• Greg J Haro, Bonnie Sheu, Nancy R Cook, Gavitt A Woodard, Michael J Mann, and Johannes R Kratz.
• Division of Adult Cardiothoracic Surgery, University of California, San Francisco.
• JAMA Netw Open. 2019 Dec 2; 2 (12): e1917062.

ImportanceImproved staging for non-small cell lung cancer (NSCLC) represents a critical unmet need. External validations of the eighth edition of the TNM staging system have yielded disappointing results, with persistently high mortality observed in early-stage disease.ObjectiveTo determine whether incorporation of a molecular prognostic classifier into conventional TNM staging for NSCLC improves estimation of disease-free survival.Design, Setting, And ParticipantsThis cohort study was conducted at an academic, quaternary care medical center from 2012 to 2018. A consecutive series of 238 patients underwent surgical resection of stage I to IIIC nonsquamous NSCLC and had molecular prognostic classifier testing performed. Data analysis was conducted in May 2019.ExposuresPatients were restaged according to the seventh and eighth editions of the TNM staging system and the novel TMMB staging system, which maintains the order and structure of the eighth edition of the TNM but downstages or upstages according to low or high molecular risk, respectively.Main Outcomes And MeasuresThe primary outcome was disease-free survival 3 years from the time of surgical resection. Reclassification statistics were then used to evaluate performance and improvement measures of the TNM seventh and eighth editions and the TNMB staging system.ResultsTwo hundred thirty-eight patients (144 [60.5%] female; median [interquartile range] age, 70 [63-75] years) were analyzed. The median (interquartile range) follow-up was 25 (14-40) months, and the disease-free survival rate was estimated to be 58.3% (95% CI, 45.7% to 69.0%). One hundred fifty-nine patients (66.8%) were reclassified by the TNMB staging system. Overall model fit remained the same for the seventh and eighth editions of the TNM staging system, whereas the R2 statistic (change from 0.22 to 0.31), concordance index (change from 0.68 to 0.73), and log-rank χ2 (change from 38 to 108) were all associated with improvements after TNMB adoption. The TNMB system, compared with the TNM eighth edition, was associated with enhanced identification of high-risk patients and better differentiation of those without recurrence from those who had recurrence (net reclassification improvement, 0.28; 95% CI, 0.08 to 0.46; P < .001), whereas the eighth edition compared with the seventh edition was not associated with improvement of this measure (net reclassification improvement, 0.02; 95% CI, -0.18 to 0.21; P = .87).Conclusions And RelevanceThe TNMB staging system was associated with improved estimation of disease-free survival compared with conventional TNM staging. Incorporation of a molecular prognostic classifier into staging for NSCLC may lead to better identification of high-risk patients.

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