Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse


  • F. Chemi
  • D.G. Rothwell
  • N. McGranahan
  • S. Gulati
  • C. Abbosh
  • S.P. Pearce
  • C. Zhou
  • G.A. Wilson
  • M. Jamal-Hanjani
  • N. Birkbak
  • J. Pierce
  • C.S. Kim
  • S. Ferdous
  • D.J. Burt
  • D. Slane-Tan
  • F. Gomes
  • D. Moore
  • R. Shah
  • M. Al Bakir
  • C. Hiley
  • S. Veeriah
  • Y. Summers
  • P. Crosbie
  • S. Ward
  • B. Mesquita
  • M. Dynowski
  • D. Biswas
  • J. Tugwood
  • F. Blackhall
  • C. Miller
  • A. Hackshaw
  • G. Brady
  • C. Swanton
  • C. Dive


  • Nature Medicine


  • Nat Med 25 (10): 1534-1539


  • Approximately 50% of patients with early-stage non-smallcell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC.