Dr. Kendal Williams (Host): Welcome everyone to the Penn Primary Care Podcast. I'm your host, Dr. Kendal Williams. So, colon cancer is the fourth most common cancer in the world and the fourth most common cancer in the United States. It is a cancer that we frequently see in primary care, and we spend a lot of time talking with patients about prevention and screening.

And it's somewhat surprising that we've done this many episodes of the Penn Primary Care Podcast without actually addressing one of the most common things we see in primary care, and that's colon cancer. In order to remedy that, I've invited two experts on. Dr. Bryson Katona has been on before. Dr. Katona is a gastroenterologist, but he is also one of the national leaders in cancer genetics as it relates to GI cancer and runs the program here at Penn. Bryson, thanks for coming back.

Dr. Bryson Katona: Thanks so much, Kendal. Really looking forward to the discussion today.

Host: Dr. Ryan Massa is Assistant Professor here at Penn in the Division of Hematology Oncology, focusing on GI malignancies. Dr. Massa's involved in a wide range of projects across Penn, innovating in cancer care, including working on developing a program for younger patients with colon cancer, something we're about to talk about in some detail. And Ryan's going to help us take us through the oncological aspects of this problem. Ryan, thanks for coming.

Dr. Ryan Massa: Thanks very much for having me.

Host: Yeah, I suppose it's all an oncological problem. It just has to do with whether or not we're trying to prevent it, screen for it, or treat it once it's there. So, let's start with some the changing map, if you will, of colon cancer.

I mean, it's always been a common cancer. And it's one we screen for quite aggressively, frankly. I mean, we do an invasive procedure every five to 10 years in as many patients as are willing to submit themselves to do it so that we can prevent this disease from harming more people.

In that, we have been successful. We are lowering the rates of colon cancer mortality in this country. But in general, we are not seeing a change in the incidence of colon cancer. It is lower now in older folks, 65 and older, but we've also seen this fairly dramatic increase in the younger patients under 45 or under 50, which has led to a change in the recommendations.

So, I'm going to start with Bryson. Bryson, you, obviously as a gastroenterologist, are very involved in the prevention and screening of patients. How has the changing epidemiology changed your practice?

Dr. Bryson Katona: One of the biggest ways is really addressing this increase in younger onset colorectal cancer that we're seeing. I can remember, even when I was training, when we would see younger individuals in their 20s or 30s with some lower GI symptoms, maybe some occasional blood in the stool, at that time, a lot of times we were just pursuing a symptom-based workup to start.

But I think, given this change in this increase in early onset colorectal cancer that we're seeing, you know, I think most of our thresholds now to move to some sort of at least an invasive procedure like a colonoscopy is pretty low now. And so, I think that that probably is the biggest change that I've seen not just in my own GI practice, but I think across my colleagues as well.

Host: In addition to the starting screening at 45, this is a point I wanted to ask you about, and that is how early should we actually be worried about this? So, you know, I had a patient, for instance, who's 36, I think, who came in with some bright red blood per rectum, you know, eventually got a colonoscopy and found to have rectal cancer.

Years ago, when I was in training, I wouldn't have even considered that as a real—maybe when they were 40, I might have sent them, but not that early. So, you're suggesting that we should really be almost treating these folks who come in with a change in bowel habits or hematochezia a little differently?

Dr. Bryson Katona: Yeah. And I think especially the blood in the stool. I have a very low threshold for recommending a colonoscopy, you know, really regardless of age. Especially the change in epidemiology we're seeing in younger individuals is we're seeing more and more rectal cancer. Rectal cancer really is the predominant increase that we're seeing in these younger people. And so, you know, of course, rectal cancer most commonly will present with red blood in stool, which could be very easily confused with hemorrhoidal bleeding as well.

And so, yeah, I think, a colonoscopy, you know, it's an invasive procedure of course. But i in a younger individual, in their 20s or 30s, it's a pretty low risk intervention that I think is definitely worth pursuing in the setting of any concerning symptoms like that.

Host: How young should I worry about it? Twenty-five plus?

Dr. Bryson Katona: I would honestly say any adult to be honest. And we see a lot of sporadic polyps, can be quite large, even in the 20s or 30s. A lot of the hereditary colon cancer predisposition syndromes or hereditary polyposis syndromes oftentimes can present de novo without any family history. And so, this may be, you know, an early presentation of that. And then, also, there are other types of polyps like juvenile polyps and things that, you know, are typically found in kids, but we're seeing those develop in young adults as well. And so, for those of us that practice adult medicine, really, there's no age that's too young at least to get a baseline in the setting of concerning symptoms.

Dr. Ryan Massa: So, I mean, the patients I see in my GI cancer clinic are obviously a selected population because I'm only seeing those patients who have been diagnosed by Bryson or one of his colleagues with colon or rectal cancer and then referred to me. So, I'm not seeing all those patients who have blood in bowel movements that have a screening colonoscopy who do not have cancer. They don't make it to my clinic, fortunately.

The story that we routinely hear from those patients in their early 30s, late 30s, or even late 20s or early 20s sometimes is symptoms like change in bowel habits or blood in bowels for which they often initially self-diagnosed as hemorrhoidal bleeding and after it persisted, sought care, was referred for colonoscopy, and now they have colon cancer.

And that's a pretty consistent story in these patients, and this is somewhat anecdotal, but these are patients who do not have a family history, did not meet the current guidelines for screening colonoscopy, but developed symptoms and had a low threshold for a diagnostic test to diagnose their disease, which led to, hopefully, treatment. That's a story we see very frequently in the 30-ish-year-old patient population.

Host: Yeah. And I want to emphasize this is a real change. Because when I was in training, if you came in with bright red blood per rectum and you were 50 or older, we sent you for a colonoscopy. If you were 40 or under, we said, "Uh, it's probably a hemorrhoid. Let us know if it continues," that kind of thing.

So, I'm going to be treating these folks more aggressively. I think the change in bowel habits issue, which is a frequent symptom in all humans, right? We have irritable bowel syndrome. People have manifestations of changes in their bowel habits all the time, and particularly in young people. That's going to be a little trickier.

And Bryson, you mentioned it's rectal cancer, which can present with bleeding. Although, you know, I was doing some prep reading for this and that is the most common scenario, rectal cancer presenting with bleeding. But other colon cancers most often present with a change in bowel habits. That's a broad field. So, we're probably going to be doing a lot more scopes on folks earlier in life now that we have this concern.

Dr. Bryson Katona: One thing to think about is that, once you get a baseline scope on somebody, you know, as long as they don't have a genetic predisposition for colon polyp or colon cancer development, which again is a very small percentage of the average population, you can be pretty certain that nothing from a neoplastic standpoint's going to pop up in their colon over the next decade. But at least until you get that baseline look, you're always going to be left guessing or wondering.

