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New TNM Classification for Lung Cancer. Part II: A review

Author: Dr. A. De la Guerra | Submitted: February 07, 2010. Updated: March 01, 2010.

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Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

 

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ABSTRACT: The American Joint Committee on Cancer and the Union Internationale Contre le Cancer have redefined the criteria for staging lung cancer based on the proposals made by the International Association for the Study of Lung Cancer, which appeared in the recently launched 7th edition of the TNM system. This article evaluates those changes and reviews the literature with particular attention to background information on the areas of controversy. As well, we examine the latest reports appraising the new staging system.

Introduction

The objective of this article is to review the changes in the lung cancer TNM staging system derived from the work of the IASLC. The changes included in the 7th edition of the TNM were based on the largest retrospective database ever accrued for the study of lung cancer. Moreover, for the first time the proposed revisions were internally and externally validated (1).

Because the LCSP database was not purposely designed to study the staging system, some TNM descriptors were not evaluated either because of insufficient number of cases or lack of validation. The following sections in this article discuss the major changes to the ISS of lung cancer and evaluates recent reports validating the new TNM system.

Anatomic extent of the primary tumor (T)

In the AJCC Cancer Staging Manual and UICC TNM Classification of Malignant Tumors the T factor is divided into four descriptors (T1-4) depending on size, site, number, and local extent of the primary tumor: the size and non-size based descriptors.

Size-based T descriptors.

The value of tumor size in NSCLC prognosis is supported by large clinical evidence (2-6). The tumor size threshold of 3 cms was set-up on the 2nd edition of the TNM classification of malignant tumors in 1974 (7), and despite the advances in surgical procedures, adjuvant treatment, and mostly in imaging technology, this measure has remained unchanged for 35 years. Several reports have stressed the need to adopt new cutoff points to subclassify and reclassify the T component to improve its prognostic relevance (8-17).

The 7th edition of the TNM for lung cancer confers more importance to the size-based T descriptors and divides them as exposed earlier in this article. These modifications have been validated by recent studies that showed better survival stratification and prognosis estimation with the new T definitions (18-20).

Two earlier publications that evaluated large databases concluded that tumor size is an independent and major prognostic factor for survival in NSCLC (21, 22), and recent reports using the new TNM system support those conclusions (23,24). Benefits of the modifications are illustrated on table 6a: survival rates exhibit stepwise deterioration as the T factor increases (24, 25); survival rates are improved with the new system due to reclassification (up- and downstaging) of patients when compared to series reporting survival rates with the previous TNM, showed in table 6b (26, 27).

Table 6a. Five year survival by pT classification with the 7th edition.

T component

5-year survival  (%)

 

Kameyama et al (25)

Li et al (24)

T1a

82.6

75.49

T1b

73.3

74.58

T2a

63.5

60.87

T2b

50.1

55.63

T3

40.6

46.15

T4

34.6

NS

NS, not shown.

Table 6b. Five year survival by pT classification with the 6th edition.

T component

5-year survival  (%)

 

Mountain CF (26)

Naruke et al (27)

T1

67

68.9

T2

57

42.5

T3

38

31.9

T4

7 (cT)

18.9

Non–size-based T descriptors.

Pleural dissemination and pericardial effusion.

According to the TNM staging manual, pleural dissemination means the presence of ipsilateral malignant pleural effusion (MPE) or pleural nodules (28). Even so, some authors use the term as a synonym for pleural nodules. Pleural nodules are defined as pleural tumor foci separated from direct pleural invasion by the primary tumor, classified as T4 (28). These pleural tumors must be differentiated from direct tumor invasion to the visceral (T2) or parietal pleura (T3).

In TNM staging, either pleural fluid cytology or clinical judgment are valid to establish the diagnosis of a MPE and consider it as a T4 factor (26). Malignant pericardial effusions are classified according to the same rules. Pleural dissemination and pericardial effusion are T4 descriptors, grouped into stage IIIB in absence of distant metastasis.

