Dr. Amanda Swain (Host): Hi, everyone. Welcome to the Penn Primary Care Podcast. I'm your host, Amanda Swain. And tonight, we have two guests talking about cancer screening and prevention, and I'm very happy to have them both.

Dr. Richard Wender is the Chair of the Department of Family Medicine and Community Health at the University of Pennsylvania. A nationally recognized leader in cancer prevention and screening, Dr. Wender has made substantial contributions to public health and population health initiatives throughout his career. Dr. Corinne Rhodes, MD, MPH, is an internal medicine physician, an Associate Professor of Clinical Medicine at the University of Pennsylvania, and the Medical Director of Population Health Penn Medicine. She has a special interest in vulnerable populations, reducing existing disparities in clinical outcomes, and population health initiatives.

Welcome to you both. I'm so happy to have you here tonight.

Dr. Richard Wender: Glad to be here.

Dr. Corinne Rhodes: Pleased to be here. Thanks for having us.

Host: So, we are going to have a conversation tonight about cancer screening updates, some population health topics within cancer screening. And I really am so glad to have you both here because not only are you both physicians, but you both have extensive experience in the public health world and kind of looking at cancer screening from beyond the clinic room.

So, I am going to start with just one of several types of cancer screenings that we'll talk about tonight. But I would like to talk a little bit first about colorectal cancer screening. And what many of our listeners may know, but not all, is that the United States Preventive Services Task Force, which the acronym is a bit of a mouthful, but I will be saying it—we will all probably be saying it tonight—which is the USPSTF, recently lowered or relatively recently lowered the recommended age for colorectal cancer screening from 50 to 45. And I wonder if you could talk a little bit about why this change was implemented, and then also how we can have this conversation with patients about getting the screening done.

Dr. Richard Wender: Yeah, I'll be happy to take the first shot at that. It's a very compelling reason why the screening age was lowered. In fact, it was first lowered in the American Cancer Society guideline in 2018. So, there's been some focus on lowering for almost a decade now. And then, when the task force was due to update, they also changed to 45.

This is work that actually came out of the American Cancer Society. Epidemiologist named Rebecca Siegel, starting several decades ago, started to observe a gradual increase in the incidence, new occurrence of colorectal cancer in people under age 50, so-called early onset. We often use it early onset. We now realize it's not so early onset. This effect has continued unabated. It continues to this day in every younger age group, going all the way down into people in their 20s, even in their teens. We are seeing a steady rise in each successive generation for the risk of developing colorectal cancer. And colorectal cancer is now the leading cause of cancer-related death in individuals under 50 in the United States.

So, the American Cancer Society commissioned modeling way back in '16, '17 that showed it was more efficient and effective to start at 45. They passed that off to the task force. Task force agreed. And there's now essentially universal agreement the starting age is 45.

Host: I think you said something really important in there, which I want our listeners to pay attention to, which is the fact that there was modeling done to show that diagnosing colorectal cancer at an earlier age made sense, not just for the purposes of having the diagnosis, but it has an impact on mortality, which is an important part of why we set cancer screenings at certain ages and not others.

Dr. Richard Wender: Absolutely. I mean, that is the standard. It's a very high evidence standard that's set for guidelines. We have to be convinced that starting screening with a particular test at a particular age will lead to lower cancer-specific mortality for that disease. That is the standard we should adhere to. And that's the standard that was met through both the combination of experience, older trials, and modeling showing that we should move earlier to 45.

Host: Thank you. And maybe one of you wants to talk a little bit about how we approach colorectal cancer screening specifically now that in addition to colonoscopy, which is still considered the gold standard, we have other kinds of testing that can be done, the home testing. And not only kind of what you think about those tests, but maybe we can talk a little bit about how to have the conversation with patients about what's on offer to really help increase the screening rates.

Dr. Corinne Rhodes: Yeah. Happy to reflect upon that, Amanda. And I think there's a couple different lenses you can bring to that question. I think there's the lens of the individual patient in front of you, as well as kind of these larger questions of how we screen as populations. But I would say the USPSTF decreased the screening rate in 2021, which was in the middle of a pandemic. And so, the way that I approached this in 2021 and now five years later has evolved.

In 2021, it was challenging to get a colonoscopy for many of our patients. There were delays, there were concerns about presenting for invasive procedures during that time. And there were patients who were avoiding cancer screening who would have usually rapidly engaged. And during that time, we also had to educate the public about a new cutoff to get a colonoscopy. Many people did know that at 50 years old you should get this, and now we had to focus on this age group between 45 and 49 to really catch them up at the same time that we were trying to catch up patients who were not engaging in usual colon cancer screening.

So during that time, I think my practice pattern changed, and I think many other physicians and APPs saw some shifts in their practice patterns. Throughout the nation, I think there are different approaches, I would say. Here in Philadelphia where I practice and I think the two of you practice, there's definitely a colonoscopy gold standard approach. And so, the majority of my patients, prior to the change of the guidelines, would get colonoscopies.

Now, I think both with increased marketing for Cologuard and at-home stool tests, there's more of an array, and I think more of my patients are aware that they have choices as they come to speak to me. Sometimes I do have to educate patients about the different choices. I want all of my patients to get screened. And so, if they ask and engage in a conversation with me, I will talk about the different modalities that are available. And if they ask my recommendation, I will give my recommendation based on their health, and what I know about the patient who's in front of me based on their resources, et cetera.

Ultimately, all of these will help us get to cancer screening. Majority of my patients opt for colonoscopies. And I think if it is safe and they are able to get an escort, if they are able to bridge off of an anticoagulant, et cetera, that is, I think, the default for the majority of us. But when I order a colonoscopy and you come back next year, if you haven't gotten that colonoscopy, I am going to be delving a lot deeper into at-home stool testing. And I think it's really important when you order an at-home stool test that you know that this patient is average risk, because an at-home stool test is not appropriate for all patients. Although we are screening for colon cancer, sometimes there's a patient in front of us that we actually find out has a family history. They're at a higher risk. They're not at average risk. It is not appropriate to do an at-home stool test. Maybe they have symptoms where it is not appropriate to do an at-home stool test.

And then, it's very important for patients, and I think of some of my patients who perhaps have more comorbidities or who are at the older end of the spectrum. If we get a positive stool test, you need to do a colonoscopy. And so, I should not be ordering an at-home stool test if there is not that understanding for a patient that if it is positive, this was an initial screener, and they need to follow through to do that diagnostic colonoscopy so that they can see kind of why this was positive.

