Next Gen in 10: Rethinking Endometrial Cancer Surveillance in Lynch Syndrome

🎙️ Next Gen in 10 is back! This episode features Arabella Helgason, a UBC Master’s student supervised by Dr. Aline Talhouk, whose research examines how endometrial cancer surveillance currently works for Lynch syndrome carriers — and how it might be improved. Using population data, Arabella is exploring surveillance patterns and investigating new approaches, including the potential role of self-sampling. 

🎧 Tune in to learn how trainee research is helping rethink cancer surveillance.

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Transcript

00:00:02 Intro 

Thanks for listening to the GOSH Podcast, the Gynecologic Oncology Sharing Hub. We share real, evidence-based discussions on gynecologic cancers featuring stories from patients, survivors, researchers, and clinicians. Our podcast is produced and recorded on traditional unceded territories of the Musqueam, Squamish, and Tsleil-Waututh Nations. It is produced by the Gynecologic Cancer Initiative, a BC-wide effort to advance research and care for gynecologic cancers. 

00:00:35 Sabrina 

Hi everyone. My name is Sabrina and I would like to welcome you back to our new segment on the GOSH podcast, which is called Next Gen in 10, where we feature GCI trainee research. Today we are joined by Arabella Helgeson, who is a master's student at the University of British Columbia in the Women and Children's Health Sciences Program. Supervised by Dr. Aline Talhouk, her thesis examines current endometrial cancer surveillance for Lynch syndrome carriers in population data and possible new approach. Welcome to the podcast, Arabella. 

00:01:10 Arabella 

Thank you so much for having me. I'm excited. 

00:01:13 Sabrina 

All right, so can you tell us a bit about the background of your research as well as the gap that your research is aiming to fill? 

00:01:21 Arabella 

Of course. So Lynch syndrome is one of the most common hereditary cancer syndromes, and it affects around an estimated one in 279 people, just to give some context for the prevalence. And it's caused by germline mutations or pathogenic variants in DNA mismatch repair genes. And these proteins are responsible for recognizing and correcting errors that occur when DNA is copied during cell division. And when the repair system doesn't work properly, mutations can actually accumulate, which increases the likelihood of cancer developing. So because of this, people with Lynch syndrome have a much higher lifetime risk for various cancers. So this includes, most notably, colorectal cancer, endometrial ovarian cancer, and other cancers can occur, usually lower risk for these cancers, but notably cancer of the stomach, the urinary tract, small intestine, the brain, the skin, etc. So there's quite a few cancers that Lynch syndrome can increase the risk for. And for my research specifically, I'm focusing on endometrial cancer, which is often the first or what's often called the sentinel cancer to present in female patients with Lynch syndrome. And people with Lynch syndrome have up to a 50% lifetime risk for endometrial cancer. So if you think about that for a second, that's pretty high. That's like flipping a coin. And endometrial cancer often develops about 15 years earlier on average than in the general population. So these patients are often being diagnosed in their mid-40s. And because that's an average, often earlier in their 30s or early 40s. So It's very young to be diagnosed with endometrial cancer in this population. And because of this risk, many patients are offered something called surveillance starting in their 30s. I want to briefly note the difference between surveillance and screening. Because screening is I feel like a term that a lot of people are very familiar with and surveillance maybe not so much. Screening often refers to testing kind of large populations of people that are at average risk. So an example of that in BC is like the BC cancer cervical cancer screening program where there's the at-home sampling. Surveillance, on the other hand, refers to ongoing testing of people who are already known to be at higher risk or elevated risk. So right now, there's a couple options for female patients with Lynch syndrome. I'm going to talk about kind of prevention, and I'm also going to talk about the surveillance aspect. And for prevention, they're often recommended risk-reducing surgery. So this is typically removal of the uterus and the ovaries because there's also the ovarian cancer risk component, but it can be just the hysterectomy or just the ovaries, but typically it's hysterectomy earlier. And this can effectively remove the risk of these cancers, but it also comes with some important consequences, like if you remove the ovaries, premature surgical menopause, or with hysterectomy and the ovaries, there's implications for childbearing. People might also just not want to go through surgery. That's also another factor that's totally fine. And you can imagine that this could be a difficult decision for people in their 30s or 40s. So many people choose to delay surgery and instead pursue something called surveillance. So surveillance options for people, for females with Lynch syndrome, are typically either a biopsy or an ultrasound, often both. But these approaches do have some limitations. For example, biopsy is pretty invasive. It can be very painful for patients as well. And ultrasounds often don't detect earlier stage disease, so it might not be that clinically useful for surveillance. And there's really no strong consensus on what surveillance should look like in this population for gynecologic cancers in particular. Recommendations really vary between providers and across health systems. And at the same time, we don't really have population-level data on how Lynch syndrome patients are actually receiving surveillance. And an aside that will kind of, I guess, help contextualize the second name of my project is that there's a really hot topic in endometrial cancer screening space right now, which is minimally invasive cervical vaginal sampling. There's a lot of research ongoing to basically collect vaginal fluid and analyze it for biomarkers that could predict the risk of endometrial cancer. And our lab is heavily working in that space. And that's just a little bit of backstory for one of the studies we're doing. But for some background, there's a study in Spain that was actually published mid last year that's doing something kind of similar to what I'm doing. That's fine. And it did show good preliminary acceptability of a similar sampling approach in their population. They're using a sampling brush, so there's a lot of different ways that the fluid can be collected, like tampons, brushes, swabs. But right now, we don't really have any data in how Canadian Lynch syndrome carriers would feel about these new approaches to self-sampling. So overall, there's a lack of good quality information research for this high risk population. And my research is trying to understand kind of two sides of a problem, what surveillance currently looks like and what a new option could potentially bring. Sorry if that was a lot of talking. 

