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Each week that newly diagnosed early lung cancer patients waited for surgery was linked with an increased risk of upstaging, according to an analysis of over 50,000 cases in the National Cancer Data Base (NCDB).

Among stage I non-small cell lung cancer (NSCLC) patients, there was a 4% increase in upstaging to any stage disease and a 1.3% increase to IIIA disease, specifically, for every week of delay, reported Harmik Soukiasian, MD, of Cedars-Sinai Medical Center in Los Angeles, and colleagues, in a presentation at the American Association for Thoracic Surgery (AATS) annual meeting in San Diego.

The results suggest that stage I NSCLC patients may benefit from surgery sooner than the 8-week window recommended by National Comprehensive Cancer Network (NCCN) guidelines.

"Surgeons should be aware of time as a significant factor of upstaging and should prioritize early resection," Soukiasian told 番茄社区app, suggesting that attention be paid to the "time of diagnosis rather than first encounter with the patient."

Overall, 25.4% of resections had been performed within 1 week of diagnosis, 78.9% had been performed by week 8, and 91.2% by week 12.

In a multivariable logistic regression that adjusted for age, sex, and other factors, the researchers found a trend of increased upstaging risk that increased each week:

• Week 2: adjusted OR 1.40 (95% CI 1.27 to 1.55, P<0.001)
• Week 7: adjusted OR 1.62 (95% CI 1.49 to 1.76, P<0.001)
• Week 12: adjusted OR 1.99 (95% CI 1.74 to 2.28, P<0.001)

But AATS session discussant Felix Fernandez, MD, of Emory University in Atlanta, cautioned that "it's difficult to avoid confounding in an analysis that tries to show us a week-by-week risk of increased progression with lung cancers," and pointed to the fact that the confidence intervals of the odds ratios overlap in the week-to-week data.

Fernandez said the thinking is that "clearly if you wait 12 weeks instead of 2 there's a greater risk of spread," but pointed to previous studies that showed more aggressive cancers are often treated earlier. "There's more of an urgency to operate on these higher-risk cancers based on their subjective appearance."

Soukiasian's group examined treatment data from 2010 to 2014 for 52,406 patients with clinical stage I NSCLC from the NCDB who had undergone anatomic lobar resection. At diagnosis, 71.4% (36,848) had stage IA disease and 28.6% (14,757) had stage IB disease.

Patients were excluded if they were treated with wedge resection or segmentectomy. Clinical stage was compared with their pathologic stage following surgery. Prior to pathologic staging, patients needed to have undergone lymphadenectomy or lymph node sampling and were excluded if they had received chemotherapy.

Upstaging from stage IA or IB NSCLC occurred in 14,434 patients. There were 5,506 cases of stage IA to IB upstaging. For stage I NSCLC there were 4,438 cases of upstaging to IIA disease, 1,863 to IIB, 2,551 to IIIA, and 76 to IIIB.

Independent predictors of upstaging to IIIA disease included treatment at an academic hospital, IB disease at diagnosis, left-sided tumors, increased number of lymph nodes examined, and weeks to surgery.

Upstaging was more likely to occur in academic versus non-academic facilities (29.7% versus 26.4%, respectively), where a higher median number of harvested lymph nodes was observed (10 versus 8). But the rate of 5-year overall survival was higher at academic facilities, according to the analysis (40.3% versus 37.4%).

Soukiasian said that while data in the NCDB cannot reveal the specific reasons for delays to surgery, factors on the patient side could include scheduling and availability of support systems, and on the provider side could include delays in follow-up, delays in operating room availability, and issues with insurance approval.

"This study brings up a lot of interesting points," said Fernandez. In 20% of the patients, he noted, surgery was performed outside the NCCN guideline window of 8 weeks.

"We need to learn more about who those patients are and why these delays happen," Fernandez said. "My suspicion is there's a lot of disparities associated with this -- age, gender, socioeconomic status, health systems -- there's a lot of access issues that need to be explored."

Soukiasian pointed to the need to improve communication so that patients understand the risks associated with delaying surgery -- "while emphasizing the benefits of earlier surgical therapy" -- and highlighted the need for clinicians to participate in multidisciplinary patient-care and decision-making, to improve lines of communication to decrease this interval from diagnosis to surgery.

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