Host: We were going to talk more about the genetic aspects later in the podcast, but I want to jump in with that right now because, Bryson, your comments in our pancreatic cancer podcast, over a little over a year ago, I think, really changed my practice in terms of the fact that we can do oncology genetic testing a lot more, a lot simpler or easier than it used to be. It's not expensive. And I've started referring a lot of folks. So, if I get a family history of even a parent with colon or breast cancer and maybe a little bit of another thing that makes me a little concerned, I send them, almost all of them, to oncology genetics. And I think that probably can help us a little bit in strategizing.

We've been talking so far about a patient presents with symptoms, I'm talking about the 35-year-old who comes in and is just there for their new patient appointment. I'm doing a more extensive family history to try and identify those folks that I might need to screen earlier. So at this stage, we need to think about that as well.

Dr. Bryson Katona: Each year that goes by, our capacity for testing patients doing germline genetic testing continues to grow. Indications for germline testing continue to expand. And so, I think each year, it gets simpler and simpler. And so, I think rightly so, most people's thresholds for referring patients for germline testing are certainly decreasing.

And I think that's really important, I agree, in the setting of patient who's asymptomatic maybe has a family history of colorectal cancer and is wondering, you know, what is the right age, whereby they should consider starting screening. Because I know even in that setting, there are some differences in opinion and differences in guidelines about when should you recommend somebody start colon cancer screening earlier, you know, what should you be thinking about first-degree or second-degree relatives, and then what age to start.

Host: How much of the increase that we're seeing in young people is specifically genetic-related? Lynch, familial adenomatous polyposis, or some other genetic syndrome?

Dr. Bryson Katona: Much of the increase that we're seeing in young people is not genetically driven. Consistently, over the last decade or two, genetic causes of colorectal cancer have made up about 5% of all colorectal cancers. We think there's a familial component in maybe about a quarter of colorectal cancers, but true germline genetic things that we can find, like Lynch syndrome, we think represents about 5%.

But I think the rate of finding a genetic cause in younger people is certainly higher than if you're testing older people with colorectal cancer. But that increase that we're seeing in incidence in young people definitely doesn't correlate with more, say, Lynch syndrome gene mutations or anything like that being identified in the population or starting in the population, I should say.

Host: That's just a parenthetical remark. I'm actually going to switch up the outline a little bit and stick with some of the screening stuff, Ryan, if that's okay with you, just because I think it flows a little better from our discussion. Is that all right? So, Bryson, I'm having a discussion with a patient about colon cancer screening, right? In my mind, sensitivity of colonoscopy is nearly 100%. I mean, I've seen in my career colon cancers that were missed on colonoscopy, so I know it's not 100%. But it's nearly 100%. It's the best test. And as you noted, everybody who's probably starting the screening process ideally would start with a colonoscopy because you're getting at least some sense of their risk. Do they have a lot of polyps? Do they have FAP or something like that? But we do have these other options out there, right? And they're getting better.

So, Cologuard is one of them that I increasingly use. I do not personally use FIT testing all that much, only because, you know, it's once a year, you got to keep up with it, and then the sensitivity isn't that great. It's in the 70th percentile. But Cologuard is reported to be about 92% to 94%. And now, we have some other new things out there as well. Can you kind of take us through that? Before we get into colonoscopy, the non-colonoscopy screening options.

Dr. Bryson Katona: Yeah. I mean, certainly that landscape is expanding, and I think it's just important to note a few things is if there's any sign, any inkling of increased risk for somebody, family history, prior polyps, things like that, you know, I mean, really colonoscopy should be the preferred method. But certainly, I think that landscape is improving. Even with all of these options out there, still one out of three people eligible for colon cancer screening is not undergoing screening. And so, I think having that litany of different tests is very helpful for individuals.

I agree with you that FIT is a tough test. I mean, getting someone to do a stool sample every single year is very, very difficult. And so, I think that that's a major downside of doing FIT. Cologuard does work pretty well and has a decent sensitivity for colorectal cancer. It also picks up a fair amount of advanced adenomas. it's not perfect, but it certainly does better than some other methods. And there's a newer stool test out there as well, something called ColoSense through a company called Geneoscopy. It does RNA-based testing in the stool.

The performance characteristics actually are very similar to Cologuard. The one thing that they tout is that you don't have to scrape the stool, so to speak. There's a single collection bucket, and that's all that you need, whereas with Cologuard, it does require some manipulation of the stool, which can be a negative for some patients.

And I think the other one to just mention, just because it's out there on the market and now FDA-approved is the Shield Blood Test. This is a test that looks for circulating cell-free DNA. It's FDA-approved. It was just on the most recent American Cancer Society guidelines. The issue with the Shield test is that it does okay for colorectal cancer, but the performance for advanced adenoma is actually very subpar, less than 20%. You know, it's probably better than not doing any test. But I think if a patient is willing to do a stool-based test, or go for the colonoscopy, I think that would still be the optimal way. But I think for somebody who is completely against doing any of those other mechanisms, if it's something to get them in the door and get them colorectal cancer screening, then I think certainly a viable option moving forward.

Host: I like the Cologuard test. I don't even think the ACP guidelines recommend it yet because there's not the randomized controlled trial evidence. But there is fairly consistent studies, cross-sectional studies showing that the sensitivity is pretty high. and I quote to patients, "Listen, you know, colonoscopy's going to detect 100% or about that, but that Cologuard is 93, 94%." And I also always tell patients, "You know, if you have a positive test, it doesn't mean you have colon cancer. You still only have a 4% risk of having colon cancer," because there's so many things that can cause it to turn positive, specifically related to blood in the stool.

But I had one this week, a patient of mine, an older physician actually, who I convinced to continue screening a little further. This is another question for you. You know, the 75-plus-year-old, I've been actually still doing Cologuard if I think somebody is healthy, because it's not that their risk is going to go down, although it is decreasing in the older population generally, there's still a pretty high risk there. We're talking about four out of every 100 people getting colon cancer. And older people do get it generally more commonly. So, I've been more aggressive. But a lot of folks are begging off of colonoscopies and choosing to do Cologuard, which is fine.

Dr. Bryson Katona: Yeah. And I think for an average risk individual who's between that 75 to 84-year-old kind of timeframe, you know, I do think that that is an okay mechanism because we know certainly colon cancer risk increases with each decade of life, but so do complications from invasive procedures.