The diagnosis of a MPE is a sign of advanced disease, and almost every cancer can involve the pleura (29, 30). However, NSCLC is the most common cause of MPE and entails the worst prognosis (31-33); only a few patients survive beyond 12 months (tables 7a and 7b). Ipsilateral MPE is a locally advanced disease that precludes surgical treatment in lung cancer (34-36). Unlike other malignant effusions, those caused by NSCLC have low sensitive to chemo- and radiotherapy (37-39); therefore patients are considered mainly for palliative therapy (40-43). In a similar way, NSCLC is the most frequent cause of malignant pericardial effusion, which has a grim prognosis too (44-46).

Table 7a. Median survival time for stage IIIB, with and without pleural effusion, and for stage IV disease.

Stage

MST (months)

Sugiura et al (39)

Mott et al (48)

IIIB without PE

15.3

12

IIIB with PE

7.5

2

IV

5.5

4

MST= Median survival time; PE= pleural effusion.

Table 7b. Postoperative survival of patients with different pathologic T4 categories (*).

pT4 Categories

5-year survival  (%)

Osaki et al (36)

Kameyama et al (49)

Satellite nodule (same lobe)

26.7

57.4

Mediastinal invasion

18.2

13.4

Pleural dissemination

0

5.0

(*) Data adapted from references 36 and 49.

The ISC proposal to reclassify pleural dissemination from T4 to the new descriptor M1a is the most anticipated change in the new TNM system after the magnitude of evidence demonstrating that survival rates of patients with stage IIIB due to MPE are no different from those with stage IV disease (35, 36, 39, 47-50). Survival rates are shown in table 8.

Table 8. Postoperative survival rates of NSCLC with malignant pleural effusion (MPE): no significant difference with stage IV disease (*).

Status at thoracotomy

5-year survival  (%)

No pleural effusion

45.4

Non-MPE

42.5

MPE

15.9

Pathologic stage IV

11.2

(*) Data from Naruke et al (35).

The analysis made by the ISC showed that patients with cT4 due to pleural dissemination had a 5-year survival rate of 2% (51, 52). Recent studies corroborated these findings, validating the upstaging of cases with MPE from the T4 descriptor to the new M1a descriptor (53, 54).

Multiple nodules.

The existence of multiple primary cancers (MPC) was initially reported by Warren and Gates in 1932 (55); though, to date accurate diagnosis of MPC is not easy due to a lack of consensus on definition and diagnostic criteria (56). Thanks to advancement in diagnostic modalities the incidence of clinically detected multiple primary lung cancers (MPLCs) has increased (57-59).

In 1975, Martini and Melamed were the first to propose clinical and histopathologic criteria for the differential diagnosis of second lung cancers (60). MPLCs may be synchronous, if detected simultaneously, or metachronous, if tumors are separated in time (61, 62). It is beyond the intention of this article to discuss second lung cancers but rather to discriminate between synchronous nodules for staging purposes.

Synchronous nodules may represent a MPLC (second primary), a metastasis, or an extension from the primary (satellite nodule) (63). Table 9 shows the most accepted definitions of second lung cancers.

In 1989, Deslauriers et al. described intrapulmonary metastasis in patients with NSCLC as satellite nodules, and defined them as “well-circumscribed accessory carcinoma foci clearly separated from the main tumor but with identical histologic characteristics” (64). The 5- year survival rates for patients with satellite nodules were 21.6% compared to 44% for patients without satellite nodules. They concluded that patients with satellite nodules should be classified as stage IIIA.

Table 9. Definitions of second primary, satellite nodules and metastasis (*).

Type

 Definition

Satellite nodule

Same histology

And same lobe as primary cancer

And no systemic metastasis

MPLCs

Same histology, anatomically separated

Tumors in different lobes

And no N2-3 involvement

And no systemic metastasis

Same histology, temporally separated

 =4-yr interval between tumors

And no systemic metastasis from either tumor

Different histology

Or different molecular genetic features

Or arising separately from foci of CIS

Metastasis

Same histology

With multiple systemic metastasis

Same histology, in different lobes

 And presence of N2-3 involvement

Or < 2-yr interval

(*) Data adapted from references 60 and 63.

