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Upstaging of lung cancer increases with surgery delay
Upstaging of non-small cell lung cancers significantly increased with each successive week between staging and surgery, according to findings presented at the American Association for Thoracic Surgery Annual Meeting.
These data suggested that early intervention after tumor staging decreased the likelihood of upstaging and improved survival rates.
Guidelines recommend that patients with NSCLC undergo surgery within 8 weeks of staging.
“Our study evaluated the possibility of cancer upstaging using a more granular analysis, looking at the rates of upstaging for each progressive week from week 1 to week 12 for patients with stage I NSCLC,” Harmik J. Soukiasian, MD, chief of the division of thoracic surgery at Cedars-Sinai Health System, said in a press release.
The researchers reviewed treatment data from 52,406 patients with stage I NSCLC in the National Cancer Database. All patients underwent anatomic lobar resection and lymphadenectomy or lymph node sampling without chemotherapy. Soukiasian and colleagues evaluated the rates at which patients were upstaged based on the time from staging to resection for the first 12 weeks. Researchers also performed subgroup analyses for stage IA and IB adenocarcinoma and squamous cell carcinoma.
Resections were most frequently performed within 1 week (25.4%; n = 13,325), and nearly 80% (78.9%; n = 41,362) were performed by 8 weeks. Nearly all (91.2%; n = 77,844) had received surgery by 12 weeks.
Researchers noted significant increases in upstaging for all patients with stage I disease: 21.7% were upstaged after 1 week (n = 2,896 of 13,325), 31.5% (n = 961 of 3,046) were upstaged after 8 weeks (P < .05) and 32.6% (n = 366 of 1,027) were upstaged at 12 weeks.
“An astonishing number of clinical stage I NSCLC patients upstaged to IIIA disease at the time of surgery,” Soukiasian said. “Interestingly, a higher proportion of both clinical IA and IB patients upstaged to IIIA vs. IIB, suggesting a possible need for more aggressive mediastinal staging, even in early-staged patients. Although current national guidelines recommend surgery within 8 weeks from diagnosis, our study demonstrates there is a benefit in doing surgery even within a week-to-week basis.” – by Andy Polhamus
Reference:
Serna-Gallegos DR, et al. Abstract 67. Presented at: American Association for Thoracic Surgery Annual Meeting; April 28-May 1, 2018; San Diego.
Disclosures: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of publication.
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This abstract has attracted considerable attention based on the finding that upstaging of NSCLC increases in frequency with each successive week between diagnosis and resection. It has been suggested that earlier intervention can decrease the likelihood of upstaging and result in improved survival.
This conclusion was based on a logistic regression analysis of patients with clinical stage I NSCLC in the National Cancer Database. Researchers found a significant association between the rate of tumor upstaging and time to resection when the latter variable was modeled in weekly intervals. This led to the conclusion that the risk for tumor upstaging increased with each successive week at a rate of 1.3%.
There are a couple of problems with this conclusion based on the data presented.
First, a closer look at their data shows that the risk for upstaging does not actually increase weekly as asserted, although the overall model based on weekly intervals was statistically significant. In fact, more than half of the effect of time to surgery on upstaging occurred in the first week, where the OR increased 40%. Over each succeeding week out to 7 weeks, the ORs were within the CI for the first week’s estimate. This indicates that there is an association between time to surgery and tumor upstaging, but it does not show the association to be linear or to be present with each passing week.
The second problem with their conclusion is that it assumes the relationship between these two variables to be cause and effect. That is, each week of delay results in a higher risk for tumor dissemination. In a retrospective study such as this, assigning such a causal relationship is neither statistically appropriate nor wise. Instead of tumor progression explaining the observed association, it is equally plausible that differences in patient presentation and patient management are responsible for the effect observed. Consider the reference group: Having less than a week from diagnosis to resection would indicate in most cases that the patient was taken to surgery for wedge resection followed by lobectomy. In this setting, it is reasonable to assume these tumors would be generally smaller and peripheral in location — both factors that are known to decrease the likelihood of occult lymph node disease (and eventual upstaging). If these patients were then compared with patients operated on later — after diagnostic biopsies for more centrally located and/or larger tumors — one would expect the rate of clinically occult node disease to be higher.
It also is plausible that differences in case volume and surgeon experience play a role in this association. Patients treated at more experienced centers may wait longer for their surgery, but they may undergo more complete node dissection/sampling, resulting in more tumor upstaging.
For these reasons, it would be unwise to alter current management based on data from this retrospective study.