First published in 1987 [1], and revised in 1992 [2], the fourth edition of the TNM Classification of Malignant Tumours was the result of a push from all national TNM committees towards the establishment of a uniform classification system that could be used worldwide. It was, therefore, the first edition of the text in which the featured classification criteria were identical to those detailed in the fourth edition of the AJCC’s Manual for Staging of Cancer of the American Joint Committee on Cancer [3].

Although the classification system was, by 1987, widely accepted, medical professionals had pointed out that some of its definitions and rules for staging were imprecise and could lead to inconsistency in its application. Discrepant understandings of organ classifications, general rules and, in particular, the requirements of pathological classification (pT, pN) were all potential risks.

In an effort to address these concerns, the TNM Project Committee of the UICC collected and reviewed criticisms and suggestions from the national TNM committees, as well as from registries, oncological associations and individual users. The solution that they found was to complement the fourth edition of the TNM Classification [1, 2] with the publication of a new book: the TNM Supplement [4]. Designed to provide guidance on the uniform use of the classification system, the first edition of this new text was published in 1993.

By 1997, the TNM Classification was in its fifth edition [5], though most descriptions of tumour sites had remained largely unchanged, with only minor additions made so as to reflect new data on prognosis and new methods of outcome assessment. The TNM Project Committee of the UICC was aware that not all classification proposals and updates received could be included in this fifth edition and so the decision was made to produce another TNM Supplement within which they may be accommodated [6]. The second edition of the TNM Supplement therefore comprised, for the most part, of the first edition’s contents, amended to include a number of new items.

Retaining much of its predecessor’s content, the sixth edition of the TNM Classification [7] again featured only small revisions but was elaborated upon in a third edition of the TNM Supplement [8].

The TNM Classification’s seventh edition [9] saw the inclusion of several novel tumour classifications. While comments on the new entities and modifications concerned had been published elsewhere [10], it was nevertheless deemed important to highlight and examine these with a fourth edition of the TNM Supplement [11].

In the current, eighth edition of the TNM Classification [12], the featured tumour sites are much the same as those found in the book’s previous edition. Some hitherto unexamined tumour entities and anatomic sites have, however, been introduced, while others have seen their analyses modified and revised to take account of new data on prognosis and prognosis assessment [13]. This strategy is in accord with the core philosophy of maintaining the classification system’s stability over time.

A new approach was adopted in the TNM Classification’s seventh edition [9] that helped to distinguish stages from prognostic groupings. This has been expanded upon in the eighth edition, which introduces new clinical and pathological stages for some tumour entities. Additionally, a helpful overview of prognostic factors for different tumour entities has been given. These prognostic factor grids are based on former publications of the UICC and have been expanded to reflect new data [14–16].

This fifth edition of the TNM Supplement contains a number of changes. While the previous edition’s contents have been largely preserved, feedback from users of the TNM classification and the TNM Help Desk (https://www.uicc.org/tnm‐help‐desk) has helped to refine and clarify certain elements. Two chapters of ‘Explanatory Notes’ have, for example, been reworked so that anatomical sites and subsites, regional lymph nodes, and T, N and M categories are more precisely defined. Elsewhere, a chapter discussing ‘Pending Questions and Problems’ has been added, while the minimum requirements for the pathological classification of individual tumour sites and entities are now described in a chapter on ‘Site‐Specific Requirements for pT and pN’.

Since the publication of the eighth edition of the TNM Classification, the UICC TNM Project Committee has reviewed several recommended changes and amendments, the details of which are outlined in this TNM Supplement’s fourth and fifth chapters, entitled ‘New TNM Classifications Recommended for Testing and Other Classifications’ and ‘Optional Proposals for Testing New Subcategories of TNM’, respectively. Relevant references have been included wherever data exist to support these recommendations. Where they do not, it may be assumed that such proposals are based on either anecdotal experience or more general considerations. All proposals included are based on the principle of ramification, whereby the T, N and M categories featured in the TNM Classification, eighth edition, remain unchanged but optional subdivisions are provided within specific categories. After classifying according to these subdivisions, one may determine to what extent a change of the present categories improves the classification process with respect to prognostic statements or the choice of treatment.