The concept of satellite nodules was not considered in NSCLC staging system until 1992 by the AJCC and in 1993 by the UICC (65, 66). Prior to this, all nodules were designated M1 disease. The evolution of satellite nodule descriptors is shown in table 10.

Table 10. Evolution of satellite nodule staging in the TNM system (*).

Location

TNM descriptor

4th edn

4th edn supplement

5th - 6th edn

7th edn

Ipsilateral same lobe

M1

T increases by one level

T4

T3

Ipsilateral different lobe

M1

T4

M1

T4

Contralateral lung

M1

M1

M1

M1

(*) Data adapted from references 65 and 66.

The T4 descriptor includes diverse tumors with dissimilar prognosis: invasion of the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, and carina; tumor with a malignant pleural or pericardial effusion, or with satellite tumor nodule(s) within the ipsilateral primary-tumor lobe of the lung (26).

The IASLC lung cancer staging project committee has acknowledged the multiple reports showing better survival for primary tumors with satellite nodules than other T4 tumors (66-75) and has downstaged them accordingly (51, 76). Outcomes of resected lung cancers with satellite nodules are shown in table 7b and table 11.

Table 11. Survival rates of patients with satellite nodules (SN) in various series.

Study (reference)

5-year survival  (%)

SN same lobe

SN different lobe

Any pT4

Rao et al (66)

57

NR (*)

18

Okada et al (70)

29.6

23.4

NS

Oliaro et al (68)

35

33

18

Nagai et al (71)

26.8

22.5

17.6

Strand et al (2)

30

22.9

8

Lee et al (72)

30.3

30.7

16.2

Okumura et al (73)

34

11

34

(*) NR = not reported.

Later studies found that the new T descriptor for satellite nodules proposed by the IASLC reflects better the outcomes of that group of patients, which showed superior survival rates (53, 54, 77). Even though there is a need of prospective trials to validate this finding, now these patients will be considered for surgery (78, 79).

Involvement of regional lymph node (N)

Analysis from the international database of the IASLC showed that current N descriptors provide good survival stratification, and therefore considered appropriate to maintain them without modifications (80). Lung cancer survival rates by pathologic N factor are shown in table 12; note the similarity on survival.

Table 12. Lung cancer survival rates by pathologic N factor. Comparison between 6th and 7th editions of the TNM system.

N factor

5-year survival (%)

6th edition (*)

7th edition (**)

pN0

63.1

56

pN1

42.1

38

pN2

17.4

22

pN3

2.3

6

(*) Data from Naruke et al (35)

(**) Data from Rusch et al (80).

Proposals to subdivide the N factor into 4 zones according to the extent of involvement of regional lymph nodes will not be part of TNM changes in the 7th edition. Although, recent reports showed that the IASLC recommendation to group patients according to nodal zones are appropriate and provide excellent survival stratification (53, 81).

Presence or absence of distant metastases (M)

The analysis of the M component made by the IASLC showed similar 5-year survival for pleural dissemination (6%) and contralateral lung nodules (3%), but worse outcome for distant metastasis (1%). Therefore, the ISC recommended dividing the M factor into M1a and M1b, to differentiate intrathoracic from distant metastasis (52); see table 13. Recent studies found the same differences in survival among these new M categories, validating the proposed changes (53, 54, 82).

A major change in the M component is the elimination of the codes MX and pM0 (except at autopsy). This proposal was not made by the IASLC, but by the AJCC/UICC members. In absence of clinical or pathologic evidence of metastasis, cases should be classified as clinical M0 (cM0). Also, since pathologists normally do not have information about metastasis, the M factor will not appear in pathology staging templates on the 7th edition (83).

Table 13. Survival of M1 subgroups with the new TNM system (*).

