Screening for prostate cancer is a shared decision

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Dr. Alicia Morgans: Hello and welcome to more of our AUA 2018 cover. We are excited to be able to speak with Dr. Matt Cooperberg, Associate Professor of Urology, Epidemiology and Biostatistics at the University of California at San Francisco . Great to see you, Matt.

Dr. Matt Cooperberg: Great to be here. I'm excited.

Dr. Alicia Morgans: So, I think one of the most exciting things in terms of localized prostate cancer and prostate cancer diagnosis in general that just came out last week are the final recommendations of the USPSTF on PSA screening guidelines. I would love to have your opinion on the changes that have just been published.

Dr. Matt Cooperberg: Sure. This is, of course, a still controversial question about how we should optimally screen for prostate cancer. The new recommendation C is not a big change from the project they published at the end of last year. This is obviously a step in the right direction. They went from recommending never to test to a screening recommendation for men aged 55 to 69, that they have at least one conversation with their primary care physicians about the question of knowing if

With this change, they are now much more in sync with most other existing guidelines. The AAU, ACS, NCCN have all recommended for several years a shared decision making. Thus, the working group is no longer isolated in this respect. This is progress. The way in which they program their analysis of evidence still has major flaws in the way they treated the data from a methodological point of view and in some details of the conclusion. But as I said, it's a step in the right direction.

I think one of the main problems is the age of 55 for screening, it is probably later than expected. There is actually a lot of evidence that earlier screening is more effective because there is less BPH, so less APS contamination, if you will, in younger men. And it is actually a good evidence base for screening in men aged 50 to 55 years, based on studies and outside the ERSPC era. Malmo and HPFS by looking even earlier.

I think they could have made a very arguable argument about screening 50 to 69 based on these RCTs and they chose not to, which is unfortunate. But again, at least now, there is a concordance between the guidelines for shared decision-making.

The question then becomes, what should this shared decision-making conversation look like? Some of the other limitations of reporting are a myopic view of the benefits of screening at age 13. The selection debate for men 50 years old, or even 60 years old or frankly, even those 70 years old, is not around 13 years old. It is a horizon of 20 or 30 years.

When you look at the patient guide that came with the guideline, it's very misleading because they talk about a life saved at age 13. Well, it is not the relevant period that a man cares to know who is 50 or 60 years old, it really is the 20 or 25 year old. And during this period, the number of lives saved through screening increases, of course.

The harms are also overestimated. They take on the worst-case scenario in terms of the risk of incontinence and long-term sexual dysfunction after treatment. You know, they quote studies that are in the literature they are published, but that's a chosen view of the literature, and they ignore a lot of studies showing the best results that are achievable in the centers at higher volume.

So, it's really progress, it's certainly a step in the right direction. I always encourage primary care physicians to learn the evidence themselves to review other guidelines. I still think the NCCN is probably closest to what we should be doing.

The problem with all the guidelines is that none of them really tells us how to screen, partly because the RCTs did not really answer these questions. PLCO has taught us that annual screening starting at age 55, 60 or 65 is not optimal.

Some of these cohort studies have clearly understood that men whose baseline test is low may differ from many tests for many years. And I think that's the concept that we're really trying to promote now, this smarter screening idea. We should think of PSA more like a colonoscopy. If your PSA is low initially and low means less than one for young men, not four, you really do not need another test for several years.

For men who have a slightly elevated PSA, we are now very interested in secondary tests with elements like 4K and PHI or we are selecting MDx, these secondary tests with a very good negative predictive value for clinically prostate cancer. significant. MRI is also in this category.

High PSA does not mean a biopsy. And then, of course, the biopsy and prostate cancer diagnosis need not and can not mean immediate treatment, and I think that risk stratification is finally coming out of the academic world into actual practice. the country.

Dr. Alicia Morgans: So, can you say a little bit more about that? I know that active surveillance is really part of your passion and the USPSTF guidelines, I think, both aimed to improve our ability to detect these high-risk cancers, but also to not over-treat patients. And I think you, as an individual and your field of urology, have really developed practices in the 90s where all people with a diagnosis of prostate cancer seemed to have a prostatectomy, and the active surveillance limits the risks for patients. useful. So, I would like to hear your thoughts about this.

Dr. Matt Cooperberg: Yes, that's exactly it. The task force focuses on the pros and cons and everyone recognizes that there are benefits to screening. The question is how to evaluate them and how to weight them? And there is no doubt that the most important harm of screening is the harm caused by overdiagnosis and excessive treatment of low-risk diseases.

We know that low-risk prostate cancer kills almost no one, even after 20 or 30 years of follow-up. There are those of us who think that we should not even talk about cancer when we talk about this microfocus of low-grade disease and we are doing a very poor service to men by giving them that label, this diagnosis. I think that active surveillance has really disappeared from the academic world, but you are absolutely right in the 90s and even during the first decade, a diagnosis of prostate cancer was diagnosed.

