title: Biopsy first: Lessons learned from Cancer and Leukemia Group B (CALGB) 140503.
abstract: Cancer and Leukemia Group B 140503 is an ongoing, multicenter randomized trial assessing whether sublobar resection is equivalent to lobectomy for the treatment of stage I A non-small cell lung cancer (NSCLC) ≤2 cm in diameter. The objective of this report is to determine the reasons precluding intraoperative randomization.
  
  
  
  From June 15, 2007, to March 22, 2013, 637 patients were preregistered to the trial. Three hundred eighty-nine were randomized successfully (61%), and 248 patients were not randomized (39%). We analyzed the reasons for nonrandomization among a subset of the nonrandomized patients (208) for whom additional data were available.
  
  
  
  Of these 208 patients, undiagnosed benign nodules (n =104, 16% of all registered patients) and understaging of NSCLC (n =45, 7% of all registered patients) were the dominant reasons precluding randomization. Granulomas represent one-quarter of the benign nodules. The understaged patients had unsuspected nodal metastases (n =28) or other more advanced NSCLC. The rate of randomization was significantly greater in those patients who had a preoperative biopsy (P <.001).
  
  
  
  In a carefully monitored cohort of patients with suspected small NSCLC ≤2 cm, a substantial number are misdiagnosed (benign nodules) or understaged. These patients may not have benefited from a thoracic surgical procedure. Preoperative biopsy significantly increased the rate of correct diagnosis. Preoperative biopsy of small suspected NSCLC will reduce the number of nontherapeutic or unnecessary thoracic procedures. Accuracy in preoperative diagnosis is increasingly important as more such small nodules are discovered through lung cancer screening.
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse, NY. Electronic address: kohmanl@upstate.edu.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Kohman
authors.affiliation: Alliance Statistics and Data Center, Duke University Medical Center, Durham, NC.
authors.forename: Lin
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of Surgery, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY.
authors.forename: Nasser
authors.initials: N
authors.lastname: Altorki
authors.affiliation: Department of Radiology, State University of New York Upstate Medical University, Syracuse, NY.
authors.forename: Ernest
authors.initials: E
authors.lastname: Scalzetti
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse, NY.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Veit
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse, NY.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Wallen
authors.affiliation: Alliance Statistics and Data Center, Duke University Medical Center, Durham, NC.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000368:Aged; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000601:surgery; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D011013:Pneumonectomy / Q000009:adverse effects / Q000379:methods; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016896:Treatment Outcome; D047368:Tumor Burden; D019564:Unnecessary Procedures
keywords: biopsy; clinical trial; lung cancer; lung nodule; non–small cell lung cancer; sub-lobar resection; surgery; understaging