M descriptor

Median Overall Survival (months)

5-yr survival (%)

Pleural Dissemination (M1a)

4

2

Contralateral nodule (M1a)

6

4

Distant metastasis (M1b)

3

1

(*) Data adapted from Groome et al (1).

Anatomic stage (Stage grouping)

Lung cancers with similar prognosis are grouped based on the assigned T, N, and M categories. Stage groups are also termed prognostic groups due to correspondence of increasing values with worse prognosis (from stage 0 to stage IV); staging is not relevant for occult carcinoma TXN0M0 (26).

The ISC has not added new subdivisions to the stage grouping (76), but changes to the T and M descriptors led to modifications in TNM subsets and consequently in stage groups, as previously described in this article.

Now staging is less intuitive than before since the designation of groups is more complex due to the new T and M descriptors, but better reflects the differences in prognosis among stages (84). Five-year survival rates according to clinical and pathologic stages between the forthcoming and the current TNM system are shown in table 14.

Table 14. Lung cancer survival rates by clinical and pathologic stages.

Stage

5-year survival  (%)

6th edition (*)

7th edition (**)

cStage

pStage

cStage

pStage

IA

61

67

50

73

IB

38

57

43

58

IIA

34

55

36

46

IIB

24

39

25

36

IIIA

13

23

19

24

IIIB

5

NR

7

9

IV

1

NR

2

13

NR = not reported

(*)  Data adapted from Mountain (26).

(**) Data adapted from Goldstraw et al (76).

The applicability and validity of the new prognostic groups has been confirmed by recent studies (19, 20, 24, 82, 85, 86); their results showed that the new TNM is superior to the current system in predicting prognosis of each stage.

Other changes

Visceral Pleural Invasion (VPI)

The definition of VPI in the existing AJCC-UICC staging documents lacks precision (87-92). As described elsewhere in this article, the IASLC has proposed a new classification of pleural invasion based on Hammar’s classification, which incorporates the use of elastic stains when H&E sections are inconclusive (93).

The IASLC was unable to carry out an analysis of data regarding this topic since there was incomplete pathologic information about VPI, thus the proposal was not validated. However, on behalf of the IASLC Staging Committee, Travis et al. (93) stated that “the goal is to define pleural invasion in a manner that will allow for accurate collection of data regarding this important T factor for future analysis in a prospective database” (page 1386). Meanwhile they advocate keeping the present TNM that classifies a tumor with VPI as T2.

However, the applicability of the new classification for VPI is supported by recent publications (94-96); survival analysis confirmed that VPI defined by the IASLC as tumor extension beyond the elastic layer is valid (see definitions on table 4). Two of these studies also suggested that VPI has impact on survival dependant on tumor size (94, 95). We should wait for larger prospective studies to confirm those findings.

SCLC.

The AJCC-UICC staging system applies to all types of carcinoma (97), but is seldom used for staging SCLC because reliability of the TNM system traditionally hinged on surgery, and less than 5% of patients with SCLC are candidates for operation (98). Thus, SCLC is classified with either the Veterans’ Administration Lung Study Group (VALSG) or the IASLC binary schemes, into limited (LD) and extensive disease (ED); LD corresponds with TNM stages I to IIIB, and ED is equivalent to stage IV (99).

For many decades both two-stage systems had been used interchangeably for SCLC, albeit their staging criteria differ (table 15). Consequently, treatment outcomes may be dissimilar depending on the staging system selected (100, 101). Another problem shows up when we need to compare surgical and medical series staged with different systems: the two-stage scheme employed by oncologists and radiotherapists, and the TNM classification used by surgeons (102, 103). Some authors state that staging SCLC with the TNM system will allow comparing results from surgery with those from chemo and radiotherapy (104-106).

Table 15. SCLC staging systems.

Stage

Staging system (reference)

VALSG (107)

IASLC (99)

LD

Primary tumor and nodal involvement limited to one hemithorax, including ipsilateral supraclavicular lymph nodes. Disease can be encompassed in a single radiation port.

