Okay, so you guys can see my screen okay? Yes. Okay, perfect. So I was asked to talk about post-cancer, post-treatment cancer surveillance, which is actually a very near and dear topic to my heart. So I have a couple of things that I want to just talk about here in this, in this brief review. Just kind of talking about what surveillance needs actually means for cancer survivors. So not talking about survivorship in general, but just really surveillance. And kind of looking at, I had the chance to look at kind of what the general practices are, but there's been a lot of data since we've done a, we did a paper for SGO and there's been a lot of data. So I have some updates. And one of my other interests, I have my MBA as well, and so I'm always really interested on how our costs or our behaviors impact the cost of treatment. And I apologize because this may be country specific. So I'd love to hear what other practices are. And then what are some of the challenges on why we have such variation in practices? So when we look at gynecologic cancer survivorship, it's really a growing field. And this is a testament to, you know, better diagnostic tools and early diagnosis, which leads to longer survivorship, but as well as better therapies. And so as you can see from 2019 to 2030, the rate of female cancer survivors across the board is also, is going to be increasing by about 30%. We expect about 1.34 million gyne cancer survivors currently, and this is also expected to grow at that same rate. And so when I was a fellow, I always kind of wondered what the best practices are for recurrence detection, because people did things differently and that was very kind of frustrating to me. And so these variations in practice, to me, kind of equated to kind of unknown, kind of an unknown, but we know that these variations, there may be some areas that are low quality care that also are high costs, and that's kind of the worst case scenario. But what was more interesting to me is we didn't really know what the impact of surveillance trends or surveillance practices were on survival outcomes. And so I had the opportunity, 2011 and 2017, to write these papers for Society of Gynecologic Oncology on kind of best practices. But I will qualify that most of this was retrospective data. So we think about surveillance, it's just important to highlight that we want to impact survival outcomes. Surveillance in the setting of no survival outcomes is a little less meaningful. We also want to balance benefits and pitfalls for patients. We know there's a lot of anxiety for patients with these tests, and then their anxiety kind of decreases after surveillance visits. But we also want to make sure that there's a clinical benefit to our surveillance tests, that these should kind of optimize our care for these patients, enhance our ability to detect cancers early or catch other cancers that may be related, but minimize kind of, where we don't have any options for these patients. And then lastly, to remain cost-effective, that we don't want to burden our healthcare systems with extra costs or unnecessary tests. And so I'm going to go through each of our main cancers kind of quickly, just to kind of give you an overview of what current practices are and maybe where we can go next. And so cervix cancer, we know is the most common gynecologic malignancy with a high rate of deaths worldwide. And we know that a lot, about 50% of cancers are caught in early stages. And this is where our therapies are the best. So our treatments are the best, and that translates to the best survival. We also know that the incidence of cervical cancer is decreasing. But when we are missing the subset of patients, so the patients who aren't getting vaccinated, who aren't getting screened, and who are presenting typically in advanced stages, or those patients who present in locally advanced stages and then recur. And most of our recurrences occur within three years of diagnosis. And this is more common in patients who have advanced disease. So when we look at cervical cancer cytology, we know this is a great tool for preventing cervical cancer or diagnosing it in early stages, but what about for surveillance? When you look across the board at abnormal cytology, it generally occurs in about anywhere from zero to 17% of patients who have a history of cervical cancer, but it's rarely an isolated finding. Oftentimes, these patients have symptoms or other clinical findings on examination. We also know when abnormal cytology is found, it's most often low-grade changes, and this can lead to unnecessary interventions such as colposcopy and even biopsies. And those are not without risk, as these can cause other complications, such as bleeding, even fistulas in rare circumstances. What's even more daunting is that when we do cytology in patients who've had prior radiation, you can actually find abnormal cytology in about a third of these patients. And once again, a majority of these are benign or mild changes in the absence of other findings, and many of them may be actually related to the radiation itself. And so kind of based on this, we recommended limiting cytology, probably max to once per year if it's needed to be done, and there is limited value of HPV surveillance. I just had the opportunity to publish a paper with some of my partners here where HPV positivity did not detect higher risk of recurrence. And we really should limit colposcopy for high-grade changes that are found when cytology is performed. I think it's something to consider, and that's to eliminate cytology testing in patients who've had radiation therapy. And there was recently a publication from MD Anderson that suggests that after trachelectomy, so for those who are having fertility sparing, the role of cytology is really unclear, and they actually recommended omitting it, which I think makes sense. And I think this is different than doing a visual inspection, which I think is still maybe an important part of these patients' care. Because we want to also evaluate the entire lower genital tract, as we know that