And so, you really do have to have those discussions and understand both the patient's education level and their ability to follow through on a colon cancer screening test.

Dr. Richard Wender: The only thing I'd add to that is we have pretty good evidence that if the patient, based on a shared decision, chooses their option, they're more likely to do it. So, I give all three options. I give colonoscopy, I give Cologuard, which is the only brand name right now, it won't be for long. But that's the only combined FIT-DNA test at the moment, or a FIT test, fecal immunochemical test. I tell them the advantages and disadvantages. I can do it pretty quickly, let them make the choice, and they're more likely to actually do it.

Love Cori's point about you get a positive stool test, I emphasize before they do it, that means that you've committed to the colonoscopy. And we have a mantra in the colon cancer screening world, and that is the best test is the one that gets done. Modeling shows that if you stick to the recommended schedule, that's a big deal. But if you stick to the recommended schedule, we can prevent the same amount of colorectal cancer deaths no matter which one you pick.

Dr. Corinne Rhodes: And that is key, I think, Amanda. The FIT test is a yearly test, right? And so, for a patient to do a test yearly, it is very infrequent that I have a patient who shows up the same time every single year and I'm handing them a FIT test at that time. And so, to do an effective FIT test program, which is a yearly test program, you really do need to have a population health program within your system or a very specific follow-up system within your clinic or, et cetera, whatever resources you have. But we see many systems, I think Kaiser's the one that most people are aware of, that run very effective FIT programs. Here at Penn we've also stood one up, and has been ongoing now for about four to five years.

Host: That's a great point. I wanted to cover that. So, thank you both for bringing that up. So, the FIT testing, the at-home stool testing, we need to be doing that yearly. The Cologuard testing or the DNA testing, the recommendation, as far as I'm aware, is every three years if they have a negative test result. And then, colonoscopy, the recommendation for follow-up will depend on what, if anything, they find during the colonoscopy, which could range from three to five to seven to 10 years.

But Rich, I totally agree. I often think about screening the way I think about the breastfeeding versus formula-fed is best. As long as they're getting screened, I'm happy. So, thank you both for your insight on that topic.

Why don't we move along to another screening test that we talk a lot about in primary care, which is more recent than colon cancer screening, which is screening for lung cancer with low-dose CAT scans.

So, what's interesting about that also is that guidelines have changed. On a somewhat similar timetable in 2021, the screening for lung cancer was expanded to include a slightly younger age than was first discussed. But perhaps one of you or both could talk about the current screening that's recommended for lung cancer and how that's working in terms of our own clinical practice in getting patients engaged in that screening.

Dr. Richard Wender: We'll divide. I'll do first, kind of how we got to the guidelines. Let Cori talk about how we're doing. We have a lot of work to do on that. That's been slow uptake across the nation. We got there because one of the largest screening trials ever performed in the United States, the National Lung Cancer Screening Trial, showed a 20% decline in mortality with annual low-dose CT screening.

And that, through a not a simple process that I had a chance to be a part of working with, for coverage through Medicare, et cetera, we got it part of guidelines with the USPSTF National Comprehensive Cancer Network, American Cancer Society all came together recommending screening based on the original criteria used in the trial: age 55 to start, 30-pack year smoking history, either still smoking or having quit within 15 years. So, those were the criteria used in the trial. So, that's what got translated into the guidelines, which is very appropriate.

And by looking at real world data and some additional trials from Europe, we're revising those guidelines. And that's a very common process. You start based on the trials, and then you look at what the data tells you. So, we've made changes in two out of those three criteria, and we need to make changes in the third. It hasn't fully happened yet. We've lowered the starting age from 55 to 50. We've lowered the pack years from 30 to 20, but we now have a difference about this issue of this 15 years since quit. The USPSTF has still maintained that 15 years since quit, both to start and to continue screening. And the American Cancer Society in their last update did a beautiful, very simple analysis, and they showed that the 15 years since quit is irrelevant. It should be eliminated. It should not be a criteria to start. It should not be a criteria to continue.

So, I have a little trick, which I'll be—or it's not a trick—just an approach to that which I'll share in a moment. But let Cori talk about that first. Unfortunately, because the task force is kind of interrupted at the moment, we're not sure when they're going to update their guideline. So from a coverage standpoint, since coverage, commercial, health plan coverage is linked to the task force, not to the ACS, we're kind of stuck with this 15 years for now, even though the evidence is pretty clear.

Dr. Corinne Rhodes: And I guess building upon what Rich said, how are we doing with the screening? One thing Rich didn't highlight is that this is a shared decision-making, cancer screening, which creates challenges, for assessing how we're doing at a population health level. It is easy for me to determine if you qualify for colon cancer screening based on age and based on sex. You know, many of the other cancer screenings that we talk about are similar. But it is very challenging to determine if a patient has had a shared decision-making discussion with a provider, and how is that documented and how have they opted in or opted out. And so, because of that, it's really challenging to see how are we doing, you know, at a population health level, for the number of patients who qualify, completing screening. And so, that is a challenge, I think, in and of itself.

Another challenge is to calculate pack years is incredibly challenging. I saw actually a husband and wife today in clinic, and both of them are active smokers. One of them turned 50 this year, and as we sat to calculate their pack years, it took a long time to reflect. "Started smoking in my teens." But when in your teens? How many cigarettes did you smoke? When did you start to be a regular cigarette smoker? When did you smoke a quarter pack, a half pack, three-quarters of a pack? This is a patient who did not smoke a pack a day, had always been less than that, but did meet that 20-pack year history. And you really have to put them within the EHR that I use. You have to put a start date and then a change date for how long did you smoke a half a pack? How long did you smoke three-quarters of a pack? And to put in each of these pieces, it then will calculate total the pack year, and I cannot move forward with ordering that order if it does not meet that criteria to be covered with 20 pack years, quitting within the last 15 years, as well as the age of 50.

So, that is a really big challenge, and absolutely the two of these lead to us under-identifying the number of patients who qualify for lung cancer screening. It required me to see the age of the patient. It did not show up as a care gap because his pack years were actually listed as 7-1/2 before I went in there and updated it. And then, at the end of the visit, it was 27-1/2. So, it's a major challenge to get started. Once you do get started, I think it is much easier to keep on the train as far as monitoring if you're doing it yearly. But I don't think the robust systems that we have in to follow up on a colonoscopy, to recall someone or to follow up on a mammography, as we'll talk about later, exist for lung cancer screening and are really still developing. So, we are, as a whole, under-screening our patients who could qualify for these tests.

