Analysis of Delayed Surgical Treatment and Oncologic Outcomes in Clinical Stage i Non-Small Cell Lung Cancer

Brendan T. Heiden, Daniel B. Eaton, Kathryn E. Engelhardt, Su Hsin Chang, Yan Yan, Mayank R. Patel, Daniel Kreisel, Ruben G. Nava, Bryan F. Meyers, Benjamin D. Kozower, Varun Puri

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Abstract

Importance: The association between delayed surgical treatment and oncologic outcomes in patients with non-small cell lung cancer (NSCLC) is poorly understood given that prior studies have used imprecise definitions for the date of cancer diagnosis. Objective: To use a uniform method to quantify surgical treatment delay and to examine its association with several oncologic outcomes. Design, Setting, and Participants: This retrospective cohort study was conducted using a novel data set from the Veterans Health Administration (VHA) system. Included patients had clinical stage I NSCLC and were undergoing resection from 2006 to 2016 within the VHA system. Time to surgical treatment (TTS) was defined as the time between preoperative diagnostic computed tomography imaging and surgical treatment. We evaluated the association between TTS and several delay-associated outcomes using restricted cubic spline functions. Data analyses were performed in November 2021. Exposure: Wait time between cancer diagnosis and surgical treatment (ie, TTS). Main Outcomes and Measures: Several delay-associated oncologic outcomes, including pathologic upstaging, resection with positive margins, and recurrence, were assessed. We also assessed overall survival. Results: Among 9904 patients who underwent surgical treatment for clinical stage I NSCLC, 9539 (96.3%) were men, 4972 individuals (50.5%) were currently smoking, and the mean (SD) age was 67.7 (7.9) years. The mean (SD) TTS was 70.1 (38.6) days. TTS was not associated with increased risk of pathologic upstaging or positive margins. Recurrence was detected in 4158 patients (42.0%) with median (interquartile range) follow-up of 6.15 (2.51-11.51) years. Factors associated with increased risk of recurrence included younger age (hazard ratio [HR] for every 1-year increase in age, 0.992; 95% CI, 0.987-0.997; P =.003), higher Charlson Comorbidity Index score (HR for every 1-unit increase in composite score, 1.055; 95% CI, 1.037-1.073; P <.001), segmentectomy (HR vs lobectomy, 1.352; 95% CI, 1.179-1.551; P <.001) or wedge resection (HR vs lobectomy, 1.282; 95% CI, 1.179-1.394; P <.001), larger tumor size (eg, 31-40 mm vs <10 mm; HR, 1.209; 95% CI, 1.051-1.390; P =.008), higher tumor grade (eg, II vs I; HR, 1.210; 95% CI, 1.085-1.349; P <.001), lower number of lymph nodes examined (eg, ≥10 vs <10; HR, 0.866; 95% CI, 0.803-0.933; P <.001), higher pathologic stage (III vs I; HR, 1.571; 95% CI, 1.351-1.837; P <.001), and longer TTS, with increasing risk after 12 weeks. For each week of surgical delay beyond 12 weeks, the hazard for recurrence increased by 0.4% (HR, 1.004; 95% CI, 1.001-1.006; P =.002). Factors associated with delayed surgical treatment included African American race (odds ratio [OR] vs White race, 1.267; 95% CI, 1.112-1.444; P <.001), higher area deprivation index [ADI] score (OR for every 1 unit increase in ADI score, 1.005; 95% CI, 1.002-1.007; P =.002), lower hospital case load (OR for every 1-unit increase in case load, 0.998; 95% CI, 0.998-0.999; P =.001), and year of diagnosis, with less recent procedures more likely to have delay (OR for each additional year, 0.900; 95% CI, 0.884-0.915; P <.001). Patients with surgical treatment within 12 weeks of diagnosis had significantly better overall survival than those with procedures delayed more than 12 weeks (HR, 1.132; 95% CI, 1.064-1.204; P <.001). Conclusions and Relevance: Using a more precise definition for TTS, this study found that surgical procedures delayed more than 12 weeks were associated with increased risk of recurrence and worse survival. These findings suggest that patients with clinical stage I NSCLC should undergo expeditious treatment within that time frame..

Original languageEnglish
Article number11613
JournalJAMA Network Open
Volume4
Issue number5
DOIs
StatePublished - May 27 2021

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