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M. Kobari and S.

Matsuno: Staging system for pancreatic cancer 121 J Hep Bil Pancr Surg (1998) 5:121127
Abstract: Differences between the clinical staging system
of the Japan Pancreas Society (JPS) and the Union Inter-
nationale Contre le Cancer (UICC) stage classication may
account for reported differences in the prognosis of pancreatic
carcinoma between Japan and the West. In the review, we
compared the characteristics of the JPS and UICC staging in
1689 patients, registered with the JPS from 1981 to 1990, who
underwent resection for carcinoma of the pancreatic head.
The survival rates correlated well with the JPS stage classica-
tion. The UICC staging did not reect differences in prog-
noses among the stages. The current JPS staging system,
introduced in 1993, still differs from that of the UICC. To
compare the results of treatment for patients with pancreatic
cancer it is important to establish a more practical and uni-
versal staging system for carcinoma of the pancreas.
Key words: staging, pancreatic cancer, UICC
Introduction
In Japan, the rst edition of the General rules for surgi-
cal and pathological studies on cancer of pancreas was
published 1980,
1
followed by two revisions the second
edition in 1982,
2
and the third edition in 1986.
3
The
registration of pancreatic cancer with the Registration
Committee of the Japan Pancreas Society (JPS) was
started in 1981 and 11317 patients were registered in the
10 years to 1990.
4
From evaluation of the results of
treatment for these patients according to stage or histo-
logical classication, and with the understanding of new
diseases such as mucin hypersecreting pancreatic
tumor, a new edition of General rules for Surgical and
pathological studies on cancer of pancreas (the fourth
Offprint requests to: M. Kobari
Received for publication on Sept 8, 1997; accepted on
March 25, 1998
edition) was published in 1993.
5
But there are still some
differences between the JPS stage classication (JPS-
SC)
5
and the Union Internationale Contre le Cancer
stage classication (UICC-SC)
6
and these differences
may account for differences in the prognosis of pancre-
atic carcinoma reported in Japan and Western coun-
tries. In this review, we compared the JPS-SC in the
third edition of the General rules for surgical and patho-
logical studies of cancer of pancreas
3
with the stage
classication of the UICC
6
according to survival ana-
lyses in the Report of cases collected during a 10-years
period, as above.
4
The features of the current stage
classication of the JPS
5
are also discussed.
Patients and methods
Staging systems were compared between the third
edition of the JPS stage classication and the UICC
stage grouping. Differences between staging systems in
the third
3
and fourth editions
5
of the JPS stage classica-
tion were also analyzed. The new stage groupings for
pancreatic cancer published in 1997 by the UICC are
also shown.
Survival analysis
The results of resective treatment were analyzed in 1689
patients with carcinoma of the head of the pancreas
registered with the JPS from 1981 until 1990. The pa-
tients who underwent resection were individually classi-
ed according to the UICC stage grouping
6
and the JPS
stage classication (third edition
3
) at the same time by
the attending surgeons according to operative explora-
tions or investigation of resected specimens. Both the
UICC and the JPS stages were recorded simultaneously
on record cards and the cards were registered with the
Registration Committee of the JPS. Survival rates were
compared in JPS and UICC stages.
Topics: Staging and treatment for pancreatic cancer
Staging systems for pancreatic cancer: Differences between
the Japanese and UICC systems
Masao Kobari and Seiki Matsuno
First Department of Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-77, Japan
122 M. Kobari and S. Matsuno: Staging system for pancreatic cancer
Fig. 1. Japan Pancreas Society (JPS) stage
classication (third edition).
3
For all Figs.,
see text for explanations of abbreviations
The survival rates of patients treated at the First
Department of Surgery, Tohoku University School of
Medicine in the past 10 years were also compared ac-
cording to JPS stages in the third
3
and fourth edition
5
of
the JPS stage classication.
Survival curves were calculated by the Kaplan-Meier
method. Differences between survival curves were
analyzed by the generalized Wilcoxon method and the
log-rank test. A probability value of less than 0.05 was
considered to be signicant difference.
Results
Stage classication of the JPS (third edition)
3
The staging classication for carcinoma of the pancreas
as proposed by the JPS is shown in Fig. 1.
3
This classi-
cation is based on macroscopic examination and each
stage is judged by preoperative imaging diagnosis or
surgical exploration, including macroscopic evaluation
of surgical specimen, as in the UICC-SC. T indicates
only the size of the tumor at its greatest dimension. T1
is a tumor with a diameter less than 2cm; T2 is a tumor
with a diameter of 24cm; T3 is a tumor with a diameter
of 46cm; T4 is a tumor with a diameter of more than
6cm. N indicates lymph node metastasis. N0 indicates
no lymph node involvement. N1 (group 1) is involve-
ment of the primary group of lymph nodes situated
close to the tumor; N2 (group 2) is involvement of the
secondary group of lymph nodes between N1 and N3;
N3 (group 3) is involvement of the tertiary group of
lymph nodes considered as juxta-regional lymph nodes.
S indicates direct anterior capsular invasion. Rp indi-
cates retroperitoneal invasion (fat, connective tissue,
nerves, or bile duct). PV designates direct tumor inva-
sion of the portal venous systems. S, Rp, and PV are
separated into four groups according to the extent of
extrapancreatic tissue invasion. 0, absence of tumor in-
vasion, for example S0, Rp0, PV0; 1, suspected invasion;
2, denite invasion; S3, Rp3, and PV3 indicate severe
invasion extending directly to adjacent organs (stomach
or colon), retroperitoneum (aorta, superior mesenteric
artery, inferior vena cava, kidney, or adrenal gland),
and portal vein, respectively.
Fig. 2. Union Internationale Contre le Cancer (UICC) stage
grouping (1983)
3
Stage I is T1, N0, S0, Rp0, PV0. If any of the staging
factors T2, N1, S1, Rp1, PV1 are found, the stage is II.
If any of the staging factors T3, N2, S2, Rp2, PV2
are found, the stage is III. The diagnosis is stage IV if
any of the staging factors T4, N3, S3, Rp3, or PV3 are
found. Distant metastasis, including hepatic metastasis
and peritoneal dissemination, is also classied as stage
IV.
Criteria for UICC grouping (1987)
6
and comparison
with JPS staging (third edition)
3
The criteria for UICC stage grouping are also shown
in the JPS staging
3
(Fig. 2).
3
The staging factors em-
ployed in the UICC-SC are: primary tumor, T; lymph
node metastasis, N; and distant metastasis, M. Assess-
ment of each category is made by physical examination,
imaging, and/or surgical exploration. In the UICC stag-
ing, T includes not only tumor size but also the extent of
tumor invasion to tissues surrounding the pancreas. In
the JPS staging, T means only tumor size, and the extent
of tumor invasion is expressed by S, Rp, or PV. In
UICC stage I, the tumor is limited to the pancreas (T1)
or extends directly to the duodenum, bile duct, or
peripancreatic tissues (T2) without lymph node
metastasis (N0). In UICC stage II, the tumor extends
directly to the stomach, spleen, colon, or adjacent large
vessels (T3), but is without lymph node metastasis
(N0). In UICC stage III, positive regional lymph node
metastasis is included (N1). UICC stage IV contains
distant metastasis, including extrapancreatic lymph
node metastasis. In the JPS-SC, we attach as much im-
portance to the extent of lymph node metastasis as
to the size of the tumor and the extent of invasion to
extrapancreatic tissues.
M. Kobari and S. Matsuno: Staging system for pancreatic cancer 123
T2, Tumors classied as one or more of the following:
S1, rP1, PV1, A1, DU1,2,3, and CH2,3, regardless
of size
T3, Tumors classied as one or more of the following:
S2,3, rP2,3, PV2,3, and A2,3, regardless of size
The T category in this latest staging system no longer
indicates only size. This point is very different from the
previous JPS staging system.
3
The grading from 0 to 3
for category S, category RP, category PV, and category
N is the same as the system in the third edition.
