8th Edition of the TNM Classification for Lung Cancer. Proposed by the IASLC

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1 8th Edition of the TNM Classification for Lung Cancer Proposed by the IASLC

2 Introduction Stage classification - provides consistency in nomenclature - improves understanding of anatomic extent of tumour - enhances capacity to indicate prognosis - facilitates tumour stratification for clinical trials - requires revision as technology changes

3 TNM7 to TNM 8 TNM 7 published at end of 2009, enacted Jan 2010 Done by IASLC for AJCC and UICC PET scanning not routinely used during period of data collection Collection of new retrospective and prospective data IASLC database included 77,156 evaluable patients diagnosed with lung cancer from 1999 to 2010, originating from 35 different databases in 16 countries of 5 continents TNM8 starts in UK in January 2018

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5 T descriptor revisions Size is important! Every cm counts T size now relevant to all T descriptors Cut point of 3cm between T1 and T2 retained, but new cut points at 1cm and 4cm added Tumour >7cm and invasion of diaphragm now classified as T4 Tumour <2 cm from carina, but not involving carina now T2, not T3. Total atelectasis/pneumonitis also T2, not T3 Therefore, tumour size measurement should be carefully performed because small changes in size mean important changes in prognosis

6 Visceral pleural invasion - VPI As previously, VPI noted to be a poorer prognostic factor. Hence T2 staging In pathological staging, Tumours > 3-4cm with VPI have similar prognosis to 4-5 cm tumours Should we offer adjuvant chemo to this group?

7 Mediastinal pleural involvement Difficult criterion to define in clinical staging Rarely described in pathological staging Different prognostic data in clinical and pathological database Hence mediastinal pleural involvement is no longer used as a T descriptor Mediastinal fat is T4, hilar fat T2

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10 T-descriptor Every cm counts Proposed (TNM 8th) Up to 1 cm: T1a >1-2 cm: T1b >2-3 cm: T1c >3-4 cm: T2a >4-5 cm: T2b >5-7 cm: T3 >7 cm: T4 Previous (TNM 7th) T1a T1a T1b T2a T2a T2b T3 Rami-Porta R, J Thoracic Oncol, 2015 International Association for the Study of Lung Cancer, 2015

11 N-Descriptor The N component remains the same, but the number of involved nodal stations has prognostic impact. Therefore, it was proposed to divide N1 into N1a (single station N1) and N1b (multiple station N1), N2 into N2a1 (single station N2 without pn1 involvement), N2a2 (single station N2 with pn1 involvement) and N2b (multiple station N2) for exploratory testing New IASLC nodal map will be used. Oncological midline will be defined to left lateral side trachea

12 N-descriptor No changes in the TNM 8th Edition Exploratory subgrouping (for future validation) - N1a: Single N1 - N1b: Multiple N1 - N2a1: Single N2 (skip metastasis) - N2a2: Single N2 + N1 - N2b: Multiple N2

13 M-descriptor M1a: as it is M1b: single metastasis in a single organ Oligometastatic disease M1c: multiple metastases in a single organ or in several organs

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15 Stages summary Stage IA is divided into IA1, IA2 and IA3 to accommodate T1a, T1b and T1cN0M0 tumours All N1 disease are stage IIB except for T3- T4N1M0 that are IIIA A new stage IIIC is created for T3-T4N3M0 tumours Stage IV is divided into IVA (M1a and M1b) and IVB (M1c)

16 STAGE T N M Occult TX N0 M0 0 Tis N0 M0 IA1 T1a(mi)/T1a N0 M0 IA2 T1b N0 M0 IA3 T1c N0 M0 IB T2a N0 M0 IIA T2b N0 M0 IIB T1a-T2b N1 M0 T3 N0 M0 IIIA T1a-T2b N2 M0 T3 N1 M0 T4 N0/N1 M0 IIIB T1a-T2b N3 M0 T3/T4 N2 M0 IIIC T3/T4 N3 M0 IVA Any T Any N M1a/M1b IVB Any T Any N M1c International Association for the Study of Lung Cancer, 2015

17 NEW STAGE T N M Occult TX N0 M0 0 Tis N0 M0 IA1 T1a(mi)/T1a N0 M0 IA2 T1b N0 M0 IA3 T1c N0 M0 IB T2a N0 M0 IIA T2b N0 M0 IIB T1a-T2b N1 M0 T3 N0 M0 IIIA T1a-T2b N2 M0 T3 N1 M0 T4 N0/N1 M0 IIIB T1a-T2b N3 M0 T3/T4 N2 M0 IIIC T3/T4 N3 M0 IVA Any T Any N M1a/M1b IVB Any T Any N M1c International Association for the Study of Lung Cancer, 2015

