Similarities and Differences Between cTNM and pTNM
Andreia Ribeiro, João Fernandes,
Eurico Monteiro
Andreia Ribeiro, João
Fernandes, Eurico Monteiro, ENT Resident at Pedro Hispano Hospital, Matosinhos, Portugal
Correspondence to: Andreia Ribeiro, ENT Resident at Pedro Hispano Hospital, Matosinhos, Portugal
Email: andreiamfribeiro@gmail.com
Telephone: +351229391000
Received: May 12, 2014
Revised: June 16, 2014
Accepted: June 22, 2014
Published online: July 18, 2014
ABSTRACT
Aim: TNM staging system aims to classify
tumour extension in a uniform, simple, homogenous and reproducible manner. The
objective of this study is to evaluate the correlation between the cTNM pTNM
and in tumors of the larynx and hypopharynx and the prognostic impact of the
subdivision of T4 tumors in T4a and T4b in these locations.
methods: A retrospective
study involving 144 patients undergoing total laryngectomy or
pharyngolaryngectomy associated with cervical lymph node dissection treated in
the Oporto Oncologic Institute ( IPOP-EPE) between 2007 and 2011.
Results: 81 patients were staged as cT3, of
which 49 (60.5%) were restaged as pT4. 63 patients were staged as cT4 of which
7 (11.1%) were restaged as cT3. 80 patients were staged as cN0, of which 32
(40%) had metastatic cervical nodes upon pathological examination. 64 patients
were staged as cN+, of which 4 (6.2%) did not have metastases upon pathological
examination. We discuss the current TNM staging model compared to the previous
staging systems.
Discussion: This article compares the various
categories in the TNM system in an attempt to understand the main difficulties
in larynx/hypopharynx cancer staging.
© 2014 ACT. All
rights reserved.
Key words: Laryngeal Neoplasms; Hypopharyngeal Neoplasms; Neoplasm Staging
RibeiroA, Fernandes J, Monteiro E. Similarities and Differences
Between cTNM and pTNM. Journal of Tumor 2014; 2(7): 193-196 Available from:
URL: http://www.ghrnet.org/index.php/JT/article/view/778
INTRODUCTION
Laryngeal tumours represent 25% of malignant tumours of the head and
neck. About 95% of larynx/hypopharynx tumours are squamous cell carcinomas[1,2].
Between 1943
and 1952, Pierre Denoix began the development of the TNM system at the
Institute Gustave-Roussy in Paris and in 1953 he proposed his concept to the
Union Internationale Contre le Cancer (UICC) and these parameters were formally
integrated into a TNM staging system. AJCC and UICC versions were unified in
1987 and, since then, the two entities have collaborated in updating the TNM
system. TNM staging system allows a uniform classification of head and neck
tumours, and is utilized to evaluate the extent of disease, select treatment
options, define patients prognoses, facilitate the exchange of information
between clinicians and researchers and support the evaluation of different
treatment outcomes.
TNM system
staging aims to classify the extent of each tumour in a simple and reproducible
manner, taking into account three variables: the extent of the primary tumour
(T) the presence or absence of metastatic cervical lymph nodes (N), the
presence or absence of distant metastases (M). The various possible
combinations are further grouped into TNM stages from I to IV.
TNM system has
undergone successive revisions since the first edition. The latest version is
the 7th, created in 2009 for implementation in 2010. With regard to
the changes undergone in recent issues, specifically in respect to cancers of
the larynx and hypopharynx, changes between the 5th (1997) and the 6th
(2002) editions focused on the subdivision of T4 tumours into T4a (resectable)
and T4b (unresectable) and on changes relating to the subdivision by stage,
with T4b tumours (regardless of nodal staging) newly included in stage IVb. In
the 7th edition the terms resectable/unresectable, as applied to T4,
were abandoned, with T4a and T4b
now applied to moderately advanced and very advanced disease, respectively.