3
However in the fourth edition,
5
A denotes the arterial
system, including common hepatic artery, superior
mesenteric artery, splenic artery, celiac artery, and
aorta. The grading from 0 to 3 for category A is: A0, no
evidence of invasion; A1, invasion suspected; A2, de-
nite invasion; and A3, marked invasion with stenosis or
obstruction of the arterial system. DU denotes duode-
nal wall. The grading from 0 to 3 for category DU is:
DU0, no evidence of invasion; DU1, invasion sus-
pected; DU2, denite invasion, but limited to the
duodenal wall; and DU3, marked invasion with tumor
penetration into the duodenal lumen or stenosis of the
duodenum. CH denotes distal bile duct. The grading
from 0 to 3 for category CH is: CH0, no evidence of
invasion; CH1, invasion suspected; CH2, denite inva-
sion; and CH3, marked invasion with stenosis or
obstruction of the bile duct. The category P denotes
peritoneal metastasis. The grading from 0 to 3 for cat-
egory P is: P0, no peritoneal metastasis; P1, metastasis
to the peritoneum adjacent to the pancreas; P2, a few
metastases to distant peritoneum; and P3, numerous
metastases to distant peritoneum. Category H denotes
liver metastasis. The grading from 0 to 3 for category H
is: H0, no liver metastasis; H1, metastasis limited to one
lobe; H2, a few metastases to both lobes; H3, numerous
metastases to both lobes. Category M denotes distant
metastasis other than those to peritoneum or liver.
Comparison of survival rates for patients treated
at our university hospital according to the third
3
and fourth editions
5
of the JPS stage classication
For the third edition of the JPS stage classica-
tion,
3
survival curves according to JPS stages were well
Survival rate according to JPS stage classication
(third edition)
3
The 3-year survival rates of resected pancreatic head
cancer in the 1689 patients registered with the JPS
from 1981 to 1990 were 66.2% in stage I (n 165),
37.2% in stage II (n 382), 25.4% in stage III (n 474),
and 12.7% in stage IV (n 668). The 5-year survival
rates were 48.1% in stage I, 27.7% in stage II, 22.3% in
stage III, and 8.8% in stage IV. The prognosis was
better in the early stages of pancreatic cancer and both
the 3- and 5-year survivals showed signicant differ-
ences between stages I and II and between stages III
and IV.
Survival rate according to UICC stage grouping (1987)
6
Of the 1521 patients with resected pancreatic head
cancer for whom all UICC staging factors were accu-
rately recorded, 320 patients (21.0%) were in stage I
and 182 patients (12.0%) in stage II. Five hundred and
eight-six patients (38.5%) were in stage III and 433
(28.5%) in stage IV. The number of patients in UICC
stage I was more than two times and the number in
UICC stage II was about half compared with the num-
bers of patients in stages I and II according to the JPS-
SC. The 3-year survival rates were 44.3% in UICC stage
I, 22.5% in UICC Stage II, 16.3% in UICC Stage III,
and 9.6% in UICC Stage IV. The 5-year survival rates
were 32.5% in UICC stage I, 11.5% in UICC stage II,
12.0% in UICC stage III, and 6.6% in UICC stage IV.
Current staging classication of the JPS
(fourth edition)
5
The current staging system was proposed by the JPS in
1993 (Fig. 3).
5
The surgical staging is shown in the
General rules for surgical and pathological studies on
cancer of the pancreas.
5
T categories are assigned ac-
cording to the extent of tumor invasion, as follows:
T1, Tumors which are S0, rP0, PV0, A0, DU0, and
CH0,1 (see below for denitions)
T1a, Tumors 2.0cm or less at the greatest dimension
T1b, Tumors more than 2.0cm at the greatest
dimension
Fig. 3. Current JPS stage classication
(fourth edition)
5
124 M. Kobari and S. Matsuno: Staging system for pancreatic cancer
The survival curves according to category N in the
fourth edition were well separated between N0 and N1
and also between N1 and N2 or N3 (Fig. 5). This differ-
ence in survival curves seems better than that in the
third edition.
separated into three groups: stage I, stage II and III, and
stage IV. In the fourth edition,
5
survival curves were
also divided into three groups: stages I and II, stages III
and IVa, and stage IVb. For both editions, each stage
group reected the prognosis well (Fig. 4).
Fig. 4. Survival rates according to the JPS stage classications (third edition
3
vs fourth edition
5
). *P 0.01
Fig. 5. Survival rates according to category N in the JPS stage classications (third edition
3
vs fourth edition
5
). *P 0.01
M. Kobari and S. Matsuno: Staging system for pancreatic cancer 125
The T category in the fourth edition signicantly well
reected the prognosis of the patients (Fig. 6).