In addition, contralateral mediastinal and  supraclavicular lymph nodes, and ipsilateral pleural effusion. No distant metastasis.

ED

Tumor outside the limits of a single radiation port, including malignant pleural or pericardial effusion and contralateral supraclavicular or cervical lymph nodes.

Any distant metastasis.

LD: limited disease; ED: extensive disease.

Almost 30 years ago, Shields and associates (108) showed the importance of TNM staging in SCLC. Since then, several authors confirmed the prognostic value of the TNM system in this type of tumors (109-117); table 16 shows survival rates of SCLC in different TNM stages.

Table 16. 5-year survival rates for patients with SCLC by pTNM stages.

Study (reference)

Pathologic stage (%)

I

II

III

Rea et al (109)

52.2

30

15.3

Shah et al (118)

57.1

0

55.5

Tsuchiya et al (119)

66

56

13 (IIIA)

Lucchi et al (106)

47.7

14.6

9

Brock et al (103)

58

18

23

Inoue et al (110)

56.1 (IA) - 30 (IB)

57.1 (IIA) - 42.9 (IIB)

--

After a thorough review and survival analysis of 12,620 cases of SCLC from their international database, the IASLC recommended the use of the TNM system for this type of cancer (120); results are shown in table 17.

Table 17. Survival for clinical TNM stage SCLC from the IASLC database (120).

Stage

5-year survival  (%) MST (months)

IA

36

31

IB

31

35

IIA

53

68

IIB

16

17

IIIA

11

13

IIIB

10

12

IV

2

8

MST= Median survival time

Further assessment of the IASLC database confirmed that TNM pathologic staging correlates with survival of resected SCLC, supporting the proposal to use the TNM system for all SCLC cases (121). The applicability of the proposal has been recently validated by Ignatius Ou et al (122): reclassification of 10,660 SCLC patients from the California Cancer Registry according to the new TNM showed improved prognostic significance.

Carcinoid Tumors.

In general, the TNM system is not used to stage carcinoid tumors. However, many authors applied the TNM for carcinoid tumors of the lung and demonstrated its prognostic value (123-127).

The 7th edition of the TNM introduces a new TNM classification: Neuroendocrine Tumors, including pulmonary carcinoids that must be staged as carcinomas. The TNM for neuroendocrine tumors of the lung was introduced following the IASLC proposals (128).

Because the AJCC-UICC staging system was not recommended before for staging carcinoid tumors, there was little information available in the IASLC database to analyze all the TNM descriptors, thus further documentation of these tumors, using the new classification, will allow a more detailed evaluation of prognostic factors.

CONCLUSIONS

Changes included in the 7th edition of the TNM are the result of an analysis of the largest number of lung cancer cases ever accumulated, and comprise the largest validation ever done so far. However, data was not collected purposely to study the lung cancer staging system, which resulted in incomplete information, with the result that many descriptors were not revised (129). This does not reduce the value of the new revision, which remains the best data review so far and is seen as a large step in the right direction.

To overcome the drawbacks of their retrospective project, the IASLC has launched a prospective project to improve upcoming editions of the staging system for lung cancer (130).

As exposed before, recent reports showed the feasibility and superiority of the new system, though we need larger prospective data to validate it.

Conflict of interest statement

No financial conflicts or disclosures to report.

CITE THIS ARTICLE:
Dr. A. De la Guerra. New TNM Classification for Lung Cancer. Part II: A review. Doctors Lounge Website. Available at: http://www.doctorslounge.com/index.php/articles/page/342. Accessed April 18 2014.

References



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March 01, 2010 04:03 PM

Dear Dr. M. Jagesh Kamath,

I am glad you enjoyed the article; thank you for your kind words.

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March 01, 2010 09:01 AM

Dr. A. De la Guerra, thank you so much for this prompt and comprehensive answer. I learned a lot from your article and your reply. The information you wrote about the diagnostic approach to PE is very useful and your comment to justify excluding the M descriptor from the pathology staging templates is very much appreciated.
Best Regards.