Kendal, I also just wanted to circle back, one thing that I think is really important, when talking to patients about these non-invasive screening tests is to really emphasize to patients that if one of these tests comes back, these non-invasive tests comes back positive, that they will be required to undergo a colonoscopy because we see a lot of patients that come in for a colonoscopy because of one of these positive tests and they're very unhappy at the fact that, they feel like they weren't told that they were going to have to get a colonoscopy if it was positive. And so, I think it seems very obvious to us, just because we live in this space every day, but I think some people may not realize kind of the flow of things.

Host: Yeah, that's a very good point. I always make a point to tell people that. Most of them, when the Cologuard is positive, the folks, they're very reticent, they get a colonoscopy, Cologuard's positive, they can't schedule it fast enough. You know? So, it really is also a good thing to help motivate folks.

So, Bryson, I send a patient to you, you see polyps, there is a defined algorithm that is available in terms of how frequently people need to be screened. We don't need to go into that in detail. But obviously, folks with family history or who have had known polyps are every five years. If you have a completely normal colonoscopy, you're every 10. And then, there are variations in between of three years and seven years. We don't have to go into all that detail, but are there any just high-level comments there?

Dr. Bryson Katona: Yeah. So, I would say, you know, there are a lot of things that factor into that interval. And so, I think, really, the gastroenterologist should be taking an active role in establishing that interval. I really feel strongly that if I do a colonoscopy on somebody, if the person's primary care physician ordered that colonoscopy, that it is my job to determine what is the next interval.

And so, I would just say that, you know, if you don't get an interval from the gastroenterologist, it's reasonable to circle back to them because the prep or how a polyp was removed or the size of the polyp, these things can all factor in to when that next one is recommended. And I think that onus really should be on the gastroenterologist.

Host: I guess including if you take out a large polyp, not sure you've gotten it all, want them to come back in a year. I see some of that. You want to see more frequently if you're concerned, right?

Dr. Bryson Katona: Correct. Yeah. Sometimes if polyps are removed piecemeal or if they can't clearly define a margin on a larger polyp that's removed, there are a lot of indications for kind of going by a little bit more of a custom interval, which again, I think really falls on the shoulders of the gastroenterologist to determine.

Host: So, let's say you're doing a colonoscopy. I imagine colon cancers are generally pretty obvious. And that, when you biopsy it, you kind of know. And I say that because I've seen a lot of colonoscopy reports that have said, "This looks like a colon cancer" and we biopsied it. So, take me through how this patient gets to Ryan, right? You biopsy it, comes back colonic adenocarcinoma. What happens then?

Dr. Bryson Katona: So usually, if we find a colon cancer or what we largely suspect would be a colorectal cancer in the endoscopy unit, usually at that point, the GI should be ordering scans. And so, usually, we try to at least get a baseline set of staging scans, get a CT chest, abdomen, pelvis.

And then, usually, at that time, you know, we're usually initially referring to colorectal surgery, which is typically the first stop, unless, of course, you know, we get the CT scans back and there's clearly evidence of metastatic disease. Ryan, I know Ryan will comment on this. But then, I think usually it's after if there's no metastatic disease, it's usually after resection of the primary tumor, staging at that point that then medical oncology gets involved. But I'll defer to Ryan as I know that, depending on tumor location, there are a lot of other possibilities too, especially in the emerging rectal cancer treatment space.

Dr. Ryan Massa: Yeah, I think that's what Bryson said is broadly the ideal algorithm, but there's always some nuance to it based on patient and tumor-specific characteristics. And what you're alluding to there is, what Bryson's alluding to, is colon cancer versus rectal cancer, although there's a lot of overlap in how we treat them in some spaces, particularly in metastatic space.

For localized colon cancer or localized rectal cancer, we actually have very different treatment approaches. And I'm going to focus right now on colon cancer. I will comment on rectal cancer too because I think we need to talk about that also, especially since, as Bryson said earlier, rectal cancer is when the younger population, that's the disease tumor site we're seeing at a higher, rising incidence of in younger people.

So for colon cancer, the typical pathway is going to be a colonoscopy that identifies a colon mass. Often, the gastroenterologist, although the biopsy is pending, is pretty sure what they're seeing is colon cancer and starts that process often that day. Order scans, CT chest and pelvis with contrast, if they can get contrast as baseline imaging. These patients do not need PET/CTs. The only unique circumstances for patients with colon cancer is a PET/CT warranted. In fact, our National Comprehensive Cancer Network guidelines, NCCN guidelines recommend or state outright on the workup slide, PET/CT is not indicated. And I say that because we get that question often, like patients, you know, "Do I need a PET/CT before I see you?" No, you don't. There are certain times we get them. But generally, for colon cancer staging, CT chest and then pelvis after the colonoscopy is the next step.

And for patients with operable colon cancer, who are candidates for surgery, the next step is usually surgery. There are some unique exceptions that I'm certainly happy to talk about, but they really are unique exceptions where we'll do preoperative treatment. For the majority of patients with colon cancer, that's localized without evidence of metastatic disease on scans or candidates for surgery, the next step is surgery.

After surgery, we have the staging. So, the staging tools for colon cancer, the scan is really to look for metastatic disease, but can't really tell us the T stage, the degree of involvement of the primary tumor, or the nodal stage. Sometimes we'll see enlarged lymph nodes, like regional lymph nodes on the scan, and it's never clear if those are pathologic lymph nodes or reactive. And it doesn't really affect our plan if they're regional and around the tumor, because that tumor's coming out by one of our excellent colorectal surgery colleagues soon.

After surgery, we get the pathologic stage. And that's going to tell us whether it's a stage I, II, or III colon cancer, and that's where medical oncology has—that's where we usually come in. Because that's where we can make recommendations about does this patient need adjuvant treatment? What sort of surveillance do they need? What further testing do they need, if any?

So, often the pathway is GI does a colonoscopy, they see colorectal surgery and get surgery. And then, ideally, medical oncology sees them a few weeks after surgery. The timeline that my colorectal surgery colleagues know I like to see these patients at is usually about three or four weeks after surgery, because that's the point where we usually have the surgical pathology back and I can make recommendations about what to do. And it's also at the point where we're not pressed up against a timeline. Because for patients with colon cancer, who have an indication for postoperative treatment, which is treatment intended to reduce the risk of recurrence, there is a window of opportunity to get that treatment started.

We aim for, I'd say in a perfect world and the patient's recovered well, six to eight weeks after surgery to start chemotherapy. There is somewhat ambiguous data, but that does suggest that the further out you get from surgery, the less benefit. There is not a firm cutoff at which you say, "Okay, there's no benefit," that data doesn't exist. But I will say that once we're past like three months, I start to question the benefit. Once we're past four months, I probably wouldn't do it in most cases. There are obviously exceptions. But once you reach that three-month mark, i you start to think hard about should we still do adjuvant therapy? Not to say it's a cutoff, it's not. But you can imagine, once we're three, four, five months out, it becomes less and less sensible to do chemotherapy because there is data that there's decreased benefit but the same toxicity profile.

