Impact of positive pleural lavage cytology on survival in patients having lung resection for non–small-cell lung cancer: An international individual patient data meta-analysis
Received 3 November 2008; received in revised form 24 April 2009; accepted 16 May 2009. published online 25 November 2009.
Objectives
Pleural lavage cytology is the microscopic study of cells obtained from saline instilled into and retrieved from the chest during surgery for non–small-cell lung cancer. The aims of this study were to collate multi-institutional individual patient data for meta-analysis to determine independence as a prognostic marker and to characterize the impact of positive results on stage-adjusted survival.
Methods
We identified 31 publications from 22 centers/research groups that performed pleural lavage cytology during surgery for non–small-cell lung cancer and invited submission of individual patient data. Actuarial survival was calculated using Kaplan-Meier methods, and comparisons were performed using the log-rank test. Cox proportional hazards regression was used to ascertain the covariates associated with survival.
Results
By January 1, 2008, submissions were received internationally from 11 centers with individual data from 8763 patients. In total, 511 (5.8%) patients had a positive pleural lavage cytology result, and this was shown to be an independent predictor of adverse survival associated with a hazard ratio of 1.465 (1.290–1.665; P < .001) compared with a reference hazard ratio of 1 for a negative result. On statistical modeling, the best adjustment for patients with a positive pleural lavage cytology result was a single increase in the T category assigned to the case, up to a maximum of T4. Correction for differences in survival were obtained in stages IB (P = .315) and IIB (P = .453), with a degree of correction in stage IIIA (P = .07).
Conclusions
Pleural lavage cytology should be considered in all patients with non–small-cell lung cancer suitable for resection. A positive result is an independent predictor of adverse survival, and the impact on survival suggests that it may be appropriate to upstage patients by 1 T category.
Address for reprints: Eric Lim, MB, ChB, MD, MSc, FRCS(C-Th), Imperial College and The Academic Division of Thoracic Surgery, The Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom (E-mail: e.lim@rbht.nhs.uk).
∗ Authors: Eric Lim, Rachel Clough, Peter Goldstraw (The Royal Brompton Hospital, London, United Kingdom); Lyn Edmonds (Papworth Hospital, Cambridge, United Kingdom); Keiju Aokage, Junji Yoshida, Kanji Nagai (National Cancer Centre East, Chiba, Japan); Yasushi Shintani, Mitsunori Ohta, Meinoshin Okumura, Teruo Iwasaki, Tsutomu Yasumitsu (Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan); Morihito Okada, Takeshi Mimura, Noriaki Tsubota (Hyogo Cancer Centre, Akashi, Japan); Tatsuo Nakagawa, Norihito Okumura (Kurashiki Central Hospital, Okayama, Japan); Yukitoshi Satoh, Sakae Okumura, Ken Nakagawa (Cancer Institute Hospital, Tokyo Japan); Masahiko Higashiyama, Ken Kodama (Osaka Medical Centre for Cancer and Cardiovascular Diseases, Osaka, Japan); Marc Riquet (Hopital European Georges Pompidou, Paris, France); Giovanni Vicidomini, Mario Santini (Second University of Naples, Naples, Italy); Christophoros Kotoulas (Chest Diseases Hospital, Athens, Greece); Jeng-Yuan Hsu, Chih-Yi Chen (Taiching Veterans General Hospital, Taichung, Taiwan).
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