Intraoperative Determination of Axillary Node Metastasis: Meta-Analysis of Diagnostic Accuracy Assessment Studies for Frozen Section, Imprint Cytology and Molecular Assays.
Authors: Bats A. , Bats A. , Trinquart L. , Trinquart L. , Le Frère-Belda M. , Nos C. , Chatellier G. , Chatellier G. , Lécuru F. , Lécuru F. 
Published: December 2010

Background: Sentinel lymph node status is highly predictive of overall axillary lymph node involvement. Intraoperative assessment potentially enables completion of axillary dissection at the same setting. The most commonly used methods are frozen section histology and imprint cytology. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays have been recently developed.Objectives: To obtain summary estimates of the diagnostic accuracy of intraoperative tests for the detection of metastases in lymph nodes of patients with breast cancer.Selection criteria: Cross-sectional studies assessing the diagnostic accuracy of at least one index test for the detection of metastases in lymph nodes of patients with breast cancer were selected. Index tests included frozen section, touch imprint cytology or RT-PCR with the One-Step Nucleic Acid Amplification (OSNA) technique (Sysmex) or GeneSearch™ Breast Lymph Node (BLN) Assay (Veridex, LCC). The reference standard was permanent section H&E analysis.Search strategy: We searched MEDLINE and EMBASE up to April 2009 with both controlled vocabulary and freetext words corresponding to 'breast cancer' and 'lymph node' and 'intraoperative test'. We also searched SABCS and ASCO annual meeting proceedings from 2006 to 2008 as well as Sysmex, Veridex and FDA websites. We checked the reference lists of selected studies and review articles for additional studies.Data collection and analysis: Two review authors independently applied the selection criteria to identify references and reached consensus at each step. Both independently assessed quality according to the QUADAS checklist and extracted data from selected studies. Meta-analysis was performed using a bivariate mixed-effect model. Per-patient and per-node combined sensitivity and specificity were calculated.Results: Among 560 screened references from MEDLINE or EMBASE, 100 references were selected (43 pending decisions because of availability or translation issues). We identified 29 additional articles or abstracts from other sources. Of these, 3 independent studies (667 nodes) assessed GeneSearch™ BLN Assay accuracy on a per-node basis: combined sensitivity was 0.86, 95%CI:0.63-0.96 and combined specificity 0.94, 95%CI:0.92-0.96. Six independent studies (2091 nodes) assessed OSNA accuracy on a per-node basis: combined sensitivity was 0.93, 95%CI:0.86-0.96 and combined specificity 0.95, 95%CI:0.92-0.97. In 5 studies reporting data corrected for sampling bias, sensitivity was 0.94, 95%CI:0.86-0.97 and specificity 0.96, 95%CI:0.94-0.97.Conclusion: Our preliminary results indicate that RT-PCR yields high per-node sensitivity and specificity. OSNA tends to show a nonsignificantly higher accuracy than GeneSearch™ BLN Assay. Updated results, including frozen section, imprint cytology and subgroup analyses, will be presented at the congress.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1005.