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Prognostic value of intraoperative pleural lavage cytology for lung cancer without carcinomatous pleuritis: importance in patients with early stage disease during long-term follow-up

^a Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan
^b Department of Cytology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan
^c Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan

Received 18 June 2008; received in revised form 29 September 2008; accepted 7 October 2008.

^_* Corresponding author. Tel.: +81 6 6972 1181; fax: +81 6 6981 8055. (Email: higasiyama-ma{at}mc.pref.osaka.jp).

Purpose: The clinical significance of intraoperative pleural lavage cytology (PLC) for lung cancer has been insufficiently elucidated. We therefore reviewed the surgical results of lung cancer patients without carcinomatous pleuritis followed up over the long term to elucidate PLC implications. Patients and methods: PLC was performed immediately after thoracotomy in consecutive lung cancer patients without carcinomatous pleuritis undergoing tumor resection between 1988 and 1997. Postoperative follow-up was generally performed for at least 5 years while checking tumor recurrence and survival. Results: Eighty-nine (13.1%) of 679 patients had positive PLC findings, which were observed more frequently in patients with advanced stage, larger tumor size, higher involvement of the pleura, lymph node, lymphatics and vessels. The overall 5- and 10-year survival rates in PLC-positive patients were 43% and 25%, respectively, while those in PLC-negative patients were 66% and 58%, respectively (p < 0.0001). Among 395 patients with stage I disease, 35 (8.9%) showed PLC-positive findings, and their overall survival rate was significantly poor compared with those with PLC-negative findings (p < 0.0001). In contrast, such differences were not observed among patients with more advanced stage diseases. In regard to histological type, a difference in the postoperative survival rate according to PLC status was statistically found in adenocarcinoma type (p < 0.0001), but not in squamous cell carcinoma type (p = 0.24). According to multivariate analysis, PLC was an independent prognostic factor for all tested patients (p = 0.007, hazard ratio = 0.60) as well as for those with stage I disease (p = 0.0135, hazard ratio = 0.51). When examining postoperative pleural recurrence, the rate for PLC-positive patients was statistically higher than that for PLC-negative patients (p < 0.0001, hazard ratio = 0.08). Interestingly, late pleural recurrence more than 5 years occurred in five (5.6%) of PLC-positive patients, all of whom were included in stage I. Conclusions: Based on the present analysis of long-term follow-up after operation, PLC may also be an independent prognostic factor. In particular, the PLC status of patients with stage I disease or adenocarcinoma type has an important impact on survival. PLC-positive findings may be a high risk for postoperative pleural recurrence. For PLC-positive patients with stage I disease, careful serial follow-up for more than 5 years is required while paying attention to late pleural recurrence.

Key Words: Lung cancer • Pleural lavage cytology (PLC) • Prognosis • Pleural recurrence