Active Surveillance of Prostate Cancer with Yushen Qian, MD

low, a medium high risk is a little bit more like a high risk and there are subtleties in those based on the Gleason score, how many medium risk factors there are and and lastly, there is also a high risk group with a subclassification of very high risk, as well as us with the specific type of survival and this is survival. This is essentially a reflection of mortality due to

prostate

cancer

. Not surprisingly, it depends on which one. The risk group is, at the top, with blue, the low risk patients who have the best survival and at the bottom, the high risk patients in green have the worst survival, so what do we do in terms of treatment?

This is a very busy slide, so we'll go through it one by one, so it's all based on life expectancy and what are we thinking about in terms of life expectancy, if so, if life expectancy is less than 10 years. years, so, for example, a patient who may have had significant heart failure due to a previous heart attack, multiple strokes, multiple stents placed on dialysis and whose life expectancy is not what we really expect to be longer than 10 years the best treatment is actually observation or watchful waiting and we will get to this a little later starting with a life expectancy greater than 10 years, let's say between 10 and 20 years with very low risk

cancer

s that we recommend

active

.

surveillance

and for others at low and very low risk, you know, very long life expectancy, completely healthy, no medical conditions,

active

surveillance

or definitive therapy, and we have alluded to some aspects of definitive therapy prior to surgery, such as Dr.

Sun said, or radiation variants. like external beam radiation, internal radiation, also known as brachytherapy, so there are a couple of technical terms, so I want to make sure we understand the concepts and the differences, so we talked about expectant observation and active surveillance. They sound similar, but they are actually very different, so what is the difference between watchful waiting and active surveillance? The watchful waiting is that there is no plan for a definitive therapy, we are not thinking about you, you know, Curative surgery when I think about radiation, but there is one that we are waiting to see.

Symptoms develop, we may prescribe palliative treatments such as androgen deprivation therapy or hormonal treatment to alleviate symptoms after surveillance, it is an active process of serial PSA monitoring with plans to initiate definitive therapy, surgery, radiation whether the disease progresses and therefore who the ideal populations are for that. Watchful waiting Act of surveillance Watchful waiting Our patients are unlikely to benefit from definitive therapy due to age or comorbidity. Again, that patient who's had heart failure, multiple strokes,

prostate

cancer probably wouldn't be what would take them, so sometimes less is more. and you don't want to put them through unnecessary procedures, whereas active surveillance are patients who want to defer therapy and, more importantly, adjust to the associated side effects of that therapy because they have a low-risk disease that may never come to be clinically significant, so what? is the surveillance strategy for active surveillance.

We recommend that you see your doctor for a PSA twice a year and a digital rectal exam and biopsy no more frequently than every year, so say you know you're still active. surveillance protocol what are the indications what are the things that would trigger a type of therapy um what are the indications to start starting definitive therapy and it's essentially the short answer is disease progression um changes in PSA, especially if something is called doubling moment when the PSA kinetics starts to increase very quickly, different findings on the exam, for example, two years ago when your doctor did a digital rectal exam, no nodules were found and now suddenly, maybe there is suspicion of a disease that is spreading outside the capsule or because you know, repeat the biopsy before, cancer Gleason three plus three, now it shows four plus four, those are indications to start therapy and lastly, but very important, also the patient's preference, it is very reasonable and we have many patients who just want to be taken this. and I think that's an important factor as well, so I'll conclude with just some evidence in terms of active surveillance and talk about some literature and evidence base that we have, which is specifically the UK shielding trial, it's a great controlled trial. randomized which was carried out outside the UK and enrolled around 1600 men, the average age was approximately 62 years in the UK there were 99 Caucasians and in this population most, but not all, were low risk;

However, 77 percent of them had Gleason three plus three cancer and a third of these men underwent active surveillance, a third had surgery and the third received radiation and this trial attempted to answer the question of what happened to them. , as you can see in this graph in the center, here, specific to prostate cancer. excellent survival almost 100 no or essentially 99 for everyone, meaning that mortality due to prostate cancer has not changed. The physician surveillance arm had a relative risk. High relative risk of developing some kind of clinical progression or developing distant metastases, which means spread of prostate cancer, but overall this rate is that the absolute risk is very, very low and if you look at the graph in the um of there with the colors um uh blue, red and green with the active monitoring group, you can see that 50 of the patients who are on active surveillance receive definitive treatment. because their biopsy showed tumor overshadowing, their PSA started to rise at 10 years, so what I tell my patients is that if they choose to undergo active surveillance, the data showed that at 10 years they have a 50 chance of requiring treatment, but also, conversely, if you choose to undergo surveillance after 10 years, you have a 50/50 chance of avoiding treatment and its associated side effects.

