Chin J Radiol 2003; 28: 131-135
A Comparison of Staging Systems for
Nasopharyngeal Carcinoma in Taiwan
K UAN -C HI C HIU 1 S TEPHEN WAN L EUNG 2 H SU -H UEI W ENG 1 Y U -FAN C HENG 1
R ENG -J YE L EE 1 Y EH -L IN K UO 1 Y U -C HANG L EE 1 C HUN -C HUNG L UI 1
Department of Radiology1, Radiation Oncology2, Chang Gung University, Chang Gung Memorial Hospital at Kaohsiung
The fifth edition of the American Joint Commi-
ttee on Cancer (AJCC) staging manual defines new
rules for staging nasopharyngeal carcinoma. The
authors tested the value of this new system by
applying these rules retrospectively to their previ-
ously treated patients and comparing the results
with those obtained using the fourth edition of the
AJCC staging manual.
Information from 196 patients who had biopsy-
proven squamous cell carcinoma of the nasopharynx
that was treated with definitive-intent radiation
therapy alone or combined chemo-radiation therapy
(CCRT) at one institution provided the data base for
this analysis. The extent of disease of each patient
was staged according to the rules of 1) the fourth
edition of the AJCC staging manual, and 2) the fifth
edition of the AJCC staging manual.
The new system appears to be better than the pre-
vious system. It separated patients into cohorts of
more equal size than did the previous system. It also
correlated with outcome for the study population
more appropriately than did the fourth edition of
the AJCC staging manual.
The fifth edition of the AJCC staging manual
appears to be an improvement over the previous edi-
tion for the staging of nasopharyngeal carcinoma.
Key words: Nasopharyngeal carcinoma, Tumor
staging, Prognosis
Reprint requests to: Dr. Chun-Chung Lui
Department of Radiology, Chang Gung Memorial Hospital
at Kaohsiung.
No. 123, Dabi Road, Niausung, Kaohsiung 833, Taiwan,
R.O.C.
131
T ZE -Y U L EE 1
A number of different staging systems of
nasopharyngeal carcinoma (NPC) have been used in
different parts of the world [1-4]. While the
International Union Against Cancer (UICC) and
American Joint Committee (AJCC) classifications are
more popular in Europe and North America where the
incidence of NPC is low, Ho and Changsha classifica-
tions has been widely used in Southeast Asia where the
incidence of NPC is one of the world’s highest [5]. The
use of different classifications causes difficulties on
comparing treatment results from different centers.
AJCC/UICC classifications are criticized for the
skewed patient number distribution among stages and
inefficacy in predicting prognosis; while, Ho’s classifi- )X
@1 ??
??
??
??
??
?
cation for its complexity [5-7]. A refinement of Ho s
3@
S5 ?
.Y ??
??
?
??
?
??
??
?
??
?
??
?
??
?
?
staging was proposed incorporating the radiological
findings into the staging criteria [8].
In 1997, AJCC has revised the classification for
NPC after the criticisms toward it in the literature and
the recognition of the prognostic significance of para-
pharyngeal extension, cranial nerve palsy, and intracra-
nial extension of the tumor [5-8].
Taiwan is an endemic area for NPC and the first
study [9] for staging of NPC can be traced up to 1985.
The sixth edition of AJCC has been published, but
there is no change to 5th edition. To the best of our
knowledge, there is no report for comparing 4th and
5th editions (Table 1&2) of AJCC staging manual in
Taiwan.
MATERIAL AND METHODS
A total of 196 previously untreated histopatholog-
ically confirmed NPC patients were treated with defin-
itive radiotherapy and /or chemotherapy according to
the staging of 4th edition between January 1996 and
July 1997. All patients were uniformly staged
according to the findings of physical examination,
nasopharyngeal endoscopy and tumor biopsy, chest
radiograph, CT and/or MRI of the nasopharynx, neck,
and upper mediastinum, abdominal ultrasonography,
132 Comparison of staging systems for NPC