Dr. Richard Wender: Yeah, that's a fantastic review of some of the barriers. The only one I would add is just—and you made this point when we were talking about the FIT, any test that we have to keep people up to date on annually is really tough. One of the huge advantages, and I share this with patients, when choosing in colon cancer, you pick colonoscopy and it's normal, you're done for 10 years.

And for busy people, that's a real appeal, that you don't get out of it with lung cancer screening. And the data's pretty compelling, by the way, that this annual interval really does make a difference. We have a pretty narrow window to make a mortality difference with lung cancer screening. It's just the nature of the disease, the nature of looking for very, very small things on the CT scan. It's why chest X-ray doesn't work. So, the annual is important.

Host: Just today in my inbox had a CT scan as a follow-up, a three-month CT scan follow-up after one of my patients had a partial lobectomy for an early stage lung cancer that was found on lung cancer screening. So yeah, she was someone that's been getting them every year for several years now, and it was caught. So, they do really move quickly.

There's something that you brought up, Cori, which is a shared decision-making, and this is going to come up again when we talk briefly about prostate cancer screening. So, maybe we can talk through it a little bit now. I'd love to hear from you what you feel are, like, the most important elements of that conversation with a patient. Like, what are the things that we as physicians really just need to hit in terms of a shared decision-making conversation about any kind of cancer screening?

Dr. Corinne Rhodes: I do think that it's really important to have that conversation, at a health literacy level of my patients. And so, I do personalize these discussions. But we talk about what is the purpose of a cancer screen is to catch something early where we can intervene and improve outcomes. And we talk about both the benefits. And so, in this case, if you catch lung cancer early, I literally talk about the fact that if we catch it early, you can remove a small piece of the lung, and prevent it from becoming bigger or needing larger treatments, if we catch it later.

So, I'll talk about the benefits of that, and then I talk about the downsides. The downsides are we will likely find a lung nodule, right? We will find something, and the first for that first baseline test, and that may cause anxiety. And so, kind of normalizing those results if we're going to find a lung nodule, will we follow that in 12 months, maybe in six months, in three months, based on what we find?

And the anxiety that can cause from that as well as the cascade of testing, which I think is something that we are familiar with as physicians and APPs. But I think to a patient, kind of that understanding that there can be a cascade of steps, and we can do harm within those if you find a nodule and it needs a biopsy and you have a complication within a biopsy and it does not end up to be cancer. I don't always walk through the entire cascade of that. But depending on the type of shared decision-making and the health literacy of different patients and based on kind of their understanding of what are those additional tests and what's the type of harm that can come, sometimes that will be a larger conversation, and sometimes it is a lighter conversation.

And sometimes, we delve a little bit further into that idea of kind of like what are your values. There are some people, and I'll use this in kind of some other cancer screenings more than lung cancer. It's like some people are the kind of people who want to know everything, right? They want to know the tests and they don't mind doing extra tests and the anxieties that it comes with because there's harm in not knowing and not doing everything possible.

And there are other patients that they know by doing those extra layers of tests, it can bring anxiety. And there's also a lot of negatives that can come from that as we talk about breast cancer screening and the supplemental screening. That is something that I definitely see, you know, with people who might choose to do extra screening. And then, after going through extra biopsies and extra testing, they may look back and say, "Man, that was a really challenging cascade of events and I do not wish to continue with that."

And so, I do think that based on the different type of cancer screening, I might go into more depths. I think for lung cancer, this tends to be a little bit of a lighter than prostate cancer or the supplemental screening in breast cancer.

Dr. Richard Wender: It's incredibly complicated. It sounds so simple. Just do shared decision-making. Nothing to it. What could be so difficult? But it's incredibly complicated to implement. We presented a paper just recently on reviewing all the literature, and primary care clinicians don't do a great job with shared decision-making.

They often don't do it at all. This is a B recommendation from the task force, meaning that they've judged that the benefits outweigh the harms. And there's evidence that if high-quality shared decision-making is done in lung cancer, it increases the uptake. It doesn't decrease the uptake because of the risks.

But my own feeling, and this is a policy issue we're still talking about, is that we should eliminate the coverage requirement for shared decision-making, because that's preventing it from being a quality measure. Getting to Cori's very first point, we don't quite know how we're doing with this. Different from prostate, which we'll get to later, which is a C recommendation. But I like what Cori said. We know that people who've smoked or who are smoking are pretty darn scared of dying of lung cancer. The majority of them are pretty relieved to know that there's actually something they can do to reduce their likelihood.

I'm going to give you my one little trick, about the 15 years because it's evidence-based. If you ask people when they quit smoking, they will tell you the date where they mainly quit smoking. "I was at a half pack a day, and then I quit." If you ask them a very different question, "When's the last year that you smoked a cigarette?" You'll get a very different answer. And over half of all people who "quit" occasionally smoke use that most recent year as your year since quit. Now, unfortunately, Cori, I tried to document that in the EMR, and that's very difficult. it gets tough to document this occasional cigarette after the predominant quit date. It takes an extra documentation hand. But we are losing millions of people who are eligible for lung cancer screening because of the 15 years. Even as their risk is going higher, we're losing them from being eligible. So, it's worth doing.

Dr. Corinne Rhodes: I agree. I think it's like such a great point, Rich, that I think for lung cancer screening, most people want to. I Not everyone knows that you can. I definitely have patients say, "Oh, you can do that?" But it is rare that a patient does not wish to proceed with lung cancer screening if they qualify. And if they don't qualify, they're often thinking, "Are you sure?" "Do we look at that again?" And I often really take the time to comb through the chart and think how do I accurately reflect, but also make sure that I'm not underselling? Because I think sometimes people will undersell how much they smoke. And so, I will probe a little extra to make sure that they qualify if appropriate.