The only caveat I would say would be to be cautious about generalizing to the type of patients that don't look like the patients that are in the study again, much younger patients or African American populations, since it was 99 Caucasian, so that's it for Me, thank you very much for your attention. I hope this was helpful and I'm happy to answer questions. Excellent thanks. Thank you very much, Dr. Chen, we are receiving some questions online and please, if you have any questions from the tables, we will take your cards. We've got quite a few for you here, so to start, what are the factors that determine advancement? from active surveillance to treatment, yeah, so a couple, in my opinion, the most important one is what the patient thinks, the patient's preference is, if someone, it's, if they know they have prostate cancer and they don't know feel comfortable looking. that and you just want this thing fixed, that's a completely valid reason to go to treatment.

However, in other cases, you know, as we continue active surveillance, if your repeat biopsy shows that there is a higher level, there is evidence. of disease progression, whether it's a Gleason score that goes from three plus three to four plus three, whether it's um uh urge, before there were only three nuclei involved, now there are 12 nuclei involved, those are factors, in addition, the PSA It's behaving like it's going up. be factors talking about prostate or Gleason three plus four can you explain the difference between three plus four and four plus three correct yeah so this is an excellent question this is something that we um that that uh that is an excellent question so the The score of Gleason police again is um uh, the first number is the number that is the most prevalent pattern seen by the pathologist and the second number is the second most prevalent pattern, so Gleason four plus three cancer means that the most common pattern is a Gleason four, while Gleason three plus four cancer means the most common pattern is a Gleason three and how and why that matters.

We talked about the different risk groups, there is a medium risk group in the intermediate risk group for cancer and they are within that. subclassification there is a medium low and a medium high with the medium low looking more like a low medium risk prostate cancer the top metal looking like a medium high risk prostate cancer a Gleason four plus three cancer is a medium risk prostate cancer high or an unfavorable intermediate risk prostate cancer and these types of patients at Stanford we tend to be more aggressive and increase treatment because we think it is approaching a higher risk, whereas a Gleason three plus four cancer if their PSA is lower to 10 yes no I don't feel anything else abnormal on the digital rectal exam.

We treat it as low-medium risk prostate cancer. Thanks, what is the role of biomarker testing, such as decoding, in treatment decisions? Does it indicate a more aggressive treatment if it has biochemicals? recurrence uh regular so this is a um uh I think it's actually two questions so um let's break them down so let's talk about biomarkers or genomic studies decoding tests the decoding test is genetics it's a genome assay um that basically looks at how aggressive the G the genomes you look at the genetic material of the cancer and basically the way we tend to use genome testing here we use the traditional risk stratification scheme that we had talked about based on those three main factors and then for patients who For example, a young patient who is otherwise healthy and wants to be on active surveillance for a long time.

I would get the decryption to verify that, you know, the genomics looks good because it gives me a little more peace of mind knowing that we know we're active. surveillance uh the question was also asked about biochemical recurrence, biochemical recurrence is actually more of a question regarding recurrence, what that means is a recurrence of PSA after treatment and in that context I suspect the question refers more to after surgery, so after surgery If you have an out prostate, the PSA should be zero. In a perfect world, sometimes the PSA goes back up and that's called a biochemical recurrence, it becomes detectable and in those cases more treatment may be needed later.

This is going into some details. but the decryption test can also be useful in those cases, yes, that's going into a little more detail, but yes, thanks for the PSA screening tests. A couple things: number one, do you need to fast? and number two, do you need? Avoid sex, do you need to avoid riding a bike? Because we know that PSA can fluctuate, yeah, um, uh, uh, again, so there can be several factors that can cause a falsely elevated PSA, so I think that's a good rule of thumb. No need to ride a bike, no need to ride a horse, no need to fast, probably for at least three days beforehand, that's fine, thank you, and if they put me on active surveillance, I'm afraid I'll get cancer.