New stage grouping proposed by the UICC
(1997)
16
(Fig. 7)
T categories. Tis, carcinoma in situ; T1, tumor limited to
the pancreas, 2cm or less at greatest dimension; T2,
tumor limited to the pancreas, 2cm or more at greatest
dimension; T3, tumor extending directly to any of the
following: duodenum, bile duct, peripancreatic tissue;
T4, tumor extending directly to any of the following:
stomach, spleen, colon, adjacent large vessels.
N categories. N0, no regional lymph node metastasis;
N1, regional lymph node metastasis; N1a, metastasis
in a single regional lymph node; N1b, metastasis in
multiple regional lymph nodes.
M categories. M0, no distant metastasis; M1, distant
metastasis.
Discussion
Despite advances made in tumor imaging diagnosis, the
proportion of patients diagnosed with pancreatic cancer
at an early stage has not increased. According to the
Japanese report on collected cases in the 10 years to
1991,
4
11.7% of 11317 patients were classied as UICC
stage I, 12.1% as stage II, 20.1% as stage III, and 56.1%
as stage IV, and resection was performed for 33.1% of
patients. In the 1994 report on 1133 collected cases,
7
15.9% of patients were UICC stage I; 10.4% stage II;
30.9% stage III, and 42.8% stage IV; the resection rate
was 43.5%. In our analysis of the 1835 patients who
underwent resection for carcinoma of the head of the
pancreas until 1994, 6.1% of patients were classied as
JPS stage I and 21.9% as JPS stage II; more than 70%
of patients were classied as JPS stage III or IV.
7
These stage distributions were comparable to those in
The National Cancer Data Base Report on Pancreatic
Cancer.
8
In our survival analyses of the 1689 patients with
resected pancreatic head cancer registered with the JPS
from 1981 until 1990, the survival rate correlated well
with the JPS-SC and survivals were longer in patients in
stage I or II than in patients in stage III or IV (the 5-year
survival rate for stage I was 48.1%, for stage II, 27.7%;
for stage III, 22.3%; and for stage IV, 8.8%). In the
UICC-SC, the survival rate was extremely high for stage
I (32.5%) compared with survival rates in other stages
(less than 10%) and there was no signicant difference
among survival rates at stages later than stage II.
9
The
survival rate dropped between stage II and stage III.
This pattern of survival rates was very similar to the
difference in survival rates between N0 (high) and N1
(low).
9
The reason for the lack of difference in survival
rates at stages later than stage II seems to be that N in
UICC-SC is simply graded as absence of involvement
(N0) or presence of involvement (N1). As stated above,
in the JPS-SC, we attach as much importance to the
extent of lymph node involvement as to the extent of
Fig. 7. New UICC stage grouping
(1997)
16
Fig. 6. Three- and 5-year survival rates according to category
T in the JPS stage classication (fourth edition
5
). *P 0.01
126 M. Kobari and S. Matsuno: Staging system for pancreatic cancer
invasion to extrapancreatic tissues. The extent of
macroscopic lymph node involvement assessed surgi-
cally was similar to the extent of histological lymph
node involvement.
7
In the UICC-SC, stage I is distinguished from stage II
by the presence or absence of invasion to peripancreatic
organs (stomach, spleen, or colon) or large vessels (T1
or T2 vs T3) and when lymph node involvement is de-
tected (N1) the stage is III. If distant metastasis is found
(M1) the stage is IV. This staging system is simple, easy,
and objective. In the JPS-SC, the extent of LN involve-
ment (N) or the extent of peripancreatic tissue invasion
(S, Rp, PV) is graded from 0 to 3 and the size of tumor
(T) is included in the staging factors.
One difference of the UICC staging system from
the JPS-SC may be that patients are classied as UICC
stage I even when anterior serosal invasion (S) or retro-
peritoneal invasion (RP) are found (UICC T23). Un-
like the JPS-SC, the UICC-SC gives no clear description
of S-, Rp-, and PV. And the denition of T2 in the
UICC-SC is that a tumor shows limited direct extension
to duodenum, bile duct, or peripancreatic tissues; this
corresponds to S02, Rp02, and PV02, in the JPS-SC.
