Serum biomarkers facilitate the recognition of early-stage cancer and may guide the selection of surgical candidates: A study of carcinoembryonic antigen and tissue polypeptide antigen in patients with operable non-small cell lung cancer

Objectives: Copious literature shows that in lung cancer many serum markers , especially the cytokeratin degradation products, correlate with the exten t of disease. In 1995, we suggested the possibility of predicting the resec tability of non-small cell lung cancer by measuring the plasma level of the tissue polypeptide antigen, a marker of the cytokeratin family. This study was designed (1) to confirm the earlier data in a new prospective evaluati on, (2) to comparatively assess another classic biomarker (ie, the carcinoe mbryonic antigen), and (3) to incorporate their results into the preoperati ve evaluation of non-small cell lung cancer. Methods: We analyzed the database of a single institution over a 5-year per iod (1994-1998) in a community-based hospital and second referral level ins titution for a province of 500,000 people. The database included 124 consec utive patients (105 men) with pathologically documented lung cancer (50% wi th adenocarcinoma) accurately staged, clinically judged operable or potenti ally operable, and eventually operated on. Anthropometric, clinical, and la boratory data (including the carcinoembryonic antigen and tissue polypeptid e antigen serum levels) and the results of a complex staging workup were pr ospectively recorded. Receiver-operating characteristic curves and diagnost ic formulas were used for data analysis. Results: Computed tomography of the thorax, upper part of the abdomen, and brain was the most accurate preoperative method to assess tumor resectabili ty (receiver-operating characteristic area: 0.76, 95% confidence intervals: 0.67-0.86, P =.000; accuracy rate: 77%, confidence intervals: 69%-84%). Ti ssue polypeptide antigen was also predictive for tumor resectability (recei ver-operating characteristic area: 0.62, 95% confidence intervals: 0.51-0.7 3, P =.035; accuracy rate at a threshold level of 110 U/L: 65%, 95% confide nce intervals: 56%-73%). Carcinoembryonic antigen was diagnostic only at th e extreme values of its distribution (accuracy rate at a level up to 10 ng/ mL: 69%, 95% confidence intervals: 60%-77%). The probability of finding res ectable disease at the time of the operation increased from 78% (baseline c omputed tomography-based probability) to 83% when the concentration of tiss ue polypeptide antigen was lower than 90 U/L and to 85% when the concentrat ion of carcinoembryonic antigen was below 10 ng/mL. The probability of disc overing an advanced disease increased from 68% (baseline computed tomograph y-based probability) to 89% when tissue polypeptide antigen levels were abn ormal and to 100% when carcinoembryonic antigen concentrations were higher than 10 ng/mL. Conversely, the predictability of computed tomography was di minished by contrasting biomarker results, requiring further clinical inves tigations. Conclusions: Computed tomography remains the gold standard for the preopera tive evaluation of non-small cell lung cancer, although it may significantl y underestimate the real tumor extension. The addition of the easy and inex pensive tissue polypeptide antigen test (with or without carcinoembryonic a ntigen) is capable of correcting this underestimation and helps to decide w hether to completely rely on computed tomography or order additional clinic al investigations.