The Impact of Frailty and Comorbidities on Lung Cancer Screening Invitation Response, Low-Dose CT Uptake, and Selection Strategies

Lung cancer screening (LCS) using low-dose CT reduces lung cancer mortality among individuals at high risk of the disease. This high-risk population may have a higher incidence of frailty and multiple comorbidities, potentially due to the influence of age and smoking history, compared to those undergoing screening for other cancers. However, the incorporation of frailty and comorbidities into LCS has not been thoroughly studied. This thesis aimed to investigate the prevalence of frailty and comorbidities and their impact on LCS invitation response, low-dose CT uptake, and selection strategies within the Yorkshire Lung Screening Trial (YLST). Study One was a systematic review and meta-analysis that examined the prevalence of comorbidities in the lung cancer screening population. This study identified several prevalent comorbidities and highlighted the lack of frailty assessment among individuals undergoing LCS. Study Two was a retrospective case-control analysis that explored the prevalence of frailty and comorbidities, as well as the response to the YLST lung cancer risk assessment invitation and subsequent uptake of low-dose CT screening. The analysis revealed that frailty of any degree was present in 47.9% of eligible individuals offered low-dose CT appointments, including 16.2% with moderate to severe frailty. Interestingly, individuals without frailty or comorbidities were less likely to respond to the risk assessment invitation but showed higher participation in low-dose CT screening when deemed eligible. Study Three was a retrospective comparative analysis that evaluated frailty, comorbidities, and survival among populations eligible for LCS, identified by different selection strategies. The study found that the risk models currently used in the UK (PLCOm2012 and LLPv2) identified similar populations in terms of frailty and comorbidities, with both models showing higher prevalence than the USPSTF2021 criteria. However, three-year overall survival appeared to be similar across all strategies. In conclusion, future LCS efforts should focus on increasing participation rates amongst fit individuals with fewer comorbidities (who appear less likely to take part currently) and comparing long-term outcomes across different levels of frailty and comorbidity.