Original article: general thoracic
Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor

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Abstract

Background. Visceral pleura invasion (VPI) by non-small cell lung cancer is a factor of poor prognosis. A tumor of any size that invades the visceral pleura is classified as T2. Few studies have been conducted concerning the prognostic significance of VPI relative to other staging factors.

Methods. Between April 1984 and December 1996, 1,281 patients with T1 (n = 430) and T2 (n = 851) non-small cell lung cancer underwent curative surgical resection. Adjuvant radiation therapy was performed in 455 patients. There were 176 women and 1,105 men aged 30 to 86 years (mean, 60.9 years). Five hundred nineteen pneumonectomies, 742 lobectomies, and 20 segmentectomies were performed. In all patients, a complete mediastinal lymph node dissection was performed. International staging was stage IA and B (n = 697); stage II A and B (n = 247), and stage III A (n = 337). The patients were divided into two groups according to the existence of VPI (group I without, group II with). Both groups were compared with regard to the size of the tumors, histology, associated lymph node involvement, survival rates, and cause of death. Univariate and multivariate analyses were conducted.

Results. VPI (group II) was identified in 19.1% of the resected specimens: group I, n = 1036; group II, n = 245. The VPI was present in only 10% of non-small cell lung cancer 3 cm or less in size, reaching 33% of patients with non-small cell lung cancer larger than 5 cm (p = 0.0001). Squamous non-small cell lung cancer were significantly less accompanied by VPI (13.5%) than the other histologic categories. The VPI was associated with a higher frequency of N2 involvement (group I = 24.6%, group II = 33.4%, p = 0.01) and N2 involvement was more extensive (two or more N2 involved stations: group I = 8.2%, group II = 15.6%, p = 0.003). Actuarial survival rates were 51.8% at 5 years and 33.8% at 10 years in group I (median, 66 months), and 34.6% at 5 years and 27.9% at 10 years in group II (median, 30 months) (p = 0.000002). Long-term survival rates significantly decreased for larger tumors. Even in patients with N2 stage tumors, the difference of survival curves between the two groups was statistically significant. Cancer-related deaths were more frequent in group II and were mainly caused by distant metastases. By multivariate analysis, visceral pleura invasion proved to be a significant independent factor of poor prognosis.

Conclusions. The VPI is a factor of poor prognosis. Its frequent association with extensive N2 involvement supports the hypothesis that exfoliated tumor cells are drained through the pleural lymphatics by the mediastinal lymphatic pathways and then into the bloodstream. The VPI is an important prognostic factor and, as such should stimulate more studies to better select the patients who could benefit from adjuvant therapy.

Section snippets

Patients and methods

From April 1984 to December 1996, 1,585 patients underwent pulmonary surgical resection for bronchogenic carcinoma at Laennec Hospital and Boisguillaume Surgical Center. The surgical procedure was a potentially curative complete resection with extensive mediastinal lymph node dissection similar to that described by Martini and Flehinger [4]. All included patients had NSCLC (patients who had neoadjuvant chemotherapy or radiation therapy, as well as patients with prior history of malignancy were

Results

The VPI (group II) was identified in 19.1% of the resected specimens: group I (n = 1,036), group II (n = 245). Survival rates were 51.8% at 5 years and 33.8% at 10 years (median, 66 months) in group I, and 34.6% at 5 years and 27.9% at 10 years (median, 30 months) in group II. The difference between groups was highly significant (p = 0.00002).

The VPI was present in 10.4% of tumors 3 cm or less, in 19.6% of tumors between 3 and 5 cm and was significantly more frequent (p = 0.0001) in tumors

Comment

In our study, VPI was observed in 19.1% of resected lung specimens. It correlated with a tumor size larger than 3 cm and a more extensive mediastinal lymph node involvement. Survival rates decreased with such tumor characteristics, and lung cancer-related deaths were more frequent. This confirms what had been reported by Harpole and colleagues [10] in a multivariate study. The VPI is encountered in 11.5% [11] to 23.6% [12] of NSCLC.

We also observed that frequency of VPI is variable according to

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