Despite the negative effects of smoking on survival outcomes and quality of life, nearly half (45%) of patients continue to smoke after being diagnosed with lung cancer. Growing evidence suggests that incorporating non-anatomical factors, such as smoking history, into staging may help improve prognostication.
“Although staging has primarily been anatomical in nature for the last few editions, there has been a lot of evidence that non-anatomical factors—including clinical, biological, and molecular factors—can impact cancer outcomes or prognosis, and it may help to better define standard prognostic factor groups,” said Lawson Eng, MD, SM, FRCPC.
During the 2025 World Conference on Lung Cancer (WCLC), Dr. Eng presented data from a retrospective cohort study evaluating the impact of smoking status on survival among patients with non-small cell lung cancer (NSCLC) using the 9th Edition IASLC Lung Cancer Staging Project Database. The session, titled Beyond TNM—New Horizons in Prognostication, is available on demand to registered WCLC 2025 attendees.
“Our specific aims were to evaluate the impact of smoking status on prognosis within each stage subgroup, how smoking status impacts prognosis within TNM stage subgroups, and how smoking status impacts prognosis relative to other analytical factors that are used in staging,” said Dr. Eng, a medical oncologist at the Princess Margaret Cancer Center and assistant professor in the Department of Medicine, University of Toronto.
The study primarily focused on patients diagnosed with NSCLC between January 2011 and December 2019. Included patient records were required to have sufficient T, N, and M categories and tumor descriptors. The study also required data on smoking status and other covariates.
Of the nearly 70,000 patients who were initially identified and met the criteria, about 49,000 cases were included in the primary analysis.
Smoking status at the time of diagnosis was defined as never smoked, formerly smoked, or currently smoked. One quarter (25%) of patients were currently smoking, 41% reported quitting prior to diagnosis, and about one-third (33%) reported never smoking throughout their lifetime.
Results
Overall, smoking status was a negative prognostic factor in NSCLC, according to the findings. Patients who were currently smoking at the time of diagnosis had worse 5-year overall survival (OS) estimates compared with patients who never smoked (5-year OS: 48% vs. 72%), as well as those who formerly smoked (54%). Similar results were observed in subgroup analysis based on sex and region of the world.
These associations were consistent across most stage groups, with poorer prognosis observed among patients who currently or formerly smoked compared with patients who never smoked.
Survival outcomes were the lowest among patients with stage IIA disease who formerly smoked (5-year OS: 63%), those with stage IIA disease who currently smoked (5-year OS: 56%), and those with stage IIB disease who currently or formerly smoked (5-year OS: 55%).
Notably, patients who had stage IB disease who currently or formerly smoked had a similar prognosis to those with stage IIA disease who never smoked (5-year OS: 66% vs. 68%), as well as those with stage IIB disease who never smoked (5-year OS: 63%).
“We found that patients in the lower stage group who currently or formerly smoked had no significant difference in OS when compared to those in the higher stage group who never smoked,” Dr. Eng said. “[This suggests] that patients who currently or formerly smoked in one stage group were similar prognostically to those who never smoked in the next highest stage group.”
Recursive partitioning analysis (RPA) was conducted on 36,000 patients with non-metastatic NSCLC to evaluate the impact of smoking status relative to anatomical factors in staging. Using staging variables and smoking status, the approach aimed to identify unique prognostic subgroups.
For patients with early-stage (up to T3N1) disease, smoking status was consistently a higher prognostic factor than N0 versus N1 and some T-stage subgroups, suggesting it may have a significant impact on prognosis.
“Based on RPA, we found that smoking status may have a greater impact on prognosis compared to nodal status among patients with early-stage NSCLC,” Dr. Eng said. “And—even for those with more locally advanced disease—smoking status still helps to identify unique prognostic subgroups.”
Future Directions
Dr. Eng said not only does this data support smoking status as a prognostic factor in lung cancer staging, but it also indicates it may have an even greater impact on prognosis compared with some of the more conventional anatomical descriptors.
Additionally, the evidence makes a strong case for incorporating non-anatomical factors, such as smoking status, into lung cancer staging to improve prognostication.
“In terms of next steps, we are planning to explore this further alongside other non-anatomical factors in the 10th Edition of TNM staging,” Dr. Eng said.
