The results of this study suggest that a minority of patients with LFS are able to adhere to the demanding high-risk cancer surveillance protocol recommended. While 52% achieved adherence for the first 12 months, there was a general trend of decreasing adherence with longer follow-up and only 29% were up to date at the time of chart review. Female sex was associated with longer duration of adherence, which may be surprising because women in the general population are typically less adherent to screening colonoscopy recommendations than men, though it is noteworthy that there were only 4 males in our study sample [12]. A personal history of cancer was also associated with longer duration of adherence. Notably, while the 2 patients with active cancer diagnoses did have a roughly average length of adherence (14 and 18 months) compared to others in the study, neither were up to date with recommended surveillance at the time of chart review, likely due to prioritizing their active cancer treatment. No other patient factors were identified that could predict who may follow recommendations for an extended period. Residing in the state of Virginia, for example, was not associated with longer duration of adherence compared to those that resided out of state. It seems reasonable to hypothesize that geography could contribute to greater adherence if being closer to UVA, where the LFS Clinic and the only hospital in the region able to perform wbMRI are located, made it easier for patients to complete their tests. However, this was not found to be the case, and in fact, one of few patients who were up to date lived farthest in the state of Florida. One could also hypothesize that insurance status could affect adherence. In our study population, 100% of the patients were insured, and thus insurance status itself could not be analyzed as a factor contributing to adherence. However, type of insurance could be examined in the future, as simply having insurance does not necessarily mean coverage is adequate to cover expenses for a specific patient, and some insurance companies may cover a greater percentage of cost.

In assessing the tests most commonly missed of those recommended, colonoscopy and EGD were at the top of the list for all patients. This pattern was similarly seen among both males and females (Fig. 1). Consistent with published literature in both the general population and in other high-risk populations such as those with Lynch Syndrome, colonoscopy and EGD are often subject to decreased adherence [13, 14]. These are invasive and uncomfortable procedures that often require preparation and anesthesia of some sort, and require a patient to be accompanied to their appointment. Skin exam was missed as frequently as colonoscopy and EGD among all patients. This is likely due to the fact that many patients receive dermatology follow-up outside of the UVA system and are responsible for scheduling appointments on their own, thus decreasing adherence. WbMRI was also commonly missed. Several patients in the study were significantly delayed in completing their wbMRI by as much as a year, with insurance issues cited as a reason in their charts. WbMRI is also very limited in geographic availability, with UVA University Hospital serving as one of the only sites in the region to offer it, likely contributing to decreased adherence as well.

The adherence rate of 29% within this study is far lower than those reported in prior studies. For example, in the Toronto protocol study, a 90–100% adherence rate was noted [7]. However, this was among the 55% of their total study population that chose to undergo surveillance and was in the context of a trial. Our results may be lower because they account for all patients with LFS in a real world clinical setting, not just those choosing to enroll in a clinical trial, which is likely a highly motivated patient population. Furthermore, it is unclear whether patients in the Toronto protocol study received more prompting or more frequent follow-up than patients may receive in the UVA LFS clinic. The patient survey study with a 78% adherence rate is limited by patient report of adherence, which may not be accurate, and is further limited by the fact that recommendations were not defined or uniform among all patients being surveyed, potentially explaining the difference between our results [9].

It is worth noting that the favorable outcomes seen as a result of surveillance using the Toronto protocol, including stage shifts and improved mortality rates, resulted when using the original, more rigorous protocol initially proposed than the modified Toronto protocol version that has since been proposed by the authors and is more in line with that being used in the UVA LFS clinic [1, 7]. Therefore, it is unclear without further research whether use of the modified protocol, and adherence to it, will result in the same benefits.

A strength of this study was access to data of an unselected population of patients with LFS, meaning that all adult patients known to the UVA system with LFS were eligible for initial review, thus reducing selection bias. Additionally, all data extracted from patient charts was recorded by the same physician and genetic counselor who run the LFS clinic, thus information was documented in a uniform manner with few missing elements.

This study is not without limitations. First, LFS is a very rare disease, thus our study sample size for evaluating adherence at a single institution was small. However, the Toronto protocol study is one of the largest studies available in a LFS population and included only 89 patients, thus for a rare disease we were able to achieve a reasonably-sized sample for study [3]. Second, by utilizing patient records retrospectively for data collection, we were limited in the variables we were able to study to those factors that would be available within the chart for every patient. It would have been interesting to investigate socioeconomic status or the extent of insurance coverage for surveillance tests and the effect each of these had on adherence, for example, as well as patient-identified barriers. However, these are not documented in a consistent manner within the medical record, and thus could not be evaluated in this study. It is likely that only insured patients with high health literacy present for high-risk care at this time based on the clinic population. Third, the average duration of adherence may be skewed by the fact that some patients presented to the UVA LFS Clinic earlier than others. For this reason, patients that presented within 12 months of the time of chart review were excluded, and adherence rates based on duration of follow-up were calculated and reported in the results section. Furthermore, the average duration of follow-up among males was shorter than for females (26 months versus 41 months, respectively), calling into question the validity of female sex being associated with longer duration of adherence. Despite differences in average length of follow-up, the observation may stand because males duration of adherence in relation to their duration of follow-up was disproportionately lower than that among females. Finally, the impact of COVID-19 on surveillance adherence should not be overlooked. The first major pandemic-related health systems shutdown occurring from March 2020 to roughly June 2020 fell in the middle of the follow-up window for this study. While it is favorable that the majority of patients that were adherent at the start of the pandemic were able to continue with their scheduled surveillance despite the shutdown, there was a difference in adherence noted between those who were followed prior to 2020 and who started after 2020. It is possible this discrepancy is related to patient avoidance of healthcare settings or other similar barriers as a consequence of COVID-19, though it is unclear. There is good evidence for patient avoidance of healthcare during the initial phases of the pandemic, but less is known about whether this tendency has continued to now, almost 3 years from the primary shutdown [15]. It would be interesting to see if this pattern was observed in other institutions with similar high-risk surveillance programs.

In conclusion, a minority of patients with LFS remain adherent to a rigorous, high-risk cancer surveillance protocol for extended periods of time within the UVA system. Longer duration of adherence seems to be associated with female sex and a personal history of cancer, while age, state of residence, and family history of LFS are not associated. Future directions include examining patients with LFS who undergo recommended risk reducing procedures, such as mastectomy, and factors that influence their decisions. Additionally, identification of barriers to surveillance will be essential moving forward. Our group is actively studying patient-reported outcomes in LFS to identify some of these barriers, specifically the role of screening fatigue, with the hope that this knowledge may lead to interventions designed to increase surveillance adherence. Only when we increase adherence to recommended surveillance will the goal of early detection of cancer, and thus a reduction in the morbidity and mortality of LFS, be realized.