Table 1. The 4th Edition of the AJCC Staging System Table 2. The 5th Edition of the AJCC Staging System
T1 Tumor limited to one subsite of nasopharynx T1 Tumor confined to the nasopharynx
T2 Tumor invades more than one subsite of nasopharynx T2 Tumor extends to soft tissue of oropharynx and/or nasal
T3 Tumor invades oropharynx and/or nasal cavity fossa
T4 Tumor invades skull and/or cranial nerves T2a: Without parapharyngeal extension
N0 No regional lymph node metastasis T2b: With parapharyngeal extension
N1 Single ipsilateral lymph node measuring<3cm in greatest T3 Tumor invades bony structures and/or paranasal sinuses
dimension T4 Tumor with intracranial extension and/or involvement
N2 Single ipsilateral lymph node measuring> 3cm but not > of cranial nerves, infratemporal fossa, hypopharynx, or
6cm in greatest dimension; or multiple ipsilateral lymph orbit
nodes, none measuring>6cm; or in bilateral or N0 No regional lymph node metastasis
contralateral lymph nodes, none measuring> 6cm in N1 Unilateral metastasis in lymph node(s) measuring <6cm
greatest dimension. in greatest dimension above the supraclavicular fossa
N2a: Metastasis in single ipsilateral lymph node N2 Bilateral metastasis in lymph node(s) measuring <6cm
measuring 3-6cm in greatest dimension in greatest dimension above the supraclavicular fossa
N2b: Metastasis in multiple ipsilateral lymph nodes, non N3 Metastasis in lymph node(s)
measuring>6cm in greatest dimension (a):>6cm in greatest dimension.
N2c: Metastasis in bilateral or contralateral lymph nodes, (b): Extension to the supraclavicular fossa
none measuring> 6cm in greatest dimension M0 No distant metastasis
N3 Massive ipsilateral lymph node(s), bilateral or M1 Distant metastasis
contralateral lymph node(s) Stage I T1 N0 M0
M0 No distant metastases Stage IIA T2a N0 M0
M1 Distant metastasis Stage IIB T1 N1 M0
Stage I T1N0M0 T2a N1 M0
Stage II T2N0M0 T2b N0-1 M0
Stage III T3N0M0 or T1-3N1M0 Stage III T1 N2 M0
Stage IV T4(any N) or N2-3 (any T) or M1 (any T, any N) T2 N2 M0
AJCC: American Joint Committee on Cancer. T3 N0-2 M0
Used with the permission of the American Joint Stage IVA T4 N0-2 M0
Committee on Cancer (AJCC), Chicago, Illinois. He Stage IVB Any T N3 M0
original source for this material is the AJCC Manual for Stage IVC Any T Any N M1
the staging of Cancer, 4th edition (1992), published by AJCC: American Joint Committee on Cancer.
Lippincott-Raven Publishers. Philadelphia. Used with the permission of the American Joint Committee on
Cancer (AJCC), Chicago Illinois. The original source for this material
is the AJCC Cancer Staging Manual, 5th edition (1997) published by
and bone scan. Table 3 showed the clinical data of Lippincott-Raven Publishers, Philadelphia, Pennsylvania.
patients recruited in this study. Histologically, 98% of
the patients had World Health Organization (WHO) Table 3. Clinical characteristics
type II or type III tumors; the rest (2%) had type I Characteristics Number of patient %
tumors [10]. All patients were treated with external Gender
beam radiotherapy using 6 MV photons generated male 134 68.8
female 62 31.2
from linear accelerator. Daily fraction was given in 1.8 Age
or 2 Gy, five fractions per week. Patients with AJCC mean 47 y/o
staging based 4th edition showed N2 and N3 disease median 45 y/o
were given cisplatin either concomitant or neoadjuvant <40 y/o 65 33
40-60 100 51
chemotherapy regimens. Median follow-up period was >60 31 16
55 months (range: 3-60). None of the patients were
lost to follow-up.
Table 4. Comparison of the number and percentage of patients
Comparisons were made by calculating the per- according to the AJCC 4th and 5th editions
centages of patients assigned to each stage by each Stage 4th Edition of AJCC 5th Edition of AJCC
system (Table 4), rates of loco-regional relapse (Table I 16 (8.2%) 32 (16.3%)
5), and distant metastasis (Table 6). The Kaplan-Meier II 42 (21.4%) 53 (27.1%)
method was used to test significance of the differences III 33 (16.8%) 42 (21.4%)
between survival curves. IV 95 (48.5%) 69 (35.2%)

