The influence of adjuvant therapy on survival in patients with indeterminate margins following surgery for non–small cell lung cancer

Published:September 30, 2019DOI:



      The significance of indeterminate margins following surgery for non–small cell lung cancer (NSCLC) is unknown. We evaluated the influence of adjuvant therapy on survival in patients whose cancer showed indeterminate margins.


      Patients whose cancer showed indeterminate margins following surgery for NSCLC were identified in the National Cancer Database between 2004 and 2015, and stratified by receipt of adjuvant treatment. The primary outcome was overall survival, which was evaluated with multivariable Cox proportional hazards.


      Indeterminate margins occurred in 0.31% of 232,986 patients undergoing surgery for NSCLC and was associated with worse survival compared with margin negative resection (adjusted hazard ratio, 1.53; 95% confidence interval, 1.40-1.67). Anatomic resection was protective against the finding of indeterminate margins in logistic regression. Amongst 553 patients with indeterminate margins, 343 (62%) received no adjuvant therapy, 96 (17%) received adjuvant chemotherapy, 33 (6%) received adjuvant radiation, and 81 (15%) received adjuvant chemoradiation. Any mode of adjuvant therapy was not associated with improved survival compared with no further treatment.


      The finding of indeterminate margins is reported in 0.31% of patients undergoing curative-intent surgery for NSCLC. This was associated with worse overall survival compared with complete resection and not mitigated by adjuvant therapy. The risks and benefits of adjuvant therapy should be carefully considered for patients with indeterminate margins after surgery for NSCLC.

      Graphical abstract

      Key Words

      Abbreviations and Acronyms:

      NCDB (National Cancer Database), NSCLC (non–small cell lung cancer), R0 (margin negative), R+ (margin positive, not otherwise specified), R1 (microscopically margin positive), R2 (macroscopically margin positive), RID (margin indeterminate for positivity)
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        • Smeltzer M.P.
        • Lin C.C.
        • Kong F.-M.
        • Jemal A.
        • Osarogiagbon R.U.
        Survival impact of postoperative therapy modalities according to margin status in non–small cell lung cancer patients in the United States.
        J Thorac Cardiovasc Surg. 2017; 154: 661-672.e10
        • Hancock J.G.
        • Rosen J.E.
        • Antonicelli A.
        • Moreno A.
        • Kim A.W.
        • Detterbeck F.C.
        • et al.
        Impact of adjuvant treatment for microscopic residual disease after non–small cell lung cancer surgery.
        Ann Thorac Surg. 2015; 99: 406-413
        • Osarogiagbon R.U.
        • Lin C.C.
        • Smeltzer M.P.
        • Jemal A.
        Prevalence, prognostic implications, and survival modulators of incompletely resected non–small cell lung cancer in the U.S. national cancer data base.
        J Thorac Oncol. 2016; 11: e5-e16
        • Hofmann H.S.
        • Taege C.
        • Lautenschläger C.
        • Neef H.
        • Silber R.E.
        Microscopic (R1) and macroscopic (R2) residual disease in patients with resected non–small cell lung cancer.
        Eur J Cardiothorac Surg. 2002; 21: 606-610
        • Massard G.
        • Doddoli C.
        • Gasser B.
        • Ducrocq X.
        • Kessler R.
        • Schumacher C.
        • et al.
        Prognostic implications of a positive bronchial resection margin.
        Eur J Cardiothorac Surg. 2000; 17: 557-565
        • Lequaglie C.
        • Conti B.
        • Brega Massone P.P.
        • Giudice G.
        Unsuspected residual disease at the resection margin after surgery for lung cancer: fate of patients after long-term follow-up.
        Eur J Cardiothorac Surg. 2003; 23: 229-232
        • Ghiribelli C.
        • Voltolini L.
        • Paladini P.
        • Luzzi L.
        • Di Bisceglie M.
        • Gotti G.
        Treatment and survival after lung resection for non-small cell lung cancer in patients with microscopic residual disease at the bronchial stump.
        Eur J Cardiothorac Surg. 1999; 16: 555-559
        • Sawabata N.
        • Ohta M.
        • Matsumura A.
        • Nakagawa K.
        • Hirano H.
        • Maeda H.
        • et al.
        Optimal distance of malignant negative margin in excision of non–small cell lung cancer: a multicenter prospective study.
        Ann Thorac Surg. 2004; 77: 415-420
        • El-Sherif A.
        • Fernando H.C.
        • Santos R.
        • Pettiford B.
        • Luketich J.D.
        • Close J.M.
        • et al.
        Margin and local recurrence after sublobar resection of non–small cell lung cancer.
        Ann Surg Oncol. 2007; 14: 2400-2405
        • Snijder R.J.
        • Brutel de la Rivière A.
        • Elbers H.J.J.
        • van den Bosch J.M.M.
        Survival in resected stage I lung cancer with residual tumor at the bronchial resection margin.
        Ann Thorac Surg. 1998; 65: 212-216
        • Winton T.
        • Livingston R.
        • Johnson D.
        • et al.
        Vinorelbine plus cisplatin vs. observation in resected non–small-cell lung cancer.
        N Engl J Med. 2005; 352: 2589-2597
        • Arriagada R.
        • Bergman B.
        • Dunant A.
        • Le Chevalier T.
        • Pignon J.P.
        • Vansteenkiste J.
        Cisplatin-based adjuvant chemotherapy in patients with completely resected non–small-cell lung cancer.
        N Engl J Med. 2004; 350: 351-360
        • Makazu M.
        • Sakamoto T.
        • So E.
        • Otake Y.
        • Nakajima T.
        • Matsuda T.
        • et al.
        Relationship between indeterminate or positive lateral margin and local recurrence after endoscopic resection of colorectal polyps.
        Endosc Int Open. 2015; 3: E252-E257
        • Mirkin K.A.
        • Hollenbeak C.S.
        • Wong J.
        Survival impact of neoadjuvant therapy in resected pancreatic cancer: a prospective cohort study involving 18,332 patients from the National Cancer Data Base.
        Intl J Surg. 2016; 34: 96-102
        • Smitt M.C.
        • Nowels K.W.
        • Zdeblick M.J.
        • Jeffrey S.
        • Carlson R.W.
        • Stockdale F.E.
        • et al.
        The importance of the lumpectomy surgical margin status in long-term results of breast conservation.
        Cancer. 1995; 76: 259-267
        • Bilimoria K.Y.
        • Stewart A.K.
        • Winchester D.P.
        • Ko C.Y.
        The national cancer data base: a powerful initiative to improve cancer care in the United States.
        Ann Surg Oncol. 2008; 15: 683-690
        • D'Amico T.A.
        Get it right the first time.
        J Thorac Cardiovasc Surg. 2017; 154: 650-651