1204 - Beyond Overall Survival: Smoking, Progression and Metastasis in Sarcoma

Purpose/Objective(s):

While there are several well-established prognostic factors in sarcoma, the impact of smoking on disease progression and metastasis remains incompletely defined. Smoking promotes systemic inflammation, immune dysregulation, hypoxia signaling, and angiogenesis, pathways integral to sarcoma biology. This study evaluated the association between smoking status and oncologic outcomes in a contemporary sarcoma cohort.

Materials/Methods:

A retrospective cohort study of patients with sarcoma treated at a single high volume tertiary referral institution was performed. Active smoking status at the time of diagnosis was recorded. Baseline clinicopathologic characteristics were compared between active smokers and non-smokers. Endpoints included overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). Kaplan–Meier estimates were used to calculate 2- and 5-year survival rates, with log-rank testing for unadjusted comparisons. Multivariable Cox proportional hazards models were constructed adjusting for age, stage, grade, histology, Karnofsky performance status, presence of cardiovascular disease and diabetes, and treatment variables.

Results:

399 patients were evaluated. Baseline characteristics were comparable between groups. Ninety-three (23%) were active smokers. Two-year OS was similar between smokers and non-smokers (89.1% vs 88.8%); however, 5-year OS was significantly lower among smokers (73.2% vs 79.3%, log-rank p<0.05). Multivariate analysis showed no factor predictive of worse OS.

For PFS (n=349), smokers demonstrated inferior outcomes at both 2 years (68.9% vs 81.2%, p=<0.05) and 5 years (55.9% vs 73.2%; p<0.05). On multivariable analysis, smoking was independently associated with worse PFS (HR = 1.7, 95% CI 1.20-2.46, p=0.003), corresponding to an approximately 70% increased risk of progression compared with non-smokers.

For DMFS (n=353), smokers had worse 2-year (67.8% vs 83.7%, p<0.05) and 5-year (56.1% vs 79.1%, p<0.05) estimates. Smoking remained independently associated with inferior DMFS on multivariable analysis (HR =1.98, 95% CI 1.26 – 3.11, p = 0.002), indicating roughly a twofold increased risk of distant metastasis. Stage was the strongest prognostic factor for all endpoints.

Conclusion:

Smoking is independently associated with substantially worse oncologic outcomes in patients with sarcoma. After adjustment for stage and other clinicopathologic factors, smokers were approximately 70% more likely to experience disease progression and nearly twice as likely to develop distant metastases compared with non-smokers. The strength and consistency of the association with PFS and DMFS suggest that smoking may influence metastatic biology rather than solely contribute to competing mortality. These findings underscore the importance of smoking cessation and support further investigation into inflammatory and microenvironmental mechanisms that link smoking to sarcoma progression.