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February 28, 2010 06:46 AM

ERRATUM: Re: New TNM Classification for Lung Cancer. Part II: A review. by Dr. A. De la Guerra. Doctors Lounge Website. Available at: http://www.doctorslounge.com/index.php/articles/page/342. Accessed February 27 2010. In the section: Pleural dissemination and pericardial effusion, in the second paragraph, lines 2 and 3, the sentence: “Notice that diagnosis of a MPE can also be made by pleural biopsy, but in such cases disease is listed as M1 - stage IV”, should not be present. Both citologic and pathologic diagnosis of a MPE were considered T4 in the 6th edition of the TNM. The author regrets the error.

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February 28, 2010 06:43 AM

Dear Dr. Safaa Mahmoud,

Thank you for your comments.

Your observation about the different forms of pleural involvement and their classification is almost exact, except for separate pleural nodules; they were T4, now M1a, the same as MPE.

On your first question, about the diagnosis and clinical staging of pleural effusions (PE) in patients with NSCLC, these are the rules for classification, word for word, according to the 6th edition of the TNM staging system (1-3):

“Most pleural effusions associated with lung cancer are due to tumor. However, there are a few patients in whom multiple cytopathologic examinations of pleural fluid are negative for tumor. In these cases, the fluid is non-bloody and is not an exudate. When these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient should be staged T1, T2, and T3.”

The opposite is also valid, that is to say, when the clinical picture is highly suggestive of MPE, despite a negative fluid cytology. We have to consider that pleural fluid cytology is diagnostic in only 60% of MPE (4, 5). There is evidence that clinical evaluation, including antecedent of cancer and CT characteristics, has a sensitivity of more than 90% in the diagnosis of MPE (6).

Clinical judgment is appropriate to establish the diagnosis of a MPE, when common diagnostic procedures had failed, in patients with microscopic confirmation of lung cancer, that due to the stage of the disease are not considered for treatment with curative intent (surgery with or without adjuvant therapy), and pathologic proof of MPE has no clinical relevance; consider that clinical stage guides initial management; pathologic stage defines prognosis.

If the diagnosis of cancer has not been established yet, or the patient has early stage disease, pathologic confirmation is mandatory. Most accepted approach for the diagnosis of exudative PE is:

• Cytological examination of pleural fluid; if negative repeat.
About 50% of MPE are negative at first thoracentesis (7).

• If second examination of pleural fluid is negative, do a contrast enhanced thoracic CT scanning to evaluate any pleural abnormality and make a decision to carry out a biopsy.
CT sensitivity for malignant pleural dissemination is about 85% (4, 8, 9).

• If thickening or nodularity is found, perform an imaging-guided pleural biopsy.
CT-guided pleural biopsy has almost 100% of sensitivity against 50% of blind biopsy (10, 11).

• If pleural biopsy is negative: do a thoracoscopy.

Your concern about the inconsistency in the statement that “diagnosis of a MPE can also be made by pleural biopsy, but in such cases disease is listed as M1 - stage IV” is absolutely justified. I appreciate very much your observation (and applaud your perspicaciousness). I didn’t notice the mistake; the correct statement must be that both, positive fluid cytology and pleural biopsy are valid to classify the tumor as T4 (according to the 6th edition). I am publishing an erratum right now.

On your commentary regarding the new pathology staging templates, I agree with you. Ideally every member of the multi-disciplinary team dedicated to the management of lung cancer should have the most complete and accurate information of the patient. In practice, communication between clinicians and pathologists is far from optimal.

The reason to exclude the M descriptor from the pathology staging templates is, as you mention, that pathologists usually do not have data about metastasis. The problem is that the pathologic assignment of the presence of metastases (pM1) requires a positive biopsy, consequently pMX does not exist. Pathologic classification of the absence of distant metastases (pM0) can only be made at autopsy. The risk of maintaining the M factor on the pathology staging templates is that if the pathologist does not know the clinical M he may consign a MX and exclude the case from staging.