And we were among the centers that showed this over and over again in the community registries we manage. In fact, during the current decade, we have really seen a paradigm shift: while before active surveillance, less than 10% of men were now at 40% in the big register that we find here. In the Michigan Consortium, which collects data across the state, it reaches 50%.

I was actually at one of the poster sessions here a few minutes ago and there is data from the Optum database, a large national database of Medicare Advantage patients. and young men with paid private insurance. about 20% of all localized prostate cancers, not just low-risk diseases. And if you do the math, this will still account for about 40 to 50% of patients with low-risk prostate cancer.

We are really seeing a real paradigm shift. It's amazing how it happened quickly. It's really in this decade. There are those of us who think that part of this was probably a reaction to the working group, and if the working group did something good with recommendation D, I think that 39, he forced this call not to accept the treatment of prostate cancer. we as a treatment community. I was definitely in the camp that had been saying for years that if we did not solve the problem of overtreatment, we could not regain control of the conversation about early detection.

Dr. Alicia Morgans: Yes, absolutely, and it is wonderful. And I just want to say that 40% to 50%, potentially, of those low risk patients who are appropriate for active surveillance are now there. And I agree with you, it's very fast. Medicine does not usually move very fast. Thus, the phenomenal work of your group and others to raise awareness and help providers and patients feel safe in this decision.

You know, one of the ways that people can feel safe in this decision is to use potentially molecular or genomic data to help stratify the risks and help them determine if this localized disease will ultimately be a bad one disease. a low-risk localized disease? Have you incorporated these risk stratification methods into your practice?

Dr. Matt Cooperberg: Yeah. So, the short answer is yes, the long answer is that it's really very complicated how to do this optimally. So, yes, what that means for active surveillance is changing quite rapidly. First of all, the figure of 40% is probably still a bit too low if we consider Sweden and other countries up to 80%. And it's probably there that we should be in terms of the proportion of low-risk men who start at least by monitoring.

But the monitoring is not completely benign. It involves serial biopsies and biopsies are a critical part of the surveillance paradigm. If you look at data like those of the ProtecT trial in the UK, if you have a surveillance strategy that does not include biopsies, you will definitely run out of progressive cases. And I think that's what the first results of ProtecT have shown.

There are risks for the biopsy, there is discomfort in the biopsy and we are really interested in modulating the paradigm of surveillance. So the first question is who should be under surveillance? And then, once men are monitored, how can we do it more safely? How can we avoid harm to men who do not need such frequent intervention and how can we avoid missing cases that will progress faster?

Genomics will play a role. I think that trying to identify exactly what this role is difficult. We have a number of markers that have now reached the clinical market in the United States. There is the Polaris test, the Oncotype and the Decipher, all of which are tissue-based tests. We have blood and urine tests that try to enter the space post-diagnosis, then we have MRI and the MRI really has to play in that same space and answer the same questions about efficiency.

I think there was this article from the New England Journal on the use of MRI in the pre-diagnosis space as a secondary test between PSA screening and biopsy. In the post-diagnosis space, MRI is of great interest as in biomarkers. But again, the devil is in the details. We know that all these tests, genomics and RM can improve the prognosis. In other words, they can improve the Gleason score, the PSA stage, the extent of involvement in the biopsy, even the PSA density in terms of predicting who is going to do wrong, who is going to do well.

But they have not been able to directly guide a clinical decision at the point of care in a manner that is sufficiently simple and reproducible for the typical patient and the typical community urologist to be able to apply it in a simple and reproducible manner. way that everyone is looking for.

To put it more clearly and everyone wants a binary test. The joke that I always use is that everyone wants a pregnancy test and if the test turns blue, you get out of the prostate. It will never be so easy because prostate cancer is not a binary disease, and it's not as simple as a low risk or high risk. It is a continuum of risk.

What tests tell us, we know it's not a black or white question. It's a shade of gray, and maybe it gives a shade of gray slightly lighter or slightly darker. But that can not tell us what to do, at least not yet. None of the tests can arrive at the binary response point. So for this reason, I think the way they are really used is still very individualized and very personalized. At UCSF and many other academic centers, we really use them to try to push the boundaries in terms of candidates for monitoring.

I think the value is not necessarily there for men who have low volume, that is for those who have the largest volume of tumors or those with low Gleason volume three for four for whom surveillance It's not the obvious decision but can be a reasonable decision. I think that in these cases, the markers can be very useful as a break in equality.