The other piece of that timing conversation is because why is this patient not fit for chemotherapy three or four months after surgery? Usually, there's a good reason why, which may have implications whether they should get chemotherapy in the first place. So, prolonged surgical recovery, comorbidities, things like that. And I can talk more about how we think about by stage, I don't want to deviate from what Bryson was talking about too much right now.

Host: Before talking about colon cancer treatment, it's helpful just to review the stages of colon cancer. So, there are four stages starting with stage 0, which is really just it's confined to the polyp itself, and that can be actually treated just by removing the polyp. Stage I is where it is involving the inner lining of the mucosa, but not invading the muscle wall for both of those circumstances, resection is curative in the great majority of patients.

Stage II can be a little bit more confusing, because the cancer's moved through the inner layers into the muscle layers, but the lymph nodes are fine. In most cases, the prognosis is also quite good with these, and, you know, resection can be curative.

Stage III is when the cancer has spread to regional lymph nodes, but not distantly, so it's not metastatic. And here again, the prognosis for five-year survival is pretty good. It's over 50%. But obviously, it's less than previous. And this is also where we start to talk about chemotherapy and other options. And then, stage IV is just basically metastatic disease, and the prognosis depends on where it is metastatic to and whether those metastases can be resected. And so, I wanted to review all that before we get in deep on the discussion of treatments because a lot of the treatments do depend on the stage.

I just want to go back to the resection part. So because you're making a decision based on the CTs that it's metastatic or non-metastatic, so you're resecting most of them that are not metastatic, right? Now, because the colon mass could grow and block off the colon, right? So, even in metastatic disease, you have to think about whether or not a resection might be valuable just to avoid a colonic obstruction.

Dr. Ryan Massa: Yeah. So, that's one that comes up, unfortunately, not infrequently. Patient gets a colonoscopy by Bryson or one of our GI colleagues. And then, we get scans, and the scans unfortunately show metastatic disease. And I will say that there are a subset of patients with stage IV colon cancer who have isolated metastatic disease, like one or two liver lesions or lung lesions, who are a candidate for aggressive chemotherapy and surgery, including surgery for the metastatic disease. That's a subset of patients with stage IV disease. But most patients with stage IV colon cancer are going to primarily be treated with palliative systemic treatment chemotherapy.

For patients who have the primary in place and have metastatic disease, we usually start with chemotherapy. We use immunotherapy in some circumstances I'll talk about too for a subset of patients that have a biomarker called mismatch repair deficiency. For most patients, we start with systemic chemotherapy for stage IV disease. But Kendal, your point is that what if they have a obstruction or a near obstruction? In those circumstances when they're nearly obstructed, we do know that for many patients, we can get disease control within a few weeks, and there's a window there where if the symptoms are felt to be mild or manageable, we'll prioritize starting expedited chemotherapy to control symptoms.

But there are those patients who have an obstructing or clinically obstructed and need urgent surgery. In most circumstances, what our surgeons will do is a diverting ostomy rather than resecting the primary tumor, because that relieves those symptoms and lets them get on chemotherapy to treat both the primary tumor and, again, if you're talking about stage IV disease, the primary tumor and the distant disease with chemotherapy.

So, diverting ostomy is a surgery with less morbidity, less complication risk than a colon cancer surgery. So, the surgeon are leaving the tumor in place and diverting around the obstruction. And then we're able to start chemotherapy within two weeks, rather than, potentially a few months, they have a colon cancer surgery.

This question was actually studied in a cooperative group study in Japan, where they asked the question: Is surgery for the primary tumor for patients with inoperable metastatic disease, is surgery for the primary tumor beneficial? And the answer was no. And I'll mention that because some patients with stage IV disease will ask the question, why can't the primary just come out?

The answer is, in a randomized clinical trial, it was not shown to be helpful, and more patients actually died earlier in that cooperative group study. The reason being there are a subset of patients who will have complications in that surgery and will not be able to get timely chemotherapy and will then have disease-related symptoms from their metastatic disease.

So, diverting ostomy in those circumstances, but generally not colon cancer surgery. But that is why we collaborate with our colorectal surgery colleagues, even for those patients with stage IV disease in many circumstances.

Host: I had a dear family friend growing up, continues to be my friend, thankfully, who was actually diagnosed with metastatic colon cancer, I think had a solitary liver met. This was about 20 years ago. He went to Sloan Kettering. They did a resection of the met. And it's 20 years later, he's still alive. He's completely cured. And I was shocked at the time. But that's a scenario you just mentioned, where there are certain conditions in which patients have solitary liver mets or not much in terms of liver disease, potentially still could be cured.

Dr. Ryan Massa: Yeah, the big point there is that early involvement with surgical oncology, if it's in the liver or thoracic surgery, if it's in the lungs, is helpful because we need a multidisciplinary plan for those patients who have oligometastatic disease in the liver or lung, and/or lung, because generally the treatment's going to involve some combination of perioperative chemotherapy, surgery for the colon primary, and surgery for the metastatic disease.

And there isn't a hard and fast rule about how much is too much disease in the liver or lung, or what's too numerous, what's too high volume. There isn't a hard and fast rule about it. And so, it really takes the collaboration with a surgery team that has seen this before and can have a thoughtful approach.

And it's not the right answer for every patient, but it's the answer for some patients. I think knowing, having that plan in place before we start a treatment plan is very important. We have long-term data on this too, that highly selected population, there are a portion of patients who are selected for surgery, for local therapy, for their metastatic disease, in addition to chemotherapy and surgery for the primary, who about 20% of those patients who are selected for that paradigm, who are alive and cancer-free and not on treatment 10 years later, less than 20%, but in that range.

And if you look at that curve, that curve has a tail to it that extends out. And I'd say if a patient has stage IV colon cancer and is like your friend who had stage IV colon cancer and is not on treatment and has not been on treatment for a decade, that's a cure. And those are definitely, unfortunately, a minority of patients with this disease that's identified when it's stage IV, but it's not a trivial number, and it's one that we should always be aware of and make sure we get those patients to the right folks at the right time.

Host: That scenario in terms of metastatic disease, as you noted, you can't tell stage I from stage II from stage III, I don't even think, without resection, right? And so, a lot of those folks are getting resected.

Now, there is an element here that you just referred to that you're interested in the somatic mutations. we've been talking about germline mutations with Bryson, right? But now, we're talking about somatic mutations of the tumor itself, right? That you're now interested in, and I assume that's more for immunotherapy purposes, right?

