Cell Free Methylated Tumor DNA in Bronchial Lavage as an Additional Tool for Diagnosing Lung Cancer—A Systematic Review

SIMPLE SUMMARY: Lung cancer causes the highest number of cancer-related deaths. The prognosis is poor, primarily because the disease is often diagnosed at an advanced stage with no curative treatment options. If lung cancer could be diagnosed at an earlier stage, survival may be improved. DNA is often changed by methylation in cancer cells compared to normal cells. This methylated tumor DNA can be detected in fluid from the lungs, bronchial lavage. Several studies have investigated this biomarker, but the evidence has not been systematically collected. The aim of this review was to identify and synthesize the existing evidence on using methylated tumor DNA in bronchial lavage to diagnose lung cancer. The review will present an overview of the current evidence and contribute to advancing this area further. ABSTRACT: This systematic review investigated circulating methylated tumor DNA in bronchial lavage fluid for diagnosing lung cancer. PROSPERO registration CRD42022309470. PubMed, Embase, Medline, and Web of Science were searched on 9 March 2022. Studies of adults with lung cancer or undergoing diagnostic workup for suspected lung cancer were included if they used bronchial lavage fluid, analyzed methylated circulating tumor DNA, and reported the diagnostic properties. Sensitivity, specificity, and lung cancer prevalence were summarized in forest plots. Risk of bias was assessed using the QUADAS-2 tool. A total of 25 studies were included. All were case-control studies, most studies used cell pellet for analysis by quantitative PCR. Diagnostic sensitivity ranged from 0% for a single gene to 97% for a four-gene panel. Specificity ranged from 8% for a single gene to 100%. The studies employing a gene panel decreased the specificity, and no gene panel had a perfect specificity of 100%. In conclusion, methylated circulating tumor DNA can be detected in bronchial lavage, and by employing a gene panel the sensitivity can be increased to clinically relevant levels. The available evidence regarding applicability in routine clinical practice is limited. Prospective, randomized clinical trials are needed to determine the further usefulness of this biomarker.