Postoperative radiotherapy might be a risk factor for second primary lung cancer: A population-based study

Surgery is the main curative therapeutic strategy for patients with initial primary lung cancer (IPLC). Most international guidelines recommend regular follow-ups after discharge to monitor patients for tumor recurrence and metastasis. As the overall survival (OS) in patients with lung cancer improves, their risk of secondary primary lung cancer (SPLC) increases. Previous studies on such patients lack separate assessment of different survival outcomes and evaluation of high-risk factors for SPLC. Therefore, we aimed to determine the correlation between high-risk factors and causes of death in patients with SPLC, based on the Surveillance, Epidemiology, and End Results (SEER) database.

We screened the SEER database for patients with IPLC and SPLC from 2004 to 2015 and included only patients who underwent surgery since the IPLC and in whom the cancer was pathologically verified of an International Classification of Diseases grade of 0-3 and to be non-small-cell lung cancer. The standardized incidence ratio (SIR) was calculated between variables and SPLC. Multivariable Cox proportional-hazards regression analyses were conducted to calculate the correlation of different variables with overall survival (OS) and cancer-specific survival (CSS). A competing-risk model was conducted for SPLC. The effect of baseline bias on survival outcomes by performing propensity score matching analysis in a 1: 6 ratio (SPLC: IPLC).

For patients aged 0-49 years, the overall SIR was higher in older patients, reaching a maximum of 27.74 in those aged 40-49 years, and at 11.63 in patients aged 50-59 years. The overall SIR was higher for patients who were more recently diagnosed with IPLC and increased with time after diagnosis. Male sex, SPLC (hazard ratio, 1.6173; 95% confidence interval, 1.5505-1.6869; P < 0.001), cancer grade III or IV, lower lobe of the lung, advanced stage and postoperative radiotherapy (PORT) were independently detrimental to OS. In terms of CSS, PORT was a high-risk factor.

Postoperative radiotherapy is a risk factor for second primary lung cancer and detrimental to overall and cancer-specific survival in patients who had initial primary lung cancer. These data support the need for life-long follow-up of patients who undergo treatment for IPLC to screen for SPLC.