Dr. Ryan Massa: Bryson's going to have some input here. For all GI cancers at Penn, and I think this should be the standard everywhere, we test on the initial biopsy for mismatch repair. And mismatch repair is an IH, immunohistochemical test, which we can do internally and have the results back fairly quickly.

Often on the initial report, we have the MMR results. And that mismatch repair-proficient is the usual finding. That's going to be on the report. You may see these reports as you get them from your patients referred for colonoscopies, where it'll say, "The mismatch repair proteins are intact," meaning they see all four mismatch repair proteins. If the mismatch repair proteins are missing, the tumor can be considered mismatch repair-deficient. And that is a signal that they may have a tumor type of microsatellite instability high. That's another way of essentially saying mismatch repair deficiency, different ways of testing for the same process.

And mismatch repair-deficient colon cancer tumors can be sensitive to immunotherapy. They also have different prognosis than mismatch repair-proficient tumors. And so, we get that testing on all these colon cancer tumors because it can affect both perioperative treatment recommendations, postoperative adjuvant treatment recommendations, and in patients with metastatic disease, affects their first-line treatment; where for those patients with mismatch repair-deficient disease who have stage IV colon cancer, we often do immunotherapy first rather than chemotherapy, and some of those patients can have a complete response to immunotherapy, which is, again, functionally a cure.

But it matters for the localized tumors because, I mentioned, I can come back to this, stage I, II, and III colon cancer after surgery in some circumstances recommends chemotherapy to reduce the risk of recurrence depending on stage and other features of the tumor. But mismatch repair deficiency suggests a better prognosis and can influence that recommendation as well. So, we really need that information upfront. And for rectal cancer, there's a paradigm of using immunotherapy rather than surgery for those patients with mismatch repair-deficient disease.

I should add these mismatch repair-deficient colorectal cancer makes about 5% to 8% of these tumors in the US. It varies by stage. Stage IIs are as high as fifteen percent. But broadly speaking, I quote patients 5% to 8%, 8% to 10% in that range for all colorectal cancers.

Host: And if you're going to have colon cancer, this is the one to have, right? Because you have a better options with immunotherapy, right?

Dr. Ryan Massa: I use that same framing. Patients often actually say that to me, before I say that to them. Like, I've read about this. And if I'm going to have colon cancer, I guess I want this kind. And I guess you don't want colon cancer, but I guess you do want this kind. If you could choose, you would pick it, because we have, again, depending on the space we're in, we may have additional options. And this is changing quickly because, just last month, for stage III colon cancer, even if it was mismatch repair-deficient or proficient, we did chemotherapy. There's very recent data out combining chemotherapy and immunotherapy for stage III colon cancer, the ATOMIC study. So, this landscape's also changing very quickly too. The guidelines are going to be updated very frequently about how we think about microsatellite instability high mismatch repair-deficient disease.

Something that does matter, and I'll turn to Bryson for this, is that mismatch repair deficiency can occur both sporadically in the tumor, meaning it happens for just the mutation the tumor acquires, or it can occur on the basis of an inherited cancer syndrome like Lynch syndrome. There's some testing we can do on the tumor to help characterize that, but many of these patients often see oncology genetics, or have germline testing done to clarify whether this is inherited or sporadic tumor.

Host: I saw possibly there is a connection there between some of the tumors that we're seeing in younger people and these somatic genetic mutations. Bryson, is that accurate?

Dr. Bryson Katona: Two, things I'll just comment on. I'll go back to one thing that Ryan said. Especially with patients and we see kind of some misperceptions about this. But if they do have a colon cancer or really any cancer for that matter, that has the mismatch repair deficiency, that still definitely is not a diagnosis of Lynch syndrome.

And in fact, you take all mismatch repair-deficient colorectal cancers, a half to a third of them will be related to Lynch syndrome, maybe even less. And further testing definitely needs be done. I've seen many patients come through the office who were getting managed, being told that they had Lynch syndrome and getting managed as if they've had Lynch syndrome just based on having a mismatch repair-deficient tumor without any germline testing.

Dr. Ryan Massa: For what it's worth, I've seen that too. I've seen patients who come in with mismatch repair-proficient colon cancer, and either they think they have Lynch or they have a diagnosis in the chart of Lynch syndrome, it's actually not the case. I think that's a really good point and an important point that that can suggest Lynch syndrome but does not prove it. I see that a lot quite often too, actually, and I've seen it several times this year.

Dr. Bryson Katona: Kendal, to get to your second point about younger individuals and having genetic susceptibility. The younger the colon cancer, the higher the rate, the higher the likelihood that that individual will have a genetic susceptibility. If you look at people under age 50 with young onset colorectal cancer, maybe one in five will have some sort of a germline genetic susceptibility, which is much higher than the one in 10 to one in 15 that we think of in the older population. But you still think that's only one in five. And so, 80% of those under age 50 don't have any germline genetic susceptibility, or at least none that we can detect using current technology.

Host: I want to ask about chemotherapy, Ryan. But I want to stick on this immunotherapy first because one of the questions I have on my list to ask you is, what does the next five years in colon cancer treatment look like? And it seems to me that more of the advances are coming in the immunotherapy domain. And you're talking about one scenario that, it sounds to me, can be quite successful, right? Because you noted complete responders. I assume there's a lot of work going on in this area, right? And we'll have more and more coming out in the next few years?

Dr. Ryan Massa: The role for immunotherapy right now for colon cancer is—let's talk about this in the stage IV space, this has been the case for more than a few years now, still recently, but a few years now that there was a pivotal study done comparing immunotherapy to chemotherapy, and then more recent studies comparing dual immunotherapies using two immunotherapy drugs rather than chemotherapy, which showed benefit too.

So, it's become with a few exceptions, because we do think that for those patients who are very symptomatic, chemotherapy may have a better chance of a faster response. So there's still some patients with mismatch repair-deficient colon cancer. Again, that's fewer than 10% of these patients are going to have that marker that lets us use immunotherapy in the stage IV space right now. But there are still some of those patients who we do recommend chemotherapy for. Those are becoming more exceptional now, but, like, very high burden of disease or very symptomatic disease where if immunotherapy we may not think has enough time to work, or if it doesn't work, the patient may not get the second-line therapy.

But for most of these patients, we're recommending immunotherapy, and we all have stories. And those of us who see people with GI cancer in the clinic every day all have stories of patients with metastatic colon cancer who got immunotherapy treatment for a year or two and either have stable disease two years later or in some cases have no evidence of disease on any of the available tests we have right now to detect negligible cancer. That has changed the paradigm entirely if we think about metastatic colon cancer treatment. The adjuvant setting for colon cancer is still evolving. And what we have now is that the way our guidelines have been adapted now, and this changes every year or so, as we get more data. But for stage I or II colon cancer that's mismatch repair-deficient, the recommendation is now observation.