these HPV-related diseases can involve the vulva, the vagina, even the anal area. So visual inspection is still very important. When we look at imaging, chest X-rays and CT scans have low rates of detection for early stage or manageable cervical cancer. And this is why we don't see any survival benefits when we do routine imaging. PET-CT scans have sensitivities of 86% and specificity of 87%. But this has really been limited, at least in the United States, to prognostic significance. So when a patient's completed chemoradiation for cervical cancer, those patients were usually surveilled at three months to make sure that they've had a good response. If they've had a good response, that's favorable. If they haven't, we know that they have a higher risk of recurring, and additional testing or studies may be warranted. But in an asymptomatic patient, we really don't know what the role of imaging is, and it's not been shown to have any benefit. And we do recommend that this is limited to when recurrence is suspected based on exam findings or on patient symptoms. And so next, I'm going to shift gear towards endometrial cancer, and here you can see the world rates of endometrial cancer at about 400,000 cases per year, with almost 100,000 deaths per year. And sadly, in the United States, this is an incidence where we're actually seeing an increase along with the mortality. A majority of patients are diagnosed in early stages, but we still have significant morbidity from this disease. Once again, a majority of these patients will recur within three years, and we see that these recurrences occur earlier in patients with advanced disease or in those with high-risk histology. And so symptoms for endometrial cancer recurrence are actually quite common, symptoms and or examination, so that's an important part of this. But when we look at our tests or tools, I want to start with cytology first. And so here's a, I put together all the studies I could find, at least up until about 2020, that had cytology as part of surveillance for endometrial cancer. And you can see that the recurrence rates vary, but generally about five, I should say about two to 20% range, and these were different populations, so there is some variation. But what I really want to highlight is that when you look at cytology alone, the rates of detection of endometrial cancer recurrence by cytology alone were pretty minimal. And so this is a pretty low-value test. And I would actually advocate for the removal of cytology for, and this is vaginal cytology at this point, for endometrial cancer recurrence detection. We also looked at single institutions that published data on cytology, and when you look at these numbers, and I won't go over this in too much detail, but you can see there's a lot of costs associated with kind of the cost per case detected. And so if you reduce pap testing in a single institution, you may be able to save about $58,000 per year by eliminating pap testing for these patients. And I strongly advocate for the elimination of this test in this patient group. And if you look at, this is in the United States generally, you could actually save about $4 million per year by eliminating this one simple test. But I do want to highlight that there was additional studies, and this is one of the few prospective studies that's been performed for surveillance in GYN cancers. And so this was a study of endometrial cancers. This is the TOTEM study, and this was presented just this past year at ASCO. They separated patients into two groups. So the first group was the low-risk endometrial cancer patients. These were patients with stage 1A, grade 1 and 2 disease. And they separated patients into what's called the intensive surveillance group or the minimalist surveillance group. And you can see here with some highlights in the table with yellow, that's the intense group. So for the low-risk patients, they did clinical examinations about every four months, pap tests yearly, and CT scans once a year for the first couple of years. And then for the minimalist group, they just did clinical examinations, and they did this at the six-month strategy for two years and then every year. They also looked at a high-risk group, and this was high-risk that was 1A, grade 3, or greater than stage 1B for endometrioid, and they did have some high-risk cytology in this group as well, but that was at less than 10%. And so once again, they had an intense strategy, which included clinical examinations, CA125, ultrasound, which was done every four months for the first couple of years and then yearly, and then pap tests as well, as well as CT scans on the interval shown. And then for the minimalist group, they just did clinical examinations and then CT scans yearly for the first two years. And just to kind of show you the overview, this was a pretty large study with about 1,000 patients in each arm, and you can see the breakdown of histology. And once again, the non-endometrioid histology made up a small subgroup of this patient population. And this is really the key takeaway. You're not seeing this incorrectly. These lines totally overlap, so they're really hard to see. There was no difference on whether you went through the intense or the minimalist surveillance strategy. And when they broke it down by low risk and high risk, these curves really don't change shape. So you can see that these completely overlap. And then when they even looked at relapse-free survival, it's almost identical. And so the takeaway from this was really that this intense surveillance protocol does not make a difference for the primary outcome, which is overall survival or relapse-free survival. And so kind of looking at this a little bit differently, this was an evaluation of patients who had early-stage disease, who underwent cytology rates, excuse me, who underwent cytology and CT scans. And this study kind of looked at this from before 2011 when we published our first surveillance guidelines to a period after 2011. And they kind of stopped at that 2011 point to see if practice had changed. And