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Masaya Yotsukura

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    MS17 - Pathology of the Future (ID 80)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Pathology
    • Presentations: 1
    • Now Available
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      MS17.05 - Controversies in Pathologic Staging (Now Available) (ID 3541)

      14:30 - 16:00  |  Presenting Author(s): Masaya Yotsukura

      • Abstract
      • Presentation
      • Slides


      The 8th edition of the TNM classification system was implemented in January 2017, except in the United States, where it was delayed until January 2018. The 8th edition was proposed by the Staging and Prognostic Factors Committee (SPFC) of the International Association for the Study of Lung Cancer (IASLC), and accepted by the Union for International Cancer Control and American Joint Committee on Cancer. The SPFC’s proposed changes from the 7th to 8th edition were essentially based on prognostic data from the IASLC database, which included 70,697 evaluable patients with non-small cell lung cancer and 6,189 patients with small cell lung cancer.

      Although the TNM system is the result of a scientific analysis of the anatomical extent of the tumor, some of the classification points are still controversial.

      1. Ground glass opacity

      Regarding the T descriptor, the main issue revolves around ground glass opacity (GGO)-related matters. The invasive area can pathologically be well-defined under microscopic evaluation, sometimes in combination with Elastica van Gieson stain. However, the difference between pathological and clinical staging has been a problem. Clinical staging depends on how to measure the GGO component by computed tomography (CT), which has not been defined very well.

      Another point to be addressed related to GGO is the separation of GGO-containing tumors from solid tumors. For example, if a tumor has a solid component of 1.5 cm without any surrounding GGO component, it will be defined as clinical T1b, whereas if a tumor has a solid component of 1.5 cm along with 1.0 cm of surrounding GGO component (total tumor diameter of 1.5 + 1.0 = 2.5 cm), it would also be defined as clinical T1b. However, the malignant capacity of a purely solid tumor is reported to be worse than that of GGO-containing tumors. Thus, from a prognostic viewpoint, it might be better to consider these two types of tumors separately.

      2. Visceral pleural invasion

      Another controversy regarding the T descriptor in pathologic staging involves visceral pleural invasion (VPI). First, data should be collected using a standardized definition. A standardized definition of VPI was incorporated into the 7th edition of TNM and maintained in the 8th edition. PL1, 2, and 3 are pathologically evaluated based on tumor invasion to the elastic layer, pleural surface, and parietal pleura. In case of doubt regarding VPI, the use of elastic stains is recommended. The collection of data using this definition and the use of elastic stains are important for accurate evaluation in future revisions.

      Second, the difficulty of clinical evaluation of VPI might be a problem. In the current staging system, clinicians have to speculate on the presence of VPI, based solely on the findings of CT imaging. A clear imaging-based definition of VPI might be beneficial.

      Third, in the current staging system, interlobar PL3 is classified as T2a. Since little is known about the prognosis of this interlobar PL3, data should be collected for use in a future revision of the TNM classification.

      3. Nodal evaluation

      Regarding the N descriptor, as previously reported in the literature, tumors with nodal metastases to multiple lymph node stations have a worse prognosis than those with single-station metastasis. Counting the number of positive nodes instead of the number of stations might be considered as well, especially from the viewpoint of emphasizing prognostic impact. However, a standardized method for pathological nodal evaluation has been lacking. How should pathologic slides be made for an accurate evaluation of nodal status? The number of nodes that are incorporated on the same slide, and the number and depth of sections to be evaluated per slide, are not well defined. It is also not clear how to handle an intraoperatively separated node, when counting the number of metastatic nodes. It would be desirable to have some consensus about the evaluation methodology to achieve a more accurate prognostic analysis.

      4. Molecular information

      There are some disagreements about how to use molecular information, in relation to TNM classification. Over the past decades, dramatic advances have been made in the fields of molecular diagnosis and precision medicine. The therapeutic strategy has been developed in detail depending on the molecular status, especially in advanced tumors. Accordingly, the prognosis has been influenced by the molecular status of the tumor, and thus molecular biomarkers have become some of the most important prognostic factors.

      In principle, the TNM classification describes the anatomic extent of tumors, arranged according to prognostic differences. From the perspective of the prognostic impact, molecular biomarkers might be as important as TNM staging. The combination of molecular status and TNM classification could be considered. However, based on the principal concept of the anatomic classification of the TNM system, it might be better to consider molecular factors as a different methodology of the classification system. Further discussions will be needed regarding the relationship between molecular markers and the anatomic TNM classification system.

      These issues reflect only some of the controversies surrounding the TNM staging system. Along with other issues, they are expected to be discussed in detail in the SPFC meetings for the forthcoming update of the TNM classification system.

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