Preoperative anemia decreases survival in patients with stage I and II non-small-cell lung cancer treated with surgery

Abstract

Surgical resection is the mainstay of therapy for patients presenting with stage I and II non-small-cell lung cancer (NSCLC). Despite optimal staging and surgery, these patients are still at significant risk for failure. The purpose of this study is to report a retrospective analysis of the outcome of patients treated with surgery alone, as well as to analyze prognostic factors associated with survival. From May 2000 to November 2002, there were a total of 125 patients treated with surgery for NSCLC at University of Maryland Medical Center. Of these, 82 stage I and II patients who received surgery alone as the definitive therapy were identified. The median age of the entire cohort was 68 years (range, 43–88 years). There were 48 males and 34 females. Sixty-three (76.8%) patients underwent lobectomy while 19 (23.2%) patients underwent wedge resection or segmentectomy. Patients who received neoadjuvant or adjuvant radiation therapy or chemotherapy were excluded from the study. Factors included in univariate and multivariate analyses were: age, sex, tumor histology, pathologic stage, p53 status, preoperative hemoglobin, and type of surgery performed. Endpoints of the study were relapse-free survival (RFS) and overall survival (OS). Median follow-up was 20.8 months (range, 0.4–43.2 months). For the entire cohort, the 2-year RFS was 66.0% and 2-year OS was 76.3%. Median survival for the entire cohort has not been achieved. In univariate analysis, the only factor that achieved statistical significance was preoperative hemoglobin level. Patients who had preoperative hemoglobin <12mg/dL experienced significantly worse RFS (mean RFS: 26.6 months versus 34.9 months, p = 0.043) and OS (median OS: 27 months versus 42.5 months, p = 0.011). For stage I patients (n = 72), the 2-year RFS and OS were 66.4% and 50.4%. For stage II patients (n = 10), the 2-year RFS and OS were 60.0% and 66.7%. In the Cox multivariate regression analysis, the only factor that achieved statistical significance was preoperative hemoglobin, with patients with hemoglobin <12mg/dL having decreased RFS (hazard ratio = 4.1, p = 0.020) and OS (hazard ratio = 2.9, p = 0.026). There was a trend towards worse RFS (p = 0.056) and OS (p = 0.068) in p53-negative (n = 39) patients. Stage, histologic type, type of surgery performed, age, and sex did not affect outcome. In our cohort of mostly stage I NSCLC patients, preoperative hemoglobin <12mg/dL predicted for significantly worse outcome. Much has been written in the literature about the possibility of anemia exacerbating intra-tumoral hypoxia, therefore, increasing radio-resistance. This has been a popular argument to explain poorer outcomes of anemic patients with solid tumors who undergo radiotherapy. However, our data suggest that anemia may be a sign of a more aggressive tumor that is at an increased risk of failure independent of the treatment modality