what you can see is that the rate of cytology has stayed pretty much consistent up until 2011 at about two thirds of patients getting cytology yearly. And then CT scans, you can see actually increased. So 11.7% in about 1992, and this increased to about 25% in 2011. And so when you look at the mean cost cytology, although it's a low cost endeavor, when you have a lot of patients getting it, it does add up. And so you can see a $63 per person and CT scans at $750 per patient. This really does add up. And so if you take every uterine cancer patient and do a pap test and one CT scan, you have about $50 million of cost that's put on the healthcare system. And I would say that those are wasted costs. So the TOTIM trial didn't really answer for high risk histology. And I think this is still an area that is really kind of a gray area. These are two studies that did look at, and they're both retrospective studies that looked at high risk histologies. And you can see that there's a high rate of recurrence, you know, about 40% of these patients recur and these were all stages. So it is a, you know, hodgepodge of a group. But when you look at recurrence, most of these were detected by symptoms and examinations. These are two separate studies here. Imaging did detect about 15% and tumor markers about 10 to 23%. And once again, cytology of very low rate. The interesting thing that the authors found is that no matter how the recurrence was detected, there was no difference in survival. And so kind of advocating for less is more in this setting. I'm next gonna shift gears to ovarian cancer. And once again, here you can see the worldwide rates of ovarian cancer at about 300,000 new cases and kind of across the board, a majority of these are in advanced stages. And then the estimated deaths, just over 200,000. Interestingly, the incidence and death rates are decreasing. This is probably due to better genetic testing, better therapies that are reducing death rates and new therapies such as PARP inhibitors. But we know that even in early stages, recurrences are quite common. And we know that symptoms such as abdominal bloating, pain, nausea, vomiting are not uncommon. And physical examination is really good for picking up pelvic disease, but we know a majority of these patients actually don't recur only in the pelvis. And so there are some limitations. We can't detect nodal disease with the exception of groin nodes or upper abdominal disease. And so I put this in here for another talk, but telehealth may be an option where you can actually assess symptoms and then bring patients in for physical examination or further assessment if they have symptoms. I want to spend a little time talking about CA-125 levels. I think this has been a little bit of a contentious area. And so many of you are probably familiar with the Rustin study, which looked at 529 patients, which were randomized to treatment based on rising CA-125 versus delayed treatment based on symptoms. And this was published in 2010. And what they found is that whether you were randomized to treatment based on CA-125 or symptoms, there was really no difference in survival between these two groups. And the study findings questioned the role of CA-125. If it didn't make a difference in early detection, maybe there's no use for this. And the European Society did recommend that CA-125 should really be used at the time of relapse or if requested. And maybe routine use is not that beneficial. There were some problems with the study. And even though patients were randomized, there was some kind of unblinding or use of the CA-125 regardless of that. And the purpose of the study was not really to find out whether CA-125 helped detect recurrences. It was really to see the outcome based on treatment. So there are some questions that I think the study leaves. And so when we look at, and I'm gonna come back to CA-125 in a second. When we look at imaging for ovarian cancer, there have been multiple modalities that have been evaluated and you can see that the sensitivities and specificities range pretty broadly. And so really there's not an ideal imaging tool and we should take this as an individual patient-based evaluation. And really my approach is to limiting imaging for what I suspect recurrences based on examination or patient symptoms. But you can see that the rates here that are presented for the sensitivity and specificity. And so imaging, once again, these are a couple of studies. These are a little bit older studies, but you can see that imaging has kind of varied in the rates of detection for ovarian cancer. It is probably one of the more sensitive tools, although most of the tools are not that great at detecting recurrences of ovarian cancer, at least early. And the key point of these studies was that really there was no survival difference when you used imaging versus CA-125 versus examination. And so I think this kind of wants us wanting more. I wanna go back to CA-125 and this is just a really cool study that I thought that was presented in 2021. This was a poster, so I don't know if it got a lot of attention, but it is a pretty cool study that looks at surveillance particularly. So this was an ancillary study of PAOLA-1 and they really evaluated the progression based on CA-125 level and imaging. And this first figure that I have shown here looked at, that showed kind of that CA-125 progression or elevation preceded imaging progression by about two to three months kind of across the board. And they looked at this in different populations, so you can see those rates here. But what I thought was really cool is that they looked at this at the start of maintenance therapy, and they actually found that CA-125 is actually a pretty good tool for monitoring progression of disease without independent of imaging. And so what I wanna highlight in this first figure, figure four, is that progression by imaging alone in patients who had an abnormal baseline CA-125 was only found in 17%. So you can have about 85% of patients detected by CA-125. So the first, the dark blue box is CA-125 