00:06:53 Sabrina 

No, that was great. That was a very thorough and I think that the right level of detail for us to be able to really get into your work here. So knowing all of that, what are your research questions or your objectives? 

00:07:07 Arabella 

Absolutely. So to address all these gaps, my thesis has two main objectives. So the first is to really understand how people with Lynch syndrome are currently engaging with gynecologic cancer surveillance and prevention in BC. So we know that these patients are high risk, but we don't really have that clear population level data picture of how often surveillance procedures are actually occurring. And the second objective of the study is to explore patient perspectives on a potential new surveillance approach in the form of an at-home vaginal self-sampling. So it's a swab, and that's being conducted as part of an ongoing study in our lab called LynchScan, which assesses the feasibility and acceptability of vaginal self-swabbing for routine endometrial cancer screening in the Lynch syndrome carriers. And that study also analyzes, just an aside there, it also analyzes somatic DNA mutations and microbiome signatures that could be associated with endometrial cancer risk. And you heard from PhD candidate Delina Dedani, I think it was in November I was listening to the podcast, on an earlier NextGen in 10, and she's leading kind of the bioinformatics work in the space in the lab. My focus for the study will be on kind of that acceptability, patient-centered experience piece. So yeah, there's two questions. Yeah, there's two questions I'm basically trying to answer. What does real-world care look like? And how acceptable might a less invasive option be? So yeah. 

00:08:40 Sabrina 

Okay, so those are clearly two very separate aims, also related, but I'm assuming the methodology behind them is quite different. Could you tell us how you're gonna go about actually answering these research questions? 