Thank you again for your interest in the article.


References.

1. Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997; 111 (6): 1710-1717.

2. Sobin LH, Wittekind C eds. Lung and pleural tumours. In: Sobin LH, Wittekind C eds. UICC International Union Against Cancer, TNM classification of malignant tumours, 6th ed. New York: Wiley-Liss, 2002; pp. 97-107.

3. Lung. In: American Joint Committee on Cancer. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 167-181.

4. Maskell NA, Butland RJ; Pleural Diseases Group, Standards of Care Committee, British Thoracic Society. BTS guidelines for the investigation of a unilateral pleural effusion in adults. Thorax 2003; 58 Suppl 2: ii8-17.

5. Villena Garrido V, Ferrer Sancho J, Hernández Blasco L, de Pablo Gafas A, Pérez Rodríguez E, Rodríguez Panadero F, Romero Candeira S, Salvatierra Velázquez A, Valdés Cuadrado L; Area de Tecnicas y Trasplantes. SEPAR. Diagnosis and treatment of pleural effusion. Arch Bronconeumol 2006; 42 (7): 349-372.

6. Alemán C, Sanchez L, Alegre J, Ruiz E, Vázquez A, Soriano T, Sarrapio J, Teixidor J, Andreu J, Felip E, Armadans L, Fernández De Sevilla T. Differentiating between malignant and idiopathic pleural effusions: the value of diagnostic procedures. QJM 2007; 100 (6): 351-359.

7. Moffett PU, Moffett BK, Laber DA. Diagnosing and managing suspected malignant pleural effusions. J Support Oncol 2009; 7 (4): 143-146.

8. Traill ZC, Davies RJ, Gleeson FV. Thoracic computed tomography in patients with suspected malignant pleural effusions. Clin Radiol 2001; 56 (3): 193-196.

9. Arenas-Jiménez J, Alonso-Charterina S, Sánchez-Payá J, Fernández-Latorre F, Gil-Sánchez S, Lloret-Llorens M. Evaluation of CT findings for diagnosis of pleural effusions. Eur Radiol 2000;10 (4): 681-690.

10. Maskell NA, Gleeson FV, Davies RJ. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361 (9366): 1326-1330.

11. Adams RF, Gleeson FV. Percutaneous image-guided cutting-needle biopsy of the pleura in the presence of a suspected malignant effusion. Radiology 2001; 219 (2): 510-514.

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February 26, 2010 02:58 PM

Dr. A. De la Guerra, thank you so much for this comprehensive article.  Based on the new staging classifications, pleural involvement in lung cancer would follow one of these forms: direct tumor extension to visceral pleura described as T2, to parietal pleura described as T3; separate pleural nodules described as T4 and malignant pleural effusion (MPE) described as M1a.  Would you please comment on this statement if correctly received: MPE is considered as T4 if diagnosed only by clinical findings, but I find it strange that MPE is considered T4 if diagnosed by cytology but M1a if diagnosed by biopsy. And this how it is stated in the article (In TNM staging, either pleural fluid cytology or clinical judgment are valid to establish the diagnosis of a MPE and consider it as a T4 factor (26). Notice that diagnosis of a MPE can also be made by pleural biopsy, but in such cases disease is listed as M1 - stage IV).

Second as mentioned in your article, (since pathologists normally do not have information about metastasis, the M factor will not appear in pathology staging templates on the 7th edition (83)). We all understand that this information is always missing in the request sent to pathologist but do not you agree that pathologists should insist of getting the request with complete information including metastasis status when available rather than omitting this part at all. Would you kindly comment on this too?
Thank you again for this very comprehensive review, great effort indeed.

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February 24, 2010 02:23 AM

Very comprehensive study on the new TNM System.Well done, and neatly presented by Dr.Guerra.Congratulations!

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