alone, and that purple or that magenta box is CA-125 and imaging. And so if you think about it, CA-125 detected about 80% of these patients. So I think that's pretty impressive. Even in patients who had a normal baseline CA-125, CA-125 alone or with imaging detected over 50% of patients. And so I think that this kind of tells you maybe imaging isn't really that meaningful in this setting. Maybe reserved for those patients with normal CA-125, because it did detect about 45% of those patients. But in those who had a normal CA-125, it may not be the most useful tool. It may be just an excess resource. They also looked at, on this right-hand side, they also looked at CA-125 progression in different cohorts, including those with BRCA mutation and those with wild type, and really found no difference. And so if you look at this, CA-125 with progression before recess versus recess alone was about split in the elaparib and bevacizumab group, but really favored the CA-125 alone in all the other groups. And so I think it's something to think about in having that individualized discussion with the patient based on their CA-125 at presentation. And so once again, I want to put a little bit of cost perspective into it. And so impact on practice. This is a multi-institutional perspective cohort that was published in 2016. And they kind of looked at, once again, the rates of CA-125 and CT scans. These really didn't change before or after 2009. CA-125 levels continue to be checked in a high rate of patients who had normal CA-125s at diagnosis. And a majority of patients, I'm sorry, one third of patients had multiple scans per year. And so what we find is that really surveillance guidelines really didn't change practice. And when we look at costs, the median cost per patient per year, when you look at four CA-125 levels per year, that's every three months and one CT scan, is about $1,000. And when you look at that kind of broad scope over the course of the country, it's about $16 million. And when you think about patients having multiple scans in one year, that's actually almost $27,000. That's just the United States. And so this kind of led to these Choosing Wisely campaigns that ASCO had advocated for. And it really tasked each society looking at something where they could reduce costs in their own kind of fields. And Society of Gynecologic Oncology came up with these five things. And I was really excited because I think a lot of these are based on surveillance. So, you know, number two, stop performing Pap tests for surveillance of women with a history of endometrial cancer. Don't perform colposcopy in patients treated for cervical cancer with low grade or less lesions on cytology if cytology is performed. And then avoid routine imaging for cancer surveillance and our patients across the board. And so I think this is something where we can really make a dent in improving our expense on the healthcare system without compromising outcomes for patients. And I just want to highlight that some, you know, I've said that there's been very slow changes in this and I wanted to kind of explore why that's happened. And so we always think randomized controlled trials are the gold standard. And I think when they can be done, they should be. We know they're cost prohibitive and they are resource intensive. And I commend the authors of the Totem trial for performing one of the first trials in surveillance in gynecologic cancers. But I think it also leads to a slow adoptions change practice. People are based practice on their anecdotal experience. I did a Pap test this one time and I picked it up. So I'm going to continue doing it because you don't know what you're going to miss. Patients also demand it. I mean, how many times have you had a patient asking you for a CT scan, even though it's not indicated? And then there's always, at least in the United States, we have a fear of lawsuits. There's a little bit of, you know, kind of defensive medication practices. And so that's something we always have to consider too. And then we have these surveillance recommendations in clinical trials. Patients go on a trial and they get scans every six weeks, every 12 weeks, and then that kind of becomes the norm. So I think it's obviously for a different intent, but it kind of blurs into our clinical practice. So kind of in summary, these are some tables on the right side that I had the chance to produce with SGO kind of recommendations. These were published in 2011, and I would actually argue that they are still relevant today. And our findings or recommendations were very consistent with the Totem study findings. I think it's important to recognize that symptoms and examinations are still the most useful tool, and they are low cost. So it's important to review signs and symptoms with patients and make sure patients have easy access to getting care if they do experience any symptoms. Once again, the role of cytology is limited, both in cervical and endometrial cancer. I didn't present the data in ovarian cancer, but it essentially plays no role there as well. And I think it's safe to advocate for avoidance of routine images, imaging and patients. But I think it's also important that we communicate with healthcare providers. It's not uncommon that I'll see a patient who her internal medicine or primary care doctor ordered a CT scan because of her history of ovarian cancer, even though it wasn't indicated. So having a surveillance plan and expecting and discussing that with the patient so they know what to expect, but also the patient's other healthcare providers. I do hope in time that our therapies get better and so that detecting surveillance, excuse me, detecting a recurrence early by any method can actually make a better difference in survival because I think that's one area that we have yet to explore. So I know I went through that pretty quickly, but I thank you for your time and happy to have any further discussion or conversation about this topic.

post-cancer

gynecologic cancers

surveillance practices

early detection

cytology

CA-125 levels