But the other place, I'm really optimistic about the markers, and it's there that we start to launch studies, can we really use them to modulate surveillance. So, if you think of the hundred men we identify as candidates for supervision, we know that about half of them will be getting treatment during the first five or so years of supervision. If you break down more, there are probably 5 to 7% of men who really have aggressive cancer, and should probably go straight to treatment, and that's the rare patient where we can really see clear evidence of progression in this short time interval. monitoring.

But there is a very large number of men who have absolutely no signs of cancer progression. The next biopsy is negative or we see a spot of 3-3, again and again, and the PSA is stable or descending. And these are men who, frankly, do not need active surveillance at all. They may be on a less active surveillance protocol. We could probably think of it more as an attentive waiting. And if we could validate a marker that could allow us to postpone the next biopsy for four years, five years, which becomes highly exploitable and highly valuable. This avoids the side effects that avoid risks, avoiding a lot of costs. I think the markers will help us achieve that surveillance goal. We are not there yet in 2018, but I think the studies we are launching will help us get there.

Dr. Alicia Morgans: And I think that to make the link between our diagnostic and diagnostic methods and to improve our understanding and ability to stratify patients, we continue to put the right patients under surveillance and the right patients to active treatment. I hope that the USPSTF guidelines will evolve with us, and we will encourage to actually screen men because, when they will be viewed, we will know what to do with the information and we can really adapt the treatment or no treatment with the patient and with his tumor.

Dr. Matt Cooperberg: We hope so.

Dr. Alicia Morgans: Yes.

Dr. Matt Cooperberg: They need to read the literature to get there, but yes, there is always a comment in the working group's statement that we can not distinguish indolent cancer from aggressive cancer. It's just ignorant. It does not matter the biomarkers. We can proceed to a stratification with an accuracy of 80% based on stage, PSA, the extent of participation in the biopsy with an extremely well validated risk stratification tool.

Biomarkers that can help us do even better. But the idea that in 2018, with standard clinical information, we can not tell rabbits turtles, that is simply wrong. Now we have not done a great job applying this information, and we are progressing as a specialty, but yes, there are a number of steps. Urologists and Radiation Oncologists Clearly Change Clinical Practice, Changing the Working Group's Position in the Way They Program Their Evidence Analysis is an altogether different conversation because the conclusions they draw reflect the decisions that they take in their original methodological planning of the program.

As they set the rules of the road for the studies that they will include and exclude, these decisions will lead to their conclusions. Many of us think that they predict the end result based on studies that include and choose to ignore, and they hope to continue to engage more and more with the experts, with those who wrote the literature about prostate cancer. for many years to come up with a better evidence-based directive.

Dr. Alicia Morgans: Absolutely. So, an evolutionary process, a process that, hopefully, will continue to change and grow over time and that will truly meet the needs of our patients, because, ultimately, that's what we all want , in my opinion. So, what are your final thoughts, your main themes to leave listeners?

Dr. Matt Cooperberg: Prostate cancer, like all cancers, is a complicated diagnosis and the devil is always in the details. I think the problem is that etiquette has such a psychological impact on patients that for many years the diagnosis has been difficult because people hear cancer and think that pancreatic cancer will last for months. .

I think the first challenge was to change this conversation because just because we used the word cancer, it's not that conversation. And then the second phase of this conversation is that in prostate cancer we have this extraordinary heterogeneity of risk ranging from the deadly disease that really needs to be treated aggressively and with a completely biologically indolent, virtually benign multimodal strategy, can -We should not even label with cancer and identify the patient so that he can understand where he lives on this spectrum or where he lies on this spectrum continues to be a challenge.

I think it's still difficult to find a man who can understand where he stands on the spectrum of risk. And those of us who eat, sleep, live and breathe nothing but prostate cancer clinically and research, even for many of us it It takes years for this conversation to become a routine and can guide this conversation reliably.

I think in a larger practice, it's a big challenge. I think that diagnosis always involves the imperative of treating from a psychological point of view, from a defensive legal point of view, a whole set of non-clinical factors that go into that decision. I think we're making a lot of progress as a specialty, not only to get the message across to our treatment community, but to the primary care community, but also to the patient community.

And I think that more and more men are aware of the possibility of active surveillance. I think they're aware that prostate cancer is not necessarily a deadly diagnosis and I think it's imperative that we all continue to improve the message and communicate the message to our patients. primary care colleagues and men in the community.

Dr. Alicia Morgans: Absolutely. So, really communicating to patients that you can live well if you have a low-risk disease under active surveillance if you have a high-risk disease, it's a deadly disease, and we have to deal with it with any appropriate intervention for this patient. These are important messages. And I think we are better aligned as an area and hope we can continue to work with the USPSTF and data generation to do our best for our patients. Thank you very much for your time.

Dr. Matt Cooperberg: Pleasure. Always a pleasure.