In the staging of patients with tumours of the larynx/hypopharynx, clinical
and endoscopic evaluations have obvious limitations in terms of assessing the
extent of the disease, namely with regard to disease extension to the thyroid
cartilage and extralaryngeal structures; imaging modalities, namely CT
(Computed Axial Tomography) allows for a more objective assessment of tumour
extension and nodal involvement[3,4,5].
Staging of the
primary lesion, coupled with the presence or absence of nodal neck metastases,
is important in the selection of treatment options and assessing the prognosis
of patients with larynx and hypopharynx tumours[6].
The objective
of this study is to evaluate the correlation between the cTNM pTNM and the
prognostic impact of the subdivision of T4 tumors T4a and T4b in tumors of the
larynx and hypopharynx
METHODS
We conducted a retrospective study that included a total of 144
patients who underwent total laryngectomy or pharyngolaryngectomy associated
with cervical lymph node dissection treated at IPOP-EPE between January 1st
2007 to December 31st 2011. All patients were classified according
to the latest 2010 version of the AJCC and UICC TNM system, although the
majority had been previously classified according to the 1997 version.
Fourteen
patients who had undergone previous treatment with chemotherapy or
chemo/radiotherapy were excluded from the study. Another 5 patients were also
excluded because of insufficient data in their clinical processes.
cTNM staging
was based on physical examination and CT of the neck, and pTNM staging was based on histopathological analysis
of surgical neck dissection specimens.
Statistical
analysis was performed using SPSS 20.0 (SPSS Inc. Chicago, IL). We calculated
the kappa coefficient for the level of agreement between cTNM and pTNM beyond
that expected by chance. Specificity, sensitivity, positive and negative
predictive values were calculated assuming the histopathological records as
gold standard. Statistical analysis was performed using Chi Square (¦Ö2)
and Mann-Whitney tests. Curves for overall survival and disease-free survival
were calculated using the Kaplan-Meier method and statistical significance was
determined by log-Rank test. Multivariate analysis was performed by Cox
regression. Results were considered statistically significant when p<0.05.
RESULTS
Out of a total of 144 patients included in the study, 140 (97.2%) were
male and 4 (2.8%) female, with a mean age of 59.0 years. 109 patients (75.7%)
had laryngeal tumours, 26 (18.1%) pharyngolaryngeal disease and 9 patients
(6.2%) had disease localizated in
the hypopharynx.
The mean
interval between the onset of complaints and diagnosis was 6.3 months, the mean
interval between between diagnosis and surgery was 2.3 months and the mean
interval time between surgery and complementary treatment was 2.1 months.
97 (67.4%)
patients underwent total laryngectomy and 47 (32.6%) total
pharyngolaryngectomy, both associated with cervical lymph node dissection.
72 (50.0%)
patients underwent additional chemoradiotherapy and 37 (25.7%) only radiotherapy.
35 patients did not undergo any additional treatment modality (24.3%).
140 patients
(97.2%) had squamous cell carcinomas and the remaining 4 patients had other
histological types (1 lymphoepithelioma, 1 spindle cell carcinoma, 1
leiomyosarcoma and 1 adenoid cystic carcinoma).
At the time of
analysis (February 2013) 95 patients (66.0%) were alive and 48 (34%) had died.
81 patients
were initially staged as cT3 and 63 as cT4. Following surgery, 39 patients were
staged as pT3 and 105 as pT4.
Of the 81 patients staged as cT3, 49 (60.5%) were restaged as pT4. 63
patients were staged as cT4, 7 (11.1%) of which were restaged as cT3 (Table 1).
Out of the 105
pT4 patients, CT scans showed no cartilage or extra-laryngeal invasion in 49
(46.7%), from which we may infer that this exam modality showed a sensitivity
of 53.3%, specificity of 82% and positive and negative predictive values of
88.9% and 39.5%., respectively, for T4 larynx and hypopharynx tumours.
The kappa
coefficient for the clinical and pathological tumour staging (T) was 0.26 (p<0.05).
With respect
to cervical lymph node staging, 80 patients were staged as cN0 and 64 as cN+.