18 8th Edition of the TNM Classification for Lung Cancer N0 N1 N2 N3 M1 a M1 b M1c T1a IA1 IIB IIIA IIIB IVA IVA IVB T1b IA2 IIB IIIA IIIB IVA IVA IVB T1c IA3 IIB IIIA IIIB IVA IVA IVB T2a IB IIB IIIA IIIB IVA IVA IVB T2b IIA IIB IIIA IIIB IVA IVA IVB T3 IIB IIIA IIIB IIIC IVA IVA IVB T4 IIIA IIIA IIIB IIIC IVA IVA IVB International Association for the Study of Lung Cancer, 2015

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21 Conclusion Implication to clinical decision making is minimal More complex - download the app! Size is important Quantification of nodal involvement is important Recognition of oligo-metastatic state Molecular developmets will mean TNM9 on its way!

22 The T component Tumor size is a much more relevant prognostic factor than in previous editions and is now a descriptor in all T categories. Therefore, tumor size measurement should be carefully performed because small changes in size mean important changes in prognosis. (2) In part-solid tumors, only the solid/invasive part counts to measure tumor size. (7) The fact that adenocarcinoma in situ Tis(AIS) and minimally invasive adenocarcinoma T1mi have their own coding in the TNM classification will increase their awareness. (7) These, together with the smallest coded solid tumors, those of one cm or less in largest dimension T1a can become the base from which to study therapeutic options, such as sublobar resections, stereotactic radiotherapy, radiofrequency ablation; tumor biology, including tumor growth, tumor density and intensity of the standardized uptake value, as well as molecular profile and genetic signatures. Visceral pleural invasion and its two categories (PL1: invasion beyond its elastic layer; and PL2: invasion of the pleural surface) have been confirmed as important prognostic factors. (2) This means that pathologists should intensively investigate the identification of visceral pleural invasion, and, if it is not evident by the standard hematoxylin and eosine stains, elastic stains should be used, as recommended in the 7[th] edition of the TNM classification. (10) The N component Although there will be no changes in the N categories, the analyses for the 8[th] edition have shown that quantification of nodal disease has prognostic implications. This had already been evident in the 7[th] edition, when it was found that the number of involved nodal zones was prognostic. The analyses for the 8[th] edition have considered the number of involved nodal stations and have found that the more nodal stations involved, the worse the prognosis; and that the prognosis of tumors with involvement of multiple N1 stations was similar to that of tumors with single station N2 without concomitant N1 disease (skip metastases). (3) The findings of the 7[th] edition already raised the issue of indicating upfront resection in patients with tumors with single N2 zone involvement, because their prognosis was the same as that of tumors with multiple N1 zones. The question will be raised again in the light of the results of the 8[th] edition. However, in both occasions, the quantification of nodal disease derived from pathological staging of those tumors that had been resected and the resection had been accompanied by a properly performed systematic nodal dissection. This is difficult to replicate at clinical staging, the moment at which therapeutic decisions are made, unless a transcervical mediastinoscopic lymphadenectomy is performed. This lymphadenectomy has been found to be equivalent to that performed at the time of resection, either by thoracoscopic or open surgery, and is the only pre-resection test that can define single station or single zone N2 disease reliably. The M component There is no change in the metastasis within the thoracic cavity (M1a), but single extrathoracic metastases have better prognosis than multiple extrathoracic metastasis in one or in several organs, and different categories have been defined for them: M1b for single and M1c for multiple extrathoracic metastases. (4) The fact that single extrathoracic metastasis have their own category will facilitate the redefinition of oligometastatic and oligoprogressive disease, the establishment of therapeutic protocols with radical intention, and the investigation of all therapeutic modalities to eliminate the advance disease. However, clinical staging will have to be precise and will have to determine the number and the organ location of the metastatic deposits. The stages Some TNM subsets have moved from one stage to another and new stages and sub-stages have been created to accommodate groups of tumors with similar prognosis. (5) As it occurred with the 7[th] edition, the question of how to treat patients whose tumors have changed stage will be raised at multidisciplinary team meetings. Taxonomic changes do not necessarily mean an automatic change in therapy if the clinical trials performed to test therapeutic options did not include the tumors that are now included in the selected stages for study. Therefore, in the absence of results from clinical trials, clinical judgment will have to determine what the best options are for a given patient with a given tumor. Lung cancer with multiple lesions The 8[th] edition will provide a set of rules with the intention to classify lung cancers with multiple lesions in a homogeneous way. (8) It is our responsibility to follow the rules to collect prospective data uniformly and validate the given recommendations with international data. Conclusion The 8[th] edition will help us refine prognosis both at clinical and pathologic staging and stratify tumors in future clinical trials, but will require more attention from us at measuring tumor size, at determining nodal disease, at searching for metastases, and at using clinical judgment to indicate treatment