One particular kind of stage II colon cancer, particularly high risk, that the recommendations say consider adjuvant therapy, adjuvant chemotherapy. But generally speaking, for most of these mismatch repair-deficient colon, stage II colon cancers, we're recommending observation.

I'm going to pivot right from talking about this to how we think about the mismatch repair-proficient space because I think it, they're still related. But for the stage II mismatch repair-deficient colon cancers, we're recommending, observation because it's thought to be a good prognostic marker, and chemotherapy probably has less benefit in that setting.

For stage IIIs, up until very recently, the recommendation was still, even for those mismatch repair-deficient immunotherapy-sensitive tumors, recommendation was still chemotherapy as per the usual paradigm. That's changing, with this recent study which used chemotherapy plus immunotherapy. And that's now in the guidelines too. Chemotherapy plus immunotherapy or chemotherapy alone for stage III colon cancer that's mismatch repair-deficient. So again, we need this testing to have these conversations. That data is something I think we're all trying to figure out how to incorporate, how to use this recent data comparing atezolizumab, which is an immunotherapy drug plus chemotherapy, compared to chemotherapy alone.

Our guidelines now have it as a preferred option, but have it equally weighted with the chemotherapy regimens, I think, because this is still something the expert opinion is evolving on, for mismatch repair-proficient colon cancer that's been removed with surgery, which is most of the patients we're going to see.

Host: This is as you said, you're not part of, I think you said 8% or so that are mismatch repair-deficient. This is the majority of colon cancers that don't have an obvious immunotherapeutic target, right? These folks are getting now chemotherapy, right?

Dr. Ryan Massa: This question of chemotherapy versus chemotherapy plus immunotherapy, I want to explain the ambiguity a little bit. The study was called ATOMIC. That regimen is now in the guidelines, but like I said, it's equally weighted to the chemotherapy plus immunotherapy versus chemotherapy alone is equally weighted.

The study showed improved disease-free survival benefit, but the overall survival was similar. And that's the reason why there's some sort of evolving expert opinion on how we should use this regimen. Because in the adjuvant space, OS, overall survival, is the gold standard. Like, we're doing adjuvant therapy to improve someone's chances of living longer and cancer-free.

And so, the disease-free survival benefit is nice to see, but you really want to see an OS benefit before you recommend additional potentially toxic therapy. I just wanted to expand on that a little bit.

Host: Yeah. And I actually wanted to summarize your points on immunotherapy maybe before we jump back into chemotherapy. And that is that if you are a candidate for immunotherapy, you're stage I, you're being resected, you don't need to do anything. If you're stage II, you get immunotherapy, no chemotherapy. And it's the stage III folks that you're just talking about there, right?

Dr. Ryan Massa: If it's stage II mismatch repair-deficient tumors, we just do observation. No chemotherapy.

Host: You don't need to do immunotherapy. You do nothing.

Dr. Bryson Katona: No chemotherapy, no immunotherapy. We don't have any data showing immunotherapy postoperatively is helpful. We do have increasing evidence base that chemotherapy probably adds no benefit for those stage II mismatch repair-deficient tumors. They have a better prognosis and a less of a response to chemo. So, the stage IIs that have this mutation, this alteration, don't get chemotherapy in most cases. There's one unique exception that it's a soft recommendation in the guidelines. But for the stage IIIs, it's either chemo or chemo plus immunotherapy, depending how you feel about this new study called ATOMIC, which showed disease-free survival benefit, the OS benefit was similar. It was 90% versus 88%. And so, that's something that I think once we get more data, more results from that study over time, people may have a different opinion on.

Host: Well, with the stage IVs that are candidates for immunotherapy, are they going to get both or are they going to get just one?

Dr. Bryson Katona: Usually, Immunotherapy alone.

Host: Immunotherapy alone. Okay. Yeah. Circling back to the folks that get chemotherapy, because they're not candidates for immunotherapy. How toxic is this? How are people doing with modern regimens, chemotherapy regimens?

Dr. Ryan Massa: Yeah. So, that's a good question, and we have some changes we've made in our practices recently to hopefully improve the toxicity profile, recently and over the last five or six years. So, can I explain how we think about adjuvant treatment first, and then I'll go through the toxicity too?

So for stage I colon cancer, the recommendation is observation, no chemo. Nobody with stage I colon cancer is getting chemotherapy. There's no data of benefit. For the stage II colon cancer patients, that's a tricky subgroup. Now, we're talking about mismatch repair-proficient tumors, which are going to make up 90-ish% of these people with colon cancer in the US.

For the stage II colon cancers, it's a controversial area with data that's somewhat ambiguous. Essentially, we look at stage IIs based on their risk of recurrence, whether they've got prognostic factors, and they suggest a higher risk of recurrence, like T4, meaning it's a more invasive local tumor compared to T3, is felt to be a higher risk tumor. There's factors under a microscope you can see, like lymphovascular invasion or perineural invasion. There's other factors like inadequate lymphadenectomy, which we rarely see, but we do see at times, meaning fewer than 12 lymph nodes evaluated, which could mean there is actually a stage III that we just didn't check for.

Perforation, all these prognostic factors. But essentially, for the stage IIs, as a group, there is some risk of recurrence, and it can be actually fairly high risk for the more high-risk stage II colon cancers. But all this data we have for adjuvant therapy comes from these larger studies of pooled groups of stage II and stage III patients. And as those stage II patients have been pulled out for meta-analyses and other studies and unplanned subgroup analyses, what we've seen is that there's probably minimal disease-free survival benefit for chemotherapy in unselected stage II patients and probably very minimal survival benefit. I say probably because there's been studies that have shown no survival benefit. These unplanned analyses and meta-analyses have shown no survival benefit. Some have shown some benefit. But whatever's there for the stage II population, it's a fairly small benefit. But it's not zero. There have been consistent studies, again, meta-analyses showing some disease-free survival benefits.

So, our guidelines reflect this ambiguity where they say for your stage II colon cancers at high risk of recurrence, are you can do chemotherapy with one drug, you can do chemotherapy with two drugs, or you can do observation. And they weight these three options equally. There is not a preferred option. There is not a recommended option. It's very much an individualized decision.

I find in my practice that, in contrast to the stage III patients for whom the recommendation is chemotherapy if they're fit for treatment, that's usually a pretty straightforward conversation. For the stage II patients, that needs to be a very nuanced conversation because it's very much dependent on someone's risk tolerance, their comorbidities, their own goals and wishes. And there are situations where, it's not just a matter of being young and fit and healthy to tolerate treatment because that young, fit, and healthy patient with stage II colon cancer is very, very possibly cured by surgery alone. Proposing chemotherapy that may have some degree of risk, even if that risk is relatively lower than your 75-year-old patient, that's a conversation.

