title: Accidental invisible intrathoracic disseminated pT4-M1a: a distinct lung cancer with favorable prognosis.
abstract: OBJECTIVE
  In the 7(th) edition of the TNM classification of malignant tumors, the prognosis for pT4-M1a stage IV lung cancer is better than for stage pIIIB. Subgroups of lung cancer patients who underwent incomplete resection (R1/R2) have a favorable prognosis. This study compares the prognosis between cases of invisible local residual disease and intrathoracic disseminated pT4-M1aIV.
  
  
  METHODS
  Patient characteristics and histological and molecular profiles were retrospectively collected for lung cancer patients who underwent resection intended to be curative but were accidentally incomplete. All patients were divided into either a local residual group or an intrathoracic disseminated pT4M1a group. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier and Cox regression models.
  
  
  RESULTS
  In total, 1,483 consecutive lung cancer patients receiving thoracotomies at Guangdong Lung Cancer Institute were retrospectively analyzed. Fifty-eight patients receiving incomplete resections (R1/R2) were enrolled, including 38 patients with local residual cancer (2.6% of all patients) and 20 patients with disseminated pM1a (1.3%). Patient characteristics, and histological and molecular profiles of the two groups were different. Compared to the local residual group, the disseminated pT4-M1a group contained more females (P=0.002), more patients younger than 60 years of age (P=0.028), more non-smokers (P=0.037), more adenocarcinomas (20/20 vs. 20/38, P<0.001), more adenocarcinomas with lepidic pattern (11/20 vs. 4/38, P<0.001), higher carcinoembryonic antigen (CEA) levels (P=0.06), higher epidermal growth factor receptor (EGFR) mutation rates (16/20 vs. 7/38, P<0.001), a higher R2/R1 resection ratio (P=0.013), a higher advanced stage IV/IIIB ratio (P<0.001), but fewer lymph node metastases (P=0.013). Median PFS for the local residual and disseminated pT4-M1a groups was 9.0 and 18.0 months, respectively [95% confidence interval (CI), 5.285-16.715; P =0.099]. Median OS was 15.0 and 45.0 months, respectively (95% CI, 18.972-39.028; P=0.001). Cox regression analysis revealed that group (local residual vs. disseminated pT4-M1a) was the only independent prognostic factor (P=0.044) for OS.
  
  
  CONCLUSIONS
  Accidental invisible intrathoracic disseminated pT4-M1a may be a distinct lung cancer subtype with a favorable prognosis. The prolonged PFS and OS might reflect the natural history of this distinct subtype, together with a favorable response to EGFR tyrosine kinase inhibitors (EGFR-TKI). For asymptomatic and slow-growing accidental pT4-M1a disease, the role of a wait-and-see strategy and the appropriate timing of systemic treatment require further investigation.
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Wen-Zhao
authors.initials: WZ
authors.lastname: Zhong
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Xue-Ning
authors.initials: XN
authors.lastname: Yang
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Ri-Qiang
authors.initials: RQ
authors.lastname: Liao
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Nie
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Song
authors.initials: S
authors.lastname: Dong
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yan
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Xu-Chao
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Tu
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Bin-Chao
authors.initials: BC
authors.lastname: Wang
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Jin-Ji
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 1 Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China ; 2 Southern Medical University, Guangzhou 510080, China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
keywords: Lung cancer; accidental invisible pT4-M1a; incomplete resection; prognosis