In light of the development of new techniques in molecular biology, the most important and widely used methods of enhancing the accuracy of the TNM classification system have also been presented here. Furthermore, several authors have emphasized that, in the current era of evidence‐based medicine, future amendments must be substantiated with data [13, 17]. Others have raised questions regarding the use and interpretation of TNM in specific situations. These, along with informative answers, can be found in the sixth chapter of this supplement: ‘Frequently Asked Questions’.

The present stage groupings – as defined in the TNM Classification, eighth edition [12] – are generally based on the anatomical extent of disease, represented by T, N and M or pT, pN and pM. For some tumour sites or entities, however, additional factors are included. These are as follows:

• For oesophageal carcinoma (excluding the anatomical stage), an additional prognostic grouping is provided to encompass squamous cell carcinoma and adenocarcinoma. This group takes into account grade and – for squamous cell carcinoma – location.
• For gestational trophoblastic tumours, a prognostic grouping is provided that considers T/pT, M/pM and relevant risk factors.
• As more non‐anatomic prognostic factors become available, this approach may provide a means of separating extent‐of‐disease staging from prognostic grouping.

Both the AJCC and the TNM Project Committee of the UICC recognize that, in addition to the anatomical extent of disease pre‐ and post‐initial treatment, the residual tumour status after treatment – i.e. the R (residual tumour) classification – and other non‐anatomical factors (e.g. host factors, biochemical markers, DNA analysis, oncogenes, oncogene products) may be important when estimating outcome. TNM and R aside, these prognostic factors are currently under investigation and it can be assumed that their roles in treatment planning, analysis of treatment and design of future clinical trials will grow.

The eighth edition of the TNM Classification [12] contains rules of classification and staging that correspond to those in the eighth edition of 2017’s AJCC Cancer Staging Manual [18] and have approval of all national TNM committees.

Institutions and physicians interested in the further development of the TNM system are encouraged to test the recommendations included in this supplement. These may concern the ramification of existing classifications or the classification of new tumour sites and entities. Equally, they may concern methods of enhancing the accuracy of the TNM system over the years to come. Publication of both retrospective and prospective studies is desired. The TNM Project Committee would appreciate receiving relevant information and is available to provide further details and consultation.

The TNM Prognostic Factors Project welcomes comments from TNM users.

Union for International Cancer Control (UICC)
31–33 Avenue Giuseppe Motta, CH‐1202 Geneva, Switzerland
F: +41 22 809 1810   http://www.uicc.org

References

1. [1] UICC (International Union Against Cancer) TNM Classification of Malignant Tumours, 4th edn, Hermanek P, Sobin LH (eds). Berlin, Heidelberg, New York: Springer; 1987.
2. [2] UICC (International Union Against Cancer) TNM Classification of Malignant Tumours, 4th edn, 2nd revision, Hermanek P, Sobin LH (eds). Berlin, Heidelberg, New York: Springer; 1992.
3. [3] American Joint Committee on Cancer (AJCC) AJCC Manual for Staging of Cancer, 4th edn, Beahrs OH, Henson DE, Hutter RVP, et al. (eds). Philadelphia: Lippincott; 1992.
4. [4] UICC (International Union Against Cancer) TNM Supplement 1993: A Commentary on Uniform Use, Hermanek P, Henson DE, Hutter RVP, Sobin LH (eds). Berlin, Heidelberg, New York: Springer; 1993.
5. [5] UICC (International Union Against Cancer) TNM Classification of Malignant Tumours, 5th edn, Sobin LH, Wittekind Ch (eds). New York: Wiley; 1997.
6. [6] UICC (International Union Against Cancer) TNM Supplement 2001: A Commentary on Uniform Use, 2nd edn, Wittekind C, Henson DE, Hutter RVP, Sobin LH (eds). New York: Wiley; 2001.
7. [7] UICC (International Union Against Cancer) TNM Classification of Malignant Tumours, 6th edn, Sobin LH, Wittekind Ch. (eds). New York: Wiley; 2002.
8. [8] UICC (International Union Against Cancer) TNM Supplement: A Commentary on Uniform Use, 3rd edn, Wittekind C, Henson DE, Hutter RVP, Sobin LH (eds). New York: Wiley; 2003.
9. [9] Sobin LH, Gospodarowicz MK, Wittekind C (eds), TNM Classification of Malignant Tumours, 7th edn. Oxford: Blackwell Publishing Ltd; 2010.
10. [10] Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed. Cancer 2010; 116:5336–5339.
11. [11] UICC (Union for International Cancer Control) TNM Supplement: A Commentary on Uniform Use, 4th edn, Wittekind C, Compton CC, Brierley J, Sobin LH (eds). Oxford: Wiley‐Blackwell; 2012.
12. [12] UICC (Union for International Cancer Control) TNM Classification of Malignant Tumours, 8th edn, Brierley JD, Gospodarowicz MK, Wittekind C (eds). Oxford: Wiley‐Blackwell; 2017.
13. [13] Gospodarowicz MK, Miller D, Groome PA, et al. The process for continuous improvement of the TNM classification. Cancer 2004; 100:1–5.
14. [14] UICC (Union for International Cancer Control) Prognostic Factors in Cancer, Hermanek P, Gospodarowicz MK, Henson DE, et al. (eds). Berlin, Heidelberg, New York: Springer; 1995.
15. [15] UICC (Union for International Cancer Control) Prognostic Factors in Cancer, 2nd edn, Gospodarowicz MK, Henson DE, Hutter RVP, et al. (eds). New York: Wiley; 2001.
16. [16] UICC (Union for International Cancer Control) Prognostic Factors in Cancer, 3rd edn, Gospodarowicz MK, O'Sullivan B, Sobin LH (eds). New York: Wiley; 2006.
17. [17] Quirke P, Cuvelier C, Ensari A, et al. Evidence‐based medicine: the time has come to set standards for staging. J Pathol 2010; 221:357–360, correspondence 361–362.
18. [18] American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edn, Amin MB, Edge SB, Greene FL, et al. (eds). New York: Springer; 2017.