RESULTS patients to more uniform sized stage groupings (Table

2). It also resulted in an overall “down staging” of the
The reported population is typical for Chinese population compared with the 4th edition of the AJCC
series [11]. As would be expected, the new system is staging system.
clearly better than the 4th edition because it assigned Furthermore, the new system correlates stage and
 Comparison of staging systems for NPC 133

prognosis of survival at least as well as, and in some Table 5. Comparison of the tumor stage and ratio of loco-regional
respects is better than the 4th edition. Figures l and 2 relapse according to the AJCC 4th and 5th editions
show actuarial survival by the staging. We can dis- 4th 5th
Ratio of Percentage Ration of Percentage
criminate stage 1 vs. 3, stage 1vs. 4, stage 2 vs. 3 and local failure local failure
stage 2 vs. 4 in the 5th edition, whereas only stage 1 T1 4/32 12.5% 7/65 10.8%
vs. 4, stage 2 vs. 4, and stage 3 vs. 4 can be discrimi- T2 5/53 9.4% 10/54 18.5%
nated in the 4th edition. It means the discriminating T3 23/54 42.6% 10/26 38.5%
T4 27/57 47.4% 32/51 62.7%
capacity of 5th edition is better than 4th edition.
Besides, the 5th edition (Table 5) shows more
powerful prediction for loco-regional relapse vs. Table 6. Comparison of the nodal stage and the ratio of the distal
staging especially in low tumor stages. Although the metastasis
5th edition is not perfect (e.g. stage 1 and 2 are 4th 5th
inverted at 2 year survival), the 4th edition similarly Ratio of Percentage Ratio of Percentage
shows the same phenomenon. metastasis metastasis
N0 4/72 5.6% 4/72 5.6%
N1 2/29 6.9% 3/41 7.3%
N2 9/72 12.5% 8/60 13.3%
N3 6/23 26.0% 6/23 26.0%
AJCC 4th Edition Survival Functions
1.1
Stage
d cb a
1.0 1 -a- DISCUSSION
0.9 2 -b-
3 -c- Throughout the four previous editions of the
Probability of overall survival

b
0.8 a 4 -d- AJCC staging manual (1977, 1983, 1988, and 1992),
c

0.7 a 1 vs. 2, p=0.885 there have been relatively few changes in the staging
b
d 1 vs. 3, p=0.121 rules for nasopharyngeal carcinoma. The groupings of
0.6 c 1 vs. 4, p<0.001 T category, N category, and M category into stages
2 vs. 3, p=0.128
0.5 2 vs. 4, p<0.001
have not changed and the definitions of T and N have
3 vs. 4, p=0.029 remained relatively constant. In the first edition, T
0.4 category was based on the size of the primary tumor
d
0.3 whereas in the later three editions the T category was
0 10 20 30 40 50 60 based on anatomic lesion extent starting from the third
MONTH edition, bilateral lymph involvement was moved from
N3b to N2c.
Figure 1. Survival Functions of 4th edition of AJCC
The TN groupings of 5th edition are different
from the previous editions. The TN groupings of 5th
edition, which facilitated a step-by-step grouping
AJCC 4th Edition Survival Functions (overall stage=T-stage and /or N-stage+1), showed
1.1
Stage good regularity [11].
1.0
d ca b One purpose of staging is to create subgroups of
1 -a-
a 2 -b- patients that have similar prognosis. For the system to
0.9
b a 3 -c- be useful clinically, each subgroup should have a rea-
Probability of overall survival