00:08:53 Arabella 

Yes, so my thesis is very mixed methods. There's a lot going on here, so we'll kind of unpack it a little bit without boring everyone with the grave details. But I have those two complementary studies that are kind of trying to approach this problem from different angles. And my first study is a retrospective population-based cohort study that's using administrative health data from BC. And I'm accessing data through population or pop data BC. And these datasets will allow researchers to link information across the healthcare system. So this could be administrative data like physician billing records, hospital databases, prescription data, et cetera, as well as some specific datasets we're also accessing, like the BC Hereditary Cancer Program data, and the BC Cancer Registry. And we're accessing data from 1999 to 2023. And using these datasets, we can identify people who are diagnosed with Lynch syndrome and follow their health care interactions over time. And this allows us to examine things like gynecologic surveillance procedures, preventive treatments, and cancer outcomes as well. And for example, We can track when people receive procedures like endometrial biopsy, ultrasounds, hysterectomies, et cetera, and how those patterns could relate to things like age or when they were diagnosed to Lynch syndrome. And the sample size is quite small. This project is still in progress, so we'll primarily use descriptive analysis for this aim. And the second study focuses on those patient perspectives, and it's embedded again within that LynchScan study that we described, or that I described briefly earlier. And through LynchScan, participants complete health questionnaires and up to three rounds of at-home vaginal self-sampling that are about eight to nine months apart. And upon sampled analysis, if we detect that there's some sort of signal that could indicate the presence of cancer or pre-cancer, we refer them to a biopsy, endometrial biopsy, to rule out malignancy. So that's kind of the Lynch scan pathway. They come in, they do a questionnaire, three rounds of collection, and then they end the study. So it's a longitudinal study. My study, nicknamed Insight LS, focuses on the first sample collection in that study. So participants will complete a health questionnaire, And then they will do that first sample collection at home. And then they'll complete a questionnaire that's specifically about their experience and their perceptions of the test. So this questionnaire is based on a modified application of something called the theoretical framework of acceptability. It informs seven key aspects that can be considered in acceptability of health interventions. So this framework defines those being effective attitude, burden, ethicality, perceived effectiveness, intervention coherence, opportunity costs, and self-efficacy. Those who complete the first collection and consent to be contacted for future research are invited to participate in semi-structured interviews with me where they can discuss their experiences with Lynch Syndrome surveillance in general, their experiences in more detail with the vaginal self swab at home, and also how a method like this could be integrated into their routine care. So frequency of how how often they'd be willing to be sampled or any barriers or facilitators to implementation, that sort of thing. So yeah, those are my two aims overall. The projects combine that large-scale population data with also patient experience data, and it kind of gives a multi-angled insight into the screening space right now. 

00:12:44 Sabrina 

Very interesting. I like that you're coming at it from two very different approaches to get a full picture of what's going on here. So where are you now in your findings? Do you have any preliminary findings that you might be able to share with us? 

00:12:57 Arabella 

I don't have any data I can share yet from the population-based study, but we do have some preliminary findings from the second aim. So LynchScan and my sub-study, Insight LS, are currently still recruiting. But right now, I have analyzed findings from 8 participants, and hopefully that number will increase sooner than later. And right now, the participants generally report positive experiences with self-sampling. Many say that the instructions are clear, the test was really easy to do at home, that it was really easy to do themselves as well was a big question. We wanted to understand if they needed any help to do it. So right now they're demonstrating a high level of self-efficacy with the procedure. And they also are describing it as pretty comfortable to do and less burdensome compared to current options like needing to go into their doctor's office, get a biopsy, et cetera. And that's really important because Things like biopsy are currently the main surveillance tools available for these patients, and it can be really painful and unpleasant, and there's also that piece of being time-consuming, especially needing to do that as often as yearly, depending on physician recommendations. Another observation is that participants often emphasize the importance of like trust in the test accuracy, which is super fair. Like while many people are really open to the idea, they want to know if it'll be effective in detecting cancer early, which of course that's critical. That is the critical piece. Why bother with a swab if it's not going to work? But right now we're running all these studies concurrently, so we don't have concrete findings on that up front. So results are still pending, some other trials. But overall, the early findings suggest that self-sampling is generally acceptable to these patients, and many individuals would be willing to incorporate it into their surveillance routine, but pending, of course, that effectiveness data, which we're still working on. And these are really important to have both aspects of understanding these tests, because it really helps us understand not just whether the test works, it's accurate, but also whether patients actually want to use it, because truly that's what we care a lot about. Developing a test that doesn't just work, but that patients are actually excited about using. 