Host: It's interesting. I find that the issue that comes up more so than not in my own practice is that people don't realize that we have treatment for lung cancer. And so, that's where the shared decision-making can make such a big difference because I'll ask, "What are your thoughts on screening for lung cancer? This is something that we can do. Here's why." And many times I've gotten the response, "Well, I don't want to know that because I'm just going to die." And I just have to say, "Well, actually, let's go into this a little bit more because we do have some treatment and there is a lot that we can be doing. And this is why we call it screening." And that I think is often a misunderstood piece, you know, the difference between screening when you don't necessarily have any symptoms and a diagnostic test where you already come in and you're having chest pain or coughing up blood, et cetera.

One thing that I notice about these guidelines for lung cancer specifically, which seems like is going to become a larger issue over time, which is that there's nothing about vaping or when people are smoking things that aren't technically cigarettes. And so, I know you don't have a crystal ball, Rich, but you think that this screening will be modified in some way to start to capture those populations?

Dr. Richard Wender: There's a lot of interest in expanding the eligibility for lung cancer screening. We are seeing a rise in the rate, incidence of lung cancer in non-smokers, particularly in women and who are younger. It still doesn't look cost-effective to start screening then, but we are seeing this rise. And if we can get the balance of risks and benefits to be better and better by lowering the risk of working up nodules, maybe we can reach the point where we could do universal screening.

Whether vaping itself will turn out to be enough of a factor to tilt it, I'm very skeptical about that. Most young people don't become lifelong vapers if they start in kids, and the overwhelming evidence that's published just in JAMA this week, New England Journal, Cochrane Review, is that we should be using e-cigarettes in adult smokers to help them quit. So, I don't think vaping is going to turn out to be the big factor, but I think there's a broad interest in looking at asbestos, occupational exposure, and maybe someday we can reach the point where it would be safe to screen everybody.

Host: Well, so why don't we move on to another kind of cancer screening, which is very well-known. And luckily, I think we have a decent uptake amongst patients, which is breast cancer screening. And mammograms have become quite easily accessed in many populations, including those that may not have easy access to a large health system like we have in Philadelphia.

We have mammography vans, for example. And I think most women are aware that they can get breast cancer screening. But maybe we can talk a little bit about the fact that there are some differences in terms of what is recommended for appropriate breast cancer screening amongst some of these large organizations like the American Cancer Society and the USPSTF. And that can be very confusing for women, what age they're supposed to start at, how often they're supposed to have mammograms, every one year, every two year. So, maybe one of you can help us parse that.

Dr. Richard Wender: It's been an area of frustration that we can't get perfectly aligned on our breast cancer guideline. And it is producing that sense of doubt or we don't quite know what we're doing and also some differences among even people working at Penn Medicine, the same system, having differences in our approach.

We actually pulled together a group about six years ago of all these guideline groups, said, "We're going to come together." It was pulled together by the American College of Obstetricians and Gynecologists, and I went into this meeting saying, "It's not going to work." And guess what? It didn't work. We couldn't agree.

Andin part, it's the task force is very committed to working independently, so they won't really adjust to match others. But here's where we're landed. Maybe that's a better way to do it. Pretty strong agreement, not absolutely perfect, to start screening at 40 in average-risk women. And Cori will comment, I think, a little bit later, because she's had a lot of interest in looking at individual risk.

But let's just take an average risk across the whole population. The American Cancer Society still says shared decisions, 40 to 44, screen by 45. It would not surprise me since breast cancer is also moving a little younger. If they come back to where they used to be, which was let's just start at 40, it sure would simplify things. Then, all the major guideline groups would be 40. So, let's go with 40.

The issue of interval remains a bit difficult. The USPSTF still says every other year in all women starting at 40. College of Radiology, NCCN said every year, all women—doesn't matter what else. And the American Cancer Society has this nuance, say every year till menopause, 55 to 60, and then every one to two. And if you look at why there's debate, there is no question, and the task force acknowledges this, that if you screen annually in premenopausal women, you are more likely to find cancers with less concerning characteristics. Little smaller, little more likely to have node negative. They just weren't convinced that it translates to lower mortality. The other groups looked at those characteristics, say, "That's good enough for me." That makes the case for annual. And I would tend to agree with what the ACS and task force say. If you look at the benefit, particularly in women over 60, very hard to find benefit of any annual versus every other year in that older age group.

So, I think the real debate is in this younger group. And in the majority, there's a couple factors that tilt me definitely towards stick with annual. If that first breast mammogram, I think this is an advantage of starting at 40, shows very dense, heterogeneously dense breasts, I stay annual. Family history stay annual. There may be some other factors as well relate to risk where I keep that annual approach.

Dr. Corinne Rhodes: I'll add that just as we highlighted with the FIT test and with lung cancer screening, it's hard to do things annually. I think that most women who aim to do a mammogram annually often drift. And so if we aim to do it every two years, I think that women will then drift beyond that two-year interval, at times.

And so when I speak with women about doing every one to two years, I will say the maximum time that you can go is two years, right? If you're going to aim for two years instead of one year, if you are postmenopausal and that's what goals are at that time, I really do try to anchor it to an event. So you are July, right? You get your mammograms in July, which means you need to call by Memorial Day, right? And I try to think about things and how do you put it in your calendar, et cetera, Because we do ask a lot of our patients to manage, you know, all of these programs if we don't have systems behind them to nudge people towards these.

And I think something that Rich highlighted, I do love to think about the personalization of cancer screening. Again, I think the majority of our discussion today is for average-risk women, but I don't want to wait until someone is 40 to realize, "Oh, there was a breast cancer history in your family, and I should have started you at 35." So, we do need to make sure that we do some sort of risk assessment when women are younger to make sure that we start at the appropriate time.

And I agree with Rich, the density really does needs to be incorporated, and I don't have that density until that first screening. Once I do have that density, I think there's a lot of messaging that women are getting from many different places, and there's a lot of differences. For example, in Pennsylvania, a woman with extremely dense breast, insurance needs to cover. That doesn't mean 100%, but there might be co-insurance, co-pays, breast MRI. That may not be true in a different state.

Within our region in Philadelphia, we have a system that really leans towards ultrasounds as supplemental screening for dense breasts. And on the other hand, we have another institution that is focusing on MRIs. And this is developing literature, but women will get the message, "You have dense breast. You should do additional screening," not even knowing that density means different things. Extremely dense is not the same as scattered density. There's kind of this layered approach to breast cancer screening. But making sure that we are at minimum getting a mammogram within these intervals, I think is key. And sometimes women will go on these, I'll call it a side quest, of these additional screening, and they won't do the mammogram. They'll be looking at those as their primary approaches. And I think it's really important to say that the mammogram is the backbone, and you may layer on top of it, but you have to do the backbone first.