Tsunoda et al.
10
reported that, with the UICC-SC, there
are some underestimations of the stage, as follows.
UICC T2 patients, i.e., patients with denite involve-
ment of peripancreatic tissues corresponding to Rp2 in
the JPS-SC, are allocated to UICC stage I. UICC T3
patients, who have invasions to the surrounding organs
or adjacent large vessels, corresponding to Rp3 and
PV23 in the JPS-SC, belong to UICC stage II. In the
JPS-SC, the patients with these conditions (S3, Rp3,
and/or PV3) belong to stage IV. This difference in
description concerning extrapancreatic tissue invasion
may account for the difference in survival curves
between JPS-SC and UICC-SC, because the survival
rates of patients with S0, patients with Rp0, patients
with PV0, or patients with N0 were much higher than
those of patients with S13, patients with R
p
13, pa-
tients with PV13, or patients with N13.
9
Tannapfel et
al.
11
reported that lymph node involvement and direct
extension of the tumor into peripancreatic tissue, as
well as invasion into peripancreatic organs, signicantly
inuenced survival. They found no relationship be-
tween survival and tumor size. Zerbi et al.
12
evaluated
the prognostic value of the UICC-SC and JPS-SC in 74
patients undergoing resection for pancreatic carcinoma
and classied according to both the UICC-SC and JPS-
SC at the same time. According to the UICC-SC, there
was a high proportion of patients in stage I (38%) and
stage III (39%) and a low proportion in stage II (16%);
most patients were in earlier stages compared with the
distribution of patients according to the JPS-SC. On
the other hand, the distribution of patients according to
the JPS-SC increased as the stage progressed. Survival
curves at each stage were separated well and the differ-
ence among the curves was signicant for the JPS-SC.
However, in the UICC-SC, the survival curves over-
lapped at stages II and III. In an analysis of survival
according to the UICC-SC in Norwegian patients,
Bekkevold and Kambestad
13
tested a minor modica-
tion of UICC-SC and showed comparable prognoses for
stages I and II and different prognoses for stages II and
III, contrary to the present UICC-SC.
16
Balzano et al.
14
evaluated the following modied UICC-SC in their 228
patients who underwent resection for pancreatic cancer,
and reported a better differentiation of stage II and
III survival than for the standard UICC-SC: Stage I,
T1N0M0; stage II, T1N1M0/T2N0M0; stage III,
T2N1M0/T3 anyNM0; stage IV, M1. However, the
JPS-SC has a greater prognostic value than either the
standard or the modied UICC-SC.
In the current JPS stage classication in the new
General rules for surgical and pathological studies on
cancer of the pancreas (4th Edn),
5
tumor size was ex-
cluded from the T category, because the survival rates
correlated well with stages even when the tumor size
was omitted from the staging.
9
On graphs of survival,
T is shown as the vertical axis, similar to T in the
UICC system, but it is graded from 1 to 3 and this
grading depends on the extent of peripancreatic tissue
invasion, graded from 0 to 3. The Horizontal axis is N,
graded from 0 to 3. This grading system is also very
different from the UICC staging and is important as, in
the analyses of survival rate among stages classied ac-
cording to the JPS-SC, the extent of lymph node in-
volvement and of extrapancreatic tissue invasion were
the most important staging factors.
4,9
In our analyses of
our small series of patients, N, T, and the stages of
the current JPS stage classication (fourth edition)
5
re-
ected prognosis very well. Therefore, it is expected
that when many cases are registered with the current
JPS-SC, better differences in survival rates among the
stages may be obtained. Last year, the JPS published
the rst English edition of Classication of pancreatic
carcinoma, which is now in use in Japan.
15
The UICC
also modied the stage classication of pancreatic can-
cer (Fig. 7) evaluated in this study and published a new
edition last year.
16
There are still differences between the current JPS-
SC and the new UICC-SC. To discuss the results of
treatment for pancreatic cancer, it will be necessary to
analyze the survival rates according to a common
staging system.
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M. Kobari and S. Matsuno: Staging system for pancreatic cancer 127
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