And there's some patients who say, "You know, I know the risk is, I know the benefit is small, but I, there's a risk of recurrence, and I don't want to be sitting here in a year thinking I should have done this or should have done that." That's something I hear very often. And I say, "Well, we should do it then. It's guideline concordant." And there's some patients who say, "I had my surgery. I'm out of here. I'll see you for my scans in six months." I think that's okay too. I think that's very... The stage II discussions are very nuanced and very individualized. In the right circumstance, I'll get real deep into the data if someone wants to talk about it, and we'll show graphs and we'll show all this stuff, which it's not always helpful in every situation, but here I think it can be because it's a really tricky discussion. These patients with stage II colon cancer are at meaningful risk of recurrence. The question is how much can we modify that risk? And the answer is probably only by a very little bit, if any.

Host: What do you quote for people, with stage II that have been resected chance of recurrence?

Dr. Ryan Massa: So, stage II includes T3N0 tumors and T4N0 tumors. And there's also these prognostic features like lymphovascular invasion, perineural invasion. And so, the stage, the high-risk stage IIs, these T4b, very locally invasive tumors, can actually have a higher risk of recurrence, which is often local risk or peritoneal, metastatic disease, can have a higher recurrence risk than the favorable risk stage IIIs, your T1N1 stage III.

AThey actually, the survival curves can actually overlap, or the recurrence curves can actually overlap. The problem is those stage IIs, the pattern of spread is different, and the chemotherapy's ability to modify that risk is probably not as substantial. It's not zero, but it's not as meaningful as it is for the stage IIIs, which stage III is colon cancer that spreads to the lymph nodes. It's a different pattern of spread. That risk for stage IIs can vary all over the place. I will say there is a population of stage II colon cancer, T3N0 colon cancer, which is the most favorable risk stage II colon cancer. And for those patients, those T3N0 stage IIA colon cancers, observation is preferred. That's the one stage II that the guidelines do say preferred, observation is preferred. And for stage IIA colon cancer, I almost always recommend observation. I can't think of a time where I have not recommended observation for.

It's very much exception. it would be an exception. But for stage IIAs, observation is preferred. There's a considered chemotherapy pathway in our guidelines, but that'd be an exceptional circumstance. They have a very favorable prognosis, but they can recur too. I've seen patients with stage IIA colon cancer who have metastatic disease, even with getting chemotherapy in that in some circumstances.

Host: One last last question, because I'm sure a lot of our listeners are thinking this thing. Can you give me numbers on this, prognosis for disease-free survival at basically cure? Let's talk about cure because that's the thing that people would—I mean. For stage I, stage II, stage III, stage IV, what numbers do you at least keep in your head? Rough ranges

Dr. Ryan Massa: So, the stage Is, actually, medical oncology, we actually often don't see the stage ones. They rarely make it to us unless often it's maybe a patient who very much wants to see a medical-oncologist. The guidelines are pretty clear though.

So, the stage I's, they're cured with surgery. I think the recurrence risk. It's not 0% recurrence risk, but the guidelines actually recommend no imaging for those patients. That's how low the recurrence risk is. They recommend only colonoscopy surveillance, no imaging. And, you know, eventually someone with stage I colon cancer, unfortunately, these things are not 100%. I'm going to answer your question, but I think one of the challenges we have talking about adjuvant therapy is that the adjuvant therapy landscape has evolved.

So, like, the modern chemotherapy we use for most patients with stage III colon cancer is a combination of a fluoropyrimidine medication, either 5-FU or capecitabine, and oxaliplatin. For most patients with stage III colon cancer, that's what we're recommending, those two medications together. And we don't have a study comparing the regimens called FOLFOX or CAPOX. And we don't have a study comparing FOLFOX to nothing. What we have is studies comparing 5-FU or fluoropyrimidine, which is one of the agents in FOLFOX, these are studies going back decades, and they compare outdated 5-FU regimens that we would never do today that are much more toxic and much less effective to observation or even less effective chemotherapy.

And then, we've built on these studies. You find some drug works and some regimen works, and you build on it. You compare it to another one. We don't have a study comparing FOLFOX versus observation, and we don't have a study comparing even modern 5-FU to observation. What we have is these older studies looking at less effective and more toxic ways of giving the same medication.

So, some of the patients will ask, "If I do nothing, what's my recurrence risk? And if I get FOLFOX, what's my recurrence risk?" And unfortunately, I don't have a good study I can just pull up from the New England Journal of Medicine and say, "Okay, here's what happened when patients got this chemo, and here's what happened to patients at observation." And I can for some cancers. I see people with gastric cancer, and we do have that data in gastric cancer because the pace of the field's been different. But for colon cancer, we don't have that.

Depending on the stage of disease, you know, you asked about stage I, II, III, or IV, would we quote people? I will say that there's substages which also matter too. Like IIA is a very fairly favorable prognosis. I say to these patients, "It's we need to do scans, twice a year for five years because there is some recurrence risk, but it's fairly low. And more likely than not, this cancer will not come back, okay? But it's not a 0% chance. We should do scans." But patients with stage IIC, which is that T4bN0 colon cancer, I tell them, "I'm very worried that this cancer may come back. it comes back, it may come back in an area that is not curable." It's treatable but not curable. And we need to do scans twice a year to look for that recurrence.

And for my patients with stage III colon cancer, again, we're doing chemotherapy, but I tell them the same thing, which is that whether we do chemotherapy or not, there's a risk this cancer comes back. And the reason to do chemotherapy is to reduce the risk of recurrence, but adjuvant chemotherapy cannot eliminate that risk. And this is a cancer that when and if it comes back, usually, but not always, comes back in a form that's treatable with chemotherapy, but not curable. And I tell patients that because that's why we're thinking about aggressive postoperative chemotherapy for a patient who has been cured with surgery and has no evidence of measurable cancer in their scans.

The question becomes, "Why am I doing this?" And the reason we're aggressive in that space is because that's their window of opportunity to give them the best chance for cure. And for stage IV colon cancer, it's a very heterogeneous population. And there's patients with stage IV colon cancer who live for many years, patients who unfortunately have more aggressive disease that do not. But the average survival of someone with stage IV colon cancer, I tell patients averages don't apply to individuals, so I'm not giving you a timeline here. But people with metastatic stage IV colon cancer diagnosed, now the median survival is now measured in years, around more than three years.

And I don't tell people you've got X number of months or years because we don't have a crystal ball, and we don't know how well or not well someone's tumor is going to respond to treatment. And we've seen all sorts of surprising outcomes one way or the other. And so if they ask, that's the answer I give them.

