, or cribriform, or atypical acinar proliferation, or intraductal.

These are very rare forms of prostate cancer that can be intermingled with normal prostate cancer, but oftentimes not in themselves risk for cancer spreading, but can be associated with cancer spread and other types of cancer.

So, we follow these men closely, but we don't restrict their participation in our program.

If you're a low-risk patient, we oftentimes won't do a confirmatory biopsy, which is doing a second biopsy immediately after the first biopsy, if we don't see anything in your MRI and we deem that your biopsy done on an outside facility was adequate. And we have ways of determining that.

We also don't do any additional genetic markers.

If you're intermediate-risk category, we do often do a confirmatory biopsy, and we sometimes also obtain secondary tests or genetic testing for better classification of risk to further bring more patients the option of joining active surveillance.

Active surveillance is a very successful story, and this is the story from the randomized control trial that was done in the United Kingdom, which recently was published with their 15-year follow-up.

And it was clear from this, when they randomized men to radiation therapy, prostate surgery, or active surveillance, that there were no differences at 15 years in survival between the three groups.

The overall risk of prostate cancer deaths at 15 years across all Gleason grades in this study was only 2.7%.

But amongst men who chose active surveillance, we see by 5 years, almost 40% of those patients went on to other forms of treatment, meaning their cancer did change, requiring them to get surgery or radiation or other forms of treatment.

And my dream is to be able to keep patients on active surveillance longer.

Is there a bridge between active surveillance and whole-gland radical surgery or radical whole-gland radiation treatment?

I believe this is one of the innovations that we have done a lot of work and research in, which I would introduce in this webinar, and it's the concept of focal therapy.

This is an area that we've done research for now over 10 years at Sloan Kettering, looking at various forms of energy devices that can go in and damage cancer cells within the prostate gland.

These include freezing, burning, using lasers, using electricity, and we've worked with regulatory agencies, including the FDA and others, to determine which of these energies are effective for our patients.

We've run multiple clinical trials at our center. These are predominantly for men with Gleason 3 plus 4 or higher prostate cancer, again as a bridge perhaps for some men who may have been on active surveillance.

Why have we not heard about focal therapy more in the past two decades? Well, it's because we knew that prostate cancer was multifocal.

When you looked at studies from Sloan Kettering looking at prostate cancer sections cut after radical prostatectomy, it was clear that over 80 to 90% of patients had different foci of cancer, inside their prostate.

But now, with the acceptance of active surveillance, we know that low-grade cancer, Gleason 3 plus 3, can be monitored.

So, maybe our best option would be to eliminate areas of higher-grade cancer and watch areas of low-grade cancer. This was the basis of allowing us to begin studying focal therapy in our studies.

One of the systems amongst many that we have at Sloan Kettering that we have studied is high-intensity frequency ultrasound, which is basically a probe that releases sound waves through a transducer aimed at the prostate.

As we can see here, this is placed in the rectum, aimed at the prostate, and aimed specifically at the tumor in which we can visualize and treat.

We first see the prostate in the MRI and define the area of tumor and create almost a one-centimeter margin around the tumor.

This is typically what a prostate gland looks like, looking at it face-on. This is a probe in the rectum, basically getting ready to treat that area, and this is the urethra where men will urinate through.

Then, after we map the tumor, set the margins, the system begins to place dots. And these are dots where heat is generated across the area of target, and we start seeing temperatures above 70 degrees being achieved across all these spots.

And in real time, as we're doing the treatment, we can monitor the temperatures across time as we move our cursor across the area of the prostate gland.

After the treatment, when we get an MRI, there's a clear area where there's no more perfusion of any sort of contrast or areas of the MRI suggesting viable tissue.

And this is illustrated here very nicely in that last case, in which there appears to be just no live tissue in the area that we have now burned.