Following surgery, 52 patients were staged as pN0 and 92 as pN+.
Out of the 80
cN0 patients, 32 (40%) had lymph node metastasis after pathological
examination. Out of the 64 patients staged as cN+, 4 patients (6.2%) had no
metastases in cervical dissection specimens (Table 1).
The
sensitivity and specificity of CT in detecting cervical metastases were 60.9%
and 92.3% respectively. Positive and negative predictive values were 93.0% and
58.5% respectively.
The kappa
coefficient for pathological and clinical lymph node staging (N) was 0.28 (p<0.05).
17 patients
were classified as Stage III, 112 as Stage IVa and 15 as Stage IVb.
One year post-
surgery, 97.4% of pT3, 76.3% of pT4, 85.9% of pT4a and 66.7% of pT4b patients
were alive (p<0.05). 2 years after surgery 85.7% of pT3, 61.7% of
pT4, 73.5% of pT4a and 50% of pT4b patients were still alive (p>0.05).
3 years post-surgery 74.2% of pT3, 42.3% of pT4, 59.7% of pT4a and 25.0% of
pT4b were alive (p> 0.05).
According to
the prior classification of 1997, the estimated median overall survival was
47.7 months for pT3 and 39.5 months for pT4 tumours; regarding the division
into pT4a and pT4b, the estimated median overall survival was 40.5 months for
pT4a and 25.1 months for pT4b (p<0.05) (Table 2). It was impossible
to calculate the survival rate at 5 years post-surgery due to the short
follow-up time for some of these patients. The overall survival curve for this
population of patients is displayed in figure 1.
Median
disease-free survival was 28.4 months for pT3 and 20.5 months for pT4,
according to the TNM classification of 1997. Regarding the latter
classifications of 2002 and 2012, the pT4a population had a median of 21.0
months and the pT4b a median of 13.0 months of disease-free survival (p>0.05)
(Table 2). It was impossible to calculate the disease-free survival at 5 years.
The curve of disease-free survival is shown in figure 2.
Median overall
survival was lower in patients with hypopharynx and pharyngolaryngeal tumours
(28.1 months for pharyngolarynx tumors vs 36.7 months for hypopharynx, vs
45.0 months for larynx, p<0.05), in patients with cervical lymph node
metastasis (54, 5 in N0 vs
30.9 in N1 vs 38.9 in N2 vs 16.1 months in N3, p<0.05),
in patients with vascular invasion according to histological criteria (48.5 vs
27.7 months, p<0.05), with capsular rupture in invaded cervical lymph
nodes (48.3 vs 34.1, p<0.05) and in patients with margins of
less than 0.5 cm (30.5 vs. 53 months, p<0.05).
Multivariate
analysis of overall survival, showed, that amongst pT4 tumours, differences
were statistically significant for location of lesion, vascular invasion and
extracapsular rupture (p<0.05). For pT4a, in addition to these
parameters, nodal staging was also statistically significant (p<0.05)
(Table 3). There was insufficient data for pT4b multivariate analysis because
of the small number of patients.
Regarding the multivariate analysis
of disease-free survival, differences proved statistically significant for
location of lesion and lymph node involvement (p<0.05), both amongst
the pT4 population as well as amongst the pT4a tumour subset (Table 3). There
was insufficient data for pT4b multivariate analysis because of the small
number of patients.
DISCUSSION
Diagnostic strategies for staging head and neck tumours have evolved
over time, especially with regard to the routine use of imaging modalities and
considerable improvements in their quality[7].
The
development of a simple and easy staging system is fundamental, and in this
sense the current TNM staging system has undergone several changes along the
years.
The importance
of proper characterization of tumour extent is of utmost importance for the
staging, with a view to select the appropriate treatment and determining
patient prognosis.
With respect to clinical and pathological staging, a large number of
cT3 patients (60.5%) were restaged as pT4. Also, for nodal staging, a
considerable number of cN0 tumours (40%) presented metastatic lymph nodes upon pathological
evaluation.
