In our cost-effectiveness analysis, we showed that a full chest scan is cost-effective in patients requiring CT calcium scoring to screen for coronary artery disease because it saves lives from lung cancer. It saved 0.03 QALY (about 11 days of life) with an additional cost of $278 for a calculated ICER of$10,289/QALY. This result showed FCT was more cost-effective than CTCS. This benefit was further confirmed by Monte-Carlo simulation, which estimated the true ICER to be between $8,039/QALY and $13,186/QALY. To put this result into perspective, implementation of mammogram for breast cancer screening has a reported ICER ranging from $60,000 to $80,000/QALY10. Screening colonoscopy has an ICER of $15,000/QALY which is comparable to the calculated ICER of FCT11. Both screening colonoscopy and mammogram are fully reimbursed by most insurances. While the NLST is currently the “gold standard” study for lung cancer screening, we believe that using the criteria within that study as the only criteria to screen for lung cancer is overly stringent. This study suggests that there is benefit to lung cancer screening in other populations as well. Coronary artery calcification is frequently identified in patients undergoing lung cancer screening with LDCT12-14. NLST data have shown that the presence of coronary artery calcification is associated with a 3 fold increase in cardiovascular death13. These studies suggest a concordance of CAD and lung cancer12-14. Therefore, adding patients who are receiving CTCS to a lung cancer screening cohort is reasonable on several levels.
The actual benefit of FCT is likely underestimated in this study. The actual malignancy rate of the MPNs in this population was unknown, and estimation of this rate was intentionally conservative. Observational studies of pulmonary nodules based on locations suggest that the upper lung fields have more nodules than the lower lung fields and that upper lung nodules tended to have higher malignancy rate6,7. These observational studies were part of our rationale to modify existing CTCS scanning protocols. Interestingly, one study noted that one patient undergoing CTCS developed lung cancer without incidental finding on CTCS suggesting possible missed nodules4. In our model, we took a conservative approach in the base-case analysis by assuming an equal malignancy of upper and lower lung field nodules. Even with this assumption, the base-case analysis is cost-effective. Given the conservative nature of our estimates, the actual benefit of FCT may be even more cost-effective than our base-case analysis result. This was corroborated by the sensitivity analysis, which showed that the higher the malignant rate of the MPNs was, the lower the ICER of FCT would become.
Our study has several limitations. Foremost, the patient population who received calcium scoring imaging was different from the NLST inclusion criteria. NLST screened patients aged 55-75 years old who were current smokers or a former smoker who quit less than 15 years prior and with at least 30 pack year smoking history8. The criteria for calcium score imaging is not specifically targeted to patient with history of tobacco use. Current expert consensus agreed that calcium score imaging is appropriate for asymptomatic patients who are 40-75 year old with a 5-20% 10 year atherosclerotic cardiovascular disease (ASCVD) risk2. The ASCVD risk is calculated based on age, sex, race, smoking status, blood pressure, cholesterol levels, smoking status and diabetic status2. Atherosclerotic cardiovascular disease shared risk factors with lung cancer which could explain the benefit of performing FCT on this population12-14. Current smoker and former smoker are reported to be around 28% and 39% in patients requiring CTCS3. We concede that as tobacco rates decrease, the malignancy rate in IPN will also decrease, thereby erasing the benefit of FCT. While this is a significant imitation, the sensitivity analysis suggests that an FCT protocol for screening coronary artery disease with CT scan will have benefit until the malignancy rate in MPN falls below 1.5%, which is much lower than current estimates3. Our model is not sensitive to the amount of the MPNs but only to the malignancy rate of the MPNs. In another word, the cost-effectiveness benefit of FCT derives from identifying malignant pulmonary nodules. As many studies have shown, the majorities of incidental pulmonary nodules found on CTCS are benign4,5. Workup of benign findings will not translate into survival benefit which is proven in our model.
As mentioned above, this study is an exploration of the potential benefit of FCT. In that regard, another weakness of this study is that FCT does not exist as an established imaging protocol. Imaging parameters are yet to be established. Our institution will be creating protocols for these studies and hope to standardize this for international adoption. We included a proposed FCT protocol in the supplemental material (Supplemental Figure 1). Other potential weaknesses of this study are that some outcomes of FCT are not modeled in the outcomes. For example, with increased lung field scanned, more incidental findings such as blebs and emphysematous change may found, and the burden of these findings are not included in the analysis. The increased workload of radiologists was not modelled in our analysis. Radiologists who read CTCS were required to recognize extracardiac findings as these were frequently found on the current CTCS15. FCS would identify more extracardiac findings which would require more work of the reading radiologist to characterize these findings. However, we expected the increased workload of FCT would be limited because these extracardiac findings of FCT were similar to that found on CTCS. From a practical standpoint, it would be very difficult to model the increased workload in our current model due to the lack of actual data. We felt it would be better explored in a prospective study. Lastly, the increased radiation exposure to the upper lung fields were not included. Recent studies have shown that the radiation exposure for CTCS is about 1 mSv17,18. Including additional apical lungs for FCT is likely resulting in a negligible increase of overall radiation exposure. Some studies have suggested high radiation exposure in cancer patient cohorts increase the risk of developing cardiovascular disease but the radiation exposure in the study was mainly from radiation therapy instead of diagnostic radiation16.
The NLST included a strict inclusion criterion to reduce unnecessary screening and interventions. At the same time, it also prevented patients who might harbor lung cancers but did not meet the inclusion criteria from screening and early detection. Patients who were at high risk for lung cancers but did not meet the NLST criteria had a difficult time to obtain a screening LDCT and get insurance to pay for it19. This practically excluded them from being screened for lung cancer. Because lung cancer is by far the leading cause of cancer in the United States, we advocate for a new lung screening strategy to combat this disease. With the theoretical benefit for FCT in our study, we recommend implementation of this protocol. Once implemented, prospective study of the true effectiveness and cost could then be realized.