This was the study that I published last year in The Lancet, which was the landmark study in our field, looking and examining 101 patients across eight centers in the United States, in which I led, where we treated these men with focal therapy, with Gleason 3 plus 4 prostate cancer and Gleason 4 plus 3 prostate cancer.

We see that all these men underwent biopsies at 6 months and 24 months after the procedure, and across all these biopsies, 88% of men had no evidence of any higher-grade cancer in the treatment area, which we deemed a success.

Importantly, when you look at these patients, 70% of men were able to achieve functional or good erections without any medications, and 90% of men were able to achieve erections with or without medications.

And this was really important because when we compared it to our standard treatments, like surgery or radiation, this treatment was either superior or comparable to many of those treatments. Importantly, as well, no patients in the study had incontinence.

It's important, finally, as we come to the close of this webinar, to understand active surveillance remains a standard of care for low-risk prostate cancer.

But as cancer changes and we think about novel treatments, like I discussed today with focal therapy, which is the basis of our research and our clinical activity now, that the standard of care for treatment of prostate cancer still extends across 30 years. And that includes either surgery or whole-gland radiation treatment.

Radical prostatectomy now is predominantly performed using a Da Vinci robotic surgery. This is where I have my proficiency. I've done over thousands of procedures with this technique.

And we are examining the role of removing or not removing the lymph nodes adjacent to the prostate gland as part of that procedure.

As well, we have a leading radiation oncology team with many experts focused on prostate cancer who perform all forms of radiation treatment: photons and protons, brachytherapy seeds, external beam therapies, stereotactic radiation therapy, or CyberKnife.

All of this is performed at Sloan Kettering, and the right treatment for you would be selected.

So, before we get to our Q and A, a couple closing remarks. I think it's important to realize that prostate cancer, the journey, has really gone through some rollercoaster ups and downs over the past 30 years.

Most importantly, we have now realized that despite having great tests like the PSA test to diagnose men, that many men don't need immediate treatment and hopefully will never need treatment with the type of prostate cancer they have.

We’ve also noted that with prostate cancer, we are able to monitor those cancers safely. Patients accept active surveillance as a viable treatment option, and our treatments after active surveillance continue to improve, especially at high-volume or specialized centers dedicated to prostate cancer management.

And lastly, the future is bright. My work and others are really inspired by you, our patients, to continue to push the envelope and find new treatments to not only effectively treat your cancer, in many cases keep you on active surveillance for a longer period of time, but reduce side effects with those treatments.

And we are hopeful that focal therapy can be one of those treatments. So, with that I think we can answer some questions.

Thank you, Dr. Ehdaie. That was very enlightening, and we have some questions that have come through the chat and others submitted through the registration form.

We'll try to get to as many of them as possible. I think a good first question to tackle would be kind of a combination of a few questions people asked about focal therapy, and what might be some of the disadvantages of pursuing that path for treatment? Someone asked, “Is it possible to miss your window for effective focal therapy by staying on active surveillance too long?”

And on the flip side, “What are some of the negatives, if any, of choosing focal therapy?”, and “Does it have any implications for potential future treatments that would be an option?”

Those are great questions. So, the first question is, again, our goal is to make sure all patients are within the window of cure during active surveillance.

Part of that is our dedication to monitoring men closely, but that's a partnership with patients to make sure they come back and see us on a regular basis.

All options should remain on the table. With that said, focal therapy isn't something, in my opinion, that may or may not appear and disappear as an option.

I think that focal therapy in some men would become a viable option based on the location of the tumor initially, the size of the tumor, their own values and expectations of treatment and risks.

And so, I don't think of it as moving from the risk spectrum of, I was a candidate for focal therapy, and now I'm not a candidate for focal therapy.

I would look at it under the umbrella of, is my cancer localized? Am I qualified for curative treatment?

If so, what are those options? And if focal therapy is an option, where are we with that research, what's the newest data, how long is that data now, and if it's the right treatment for me?

Thank you. Boy, a lot of questions coming in.