Host: I've definitely found myself getting in the weeds a little bit with the different levels of density and then how do you then take it a step further with a patient, because then are we bringing in things like the Gail Risk scoring. And then, we're very lucky here at Penn to have the breast center, but not everyone has access to that next level of care.

So, I will say my own personal practice is just to talk about mammograms being every year, to your point, Cori, that I may not see that person every single year at the same time, but then I am pretty confident that at least they're getting it in within that two-year timeframe. And clearly, health literacy has nothing to do with it because of course I tried to schedule my mammogram and they weren't able to be scheduled for three months. So now, I'm off. And so, there you go, right? It's just how the health system works and how busy we get, and it just happens to all of us.

Dr. Corinne Rhodes: Absolutely. But I think health literacy is important. If you have a radiology letter that tells you to come back in a year, but your provider said to come back in two years, the difference in the messaging is really challenging. You mentioned a Gail risk score. That's something that I do for women as they enter. We actually have it within our EHR now. It takes, I think, like not seven clicks, that might be an exaggeration, but at least four, if not five clicks, to get to it. But we need those tools to be at our fingertips to incorporate them to your point.

And then, there's also the layered discussions. It adds a lot. As primary care doctors, we all know there's a lot that happens within a primary care visit, but making sure that we are hitting the minimum, right, of regular breast cancer screening. I personally order that next mammogram when I get the results, just so that same thing for my lung cancer screening. It's just a cue for myself. I order one. And if they do supplemental screening, I order mammogram, MRI, mammogram, MRI. But I think that those are all individual systems that fail. And so, you really need systems behind all of this, whether it's bulk orders or in Pennsylvania, you actually don't need a mammogram to get screened. There are systems that require it. But some of our colleagues work in places where you can go online and schedule it. When you are scheduled, you can then tell them who the results should be released to. Certainly a woman who does not have a primary care doctor, that can create a risk, right? So if that woman has a positive result and she needs to establish care, how do you make sure that you have a system to also kind of bring them in? So, there's so many layers of logistics, even for the easiest of our cancer screening.

Host: Right. I think you meant referral. You don't necessarily need an insurance referral to get the mammogram. Yeah, it depends a bit on the insurance. But yes, technically speaking, people don't necessarily need to be referred formally. I love that tip about as soon as you get the result, you're putting in the order for the next one. That's really smart. I'm stealing that. What were you going to say, Rich?

Dr. Richard Wender: Oh, just that I was going to make sure to give an order. And I'm going to give a little technology advertisement for the future. At Penn, we are leaders in testing rapid MRI, really accurate, easier to do, affordable—surprisingly affordable, just not widely available. And what insurance is covering is the full MRI, not the rapid. But coming down the road will be rapid.

And the other great way to evaluate dense breasts is contrast mammography, which is very quick, can be done at the same time, very low-dose contrast, and amazing. Out of the middle of this very dense area, you can pick out cancers even if you're not a mammographer. So again, that's probably 10 years, 15 years before it becomes widely available, but exciting technologies that are going to help us.

Host: That's really great to know. So, well, since we're talking about body parts that we see in women, why don't we continue on with cervical cancer screening? I think we're just making our way—well, we started with colon, we went up to the lung, now we're making our way back down to the body, the bottom half.

What's really amazing for me about cervical cancer screening is that it's changed so much even within my lifetime as a physician, which is not insignificant now. I mean, I've been in practice for just over 20 years since residency. But in that time, I remember in the early 2000s, we were just starting to talk about the HPV vaccine. And then since then now, we have what's called co-testing, where we do the swab to look for cells, but then we're also looking for human papillomavirus in the test itself, which can then help us risk stratify.

So, maybe we can talk a little bit about what the current recommendations are, and then I'd love to talk a little bit about the patient-collected Pap techniques that I'm hopeful are going to continue to bring cervical cancer rates down.

Dr. Richard Wender: I just had the chance to review cervical cancer screening guidelines around the world. I looked at almost every high-resource nation. Here in the United States, we are an absolute outlier. We are the only country starting screening at 21. Every other country starts at 25 and a few at 30.

We have it backwards in the United States. We're starting really young to pick up a tiny number of cases, and then we're ending screening a bit too early. Twenty-five percent of all cervical cancer deaths occur in women beyond the usual screening age because they finished, "got to the screening age," but they were not actually up to date. In Australia now, they're screening up to 75. So, I do think we have it backwards. Having said that, I think everyone knows it's 21, every three years Pap alone. And then, at 30, switching the preferred test of co-testing. But that is on its way out. The American Cancer Society's primary guideline now says a primary HPV alone starting at 25 every five years. No Pap 21 to 29. Very similar to what the rest of the world is now recommending. You don't see any Paps around the world anymore.

And the USPSTF had also drafted a guideline that made a stronger statement. They still had the Pap smear 21 to 29. They didn't eliminate that. But they did have a stronger statement that HPV alone was the every five was the preferred for strategy 30 and over. But because of the dismantling or partial dismantling of the task force, it never got final approval.

But honestly, that's where the world is going. That's where the rest of the world already is. that's where we will be, is HPV alone every five years. I'd like to see us get to the age where we start screening a little later and finish screening, also at an older age later. We're not quite there yet in the guidelines.

Host: Right. Because right now, it says 65. When I look at the care gaps, it says—and that's a very good point also that it's not just, "Oh, you've crossed the finish line, you're now 65." It's are you actually up to date with cervical cancer screening up until age 65.

Dr. Richard Wender: I just had a patient who was beyond the screening age, well beyond, but I looked back and realized that they'd had an ASCUS. They had not had a perfectly normal Pap, and interestingly had an abnormal—I won't go into the details—but had an abnormal finding requiring colposcopy at an age where, honestly, I'm not patting myself on the back, I'm just relieved that I did it. But I know that in many primary care settings or if she'd not had a primary care doc, that would have not been found.

Dr. Corinne Rhodes: Amanda, I'm going to pick up something that you talked about, which is self-collect versus clinician collect, because I think that's an important point. And I think that we're in a logistics time as far as, like, implementation. To Rich's point, it is very easy to do co-testing right now, because it is intended to run both the HPV as well as to do the cytology. But if you're doing an HPV primary strategy a clinician collect can be reflexed to cytology if the HPV is positive. So, it's the opposite of kind of the old cytology to reflex HPV. We're now going the reverse.

