To our knowledge, our cost-utility analysis is the first to demonstrate how incorporating QoL related to medical services for Lynch syndrome affects the cost-effectiveness of screening for Lynch syndrome. Our results demonstrate that the duration of decreased QoL related to germline testing and management of Lynch syndrome is a key determinant of the cost-effectiveness of screening for Lynch syndrome.
By comparing current results with those from our recent cost-effectiveness analysis, one can appreciate the importance of incorporating patient preferences in estimating the cost-effectiveness of screening for a hereditary cancer syndrome. Using IHC followed by BRAF
testing compared with no screening as an example, we previously estimated the cost per life-year gained to be $36,200, absent consideration of QoL.4
When we included only cancer state and general population utilities in one of our current analyses, we calculated a similar cost of screening of $38,100 per QALY gained. When we accounted for the potential short-term decreases in QoL related to germline testing and management of Lynch syndrome, we estimated a higher ICER of $59,700 per QALY gained. Multiplying base case Medicare costs by 1.5 and 2 to model commercial payer costs increased the ICER to $90,800 and $122,000 per QALY gained, respectively. These ICERs may be acceptable to third-party payers and policy makers, as evidenced by coverage of cancer services with comparable ICERs.42
Our cost-utility analysis identifies three factors that underscore the importance of including preferences to estimate the value of screening. First, the cost-effectiveness of screening depended on how long people experienced decrements in QoL related to germline testing and management of Lynch syndrome. Screening was relatively cost-effective if decrements to QoL lasted ≤ 12 months. The ICER worsened as the duration of disutility increased, exceeding $100,000 per QALY gained after 21 months. As duration approached 36 months, the decrements in QoL after germline testing and management decisions outweighed increases in overall survival when measured in QALYs.
Although a number of small studies have reported transience of distress associated with Lynch syndrome testing lasting from 2 weeks to 12 months,10,25–33
specific subgroups defined by demographic factors and cancer risk may experience longer intervals of disutility. One study has shown that young men may continue to feel anxiety about Lynch syndrome over time.33
In addition, persons who do not receive counseling may experience long-term disutility. Therefore, strategies to improve the effectiveness and cost-effectiveness of screening may include ensuring that genetic counseling is offered as part of genetic testing and target additional follow-up and counseling services to persons most likely to experience disutility longer than 12 months. Further research to better identify at-risk individuals is required.
Second, screening became less cost-effective if either probands or relatives with Lynch syndrome experienced extreme disutility after decisions about medical services. Studies have documented differences in distress between persons with a personal history of cancer compared with relatives at risk for cancer.27,28,30
To examine whether cost-effectiveness was more sensitive to changes among probands or relatives, we conducted scenario analyses that showed the ICER was sensitive to variation in utilities for both groups. Although our results represent mean estimates at the population level, we suggest that personalized clinical care and counseling addressing the individual needs of both probands and relatives may enhance the effectiveness and cost-effectiveness of screening.
Third, disutility after declining services had negative effects on the value of screening. Persons may forego germline testing because of concerns about family and abilities to manage the emotional aspects of receiving genetic test results.43
Although counseling is intended largely to help persons who undergo testing understand and manage their cancer risk, counseling may also benefit persons who decline testing by addressing their concerns, thus further improving the value of screening.
In summary, we suggest tailoring interventions to persons who experience long-term disutility, probands and relatives, and persons who decline services. We recommend additional research to validate whether tailoring interventions can preserve the cost-effectiveness of screening.
We acknowledge limitations in our study that can be addressed in future research. We have incorporated health state utilities representing potential QoL outcomes after decisions about medical services among probands and relatives. However, our model does not distinguish utilities for specific subgroups, such as younger versus older men.33
Studies that measure QoL among probands and relatives with different demographic characteristics may provide data for incorporation into future cost-effectiveness models.
We found that cost-effectiveness was sensitive to duration of disutility, but we assumed that everyone experienced the same duration. Probands, relatives with Lynch syndrome, and relatives without Lynch syndrome may each experience distress for different lengths of time. Modeling this would help to identify specific subpopulations that could affect the overall cost-effectiveness of screening as well as persons to target for additional monitoring and counseling.
Finally, our model assumes that everyone who considers germline testing accrues a specific cost for genetic counseling, but this does not account for variable clinical or economic consequences for people who decline counseling or for differences in QoL depending on the intensity of counseling. When relevant data become available, cost-effectiveness studies can include longer-term counseling as an intervention among those who experience unusually long-term decreases in QoL.
In conclusion, our study suggests that universal screening of all patients with newly diagnosed colorectal cancer for Lynch syndrome is cost-effective, even after accounting for the impact of decisions about germline testing and management of Lynch syndrome on short-term QoL. In addition to increasing tumor screening rates, germline testing rates, and adherence to intensive management,4
policy makers and clinicians can maximize the value of screening for Lynch syndrome by attending to the psychosocial needs of probands with colorectal cancer and their relatives who face decisions about germline testing and management of Lynch syndrome.