The next one that I thought we could tackle is about, “How does the protocol for active surveillance change as a person ages, and is there any reason why you would adapt that protocol once someone reaches a certain age?”

Another great question. I think that active surveillance should become less active as one ages, because the purpose of active surveillance is to make sure that patients stay within the window of cure, but also get curative treatment when there's disease progression.

Obviously, if a patient has reached a certain age or has certain levels of other medical comorbidities, our goal would not be, in that patient, to aggressively treat prostate cancer, even if the cancer shows small signs of disease progression.

So, in those men, we transition them to watchful waiting, basically saying, yes, there may be cancer that could change or rarely may spread, but even in those conditions, it will never affect your life or your life expectancy because these other factors associated with higher increased age or comorbidities will more likely be more impactful on your longevity.

So, I do believe active surveillance becomes less active as you age, but within a window, I would say of a life expectancy less than 10 years. We are more selective and careful about how aggressive we are in those men.

But in every decision we have, it's shared with our patients, and we have this conversation that becomes an area of importance.

Thank you. That's great.

Some other questions are coming in around symptom management and whether any of these treatment options that are available can help with management of symptoms that could stem from an enlarged prostate or other causes, even if the PSA and Gleason score remains stable.

One of the true successes of our active surveillance program is partnering with world experts in sexual medicine and urinary function.

Our sexual medicine team has continued to expand, with more attending physicians dedicated with restoring sexual longevity and function in our patients.

So, we are very quick to refer patients who have any questions about sexual medicine, erectile dysfunction, to our clinic, and it's important as part of our active surveillance monitoring of men.

In regards to urinary functions, similarly, we now have over three attending physicians focused on this one issue.

We do refer patients they offer both initially medical management, lifestyle habit changes, but also we are fortunate to have leaders in the field of benign prostatic hypertrophy, or BPH, leading guidelines, who would be able to pick the appropriate treatment, whether that's a laser procedure to open up the prostate urethra, or vaporization procedure, or a surgery.

All of those things we have tremendous experience with, not only doing those procedures, but someone like our team being able to follow them in active surveillance after those treatments.

So, it's critical. It's part of what we do, and we try to screen for that in our active surveillance clinics as well.

Great, thank you. Thanks for plugging those clinics that we have relationships with.

Several questions that have come in about something called the GreenLight procedure. Seems like that rings a bell to you, and people are asking, “What effect that might have on someone’s prostate cancer?”

So, this goes on similar to the prior question about procedures for benign prostatic hypertrophy, or benign growth of the prostate gland, pinching in on the urethra that passes through the prostate gland, making urination more difficult or increasing one's urgency to urinate.

So, we have now over 5 or 6 procedures related to improving those symptoms. We offer all of them at Memorial Sloan Kettering.

One of the most common procedures is a laser or GreenLight laser procedure, where we go in through the urethra while patients are under anesthesia and open the hole within the prostate to allow urine to pass.

That's called a GreenLight TURP. That's associated with significant improvement in urinary flow, reduced urgency, reduced risk of infections, and reduced risk of having full blockage of urine.

Again, we're very blessed to have experts be working with us, but we also have expertise in following men after these procedures.

Our radiologists can still read MRIs after these procedures without any contamination of the MRI images. I and our team can perform biopsies in men after these procedures, and we are aware of changes in PSA that occur after these procedures and making sure that it doesn't change our ability to follow men on active surveillance.

Great, thank you. Going back to an earlier question you were addressing, some folks have asked for a little bit more clarification about the distinction between active surveillance and watchful waiting. Could you expand on that?

Watchful waiting is predominantly for men who I expect to have a life expectancy less than 10 years from multiple reasons, whether age or comorbidity related, or they share with me their values and ideas about their management of disease.