But if it is a patient-collected patient-collected sample, you do not do that reflex. The patient comes back for another collection. And that's the reason because if a patient is collecting, it's considered a vaginal source as opposed to a clinician collect, where again, if you're doing a speculum exam, it is kind of anticipated that you are going to be doing a cervical sampling.

And so, I think that's important to know, and I think it's the reason why we have not yet seen the uptake of patient collection is probably how does the lab deal with these different tests, and how do we differentiate these different tests from each other? How do we make sure that a patient collection versus a clinician collection is not usually something—I used to have to label for my samples and now we do, and how do we run these samples through the system appropriately?

I think there's also a piece of excitement, right? As far as a home collect, it could really extend the screening rates for many women. And we're not quite there yet, but I'm very excited about that piece. But even the primary HPV, the size of the brush that I use in my practice, I use kind of the broom, which is a little bit wider if I am doing a HPV and cytology collection. I personally care for a number of patients who are complex Med-Peds transfers into internal medicine. Some of them have contractures. Some of them have never been sexually active. They have various reasons why that may be a more challenging collection. And using a CytoBrush for an HPV primary collection really kind of opens up for some women who previously had to go under general anesthesia to get to some of these. These are edge cases. But think it's really exciting to be at the precipice. And this has been something that I have been asking the experts within our institution, on the regular, "Are we ready for this yet? Is it time to deploy it yet?" But we have not yet made that huge transition where I practice.

I assume that there are other places in the nation where they've been a little bit forward. ACOG came out more strongly for the preference of primary HPV screening, Rich. So, I do think that maybe in some gynecologists opposed to I'm an internist looking at, USPSTF is where we often look. And so, I'm really interested to see how this will change over the next few years.

Host: I think that could be huge. I mean, for various reasons, I do have several patients that will not engage in an exam for a Pap smear, and it is really exciting to have some other way to do that screening for both of our sakes, right? I mean, it feels terrible to know that there's something out there that potentially could be prevented if we knew it was there, and patient's sharing that.

Dr. Richard Wender: It's such an exciting moment, because think of all the primary care offices out there that say, "Well, we don't do Paps. You have to go to your gynecologist for that." All they have to learn now is how to supervise the collection of a self-sample, label it correctly, like Cori said, and get it off. But every primary care office should be able to screen for cervical cancer going forward.

Host: So, one last cancer screening test that I'd like to just spend a couple minutes on, which is a cancer screening that is not patient collected, and maybe never will be. But right now, it's the PSA, the prostate-specific antigen for prostate cancer screening. And we talked earlier about shared decision-making, which is something that we've known for a long time is the way we should be approaching prostate cancer screening.

But I'm really interested in hearing what your take is on the current landscape of prostate cancer screening. And my perception is that over time, we've kind of wanted to screen people at a later and later age because prostate cancer is often thought of a cancer that is so slow-growing that there isn't really a benefit necessarily to diagnosing it at a much younger age because we don't necessarily see that mortality benefit that we see with other types of cancer screening.

So, I would love to hear some of your thoughts about shared decision-making in prostate cancer screening specifically, and then if there have been any changes in the recommendations that we should know about in primary care.

Dr. Richard Wender: I love talking guidelines, so I'll go first. In a way, the good news about prostate cancer screening, even though there's a sense of controversy, the reality that all the major guideline groups have tessentially the exact same guideline, which is to start PSA screening. A little bit of debate about the age to start. There are some organizations really aggressive in Black men, any man of African descent, which is our entire Black population has some roots with Africa, that some ACS and others recommend starting early, 45. Family history, maybe even at 40.

This is one cancer that does appear to have some genetic component linked to African ancestry. I take care of an expert geneticist who, you know, was telling me about his work in this area that confirms that. It's the largest disparity between Black and white men is in prostate cancer. It's also the largest disparity in the wrong direction in screening level. Black men should have higher screening rates, and they have lower screening rates, so we need to do a better job there. But then, to start screening whatever the age you start. There is some debate about how often to repeat it. If somebody has a low initial PSA, under 1.6, you don't need an annual test. Some are now saying that every four years if the initial one is very low is fine.

The one thing I would reverse a little bit of what you said, and that is because the mortality occurs at older age, average age of death for those who die is 79, that therefore we should screen more older and less younger. It's actually the reverse. This disease takes a long time to become potentially fatal to threaten your life. And I actually think the priority is finding prostate cancer in these younger men who are going to live long enough to die from prostate cancer. So, it is true the rates are much higher in older men, but the benefit of finding an early prostate cancer in a 75-year-old man is probably zero. Very unlikely to live healthy and long enough to benefit from the screening. So even though the rates are lower, I think we really need to think, "Let's catch those prostate cancers in younger men"

Host: That makes a lot of sense.

Dr. Corinne Rhodes: Thinking about kind of your question about shared decision-making, I think this is the one where I do talk about the cascade of testing, right? Because it's so easy to order a blood test, right? This is one where if you just say, "Oh, do you want me to check your PSA?" And you kind of like throw it on there, and then we get the results, and then you're having a discussion of cascade of testing after you have an abnormal test, or a borderline, you know, like abnormal test. That's really challenging. And so, I do like to talk through that cascade of testing, and I think it's particularly around some of the morbidity that can happen with some of the surgeries, et cetera, where it can be challenging for some men.

And so, I want to make sure that if we're going to test that this is someone who would then follow through on that MRI to kind of then understand, and so they can go to the urologist and have a discussion and know that this is perfectly acceptable to monitor, right? And so, the fact that you can find a test—not every patient who sees a urologist will get that opportunity to monitor, but many men will. And so, knowing before you go there and kind of knowing in your head about some men who get this, this is a slow-growing cancer, and it may not affect me during my lifetime, and it would be okay to monitor over time as opposed to rushing into a decision where surgery is one of the options that are on the table.

I think that is really important to then have a bit of a discussion in the beginning for me and for the patients who I care for. And again, around those health literacy levels, I think it's really challenging, that idea of many men die with prostate cancer, not of prostate cancer I remember as being kind of a line that was taught to me when I would go about this. I found that does not land well with many of the patients who I care for, and would often get like blank stares of, "What do you mean? I don't understand." And so, I do think that this is worth having discussions, but I think it wonderful that we have, the ability to do additional testing like an MRI before you can go forward to a biopsy. Again, reflecting, Amanda, about during the time that I've practiced as a provider, that didn't always used to be the case. Now, there's a very clear pathway before men make that decision about a biopsy and then continue to cascade.

