In patients with non–small cell lung cancer (NSCLC) designated stage I by conventional histopathology, occult metastases were detected by immunohistochemistry (IHC) staining of cytokeratin in 14% of patients and by reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen in 69% of patients; however, only IHC-positivity within N2 nodes was correlated with overall survival.
Patients who were IHC-positive within an N2 node had worse overall survival than did IHC-negative patients (HR, 2.04; 95% CI, 1.14 to 3.66); 5-year survival for N2 IHC-positive patients compared with IHC-negative patients was 50% (95% CI, 29.1% to 67.8%) vs. 66.9% (60.9% to 72.2%), P = .017. Patients who were IHC-positive within N1 nodes had survival similar to that of IHC-negative patients.
Although the majority of patients in the study (69%) had occult metastases by RT-PCR, no relationship between PCR status and overall survival or disease-free survival emerged from the data.
Surgical resection in early stage NSCLC yields unpredictable outcomes, and one explanation for this is the presence of occult metastases in regional nodes.
“The presence of (occult metastases) is a logical explanation for tumors that are classified as stage I by conventional histopathology to demonstrate a worse prognosis. However, the current rigorously designed and executed prospective study only showed a significant difference in survival when N2 nodes demonstrated positivity by IHC, but not by RT-PCR,” wrote Dr. Linda W. Martin of the University of Maryland, Baltimore, and colleagues (J Clin Oncol. 2016 Feb 29. doi: 10.1200/JCO.2015.63.4543).
“Clearly RT-PCR is more sensitive, but perhaps (carcinoembryonic antigen) is not as specific for NSCLC and thus the clinical impact is insignificant,” they wrote. RT-PCR data showed poor concordance with IHC data in the study, and did not correlate with outcomes, pointing to a lack of clinical utility for RT-PCR in NSCLC, the authors stated.
The Cancer and Leukemia Group B (CALGB) 9761 trial accrued 501 patients from 1997 to 2002, 304 of whom had stage 1A or 1B NSCLC. Median follow up was 8.4 years (range: 0.97 to 11.4 years). Local only recurrence occurred in 24 patients, local and distant in 18, and distant only in 27.
Dr. Martin and coauthors had no disclosures.