Impact of time-to-treatment on overall survival of non-small cell lung cancer patients - An analysis of the national cancer database

Background: The association between time-to-treatment and outcomes for lung cancer has not been conclusively established. In this study, we evaluated the effect of time-to-treatment on the overall 5-year survival of patients with non-small cell lung cancer (NSCLC) with cancer stage at diagnosis. Methods: We analyzed data in the National Cancer Data Base for adult patients newly diagnosed with NSCLC in 2003-2011 (N=693,554). Extended Cox regression with counting process was used to model the effect of time-to-treatment on survival, adjusted for demographic and clinical factors. Multivariable analyses were performed separately for the groups with different stages at diagnosis. Time-to-treatment was defined as the interval between diagnosis and treatment initiation, with the categories of (I) 0 day, (II) 1 day-4 weeks, (III) 4.1-6.0 weeks, and (IV) >6 weeks (the 1 day-4 weeks group was considered the reference group). Results: Compared to treatment initiated between 1 day and 4 weeks after diagnosis, time-to-treatment at 4.1-6.0 weeks was associated with a lower risk of death for patients with early-stage cancer [adjusted HR (aHR), 0.84 (95% CI, 0.82-0.85)], with locally advanced cancer [aHR, 0.82 (95% CI, 0.80-0.83)], and with metastatic cancer [aHR, 0.75 (95% CI, 0.74-0.76)]. Similarly, a lower risk of death was associated with timeto- treatment longer than 6 weeks for patients with any cancer stage at diagnosis. However, a subset analysis for early-stage patients who received surgery only showed that extended time-to-surgery was associated a higher risk of death [aHR 4.1-6.0 weeks, 1.06 (95% CI, 1.03-1.09); aHR>6 weeks 1.17 (95% CI, 1.14-1.20)]. Conclusions: The findings show that, although time-to-treatment should not be compromised, it is imperative to ensure that patients receive optimal pre-treatment assessments rather than rushing the treatment. Future research should focus on examining clinical characteristics to determine an optimal timeto- treatment to achieve the best possible survival for NSCLC patients.