Incidence and Risk Factors of Pulmonary Metastasis as the Initial Site of Metastasis after Surgical Resection for Rectal Cancer by TNM Stage

BACKGROUND: There is scant data on the incidence and risk factors associated with pulmonary metastasis in rectal cancer, particularly according to TNM stage. OBJECTIVE: To determine the incidence of pulmonary metastasis in stage I-III rectal cancer patients following surgical resection and to identify stage-specific risk factors. DESIGN: A retrospective analysis was conducted on rectal cancer patients who underwent radical resection. SETTINGS: Samsung Medical Center from January 2007 to December 2019. PATIENTS: A total of 3,504 patients were diagnosed with either a pathologic complete response following neoadjuvant concurrent chemoradiotherapy and subsequent radical resection or stage I-III rectal cancer with no initial metastasis. MAIN OUTCOME MEASURES: The main outcomes were the incidence of pulmonary metastasis and overall survival. RESULTS: Of the patients, 313 (8.9%) developed pulmonary metastasis. The median time to pulmonary metastasis was 16 months (range, 6-92 months). The incidence rates of pulmonary metastasis by TNM stage were: 2.0% (pathologic complete response), 2.4% (Stage I), 8.0% (Stage II), and 17.4% (Stage III). For the neoadjuvant chemoradiotherapy group, the incidence rates were 2.0% (pathologic complete response), 5.1% (Stage I), 9.9% (Stage II), and 21.4% (Stage III). In the non-neoadjuvant chemoradiotherapy group, the incidence rates were 1.0% (Stage I), 6.5% (Stage II), and 15.8% (Stage III). Major risk factors for pulmonary metastasis included neoadjuvant chemoradiotherapy status, elevated carcinoembryonic antigen ≥ 5 ng/mL, tumor location, (yp)TNM stage, (yp)T stage, vascular invasion, perineural invasion and tumor budding. LIMITATIONS: Single-center retrospective study. CONCLUSION: As TNM stage increases, the incidence of pulmonary metastasis also increases, regardless of neoadjuvant chemoradiotherapy. Elevations in carcinoembryonic antigen levels, neoadjuvant chemoradiotherapy status, tumor location, vascular invasion, perineural invasion, and tumor budding were identified as risk factors for pulmonary metastasis in rectal cancer. Patients presenting these risk factors may benefit from protocolized surveillance to facilitate timely detection and management. See Video Abstract.