In which we start to now move back away from doing biopsies regularly. We follow men even if there's changes on their PSA with an increase or MRI with concerning findings. Instead, evaluating them to make sure if the cancer does spread that it doesn't affect their life or their symptoms, and being able to refer those patients to get medical management of their prostate cancer in the case of spread.

So, for watchful waiting it’s a less active, active surveillance without biopsies, typically, and really evaluating for symptoms of disease spread as opposed to disease changes within the prostate gland.

Active surveillance is a treatment for the prostate cancer in which we see patients, again, regularly, but include biopsies as part of that follow-up routinely.

Great. I hope people found that helpful.

Somebody asked about looking down the line 5, 10, 15 years, “What additional treatment options do you see becoming available to prostate cancer patients?”

So, I almost can put together an entire presentation of vision for the future.

My hope is that we can lead the way in advanced tracers that we currently use to light up prostate cancer within the patients both prostate and lymph node and bone, and see if we can tag those tracers with treatments.

So, our treatments are like, you know, I apologize for the crude analogy, but like cruise missiles in the military, going directly through the target to kill the cancer cells without disrupting any other organs or other systems in the body.

I see that happening in real time. We have some exciting projects that we are hoping to get started soon, but that is where I think the future with prostate cancer and probably many cancers will go.

Great. Thank you.

You've been very patient with all these questions. Here's one that maybe I can help answer if you want, which is someone is asking about the announcement that went out.

We've been sending an announcement out to patients in the prostate active surveillance program about some changes to the program. That took effect this summer and just asking for any comment about the improvements that have been made to the program.

So, I'll let you speak to it, and I'm happy to also chime in if you want to take a break.

So, I will start to answer, and Emily and her team can continue.

We've been fortunate that Sloan Kettering has really focused on our program and really has highlighted it as one of the milestone programs at Sloan Kettering.

And because of that, they provided us with resources to not only make this a program that I run in my silo, but really make this a big program in our institution for our patients.

Expanding access the program for patients. And so, we had to do a relook to find ways to really make this program even better.

And so, if you would like, Emily, you can just highlight some of those changes for the audience.

Absolutely. So as folks who received that announcement will know, we've made some improvements on a number of levels.

One is in our patient education materials. So, we have a new welcome packet that new patients receive upon entering that explains much of what Dr. Ehdaie went through today in terms of the protocol for what types of procedures you undergo in active surveillance.

As well as the options for referrals to adjacent clinics like sexual medicine and clinics that support with urinary incontinence, so giving people an overview of what the program will entail.

I see another question in the chat about the new biopsy procedure. So, transperineal biopsy is the approach that Kenny, Natalie, and Dr. Ehdaie and the team has converted over to in recent times.

So, we created kind of a new patient education material to introduce that and help answer people's questions about it.

And then many of the other improvements center on making telemedicine more of an option for people who choose it, so that it is easier to participate and less taxing for people who live outside the city to come in and out for their regular appointments.

And then a few new things that we're trying. This webinar is part of that. Piloting a shared medical appointment where a few patients could come together, and have a conversation led by Kenny, or in the future by Natalie, is another part of that.

Those are opportunities for us to share information about topics of interest like nutrition and other areas that people seem to be curious about.

So, that's just a little taste of some of the things that we have introduced. And yeah, would love to hear any feedback from people who have encountered some of those changes about how that's working out for you.

Yeah, and I would add; this is just the beginning.

I have webinars we are planning centered around diet and nutrition. I know that has become a question that comes up frequently.

I think that deserves its own webinar instead of a quick response, because there are controversies, the benefits that we can speak about, and other ideas.

I think based on some of the questions, the transition from active surveillance to watchful waiting, as one comment says they are used interchangeably in the media erroneously.

I'm very clear that there's active surveillance, which is separate from watchful waiting, and really any other developments that we have in our program that we would highlight for our patients.

I think benign prostatic hypertrophy enlargement, sexual medicine, are all interesting topics that are critical for our patients to have separate webinars.