00:15:24 Sabrina 

Very interesting. Well, we'll have to continue to follow your study to see your final results, but it sounds very interesting to start. So in your population data, which I know you can't share your results of yet, but are you looking at differences in surveillance patterns across age groups or regions or over time or anything more detailed like that? 

00:15:44 Arabella 

Yeah, examining those kinds of patterns are really key to the study. So using the admin data or administrative data really allows us to look at how surveillance and preventive care can vary across this population in BC. So for example, some things we're going to be looking at are examining whether surveillance procedures occur more often in certain age groups, so particularly around ages where clinical guidelines suggest surveillance or preventive surgery might begin. And we can also examine differences based on specific Lynch syndrome gene variants because the lifetime cancer risks vary quite a bit, actually, depending on which mismatch repair gene is affected. And another key factor is geography or geographic region, such as whether someone lives in a more urban region of the province or more rural region, because access to gynecologic specialists and cancer prevention services vary a lot, of course, depending on where someone lives. So this could influence surveillance patterns. And we can evaluate how surveillance practice have also changed over time. Of course, we only have 24 years of data, so maybe they won't change that much over that period of time, but we can kind of see if there's any trends as the years go on. And this could also reflect changes in like clinical recommendations or just general improvement in awareness of Lynch syndrome or diagnosis of Lynch syndrome as well. And understanding these patterns is really important, so we can identify gaps or inconsistencies in care. For example, if surveillance procedures are occurring less frequently than we expect or only after symptoms appear, that might indicate that there are some missed opportunities for earlier detection. And if surveillance is happening less frequently and people living in rural populations, let's say, this could also be some justification for pursuing at-home self-sampling methods to improve accessibility to surveillance. So yeah, overall, this type of analysis really helped, well, hopefully will help us understand how care is actually delivered in the real world, which is essential for kind of improving those patient care pathways. 

00:17:56 Sabrina 

Okay, and from a methodological standpoint, How are you actually identifying surveillance in the administrative data and what kinds of codes or indicators are you using? 

00:18:08 Arabella 

That's a really great cue because that is actually one of the more complex aspects of the study and it's something that's still being iterated on as time goes. But admin data, administrative data contains records of like procedures, diagnoses, healthcare encounters, et cetera, but they don't always indicate the clinical reason why the procedure is being performed. So for example, an endometrial biopsy might be done as part of routine surveillance for someone with Lynch syndrome, but it could also be done because they've had a symptom of cancer like abnormal uterine bleeding. And because of this limitation, we are identifying procedures that are commonly used to detect endometrial cancer, such as biopsies, ultrasounds, like hysteroscopy, et cetera. And these procedures can be identified using physician billing codes and hospital procedure codes with the admin data. But rather than just assuming that these procedures always represent surveillance, we're going to be a little careful in our interpretation and refer to them more as like gynecologic interventions is kind of what we're workshopping here, which may serve as a proxy for surveillance. So we're not going to say there is X many patients who got surveillance, we might say there's X many patients with Lynch syndrome who got a biopsy in this year and that could indicate the surveillance or the number of people getting surveillance. So we need to be a little bit careful because we don't exactly know if a code specifically means it was surveillance or not but we're using it as a proxy for surveillance, basically. So same thing kind of goes for the preventive care. And that's another aspect we're looking at kind of secondarily in this study. So for example, hysterectomy is a risk reducing surgery. So this could be done for prevention of endometrial cancer in this population, but it could also be done because a patient has cancer or pre-cancer actively or using hormone therapies, which might reduce cancer risk. That could just be that the patient wants to, you know, prevent pregnancy. You don't know. So prevention is a bit more clear because whether or not the intent is there, the interventions are preventing the cancer. But yeah, so we can examine the timing of these procedures relative to factors like the lynch syndrome diagnosis or symptom codes, et cetera, which can provide context. But it's definitely not perfect. Admin data can't capture clinical intent perfectly, and this is a key limitation of the site. 