Dr. Richard Wender: Amanda, you know me, I love to predict the future, so I'm going to put myself out there. There's a couple really cool new blood tests coming out. One called Stockholm3. Guess where it was developed? Yes, it was developed in Stockholm. That is significantly outperforming PSA head-to-head. So, I think we may get some new options. And because active surveillance instead of immediate prostatectomy or radiation is becoming more common for the lower Gleason score tumors, I wouldn't be shocked if the new American Cancer Society guideline, which is the next one we're going to see, it's going to be pretty soon diminishes the importance and need. I'm not sure they'll fully eliminate it for shared decision-making, where they say that, as long as you manage this, just like Cori was saying, based on the data we have today, in good hands, it's safe to screen every man and let them make those cascaded decisions down the road. All of those decisions tied up into whether to have that blood test up front. So, we'll see, but I don't think it's impossible that we'll see a pretty major change there.

Dr. Corinne Rhodes: I think that's such a lovely, like, reflection, Rich, of saying you don't have to make all the decisions up front. Like, these decisions can be made as you move forward, but making the space, right, to have those discussions and making sure that men are able to understand fully and engage in those decisions.

Host: Yeah, I mean, I think having the fact that there is more nuance there makes a tremendous difference. I think the flip side of that brings me to my final topic that I wanted to talk about, which are these multi-cancer early detection blood tests, which provide a lot of information on which there is quite a lot of nuance that is not necessarily explained in the findings that people may get when they do these tests.

So, people are often left in this very uncomfortable limbo without any guidance as to what it means if they have a genetic tendency towards X kind of cancer or some other result. And I think about this even in some of the staging, and I honestly don't know the most up-to-date aspect of this where there's a stage zero cancer, right? Where someone is kind of unclear is this cancer, is this not cancer, I think some of that changed to make it a little bit more clear for patients. But what are your thoughts on some of these blood tests that are giving patients cancer risk information? And have you had to have any of those conversations with patients about that data that they show up with or that they ask about getting?

Dr. Richard Wender: The best-known multi-cancer early detection test is made by a company called Grail. It's called the Galleri test. Those are brand names, G-A-L-L-E-R-I. Abbott has another test called CancerSEEK, and there will be others coming down the road. But the one that is most easily orderable right now is the Galleri test through Grail.

And I just looked at all the recent data and actually within the week from PATHFINDER2, which is their largest study. Hard to get your head around. They are screening tests. They're not risk tests. They are looking for cancer. They are intended as screening tests. They work exactly the reverse of the typical screening tests we use. They have very high specificity, but relatively low sensitivity. We tend to favor high sensitivity over low specificity. So, as a result, if you get a positive signal on a Grail test, you have about a 40% to 50% chance that you have a cancer. before you get this test done, you got to understand that if it's positive, you are committing to going through the testing that they recommend, because your risk of having a cancer is actually quite high.

Their bigger risk is just missing cancer, particularly early cancers. They're great on stage III and IV, or quite good. They're not great on stage I and II. Maybe 50% to 60% sensitivity, not awful. But not all of those cancers are ones that we know we can treat. So, they are very much in progress. I think they need more study, more investigation. There's a lot of interest in whether they might have a role in the patient who we're a little worried about. They have some suggestive symptoms, which means that if it were due to cancer, it would probably be on an advanced stage because otherwise it wouldn't have symptoms.

And instead of doing total body CTs and PET CTs, maybe we could do a multi-cancerdetection test. The Grail test is 91% accurate for telling you what organ the cancer started in. So, it's amazing technology. The big question is whether it's going to find curable early cancers. That's the big question. It's out-of-pocket, $900 test. And then, for the most part, the insurance will cover the follow-up testing as long as you have good insurance. That's definitely a test that you should not have unless you've had a really full discussion and you understand what this test is all about.

Dr. Corinne Rhodes: Amanda, I have had patients ask about this. I am not as educated as Rich about rattling off the benefits and the risks of these different tests. And so, I have not ordered them yet. Initially, I can remember looking for them as an orderable test. It was not immediately available in our EHR. I think it is, some of them may be now.

But I think there's kind of two different buckets. There's a patient who does not wish to get a colonoscopy, does not wish to do a stool test, but is willing to do a blood test. And I do worry about the reassurance that a test like this will provide. And blood tests are easier to get. Patients are often going for other things. So, this is kind of very easy to add on. And so, thinking about getting yearly blood work as opposed to scheduling that lung CTs, and that mammogram, and doing your colonoscopy, I think, that is where my worry is that, like, what is the intention to use these? I do think that there is a type of patient that will not engage in those, but if there was a positive test for this similar to an at-home stool test, might be willing to go through additional cascades. But I don't think that's the intent of these tests.

And then, there's another type of patient who is up to date, right? They're up to date, and they've heard about this and kind of like, "Oh, should I do this?" And I've gotten questions like throughout my career of, "Oh, that full body CT or that full body MRI." And so, I think it's interesting to know. And what I often tell my patients, I think similar to some of my patients get these like large panels of, lab work from like a homeopathic doctor. Often what I'll say is, "I'm a Western-trained doctor. And I order tests that I know how to interpret. And if I don't know how to interpret a test, sometimes I do pause and think about like, "How do I have to educate myself before I order these tests and move forward?"

And there's that piece of like genetic risk, Rich. Like, there are maybe some genetic tests that I will order as opposed to send to a geneticist. And so, where does this fit? I think it's an edge and I think it's going to rapidly evolve and we're all going to have to incorporate into our practice within the next few years, I presume.

Dr. Richard Wender: We overlooked one aspect when we're talking about colorectal that's important to differentiate here, that multi-cancer early detection test that GRAIL puts out is not intended to replace existing recommended screens. But the new American Cancer Society guideline for colorectal for the first time added second-line tests for people who will not do a colonoscopy, won't do Cologuard, won't do FIT. And when I say won't, meaning we recommended them, we gave them a year, we gave them two years, they just won't do them. But like Cori said, they will agree to have Shield, one of the new blood tests, or Freenome just got FDA approval. And if positive, then would agree to have colonoscopy and either have Medicare, because that covers these tests, or can afford $895 because that's what they cost.