One of the questions that I just saw as I reviewed some of the comments was a question regarding, “Is focal therapy likely to be a final treatment or just an interim treatment to delay radiation or surgery?”

I believe that we must think of it in some terms as expanding the time horizon for patients to remain on active surveillance and avoid radical treatment.

For some men, again, treatment may be effective or their cancer may respond in a way, or their cancer location may be more amenable based on lack of multifocality, in which the cancer either is cured or it doesn't progress any further during that patient's lifetime.

And in that case, it was curative, but if we can imagine a world where humans live forever, I think a treatment like focal therapy, because there's still viable and working prostate gland in the patient.

Those areas, at some point, will probably acquire cancer over a period of time. But the thought period being it won't be in the patient's subsequent lifetime.

But we do monitor patients after focal therapy similar, in many ways that we do for patients after active surveillance.

Anything else catching your eye in the questions submitted through the chat?

So many great questions. I mean, I think it really , it's a testament that our patients are really, you know, not only dedicated to their own health, but up to date on what the newest things are in prostate cancer.

So, I think sticking with the concept of focal therapy, there's a question: Why can't we apply this to the entire prostate gland?

And the reason for that is the purpose of focal therapy, is that we can reduce side effects.

When you apply that level of energy, whether it's freezing or burning or electrocuting the prostate, to the entire prostate gland, it's just overwhelming.

And the side-effect profile actually, in many cases, could be worse than surgery or radiation.

So, it's such a strong amount of energy being applied to an organ that it can only be done, in my opinion, safely in a very focal and small area.

I think one of the points that you brought up, Emily, that's being discussed as well is our biopsies in active surveillance.

There are a few questions in that area. So, I think that one, there are exceptions for us to do biopsy at three years.

Every invasive procedure, and I consider biopsy an invasive procedure; we should communicate with our patients.

I've had patients who say, “Can I avoid a biopsy? What are the risks?” And we discuss those risks.

We know that 10 to 15% of higher-grade cancers will be missed on MRI for patients, which is why we do not only a targeted MRI biopsy, but in many cases systematic biopsy.

We biopsy men, even when their MRI is stable or even if there is no lesion within the MRI.

But one of the things that we have put tremendous amount of research resources, and our attention is to find more ways to avoid biopsy for patients.

And I can assure you that's on the forefront of our minds for our patients.

The second question was, well, there's a new biopsy procedure. Why? Why are we doing different types of biopsies?

Well, we knew that 3 to 5 percent of our patients at Sloan Kettering were getting the normal biopsy, which was through the rectal route, were experiencing infections.

In many cases, serious infections, despite antibiotics. So, we knew that across really a global trend of bacteria more resistant to antibiotics, we need to be smarter.

And so, we worked with many of the urology community, not only in the United States, but worldwide, and developed biopsy techniques through the skin right above the prostate.

So, the next question is, is it more effective? So, I've been fortunate to be part of the landmark trial currently undergoing, comparing the traditional biopsy to the transperineal biopsy, to ask the question, do we indeed reduce the risk of infection in men?

So, stay tuned for those results. And thank you for the men who participated in that trial.

But again, it goes back to my earlier point. Although we call it active surveillance, our goal is to be as less invasive as we can, and reduce morbidity associated with active surveillance in all our treatments.

Absolutely. Well, I'm sure people appreciate you going into a little more detail on those questions about focal therapy.

Obviously, with three or four minutes left, we are not going to have time to answer every single question that's been shared here.

But I want to reinforce your point, Dr. Ehdaie, that this is just the beginning. And we will be able to kind of comb through these questions as inspiration for future webinar topics.

So don't feel like your question is lost, but in the spirit of staying on topic, now might be a good point to wrap up.

I appreciate it, Emily. I appreciate the team who put this together. I especially am grateful for the patients.

You are inspiration. And I hope we continue to deliver the best care we can, and the future looks bright.

Thank you so much.