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J Thorac Cardiovasc Surg 2004;127:1574-1578
© 2004 The American Association for Thoracic Surgery

General thoracic surgery

Visceral pleural invasion classification in non–small cell lung cancer: A proposal on the basis of outcome assessment

^a Division of Thoracic Oncology , Kashiwa Chiba, Japan
^b Pathology Division, National Cancer Center Research Institute East, Kashiwa, Chiba, Japan

Received for publication August 15, 2003; revisions received October 13, 2003; accepted for publication November 4, 2003.

^* Address for reprints: Kimihiro Shimizu, MD, PhD, Second Department of Surgery, Gunma University Faculty of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan
kmshimiz{at}showa.gunma-u.ac.jp

	Abstract

Top Abstract Patients and methods Results Discussion References

 
OBJECTIVE: The definition of visceral pleural invasion in lung cancer TNM classification of the International Union Against Cancer lacks detail. The purpose of this study was to evaluate the significance of the extent of pleural involvement as a prognostic factor and to propose a refined TNM classification on the basis of visceral pleural invasion.

METHODS: We reviewed 1653 consecutive patients with T1, T2, and T3 surgically resected non–small cell lung cancer for their clinicopathologic characteristics and prognoses. Visceral pleural invasion was classified by using the Japan Lung Cancer Society criteria: p0, tumor with no pleural involvement beyond its elastic layer; p1, tumor extension beyond the elastic layer but no exposure on the pleural surface; and p2, tumor exposure on the pleural surface.

RESULTS: The 5-year survivals for patients with p1 or p2 tumors of 3 cm or less were identical and significantly worse than those for patients with p0 tumors of the same size. Patients with p1 or p2 tumors of greater than 3 cm and patients with T3 cancers had essentially identical survivals.

CONCLUSIONS: Visceral pleural invasion should be defined as tumor extension beyond the elastic layer of the visceral pleura, regardless of its exposure on the pleural surface. A tumor of 3 cm or less with visceral pleural invasion should remain classified as a T2 tumor, as presently occurs in the International Union Against Cancer staging system, and tumors of greater than 3 cm with visceral pleural invasion should be upgraded to T3 status in the International Union Against Cancer TNM classification.

Dr Shimizu

Lung cancer pleural invasion was recognized as a poor prognostic factor as early as 1958 by Brewer and colleagues.¹ Visceral pleural invasion (VPI) was adopted as a specific description in the TNM classification of the International Union Against Cancer (UICC) staging system in the mid-1970s² and has remained unchanged until today: a tumor of any size that invades the visceral pleura is classified as T2. Although a tumor of 3 cm or less is upgraded to T2, a tumor of greater than 3 cm remains T2 in this system if a tumor has VPI.

The UICC TNM classification describes little on VPI definition. The Japan Lung Cancer Society (JLCS) classifies VPI as follows: p0, tumor with no pleural involvement beyond its elastic layer; p1, tumor that extends beyond the elastic layer of the visceral pleura but is not exposed on the pleural surface; p2, tumor that is exposed on the pleural surface but does not involve adjacent anatomic structures; and p3, tumor that involves adjacent anatomic structures.³ The Society classifies a p2 tumor of any size as T2 and a p1 tumor of 3 cm or less as T1. The UICC TNM classification does not clarify whether VPI includes p1. Given that p1 pleural involvement is interpreted as VPI in the UICC classification, there appears to be an inconsistency in the T1/T2 definition between the UICC and JLCS TNM classifications. To the best of our knowledge, there have been no studies reported on p1 pleural involvement as a prognostic factor.

The purpose of this study was to evaluate the significance of p1 pleural involvement as a prognostic factor and to propose a refined TNM classification on the basis of VPI.

	Patients and methods

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From February 1979 through March 2001, 1653 consecutive patients with T1, T2, or T3 non–small cell lung cancer underwent pulmonary resection (segmentectomy or more) and systematic mediastinal lymph node dissection at our institution, as described previously.⁴ All these patients had curative resection, which was defined as complete removal of ipsilateral hilar and mediastinal lymph nodes together with the primary tumor. Patients who had induction chemotherapy or radiotherapy and patients with evidence of residual tumor at the surgical margin, malignant effusion, satellite lesion, or distant metastasis verified intraoperatively or by means of postoperative pathologic examination were excluded from this study. Patients were pathologically staged on the basis of the UICC TNM classification.² Patient characteristics are shown in Table 1.

View larger version (106K): [in this window] [in a new window]   Figure 1. A, Tumor cells extend beyond the visceral pleural elastic layer (arrowheads) but are not exposed on the pleural surface: p1. B, Tumor cells extend beyond the visceral pleural elastic layer (arrowheads) and are exposed on the pleural surface but do not involve the parietal pleura: p2.

	Results

Top Abstract Patients and methods Results Discussion References

 
Patient characteristics and VPI
Table 1 shows the patient characteristics. There were 568 women and 1085 men aged 30 to 89 years (mean, 63 years; median, 65 years). Extents of pulmonary resection were pneumonectomy (n = 112), lobectomy (n = 1512), and segmentectomy (n = 29). Histologic types were adenocarcinoma (n = 997), squamous cell carcinoma (n = 513), large cell carcinoma (n = 79), and adenosquamous carcinoma (n = 64).