Host: I've seen surprising outcomes both directions. Some happy instances. I had a patient with melanoma that hit the wave. I mean, just as they were coming into really effective therapies, got advanced melanoma and ended up being cured and died 20 years later of something completely different.

But this discussion does get us back to the importance of early detection, because obviously patients who are earlier do better, right? Bryson, I have two questions. First off, if somebody's sticking to the screening program, they follow your advice, they get the colonoscopy, they follow up with the five years, there are very few cases that slip through, right? Most of the time we're able to catch these really early if we're sticking to the screening program, right? At least colonoscopies.

Dr. Bryson Katona: I agree. I mean, you will hear stories. I mean, there are some post-colonoscopy colorectal cancers that do develop. Colonoscopy in and of itself, I mean, really has been shown to lead to a substantial reduction in death from colorectal cancer. I do still firmly believe it's the gold standard screening. Nothing's perfect, but I think it's pretty good. And I think, part of that is just because actually maybe I could soapbox for a minute and say that I don't like the term colon cancer screening, because with colonoscopy you have the ability to intervene and intercept a colon cancer before it develops.

And in the ideal world where we're not screening for colon cancer, we're screening for polyps, which we'll remove and prevent cancer. But I think it is an effective intervention.

Host: I was told early in my career by an expert, at the place I trained, in colon cancer that it really takes about five years to go from nothing to an advanced polyp. And that is a useful thing to have in my head when these things come up. is that right?

Dr. Bryson Katona: Yeah, I would actually lengthen that interval. I think going from even a small polyp, small adenoma to a cancer is going to take a decade or more.

That's why we feel comfortable with that 10-year interval, with the thought being that if you go through examine the colon and you do not find any polyps, that even if a adenoma, it does form like the day after your colonoscopy. In 10 years, we would not really expect that adenoma to be a true cancer. So, it is a very slow process.

Now, I will say that the one situation where that is not the case is in individuals with Lynch syndrome, where that polyp-to-cancer progression happens a lot faster. It can happen within a year or two. And so, it's way accelerated. So, they're getting scopes every one to two years because we think things pop up quickly. But with somebody in the general average risk population, it is a very, very, slow process. That's one benefit that we have in the colon cancer screening world, is that we do have this precursor that's identifiable and removable and just takes a long time to progress.

Host: This comes up clinically a lot actually in primary care. Patients will come in a couple years after a perfectly clean colonoscopy really worried they're constipated and now they're really worried they have colon cancer. I'm like, "You know, really it's very low chance." I mean, there are circumstances where colon cancers are missed, but I reassure them that that's very unlikely. But if your symptoms continue, we'll go down that route. But I usually reassure them based on that knowledge that really if you're starting from scratch, it's going to take more than two years to get to a full colon cancer.

Dr. Bryson Katona: Certainly. And one issue that we oftentimes will see see come up in the screening space is somebody, If they're average risk, they have a good quality normal colonoscopy, the next year, they twist one of their provider's arms into ordering them like a FIT test or a Cologuard or something, you know, and it comes back positive. You know the colonoscopy's going to be negative, but then you're kind of stuck. You have to repeat it. That's another thing it's oftentimes hard to talk patients off off the ledge, if they're really worried about it.

If they had a normal, high-quality colonoscopy, you really shouldn't be ordering any other colon cancer screening test, regardless of what it is, until that interval when they're next due. Because the chance for false positives is high, and then you're putting them in more harm's way due to potential risks from additional invasive procedures.

Host: I've really gotten a lot out of this discussion, and I I'll just highlight a couple things quickly. I mean, I'm definitely going to be looking at that young people population, particularly if they're presenting the symptoms a little differently. Bryson, based on your comments in our previous podcast and this one, I'm still going to be aggressively thinking about GI malignancy risk based on family history, and very low threshold to send people to oncology genetics, who are great, by the way.

I'm at Radnor, and the person at Radnor is wonderful. She does a great job. That's very helpful. Screening is about identifying people at high risk, and then focusing on those people, maybe screening them early. And so, that's a strategy that's been very helpful.

I thankfully don't have to have colon cancer to get involved in a discussion with you about what it's like to have colon cancer. Hopefully, I'll never be there, but I can see the subtleties involved in the decision-making of what you have to do. And I appreciate you taking us through all that. Any thoughts before we sign off? Last things that you want to make sure we get across to the primary care audience?

Dr. Bryson Katona: Just reemphasize from the early detection standpoint, there's so many different options available. And if your patient's are at all interested in colorectal cancer screening, you know, and their average risk, it's of great importance to explore some of those other options just so that we're doing better than getting only two out of three people in for colon cancer screening, because I think we certainly have room to do a lot better.

Dr. Ryan Massa: I think something I'll highlight I think for the primary care audience is that GI cancer care and cancer care in general is multidisciplinary. I tell our patients, they come meet me for their new diagnosis, like I still need you to see your primary care doctor because your cancer care is only one component of your entire health profile.

But the other piece of that is that it can be difficult, I think, for anybody, including oncologists or surgeons, a gastroenterologist to figure out what patient with their specific situation, stage, and biomarkers should see who. And I think that's something that we in oncology and in surgical oncology and colorectal surgery can help coordinate.

So, I think if there's any, for our primary care audience and our primary care, colleagues at Penn, if there's any uncertainty about does this patient really need to see oncology, the best thing to do is just have them see a medical oncologist. And I explained how the, for many patients with stage II colon cancer, we end up not recommending chemotherapy, but it's a discussion with the patient.

And I think what I tell our surgeons is they'll say something sometimes, "Does this patient with stage II colon cancer need to see you?" And I'll say, "Well, I don't actually know until I meet them." So, let's have that conversation. I think it's good for us to do what we are, trained to do. And so, I'd invite our primary care colleagues if they're not sure if this patient needs medical oncology, we are happy to see them and help in any way we can, even if the answer is, "No, you don't." Which I love saying sometimes when I see a patient with relatively early-stage disease that they don't actually need to see a medical oncologist in the future, but I can at least explain why and what the options are and how we reached that conclusion.

Host: You and your colleagues are great. I mean, I've been so happy and impressed when we're stuck. And you'd be amazed how many patients come back, have a discussion with you, and then they come back to me and say, "What do you think?"

Dr. Ryan Massa: Yeah.

Host: That's one of the reasons I started this podcast, because I need to understand this in a little more granular level, because patients are going to come back with questions.

So, this was great. I really appreciate you guys. We've run over time. So, I got to sign off. this was a great discussion and I'm glad we covered it in detail because it was a topic worth covering. So with that, I'll end the Primary Care podcast. Please join us again next time.