Diagnosis-to-surgery interval and survival for different histologies of stage I-IIA lung cancer

Background: Guidelines on timeliness of lung cancer surgery are inconsistent. Lung cancer histologic subtypes have different prognosis and treatment. It is important to understand the consequences of delayed surgery for each lung cancer histologic subtype. This study aimed to examine the association between diagnosis-to-surgery time interval and survival for early stage lung cancer and selected histologic subtypes. Methods: Patients diagnosed with stage I-IIA lung cancer between 2004 and 2015 receiving definitive surgery and being followed up until Dec. 31, 2018, were identified from Surveillance, Epidemiology, and End Results database. Histologic subtypes included adenocarcinoma, squamous or epidermoid carcinoma, bronchioloalveolar carcinoma, large cell carcinoma, adenosquamous carcinoma, carcinoid carcinoma, and small cell carcinoma. Diagnosis-to-surgery interval was treated as multi-categorical variables (<1, 1-2, 2-3, and >= 3 months) and binary variables (>= 1 vs. <1 month, >= 2 vs. <2 months, and >= 3 vs. <3 months). Outcomes included cancer-specific and overall survival. Covariates included age at diagnosis, sex, race, marital status, tumor size, grade, surgery type, chemotherapy, radiotherapy, and study period. Kaplan-Meier survival curves and Cox proportional hazards regression models were applied to examine the survival differences. Results: With a median follow-up time of 51 months, a total of 40,612 patients were analyzed, including 40.1% adenocarcinoma and 24.5% squamous or epidermoid carcinoma. The proportion of patients receiving surgery <1, 1-2, 2-3, and >= 3 months from diagnosis were 34.2%, 33.9%, 19.8%, and 12.1%, respectively. Delayed surgery was associated with worse cancer- specific and overall survival for all lung cancers, adenocarcinoma, squamous or epidermoid, bronchioloalveolar, and large cell carcinoma (20-40% increased risk). Dose-dependent effects (longer delay, worse survival) were observed in all lung cancers, adenocarcinoma, and squamous and epidermoid carcinoma. No significant association between surgery delay and survival was observed in adenosquamous, carcinoid, and small cell carcinoma. Conclusions: Our findings support the guidelines of undertaking surgery within 1 month from diagnosis in patients with stage I-IIA lung cancer. The observed dose-dependent effects emphasize the clinical importance of early surgery. Future studies with larger sample size of less frequent histologic subtypes are warranted to provide more evidence for histology-specific lung cancer treatment guidelines.