On the basis of their findings, Dr. Kratz and his associates proposed a new variation on the conventional tumor size, lymph node status, metastases (TNM) staging system that they called TNMM; the second M stands for multigene assay.
Their revised system designates patients judged stage Ia or Ib by TNM who have a low-risk gene test result as a new class Ia. Patients who had been classified Ia or Ib by the old system who have intermediate- or high-risk gene test results form a new stage Ib, a stage that also includes old IIa patients by TNM who had a low-risk gene test outcome. Finally, the new stage IIa consists of patients scored as IIa by the TNM system who also score as intermediate or high risk on the genetic test.
To further assess the prognostic value of adding the gene test, the researchers ran receiver-operator curves for the standard and revised staging methods in each of the two validation cohorts, and found that adding the gene test led to statistically significant increases in the area under the curve for prognostic accuracy.
In commenting on the study, Dr. Giorgio V. Scagliotti, the designated discussant, said the prognostic factors in current use – tumor size, differentiation, vascular invasion, and surgical margins – are not enough. Additional prognostic factors are needed to identify the completely resected stage I patients who might benefit from adjuvant chemotherapy. "We also need to better identify the stage II patients who have a low risk of recurrence and will not benefit from adjuvant chemotherapy," he said.
Previously reported genetic tests for early-stage non–small cell lung cancer involved complicated microarray test methods and a need for fresh tissue. They lacked reproducibility and validation, and had other problems as well. "The new study avoided these pitfalls, but despite its advances, it remains a set of post hoc analyses that lack prospective, randomized testing. Additional study must prospectively establish the medical utility of the prognostic information before routine use begins. Do patients identified by the test as high risk get any benefit from systemic treatment? Is the genetic test significant in the context of tumor stage, patient age, and treatment with adjuvant chemotherapy? Adjuvant therapy has so far not been included in the analysis," said Dr. Scagliotti, professor of medicine at the University of Torino (Italy).
He said he has been a consultant to Eli Lilly, and has been on the speakers bureaus of AstraZeneca, Eli Lilly, and Roche. Dr. Kratz said that he has been a consultant to and has an equity interest in Pinpoint Genomics, the company that developed the genetic test used in the study.