CDC

Centers for Disease Control and Prevention (USA)

FIGO

International Federation of Gynaecology and Obstetrics

IACR

International Association of Cancer Registries

IARC

International Agency for Cancer Research

IASLC

International Association for the Study of Lung Cancer

ICCR

International Collaboration on Cancer Reporting

WHO

World Health Organization

Members of UICC Committees Associated with the TNM System

In 1950, the UICC appointed a Committee on Tumour Nomenclature and Statistics. In 1954, this committee became known as the Committee on Clinical Stage Classification and Applied Statistics and, in 1966, it was renamed the Committee on TNM Classification. With new prognostic factors taken into consideration, the committee was renamed twice more, becoming the TNM Prognostic Factors Project Committee in 1994 and then the TNM Prognostic Factors Core Group in 2003.

The editors appreciate the advice and assistance received from the members of the UICC TNM Prognostic Factors Core Group, the national TNM Committees and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (USA).

We thank Professor Patti Groome and Ms Colleen Webber for supervising and performing the literature watch from its inception until 2015 and 2016, respectively and subsequently Dr. Malcolm Mason and Ms. Bernadette Coles. The fifth edition of the TNM Supplement is the result of a number of consultative meetings organized and supported by the UICC and AJCC secretariats.

This publication was made possible by grants 1U58DP001818 and 1U58DP004965 from the Centers for Disease Control and Prevention (CDC) (USA). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC.

The authors are grateful for comments, additions and questions from Ramon Rami‐Porta, Mary Gospodarowicz and Brian O’Sullivan.

The Union for International Cancer Control (UICC) provided encouragement and support and its secretariat arranged meetings and facilitated communications.

a

autopsy, p. 23

c

clinical, p. 1

G

histopathological grading, p. 26

ICD‐O

International Classification of Diseases for Oncology, 3rd edition, 2000

ITC

isolated tumour cells, p. 10

L

lymphatic invasion, p. 24

m

multiple tumours, pp. 5 and 20

M

distant metastasis, p. 11

N

regional lymph node metastasis, p. 9

p

pathological, p. 1

Pn

perineural invasion, p. 24

r

recurrent tumour, p. 21

R

residual tumour after treatment, p. 15

sn

sentinel lymph node, p. 11

Stage

anatomical Stage, p. 13

T

extent of primary tumour, p. 7

V

venous invasion, p. 24

y

classification after initial multimodality treatment, p. 20

Substantial changes in the 2019 fifth edition compared with the 2012 fourth edition are marked by a bar at the left‐hand side of the page.