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Effect of Time to Surgery on Recurrence and Survival in Clinical Stage I NSCLC


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In a retrospective cohort study reported in JAMA Network Open, Heiden et al found that increased time from preoperative diagnostic computed tomography imaging and surgical treatment was associated with an increased risk of disease recurrence and poorer overall survival in patients with clinical stage I non–small cell lung cancer (NSCLC).

As stated by the investigators, “The association between delayed surgical treatment and oncologic outcomes in patients with NSCLC is poorly understood given that prior studies have used imprecise definitions for the date of cancer diagnosis.”

Using a more precise definition for time to surgical treatment, 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.
— Heiden et al

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Study Details

The study involved data from patients in the Veterans Health Administration (VHA) system with clinical stage I NSCLC who underwent resection from 2006 to 2016. Time to surgical treatment was defined as the time between preoperative diagnostic computed tomography imaging and surgical treatment.

Key Findings

Among 9,904 patients included in the analysis, 9,539 (96.3%) were men, 4,972 (50.5%) were current smokers, and mean age was 67.7 years.

The mean time to surgical treatment was 70.1 days (standard deviation = 38.6 days). Time to surgical treatment was not associated with increased risk of pathologic upstaging or positive margins.

After median follow-up of 6.15 years (interquartile range = 2.51–11.51 years), disease recurrence was observed in 4,158 patients.  

Longer time to surgical treatment was associated with increased risk of recurrence, with risk increasing significantly after time to surgical treatment of 12 weeks. For each week of delay beyond 12 weeks, the hazard for recurrence increased by 0.4% (hazard ratio [HR] = 1.004, 95% confidence interval [CI] = 1.001–1.006, P = .002). Patients undergoing surgery at > 12 weeks had significantly poorer overall survival (HR = 1.132, 95% CI = 1.064–1.204, P < .001).

Factors significantly associated with delayed surgery included:

  • Black race (odds ratio [OR] vs White race = 1.267,  P < .001)
  • higher area deprivation index score (OR for every 1-unit increase in score = 1.005, P = .002)
  • lower hospital case load (OR for every 1-unit increase in case load = 0.998, P = .001)
  • less recent year of diagnosis (OR for each additional year = 0.900, P < .001).

Additional factors significantly associated with increased risk of recurrence included:

  • younger age (HR for every 1-year increase = 0.992, P = .003)
  • higher Charlson Comorbidity Index score (HR for every 1-unit increase in composite score = 1.055, P < .001)
  • segmentectomy (HR = 1.352, P < .001) or wedge resection (HR = 1.282, P < .001) vs lobectomy
  • larger tumor size (eg, HR for 31–40 mm vs < 10 mm = 1.209, P = .008)
  • higher tumor grade (eg, HR for II vs I = 1.210, P < .001)
  • lower number of lymph nodes examined (eg, HR for ≥ 10 vs < 10 = 0.866, P < .001)
  • higher pathologic stage (HR for III vs I = 1.571, P < .001).  

The investigators concluded, “Using a more precise definition for time to surgical treatment, 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.”

Brendan T. Heiden, MD, of the Division of Cardiothoracic Surgery, Washington University School of Medicine in St. Louis, is the corresponding author for the JAMA Network Open article.

Disclosure: The study was supported by grants from the National Institutes of Health and U.S. Veterans Administration. For full disclosures of the study authors, visit jamanetwork.com.


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