ST. LOUIS—How does delayed surgical treatment affect oncologic outcomes among VHA patients with non-small cell lung cancer (NSCLC)?
Researchers from Washington University School of Medicine and the VA St Louis Health Care System addressed this question in a study published in JAMA Network Open.1
The retrospective cohort study of 9,904 VHA patients with clinical Stage I NSCLC determined that surgical procedures delayed more than 12 weeks from the date of radiographic diagnosis were associated with increased risk of recurrence and worse overall survival.
The authors advised that patients with clinical Stage I NSCLC should receive surgical treatment within at least 12 weeks of radiographic diagnosis.
Researchers point out that the association between delayed surgical treatment and oncologic outcomes in patients with NSCLC is not well understood at least partly because previous studies have used imprecise definitions for the date of cancer diagnosis.
The study sought to use a uniform method to quantify surgical treatment delay and to examine its association with several oncologic outcomes.
Included in the research were patients who had clinical Stage I NSCLC and were undergoing resection. Investigators evaluated the association between time to surgical treatment (TTS), defined as the time between preoperative diagnostic computed tomography imaging and surgical treatment, and delay-associated outcomes. Those included overall survival, pathologic upstaging, resection with positive margins and recurrence.
Most of the participants, 96.3%, were men, and more than half, 50.5%, were currently smoking. The veterans had a mean age of 67.7.
Results indicated that the mean (SD) TTS was 70.1 (38.6) days. While TTS was not associated with heightened risk of pathologic upstaging or positive margins, recurrence was identified in 4,158 patients (42.0%) with median (interquartile range) follow-up of 6.15 (2.51-11.51) years.
Researchers pointed out that 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 = 0.003),
- higher Charlson Comorbidity Index score (HR for every 1-unit increase in composite score, 1.055; 95% CI, 1.037-1.073; P <0.001),
- segmentectomy (HR vs. lobectomy, 1.352; 95% CI, 1.179-1.551; P < 0.001) or wedge resection (HR vs. lobectomy, 1.282; 95% CI, 1.179-1.394; P < 0.001),
- larger tumor size (eg, 31-40 mm vs <10 mm; HR, 1.209; 95% CI, 1.051-1.390; P = 0.008),
- higher tumor grade (eg, II vs I; HR, 1.210; 95% CI, 1.085-1.349; P < 0.001),
- lower number of lymph nodes examined (eg, ≥10 vs <10; HR, 0.866; 95% CI, 0.803-0.933; P < 0.001),
- higher pathologic stage (III vs. I; HR, 1.571; 95% CI, 1.351-1.837; P < 0.001), 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 = 0.002),” the authors wrote. They added that 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 < 0.001),
- higher area deprivation index [ADI] score (OR for every 1 unit increase in ADI score, 1.005; 95% CI, 1.002-1.007; P = 0.002),
- 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 < 0.001).
Researchers pointed out that 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 < 0.001).
“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,” according to the authors. “These findings suggest that patients with clinical stage I NSCLC should undergo expeditious treatment within that time frame.”
The authors emphasized that the issue of delayed surgical treatment was further exacerbated in March 2020 when the World Health Organization declared COVID-19 to be a global pandemic. In response to local and state mandates, the American College of Surgeons, Society of Thoracic Surgery and American Association for Thoracic Surgery created a consensus statement for delaying surgical treatment during the pandemic. It generally recommended proceeding with lung cancer resections.
“Delayed surgical treatment imposes a particularly stressful burden at academic and Veterans Health Administration (VHA) medical centers, where patients are known to wait longer for operations, with unclear consequences,” they wrote.
Researchers suggested their results “fill an important gap in the medical literature and overcome some of the limitations of previous publications, including those from our own group. Prior studies have provided conflicting information regarding the association of delayed surgical treatment with oncologic outcomes, with some finding an association and others finding no association.”
The issue, according to the study team, was that most of those reports used arbitrary cutoffs to define delayed surgical treatment, “a method that is inherently flawed.” Based on more-precise models, the researchers determined that surgical procedures delayed beyond 12 weeks had a significantly higher risk of recurrence.
“It is worth noting that veterans appear to wait longer for surgical treatment than the general population,” the study noted. ‘According to the CTTS definition (even though it is flawed), patients waited a mean of 48.5 days (7 weeks) between diagnosis and surgical treatment.”
It added, “While this discrepancy warrants further study, veterans appear to have a high comorbidity burden while maintaining similar rates of short-term complications as the general population. It is possible that the observed delays among veterans allow for more complex care of patients with more severe illness. If comorbidities are the driving factor associated with delays, then marginally delayed surgical procedures seem acceptable and likely necessary.”
1. Heiden BT, Eaton DB Jr, Engelhardt KE, Chang SH, Yan Y, Patel MR, Kreisel D, Nava RG, Meyers BF, Kozower BD, Puri V. Analysis of Delayed Surgical Treatment and Oncologic Outcomes in Clinical Stage I Non-Small Cell Lung Cancer. JAMA Netw Open. 2021 May 3;4(5):e2111613. doi: 10.1001/jamanetworkopen.2021.11613. PMID: 34042991; PMCID: PMC8160592.