So, they are not first-line. Everything Cori and I said about colorectal still stands. But we do have these blood tests for the patients who've proven to us that they just are not going to do any of these other tests, and they would be willing to do the blood.

Host: I think that's a great point, Rich. Yeah, I mean, there is maybe a potential for them to be complementary, but not in lieu of the other cancer screening guidelines that have good evidence behind them.

And maybe just really quickly for those in the audience that not be so much into the research and statistics. So when we're saying specificity, we're saying that if the test is positive, there is a good chance that is a true positive. And if the test has a high sensitivity, then if it is a negative result, that you want to trust that negative result, which is the problem with these tests when maybe you can trust the positive more than you can test the negative result, and that can give you a very false sense of security.

Dr. Richard Wender: Yeah. Although again, the positives have a pretty amazing specificity, and if they're positive, you do need to follow them up. This is not the colorectal second-line test. This is specifically the multi-cancer test.

Host: That's very helpful information. One last thing that I want to touch upon. And Cori, I know this is a lot of what you do. And, Rich, obviously you can speak to this, but we know and mentioned several times already this idea of health disparities, right? People have access to different levels of care, different kinds of care, even in a very urban city as Philadelphia is. Even when our patients are connected to tertiary care hospitals, we still struggle with health disparities across cancer screening.

So if you are speaking to folks in primary care, whether they're physicians or nurses or PAs or nurse practitioners, if we want to be mindful about health disparities, are there certain steps that we can take as individuals with our patients to try and get people connected to the care that is available? Are there things that we should be mindful of or that we can educate ourselves on to try and maybe not eliminate the health disparities, but on a one-to-one level, address them?

Dr. Corinne Rhodes: That's a great question and one I struggle with in my job all the time, as Rich knows. We have existing disparities, in our health system, and those are mirrored across the nation. And we can look at those from like a payer perspective, patients with Medicaid- Medicare versus commercially insured patients versus Medicaid. You can also look at that. You can cut that data in many different ways. You can look at it with a racial lens. You can look at it at where do you get your care? Are you getting your care with more continuity? Are you getting in a training site? For us, that's been something that's been replicated across the nation.

There's many different ways, right, that you can find disparities in the care that our patients get, and that is true in chronic disease as well as cancer screening. I also think about language, right? So, one of the clinics that we have a real challenge with within our health system is primarily Spanish-speaking. And it's also about, like, do the patients have insurance? Do they have access to screening? And where are the modalities that they can get screened and also add an extra layer of do they feel safe seeking care?

I think that it is really important for us to think about, each patient who comes in front of us. I think as a individual clinician, if a patient has not followed through on a mammogram order that I put next year, I do not just order another mammogram and say, "Hey, do it." It is worthwhile to do some motivational interviewing, right? There's a myriad of reasons why patients may not do it.

Sometimes it's the fear because "My mom had breast cancer." Sometimes it is the logistics of childcare or the logistics of the hours that it's open, and sometimes these are things that we can solve. sometimes it's an escort within a colonoscopy, that is needed. You can't do an at-home stool test, but you need a colonoscopy and I can't afford the prep. Sometimes there are things that we can help solve, and a lot of those do have to do with health-related social determinants of health. And some of them we can solve, some of them we can't, right? Some of them are more challenging.

I do think we need to ask and probe to find out one by one. I think it's been challenging to solve at a system level, but there have to be additional layers for patients who have challenges. As I send out a portal message to patients, there is a greater uptake in patients who have more means, who are active on a portal, who have higher literacy, who are able to go and schedule a mammogram. It takes seven days to get a mammogram in some of our suburban sites, and closer to six weeks in some of our urban sites. And so, you referenced that beforehand. At one point, it was a three-month wait. We have been doing work as a system to reduce those waits and reduce some of those barriers to remove friction.

If you have to call for a mammogram, and you have to get at first you get a call center, and then it goes to a nurse who pens it to a doctor who signs it, and then it has to get back to you, and then you schedule again. Those are all levels of friction that we need to remove for a patient who has competing priorities within their life.

So how do you bundle care? How do you say, " Let's do your lab work and let's walk in to get a mammogram today"? Do you know that you could walk in before you leave? And so, I do think it takes a lot of extra effort, and you have to know the resources that you can use. There might be a case manager or a care manager. There might be additional reminders that we can set. But much of the work that we do at a system level can expand those disparities. And so, it's a lot of work, and I don't know what the special sauce is, but I think it is very valuable work that we need to keep doing.

Dr. Richard Wender: And Mandy, the only thing I would add, I mean, that was a great discussion. If you look specifically at Black-white disparity, and I like what Cori said, there are many ways to look at disparity. Relatively close on screening rates, very far apart on mortality with Blacks having much higher mortality. So, there's lots that happens after the screening event that is contributing to that disparity. So, this takes a family, takes a village, takes all of us. This is the disparities which we ultimately care about are the mortality disparities, and there are many factors. Screening rates are part of it, but there's a lot that happens downstream that is contributing.

Host: Absolutely. Thank you both for those points. And I think, when primary care works well, when we're able to see patients over the longer term, when we get to know them and their families, and we're doing what we always wanted to do as primary care physicians, that plays into these kinds of decisions that patients make because they know that we know them, they can express their concerns.

We have a better handle on what those challenges may be to getting them to screening and/or to getting them to treatment. But even that becomes that much harder when we, for various reasons, don't have the opportunity to develop those longer term relationships, which can be frustrating on both sides.

Dr. Corinne Rhodes: And then, Amanda, patients have to come, right? Those discussions still are happening in person, right? And so if you are on Medicaid and you are on and off of insurance over time, that creates gaps, and you might be missing those opportunities for regular screening that we just highlighted kind of throughout this conversation.

And so, there's so many layers, right, to this discussion. And think it takes a lot of both policy work as well as system work. And I think it's not just within a system, but kind of within a larger community to make sure that we can address, a number of these needs

Host: Absolutely right. Our goal is the same whether we're the physician or the patient, right? The goal is to be as healthy as possible. It's just all the things that intervene to making that such a complicated proposition. So, those were all the questions I had. I'm happy to end our podcast here, and I want to thank you both so much for your time and your insight and your expertise.

Dr. Corinne Rhodes: Thank you so much for having us.

Dr. Richard Wender: Thank you, Amanda.