00:20:36 Sabrina 

Okay. Well, thank you for explaining that. Why is it so important to explore alternatives like self-sampling for endometrial cancer surveillance in Lynch syndrome carriers? What are the potential benefits that this approach can really bring to this population? 

00:20:53 Arabella 

Yeah, that's great. So exploring these alternatives is really important because the current surveillance options, as we talked about, are not perfect and they really aren't super ideal for long-term repeat monitoring. So the biopsy, which is one of the main procedures used to evaluate the uterine lining, can be very painful. It can be very invasive, like we've heard from some patients that in the past, they've reported it feeling barbaric or like torture. And it also requires a clinic visit with a provider. So for patients that need surveillance repeatedly over many, many years, That's a pretty significant burden to need to go in every year, and if there's something inconclusive, they need to go in for another biopsy. It's just not perfect. There are also access barriers, which I touched on a little bit before. Not everyone lives close to a specialized clinic or their gynecologist, and accessing procedures like the biopsy or hysteroscopy can require travel, time off work, and there's other logistical challenges that go in that, like childcare, et cetera. A minimally or non-invasive option like self-collected vaginal sampling through a swab or other similar methods could potentially address several of these barriers. And because the test can be performed at home, it may improve convenience, accessibility, and also autonomy because patients are really, you know, the swabs are in their hands. They are in charge of their own surveillance. And from the scientific perspective, there's growing evidence that these surgical vaginal samplings can actually work. So This means that this type of sample could potentially be used to detect cancer, pre-cancer in the future. And of course, this is widely still in the research space, but hopefully we get there and make a new option that's better for patients, more clear, easier to get to. And if this approach proves to be feasible, accurate, acceptable, etc., it could become a very important addition to the surveillance toolkit for people in this population. So the goal is ultimately to move towards surveillance strategies that are effective, patient-centered, and accessible so that these high-risk individuals can be monitored in a way that actually fits into their lives. 

00:23:01 Sabrina 

Yes, I really hope that your study finds it is acceptable and there is continued evidence supporting its accuracy because that would be a great relief, I think, for a lot of Lynch syndrome carriers. Okay, last question that we ask all of our guests on the Next Gen in 10 segment. If you could only say one thing to everyone who will listen to this podcast about your field of research, what would it be? 

00:23:29 Arabella 

One thing might be tricky. There might be a couple things in this answer, so don't reprimand me. But one thing that really stands out to me about being kind of in this niche space is how many of these patients are really navigating these decisions with limited options. There's another study that we're working on concurrently. We're doing a mixed method study. I'm really into mixed methods these days in which we analyze qualitative findings from interviews to guide a scoping review and gain a really comprehensive understanding of the experience of Lynch syndrome carriers. And the study so far really shows the gaps that current systems leave for these patients from knowledge to the options that are available. My second piece that I found really crazy is Lynch syndrome also disproportionately affects female carriers. There was a study that, I'm trying to remember the numbers, they said they found I think 75% of females in their population were diagnosed with cancer compared to only about 58% of male carriers. So this really emphasizes the role that gynecologic cancers have in Lynch syndrome patient outcomes. I really can't help but be surprised that... gynecologic cancer surveillance recommendations fall short behind other cancer recommendations in this population like colorectal cancer, as women's health is so consistently understudied and underfunded across research niches. 

00:24:55 Sabrina 

Yes. Well, I hope that's a call to action for everyone to keep doing good research like you are doing in the women's health field. Thank you so much for joining us on the podcast today, giving such a great in-depth explanation of your project and I know our audience will definitely want to follow up with you to hear your results. 

00:25:12 Arabella 

Yeah, thanks so much. That was so exciting. 

00:25:16 Outro 

Thanks for joining us on the GOSH podcast. To learn more about the Gynecologic Cancer Initiative and our podcast, make sure to check out our website at gynecancerinitiative.ca.