Survival difference
The overall 5-year survivals for groups A through G were 79%, 63%, 42%, 60%, 39%, 35%, and 36%, respectively (Figures 2 and 3). The difference in survival between groups A and B, between groups A and C, between groups B and G, and between groups C and G (Figure 2) and the difference in survival between groups D and E and between groups D and F (Figure 3) were significant. In contrast, the survival curves for groups B and D almost overlapped with each other, and there was no statistically significant difference in survival between the groups (Figure 2). Similarly, there was no statistically significant difference in survival between groups C and D and between groups B and C (Figure 2), nor was there a significant difference in survival between groups E and F (Figure 3). Also, the differences in survival between groups E and G and between groups F and G were not significant (Figure 3). Outcomes were also examined in the n0 patient cohort, and similar relationships were observed.

View larger version (22K): [in this window] [in a new window]   Figure 2. Survival curves and overall 5-year survivals for groups A, B, C, D, and G. The differences in survival between groups A and B, between groups A and C (P < .01), between groups B and G (P < .01), between groups C and G (P = .04), and between groups D and G were significant. There was no statistically significant difference in survival between groups B and C, between groups B and D (P = .38), and between groups C and D.

View larger version (21K): [in this window] [in a new window]   Figure 3. Survival curves and overall 5-year survivals for groups D, E, F, and G. The differences in survival between groups D and E, between groups D and F (P < .01), and between groups D and G (P < .01) were significant. There was no statistically significant difference in survival between groups E and F, between groups E and G (P = .38), and between groups F and G.

	Discussion

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Brewer and colleagues,¹ Ichinose and coworkers,⁸ and Manac'h and associates⁹ demonstrated that pleural invasion is an important poor prognosis factor. In their reports, however, p1 and p2 invasions were combined and analyzed as a single VPI category. In our study we conducted uniform hematoxylin and eosin and Victoria-blue van Gieson staining on all tumors and performed histologic review in all cases, with special interest in VPI and its JLCS subclassifications, p0, p1, and p2. We retrospectively analyzed postoperative survival in patients with p0, p1, p2, or T3 cancer to evaluate the significance of pleural involvement extent as a prognostic factor.

In our series the 5-year survivals for the patients with p1 or p2 tumors of 3 cm or less were identical and significantly worse than those for patients with p0 disease with the same size cancers. Similarly, the 5-year survivals for patients with p1 or p2 tumors greater than 3 cm were identical, whereas they were notably worse than those in patients with p0 disease with the same size cancers. Furthermore, there was no statistically significant difference in survival between the patients with p1 or p2 tumors greater than 3 cm and the patients with T3 cancers. Similar relationships were observed among patients with n0 disease.

These results indicate that p1 and p2 pleural involvement should be combined as a single category as VPI. A tumor of 3 cm or less with p1 involvement should, unlike the JLCS classification, be classified as T2. Although the UICC classifies a tumor of greater than 3 cm as T2 regardless of pleural involvement, our results suggest p1 or p2 tumors of greater than 3 cm should be upgraded to T3 status (Table 3).

	Acknowledgments

 
We thank Professor J. Patrick Barron (International Medical Communication Center, Tokyo Medical University) for reviewing the English manuscript.

	Footnotes

 
Supported in part by a Grant-in-Aid for cancer research from the Ministry of Health, Labour and Welfare, Japan.

	References

Top Abstract Patients and methods Results Discussion References

 

1. Brewer LA, Bai AF, Little JN, Pardo GR. Carcinoma of the lung: practical classification of early diagnosis and survival treatment. JAMA. 1958;166:1149–1154
   
2. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest. 1997;111:1710–1717[Abstract/Free Full Text]
   
3. The Japan Lung Cancer Society. General rule for clinical and pathological record of lung cancer. [in Japanese]5th ed. Tokyo: Kanehara; 1999.
   
4. Naruke T, Suemasu K, Ishikawa S. Surgical treatment for lung cancer with metastasis to mediastinal lymph nodes. J Thorac Cardiovasc Surg. 1976;71:279–285[Abstract]
   
5. World Health Organization. The World Health Organization histological typing of lung tumors. 3rd ed. Geneva: World Health Organization; 1999.
   
6. Kaplan EL, Meier P. Non parametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481
   
7. Peto R, Peto J. Asymptomatically efficient rank invariant test procedures. J R Stat Soc [A]. 1972;135:185–207
   
8. Ichinose Y, Yano T, Asoh H, Yokoyama H, Yoshino I, Katsuda Y. Prognostic factors obtained by a pathologic examination in completely resected non small-cell lung cancer. An analysis in each pathologic stage. J Thorac Cardiovasc Surg. 1995;110:601–605[Abstract/Free Full Text]
   
9. Manac'h D, Riquet M, Medioni J, Le Pimpec-Barthes F, Dujon A, Danel C. Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor. Ann Thorac Surg. 2001;71:1088–1093[Abstract/Free Full Text]
   

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Junji Yoshida Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shimizu, K. Articles by Nishiwaki, Y. Search for Related Content PubMed PubMed Citation Articles by Shimizu, K. Articles by Nishiwaki, Y. Related Collections Lung - cancer