The kappa
coefficient showed a low agreement rate between clinical staging and
pathological grading which suggests a low concordance when taking into account
that which would be expected by chance. This low kappa coefficient, both
locally and regionally, may be explained not only by the limitations inherent
to physical examination and imaging exams but also by the time elapsed between
diagnosis and surgery[5]. However, these data seem to indicate that,
in a large number of patients, pathological staging is more advanced than
clinical staging.
With regard to
the TNM system in use since 2002 (updated in 2010 when the terms ressectable
and irressectable were abandoned and replaced with moderately advanced disease
and very advanced disease), this study showed that T4b patients have a worse
prognosis when compared with T4a patients, both in terms of median overall
survival (40.5 months for pT4a vs 25.1 months for pT4b) and of median
disease-free survival (21.0 months for pT4a vs 13.0 months for pT4b),
although the differences in terms of median disease-free survival did not prove
statistically significant. The short follow-up of some of the patients in this
analysis has conditioned the calculation of 5-year survival rates and the small
number of T4b tumours in the sample has also affected the significance of the
results. The small number of T4b tumours may be due to earlier diagnosis, the
greater likelihood of distant metastases at diagnosis ruling-out the option of
surgery as an initial treatment option or the selection of some of these
patients for nonsurgical treatment regimens.
However,
despite these limitations, the results validate the subdivision of larynx and
hypopharynx tumours into T4a and T4b with regard to the prognostic impact.
However
further studies will be important so that the TNM system can evolve to overcome
its limitations.
In conclusion,
the analysis of the data collected for this study seems to suggest that
clinical staging, even when supported by imaging modalities (CT), shows a
considerable tendency to understage tumours, both locally and regionally. The
implications of the staging process in terms of prognosis may have been harmed,
in this study, by the low calculated agreement coefficient.
The current
division of T4 into T4a and T4b has been shown by this study to yield
statistically significant prognostic implications, with respect to overall
survival, and as such this subdivision may be considered relevant.
CONFLICT OF
INTERESTS
There are no
conflicts of interest with regard to the present study.
REFERENCES
1
Browning G, Burton M, Clarke R et al.
Scott-Brown¡¯s Otorhinolaryngology: Head and Neck
Surgery. London, Hodder Arnold; 2008. Book
2
Chapter: Gleeson M, Birchall
M, Pope L. Tumours of the Larynx. p 2598-2622
2 Flint P, Haughey B, Lund V, Niparko J. Cummings Otolaryngology Head & Neck
Surgery. Mosby Elsevier; 2010. Book Chapter: Armstrong
W, Vokes D, Maisel R.
Malignant Tumors of the Larynx. pp 1497-1526
3
Connor
S. Laryngeal Cancer: How Does The Radiologist Help? Cancer Imaging
2007; 7: 93-103
4 Hermans R. Staging of
Laryngeal and Hypopharyngeal Cancer: Value of Imaging
Studies. Eur Radiol
2006; 16: 2386-2400
5 Zbaren P, Becker M, Lang H. Pretherapeutic
Staging of Laryngeal Carcinoma. Clinical findings, computed tomography, and
magnetic resonance imaging compared with histopathology. Cancer; 1263-1273
6 Blitz AM, Aygun N. Radiologic Evaluation
of Larynx Cancer. Otolaryngol Clin North Am 2008; 697-713
7 Yousem
D, Gad K. Ressectability issues with head and neck
cancer. AJNR Am J Neuroradiol 2006; 27(10):
2024-2036
Peer reviewers: Raghav C Dwivedi, Department of
Otolaryngology & Head & Neck Surgery, Addenbrooke¡¯s Hospital, Cambridge
University Teaching Hospitals Cambridge, CB2 0QQ, Cambridge, the United
Kingdom; Anjia Han, M. D. Ph.D., Professor, Department of Pathology, The First
Affiliated Hospital, Sun Yat-Sen University, 58, Zhongshan Road II, Guangzhou,
510080 China.
Refbacks
- There are currently no refbacks.