Detection of occult micrometastases in patients with clinical stage i non-small-cell lung cancer: A prospective analysis of mature results of CALGB 9761 (Alliance)

Linda W. Martin, Jonathan D'Cunha, Xiaofei Wang, Debra Herzan, Lin Gu, Naif Abraham, Todd L. Demmy, Frank C. Detterbeck, Shawn S. Groth, David H. Harpole, Mark J. Krasna, Kemp Kernstine, Leslie J. Kohman, G. Alexander Patterson, David J. Sugarbaker, Robin T. Vollmer, Michael A. Maddaus, Robert A. Kratzke

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Purpose Outcomes after resection of stage I non-small-cell lung cancer (NSCLC) are variable, potentially due to undetected occult micrometastases (OM). Cancer and Leukemia Group B 9761 was a prospectively designed study aimed at determining the prognostic significance of OM. Materials and Methods Between 1997 and 2002, 502 patients with suspected clinical stage I (T1-2N0M0) NSCLC were prospectively enrolled at 11 institutions. Primary tumor and lymph nodes (LNs) were collected and sent to a central site for molecular analysis. Both were assayed for OM using immunohistochemistry (IHC) for cytokeratin (AE1/AE3) and real-time reverse transcriptase polymerase chain reaction (RT-PCR) for carcinoembryonic antigen. Results Four hundred eighty-nine of the 502 enrolled patients underwent complete surgical staging. Three hundred four patients (61%) had pathologic stage I NSCLC (T1, 58%; T2, 42%) and were included in the final analysis. Fifty-six percent had adenocarcinomas, 34% had squamous cell carcinomas, and 10% had another histology. LNs from 298 patients were analyzed by IHC; 41 (14%) were IHC-positive (42% in N1 position, 58% in N2 position). Neither overall survival (OS) nor disease-free survival was associated with IHC positivity; however, patients who had IHC-positive N2 LNs had statistically significantly worse survival rates (hazard ratio, 2.04, P =.017). LNs from 256 patients were analyzed by RT-PCR; 176 (69%) were PCR-positive (52% in N1 position, 48% in N2 position). Neither OS nor disease-free survival was associated with PCR positivity. Conclusion NSCLC tumor markers can be detected in histologically negative LNs by AE1/AE3 IHC and carcinoembryonic antigen RT-PCR. In this prospective, multi-institutional trial, the presence of OM by IHC staining in N2 LNs of patients with NSCLC correlated with decreased OS. The clinical significance of this warrants further investigation.

Original languageEnglish (US)
Pages (from-to)1484-1491
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number13
DOIs
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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