It's going to spread, can you talk about that a little more? Yes, so the goal of active surveillance is that the act of surveillance is an active serial monitoring protocol in which we are watching things very carefully with the goal and intention of sparing you from the side effects of the therapy, um, uh, whether it's erectile dysfunction, whether it's leaking urine, for as long as possible until you need the treatment and by watching it very carefully, you'll get the PSAs twice a year. Regular. checks with MRIs repeat biopsies to make sure your cancer has progressed so again this is different from watching this is different from waiting carefully or observation so we are monitoring this very closely the chances of it progressing while all those other factors were watch out We're looking at the Gleason score or, you know, by the Gleason score on the PSA biopsy if they're otherwise stable, it's very rare to go to other places and we've heard that sugar can feed cancer, so we should avoid sugar and what others. what foods should we avoid and what should we eat in our diet so I'm not the best person to answer this question because I love sugar and um there are several so the data on the risk factors for prostate cancer in diet are limited.

There is limited evidence to show that excessive consumption of high fat, such as red meat, which I also love, and dairy, may contribute to an increased risk of prostate cancer. This evidence base is limited, not that much. I don't know much about sugar, there is limited evidence that the carotenoids found in processed tomatoes can potentially lower prostate cancer risks again. The strength of this evidence is limited, but in general I would recommend a healthy lifestyle, you know, as Dr. Sun had alluded to.to a healthy heart, a healthy prostate, a healthy body, um, 30 minutes of exercise a day, um, and then, uh, lots of fruits, lots of vegetables, can't go wrong, okay, if I'm a low-risk Gleason or a low-risk or low-risk candidate. prostate cancer, but still the decryption shows that I am at high risk.

Would you still recommend active surveillance? So it depends on several factors. We would have it, it would probably be a 45 minute discussion in the clinic where we would essentially discuss the nuances of your pathology, tell your needs and desires and then do your deciphering test, yes, strange, PSA increases due to cancerous cells versus non-cancerous cells. , sorry, psma can psma yes, so, psma um, what Dr. Agaru has talked about is specific to um uh prostate. specific membrane antigen, so it's targeted at prostate tissue, but in terms of the way we look at it, the reason psma is the way we use it in clinical practice to help us determine if there is or not cancerous tissue is, if there is a normal lymph node somewhere in the pelvis that is lighting up, it is probably cancer if they are, but there may be background uptake from various tissues, such as the salivary glands of the liver or the parotid glands, the submandibular glands, those will also light up, so they are not cancer. on its own, I would say I would trust the PD in the radiologist's interpretation, okay and the last question before our break, and this is actually for radiotherapy.

Is there any evidence or trial looking at radiotherapy for lung metastases? oligo oligomedasstatic prostate cancer with a rising PSA with systemic hormone therapy uh, yes, so my dear colleague, uh, uh, uh, you will receive an update after this. Dr. Bakshaw will talk a lot more about the prostate, about radiation therapy for prostate cancer, um, but I. can we give it a first chance, what is it, so this is an emerging role in that um pre in that recently oligo uh, the term oligom metastatic disease in prostate cancer has emerged and what does that mean that means oligo means a few means prostate cancer that has spread outside the body with only one, two, three, a few lesions that have spread outside the pelvis, so let's take the example of lung metastases if there are only a couple, one or two metastases, our focus on Stanford needs to be aggressive and treat them definitively or with curative intent with high doses of radiation to try to cure and combat those cancers and there is that which is supported by evidence in the literature from multiple institutions that suggests that aggressive treatment for an oligo or a few metastatic sites of the disease may actually be associated with better outcomes, which is why we are in favor of this at Stanford.

Excellent. I appreciate all your questions and answering questions and a wonderful chat. Thank you very much Dr. Chen. At this point, we have. Let's have coffee and a biological break. We will meet again at 10.45am. m., followed by two more sessions and then we will be. We will have a lunch break and two sessions, one of which will include three patient perspectives. Thank you so much.