Understanding the Effects of Time to Surgery on Upstaging for Stage I Non-Small Cell Lung Cancer

[L - R] Mr. Russell Bahar & Dr. Elliot Wakeam

By Russell Bahar, Bsc and Elliot Wakeam, MD, MPH
Posted: April 1, 2019

IN REFERENCE TO: Serna-Gallegos DR, et al Effects of time from completed clinical staging to surgery: Does it make a difference in stage 1 nonsmall cell lung cancer? AATS 2018; Abstract 67.

Pathologic upstaging of NSCLC occurs in an estimated 14% to 25% of patients postoperatively and is known to be significantly associated with poor patient outcomes.2-4 Delay to surgery may be one factor that leads to greater rates of upstaging. However, the precise relationship between time to surgery and upstaging remains unknown, as does the ideal time to surgery. The National Cancer Comprehensive Network (NCCN) recommends not delaying surgical resection beyond 60 days following completion of clinical staging—a timeline comparable to previously published recommendations by the British Thoracic Society and the RAND corporation, which have advocated for 8 and 6 weeks, respectively.5-7 However, recent work by Serna-Gallegos and colleagues argues that 8 weeks may still be too late. Their retrospective investigation of 52,406 patients from the National Cancer Database suggests that a surgical delay of as little as 2 weeks may have significant implications for rates of pathologic upstaging in patients with stage I NSCLC.

Comparing the rates of pathologic upstaging between patients with varying degrees of surgical delay, this study revealed a 4% increase in upstaging frequency for every week of delay between staging and resection. This finding is particularly worrisome given that 21% of patients in the study did not undergo resection within 8 weeks of staging completion. The authors, therefore, advocate for earlier intervention following staging completion. Although these numbers are certainly concerning, the limitations of the study should not be overlooked. First, the confidence intervals of the week-to-week data demonstrated significant overlap. For example, the odds ratios observed between 1 and 8 weeks of surgical delay were not statistically significant. Additionally, the study was retrospective and, as such, it is unclear what effect selection bias may have had on the results: Are patients who undergo delayed surgery experiencing the delay because they are sicker, or are there other oncologic or comorbidity issues that are not captured in the data? Patients with greater medical morbidity are more likely to be upstaged in general, and their increased time to surgery may have resulted from other factors such as time taken to mitigate those comorbidities, social issues, or functional impairment, thus confounding the results of the current study.

The study raises several important questions. The percentage of patients who failed to undergo surgical intervention following the NCCN-recommended maximum of 8 weeks was a surprising 21%. The authors identified increased medical comorbidity score as a factor, as well as African American race. This observation highlights the significance of social, as well as medical, factors as important determinants of outcomes in patients with resectable NSCLC, especially given the recently estimated 52-day median time to treatment in the United States.8 From a healthcare-resource perspective, the argument could, therefore, be made that reducing the number of patients who wait beyond 8 weeks should be the priority, rather than prioritizing more urgent resection in all patients.

Another relevant factor in NSCLC management that this paper reinforces is the importance of adequate lymph node dissection. Patients who underwent resection at academic hospitals were more likely to be upstaged, yet they also demonstrated overall higher survival rates. The authors explained this finding with reference to the observation that academic centers sampled two lymph nodes on average more than nonacademic centers. This argument is supported by several studies demonstrating significantly increased survival associated with more systematic lymph node dissection or sampling, generally peaking between 10 and 18 nodes.9-11

Ultimately, this study raises several important points with regard to surgical delay and its implications for upstaging of NSCLC. Although the authors’ claims of significant week-to-week variability may not be strongly supported by the data presented and may require further study, they succeed in highlighting the importance of reducing surgical delay to a maximum of 8 weeks as well as performing adequate lymph node sampling in patients with NSCLC. ✦

About the Authors: Mr. Bahar is a third-year medical student in the School of Medicine, University of Toronto, Toronto, Ontario. Dr. Wakeam is a surgical fellow in the Division of Thoracic Surgery at the Toronto General Hospital, Toronto, Ontario.

1. Serna-Gallegos DR, Mercado F, Imai T, Berz D, Soukiasin HJ. Effects of Time From Completed Clinical Staging to Surgery: Does it Make a Difference in Stage 1 Non-Small Cell Lung Cancer? Presented at: AATS 98th Annual Meeting. Los Angeles; 2018: Abstract 67.

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11. Liang W, He J, Shen Y, et al. Impact of examined lymph node count on precise staging and long-term survival of resected non-small-cell lung cancer: A population study of the US SEER database and a Chinese multii-nstitutional registry. J Clin Oncol. 2017;35(11):1162-1170.