0.8 b
4 -d- sonable number of patients. An ideal system would
c 1 vs. 2, p=0.36 assort patients into equal-sized group [13].
0.7
d 1 vs. 3, p=0.049 Subgrouping of T2 category is a new classification
0.6 1 vs. 4, p=0.002 dependent on the parapharyngeal extension. The prog-
c 2 vs. 3, p<0.001 nostic significance of parapharyngeal extension
0.5 2 vs. 4, p<0.001 appears too uncertain to warrant upstaging at present.
3 vs. 4, p=0.198
0.4 d
The study by Teo et al. [14] and Lee did not show any
0.3
significant effect on survival, which are in contrast to
0 10 20 30 40 50 60 the studies by Sham and Choy [15] and Chua et al.
MONTH [16]. One possible explanation is that parapharyngeal
involvement has been defined differently in different
Figure 2. Survival Functions of 5th edition of AJCC studies. The current edition of TNM designates para-
134 Comparison of staging systems for NPC
pharyngeal tumor extension as T2b, so as to facilitate
further evaluation.
The loco-regional relapse and distant metastasis
are the prognostic factors in patients with NPC [17].
Table 5 shows the 5th edition provides better predic-
tive capacity for loco-regional relapse, whereas we can
not see any significant difference of prediction for
distant metastasis between 4th and 5th. One possible
explanation is that there is no obvious change in N0
and N3 definition.
CONCLUSIONS
The 5th edition for NPC was published in 1997
in accordance with the regulation following the last 10
years of the 4th edition in use since 1988. The 6th
edition of AJCC staging manual has been published in
2002 without change in staging criteria from the 5th
edition. It is important that the new system be adapted
worldwide to facilitate communications, data
reporting, and clinical decisions among oncologists.
Although it remains to be improved, the 5th edition of
AJCC staging manual is prognostically useful for the
Taiwanese patient populations on the basis of our
current data. It seems reasonable that every oncology
center should stage the NPC patients with the new
system before a better stage classification emerging
for the 5th and 6th editions.
REFERENCES
1. Harmer MN, editor. TMN classification of malignant
tumors, 3rd ed. Union Interationale Contra la Cancer:
Geneva; 1978
2. Ho JHC. Stage classification of nasopharyngeal carci-
noma: A review. IARC Sci Publ 1978; 20: 99-113
3. Li ZQ, Pan QC, Chen JJ. Clinic of NPC and experimen-
tal research. Technological Publication Press:
Guandong; 1983
4. Irvin DF, Jay SC, Donald EH, et al. Staging of cancer at
specific anatomic sites. AJCC Cancer Staging Manual.
Fifth edition. Philadelphia Baltimore New York:
Lippincott Williams&Wilkins, 1997: 31-39
5. Altun M, Fandi A, Dupuis O, et al. Undifferentiated
nasopharyngeal cancer (UCNT): Current diagnostic and
therapeutic aspects. Int J Radiat Oncol Biol Phys 1995;
32: 859-877
?
??
?
??
?
6. Teo PML, Leung SF, Yu P, et al. A comparison of Ho
?
)X
@1 ??
3@ ?
S5
.Y ??
?
??
?
??
?
??
??
??
??
?
?
??
?
s, International Union Against Cancer, and American
??
?
??
Joint Committee Stage Classifications for nasopharyn-
geal carcinoma. Cancer 1991; 67: 434-439
7. Prez CA, Venkata RD, Marcial-Vega V, et al.
Carcinoma of the nasopharynx: Factors affecting prog-
nosis. Int J Radiat Oncol Biol Phys 1992; 23: 271-280
8. Teo PML, Tsao SY, Ho JHC, et al. A proposed modifi-
cation of the Ho stage-classification for nasopharyngeal
carcinoma. Radiother Oncol 1991; 21: 11-23
9. Huang SC, Lui TL, Lynn TC. Nasopharyngeal cancer:
study III. A review of 1206 patients treated with com-
bined modalities. Int J Radiat Oncol Biol Phys 1985;
11:1789-1793
10. Shanmugaratnam K, Sobin LH. International histologic
classification: Histologic typing of tumors of the upper
respiratory tract and ear. 2nd ed. Berlin: Springer-
Verlag; 1991: 32-33
11. Ma J, Mai HQ, Min HM, et al. Is the 1997 AJCC stag-
ing system for nasopharyngeal carcinoma prognostical-
ly useful for Chinese patient populations? Int J Radiat
Oncol Biol Phys 2001; 50: 1181-1189
12. Ozyar E, Yildiz F, Akyol FH, Atahan IL. Comparison
of AJCC 1997 classifications for nasopharyngeal carci-
noma. Int J Radiat Oncol Biol Phys 1999; 44: 1079-
1087
13. Cooper JS, Cohen R, Stevens RE. A comparison of
staging systems for nasopharyngeal carcinoma. Cancer
1998; 83: 213-219
14. Teo P, Yu P, Lee WY, et al. Significant prognosticators
after primary radiotherapy in 903 nondisseminated
nasopharyngeal carcinoma evaluated by computer
tomography. Int J Radiat Oncol Biol Phys 1996; 36:
291-304
15. Lee A. Staging and prognostic factors in NPC-the HK
experience. UICC Workshop on Nasopharyngeal
Cancer: Issue and challenges. UICC; 1998: 77-79
16. Chua ST, Sham JS, Kwong DL, et al, Prognostic value
of paranasopharyngeal extension of nasopharyngeal car-
cinoma. A significant factor in local control and distal
metastasis. Cancer 1996; 78: 202-210
17. Cheng SH, Yen KL, Huang AT, et al. Examining prog-
nostic factors and patterns of failure in nasopharyngeal
carcinoma following concomitant radiotherapy and
chemotherapy: Impact on future clinical trials. Int J
Radiat Oncol Biol Phys 2001; 50: 717-726
Comparison of staging systems for NPC 135